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PMC11276581_p24
|
PMC11276581
|
sec[2]/sec[4]/sec[1]/p[0]
|
3.5.2. An Elusive Coding Mutation
| 3.199219 |
biomedical
|
Study
|
[
0.998046875,
0.0011301040649414062,
0.0009241104125976562
] |
[
0.6904296875,
0.2958984375,
0.00362396240234375,
0.01000213623046875
] |
Further illustrating the complexities of genetic diagnostics, an intriguing and elusive nonsense pathogenic mutation in the EYS gene was identified.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276581_p25
|
PMC11276581
|
sec[2]/sec[4]/sec[1]/p[1]
|
3.5.2. An Elusive Coding Mutation
| 4.175781 |
biomedical
|
Study
|
[
0.98046875,
0.0192108154296875,
0.0003101825714111328
] |
[
0.80029296875,
0.024932861328125,
0.005146026611328125,
0.1697998046875
] |
The index case, MOL2142-1, was diagnosed with ARRP due to extinguished ERG responses at the age of 55 years, a fundus appearance that included typical signs of RP (bone-spicule pigmentation and attenuated blood vessels), and a reduced BCVA of 0.25. An analysis of SVs in IRD genes, as part of the panel analysis, revealed a heterozygous deletion of a single EYS exon (#34), as well as two nucleotide changes (one synonymous and the other nonsynonymous), affecting neighboring nucleotides . Interestingly, this combination of variants was identified in multiple cases with an RP of Arab Muslim origin and confirmed to be in cis. The combination of the two variants results in a nonsense mutation . Such a complex mutation can be overlooked in many NGS pipelines, highlighting the challenges of variant interpretation and the importance of comprehensive genetic panels.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276581_p26
|
PMC11276581
|
sec[2]/sec[4]/sec[2]/p[0]
|
3.5.3. Novel Genetic Discoveries in Israeli Patients: Unveiling Rare Variants and First Cases
| 4.21875 |
biomedical
|
Study
|
[
0.99951171875,
0.0003407001495361328,
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] |
[
0.9990234375,
0.0003533363342285156,
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0.0001608133316040039
] |
Joubert syndrome, a recessive and genetically heterogeneous neurodevelopmental ciliopathy, is characterized by a distinctive brain malformation, often presenting with a complex phenotype that may include retinal dystrophy. In our study, we identified two cases, MOL2246-1 and MOL22151-1, marking the first documented instances in Israel of Joubert syndrome associated with mutations in the ARMC9 and LAMA1 genes, respectively. Notably, these genes are rare contributors to this syndrome; in the literature, only 19 cases of ARMC9 mutations have been reported across five different articles from Japanese , Chinese , Turkish , and Indian populations, while LAMA1 mutations have been documented in just five cases from British and Japanese cohorts spanning two articles. This underscores the rarity and global diversity of genetic variants contributing to Joubert syndrome.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276581_p27
|
PMC11276581
|
sec[2]/sec[4]/sec[2]/p[1]
|
3.5.3. Novel Genetic Discoveries in Israeli Patients: Unveiling Rare Variants and First Cases
| 4.066406 |
biomedical
|
Clinical case
|
[
0.71533203125,
0.28271484375,
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] |
[
0.07086181640625,
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0.9111328125
] |
Case MOL2246-1 was diagnosed with a congenital syndrome due to polydactyly (of both fingers and toes), nephrolithiasis, dysmorphism, hypotonia, developmental delay, patent foramen ovale in the heart, ocular gaze abnormality, and hypermetropia (+5.0 diopter). An ERG examination at the age of 7 months was performed under anesthesia and revealed reduced cone function in the right eye (to 60% of lower normal limit). The parents of the index case were consanguineous of Bedouin origin and no other affected individuals were reported in the family. The genetic analysis revealed a homozygous splice-site variant, c.51+5G>T (IVS2+5G>T) in the ARMC9 gene. This variant has already been reported in an Israeli patient with similar symptoms , and in addition, it has been reported as a VUS (two reports), LP (likely pathogenic) and P (one report each) in ClinVar. It is predicted to affect splicing by multiple splicing analysis tools (SpliceAI, dbscSNV Ada, and dbscSNV RF).
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276581_p28
|
PMC11276581
|
sec[2]/sec[4]/sec[2]/p[2]
|
3.5.3. Novel Genetic Discoveries in Israeli Patients: Unveiling Rare Variants and First Cases
| 3.966797 |
biomedical
|
Clinical case
|
[
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[
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0.931640625
] |
Case MOL2215-1 was diagnosed with molar tooth sign, dysplastic cerebellum, developmental delay, growth delay, high myopia (−17 diopters), and esotropia. His visual acuity at the age of 5 years was 6/45 both eyes and latent horizontal nystagmus was noted. ERG testing at the age of 11 years showed low rod (75% of normal) and cone (30% of normal) amplitudes. The parents of the index case are consanguineous of Arab-Muslim origin and no other affected individual were reported in the family. The genetic analysis revealed a homozygous splice-site variant, c.2344C>T (p.R782*), in the LAMA1 gene. The variant has already been reported in two patients with similar phenotypes and is expected to create a pre-mature stop codon in exon 17 out of 62 exons.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276581_p29
|
PMC11276581
|
sec[2]/sec[4]/sec[2]/p[3]
|
3.5.3. Novel Genetic Discoveries in Israeli Patients: Unveiling Rare Variants and First Cases
| 4.210938 |
biomedical
|
Study
|
[
0.99951171875,
0.0005869865417480469,
0.00012874603271484375
] |
[
0.99853515625,
0.0005240440368652344,
0.0005159378051757812,
0.00032591819763183594
] |
In addition to the aforementioned cases, our study unveiled several other rare variants, each representing the first documented instances in Israel. One such case is patient MOL1437-1, who exhibits a compound heterozygosity for missense mutations in the WDR19 gene, resulting in non-syndromic RP. Another noteworthy finding is a homozygous nonsense mutation in the SAG gene in patient MOL2008-1, leading to Oguchi disease. Lastly, patient MOL2079-1 was identified as homozygous for a nonsense mutation in the SRD5A3 gene, which is associated with a congenital disorder of glycosylation . The patient was 33 years old and was diagnosed with RP associated with learning difficulties. ERG testing at the age of 20 years showed extinguished rod and cone responses. These five cases represent novel discoveries in the Israeli population, highlighting the significance of our study in expanding the understanding of rare genetic variants and their clinical implications.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276581_p30
|
PMC11276581
|
sec[3]/p[0]
|
4. Discussion
| 4.15625 |
biomedical
|
Study
|
[
0.99951171875,
0.0003974437713623047,
0.00019216537475585938
] |
[
0.99951171875,
0.00019741058349609375,
0.0003814697265625,
0.00008779764175415039
] |
In the current study, we used a single IRD gene panel to screen 252 IRD samples for mutations in 351 IRD-causing genes. Previous studies reported a yield of positive genetic results in 40–75% of analyzed cases and our study, with 55%, falls within this range as expected . Our cohort could be divided into newly recruited cases who were not screened for any IRD-causing mutations and those who underwent genetic analysis (including genotyping founder mutations, IRD gene panels, and WES). The power of the current panel analysis can be appreciated by the much higher detection rate of 74% compared to only 26% of those previously analyzed (mainly due to mutations in genes that were not included in the previous analyses or SVs). This high rate can partly be attributed to SV analysis performed on the NGS data. Improved recent NGS analysis pipelines include the detection of both homozygous or heterozygous SVs, which assist in the identification of such mutations on 10–15% of pathogenic alleles . Switching to WGS is likely to increase this rate and improve the overall detection rate of pathogenic alleles in IRDs.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276581_p31
|
PMC11276581
|
sec[3]/p[1]
|
4. Discussion
| 4.175781 |
biomedical
|
Study
|
[
0.99951171875,
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0.0001513957977294922
] |
[
0.99853515625,
0.0004017353057861328,
0.0011396408081054688,
0.00007891654968261719
] |
The genetic analysis of newly diagnosed IRD cases depends on the phenotypic complexity and the available information on IRDs in the relevant population. The spectrum of IRD mutations in the Israeli population was studied comprehensively, mainly by a nationwide collaborative effort of the Israeli inherited retinal diseases consortium (IIRDC), leading to enriched information on the disease prevalence of various IRD phenotypes , the development of an NGS founder mutation gene panel , and the identification of a large number of mutations in each sub-population . This continuous effort allows us, in some cases, to pinpoint the pathogenic mutation quickly, without the need of time-consuming and costly analyses. However, in the majority of cases, either due to the lack of known common founder mutations or challenging phenotyping, gene panels, such as the one used in the current study, can aid in the identification of the cause of disease in about 75% of cases.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276581_p32
|
PMC11276581
|
sec[3]/p[2]
|
4. Discussion
| 4.105469 |
biomedical
|
Study
|
[
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] |
[
0.99951171875,
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] |
Another factor that makes the process of gene identification even more challenging is the relatively high carrier frequency rate for mutations that cause IRDs. We have shown previously using worldwide datasets that, on average, 36% of healthy individuals are carriers of AR-IRD pathogenic mutations . This high value is also valid for solved IRD cases who carry an AR mutation in a second IRD gene by chance. Therefore, identifying a single heterozygous AR mutation in a patient with IRD does not necessarily mean that this gene is indeed the cause of disease. In line with this previous IRD carrier analysis, we identified here heterozygous AR mutations that were not the cause of disease in 36% of solved cases.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276581_p33
|
PMC11276581
|
sec[3]/p[3]
|
4. Discussion
| 4.097656 |
biomedical
|
Study
|
[
0.99951171875,
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] |
[
0.9990234375,
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] |
Quick and reliable gene identification is important for a more efficient genetic counseling and disease prevention in coming generations , participation in gene/mutation-specific clinical trials , or FDA-approved IRD therapies . The analysis performed in this study shows that gene panels can be highly efficient in identifying the cause of disease and, in some cases, identifying also additional IRD-causing mutations that one out of three patients with IRD carry by chance, as we previously reported . Including the mitochondrial genome and performing SV analyses on the NGS data further improves the yield of gene and mutation identification, and therefore, such panels are highly recommended.
|
[
"Maria Abu Elasal",
"Samira Mousa",
"Manar Salameh",
"Anat Blumenfeld",
"Samer Khateb",
"Eyal Banin",
"Dror Sharon"
] |
https://doi.org/10.3390/genes15070926
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p0
|
PMC11276593
|
sec[0]/p[0]
|
1. Introduction
| 4.324219 |
biomedical
|
Review
|
[
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[
0.00946044921875,
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] |
Glucocorticoids (steroids) are potent anti-inflammatory medications that are frequently used in the treatment of critically ill patients. Systemic glucocorticoids, prednisone, methylprednisolone, and hydrocortisone mimic the action of naturally occurring glucocorticoids by binding intracellular glucocorticoid receptors in the cytoplasm. This glucocorticoid-receptor complex regulates transcription of glucocorticoid response elements such as nuclear factor receptor-κβ, which modulates the transcription of proinflammatory cytokines. Glucocorticoids also promote the activity of anti-inflammatory cytokines and inhibit fibroblast production. In addition to their effect on the immune system, glucocorticoids are key mediators of the stress response. They increase cardiac output, increase the responsiveness of vascular adrenergic receptors, and decrease vascular permeability. Glucocorticoids also have significant effects on metabolism, resulting in increased gluconeogenesis and altered metabolism of fat, bone, and protein . In light of these mechanisms, a trial of glucocorticoids is often used in critical illness when dysregulation of the inflammatory response is proposed to underly the pathology in order to limit organ damage, and promote recovery of organ function, with the goal of improving mortality.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p1
|
PMC11276593
|
sec[0]/p[1]
|
1. Introduction
| 2.759766 |
biomedical
|
Other
|
[
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] |
[
0.0019464492797851562,
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] |
However, glucocorticoids are not without serious potential side effects. In the critically ill population, these side effects include but are not limited to new infections, hyperglycemia, and critical illness myopathy. In order to maximize benefit and limit harm, practitioners must be aware of the evidence justifying the use of glucocorticoids.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p2
|
PMC11276593
|
sec[0]/p[2]
|
1. Introduction
| 4.035156 |
biomedical
|
Review
|
[
0.9716796875,
0.019805908203125,
0.00870513916015625
] |
[
0.0019817352294921875,
0.00390625,
0.99267578125,
0.0012989044189453125
] |
In this review, we aim to present the evidence justifying the use of glucocorticoids in septic shock, acute respiratory distress syndrome (ARDS), severe pneumonia, severe SARS-CoV-2 infection (COVID), and hypercapnic respiratory failure due to exacerbation of chronic obstructive lung disease (COPD). We will focus on prospective randomized trials as they provide the highest level of confidence for any recommendation.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276593_p3
|
PMC11276593
|
sec[1]/p[0]
|
2. Steroids in Septic Shock
| 3.955078 |
biomedical
|
Review
|
[
0.99755859375,
0.0018091201782226562,
0.0006761550903320312
] |
[
0.041656494140625,
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Sepsis and septic shock develop when inflammation spreads beyond the initial site of an infection, resulting in a systemic proinflammatory cascade, which overwhelms the body’s anti-inflammatory processes and leads to diffuse cellular injury and multiorgan damage. This inflammatory mechanism provides a rationale for the use of steroids in the treatment of septic shock. Table 1 summarizes the randomized trials addressing this potential over the last several decades.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276593_p4
|
PMC11276593
|
sec[1]/p[1]
|
2. Steroids in Septic Shock
| 4.089844 |
biomedical
|
Study
|
[
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] |
[
0.9970703125,
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] |
Descriptions of glucocorticoids in the treatment of sepsis date back to the 1950s , with small randomized controlled trials published in the 1960s and 1970s with contradictory results . In a 1988 study, Luce assessed the effect of high-dose methylprednisolone on mortality and the development of ARDS . Seventy-five patients with septic shock were enrolled within 1 to 2 h of admission or development of shock; patients were required to have a positive culture to ultimately be included in the study. Methylprednisolone, 30 mg/kg per dose for a total of 4 doses, was compared to placebo, and no difference in mortality or risk of ARDS was seen.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p5
|
PMC11276593
|
sec[1]/p[2]
|
2. Steroids in Septic Shock
| 4.148438 |
biomedical
|
Study
|
[
0.99072265625,
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] |
[
0.98095703125,
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] |
A decade later, the concept of relative adrenal insufficiency in septic shock patients and systemic inflammation-induced glucocorticoid receptor resistance prompted renewed interest in longer courses of low-dose corticosteroids. In 2002, in a trial published by Annane et al., 300 patients were randomized to low-dose hydrocortisone (50 mg IV every 6 h) plus fludrocortisone (50 mcg daily) compared to placebo, for a total of 7 days . Patients were enrolled early, within 8 h of meeting criteria for septic shock. An ACTH stimulation test was performed in all patients at the time of enrollment. Responders were defined as patients with an increase in the plasma cortisol level of at least 9 mcg/dL. Overall, a significant improvement in the 28-day survival was seen in the steroid group (hazard ratio 0.71, 95% CI: 0.53 to 0.97, p = 0.03). No difference in the rate of adverse events was noted. When analyzing the survival based on the response to the ACTH stimulation test, only patients with relative adrenal insufficiency (i.e., non-responders) showed an improvement in survival or hemodynamics with steroids (hazard ratio 0.67, 95% CI: 0.47 to 0.95, p = 0.02). No difference was seen in patients without relative adrenal insufficiency.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p6
|
PMC11276593
|
sec[1]/p[3]
|
2. Steroids in Septic Shock
| 4.09375 |
biomedical
|
Study
|
[
0.9580078125,
0.041290283203125,
0.0008664131164550781
] |
[
0.93212890625,
0.063232421875,
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] |
In 2008, Sprung assessed the use of hydrocortisone (50 mg every 6 h) in septic shock . Fludrocortisone was not used based on the assumptions that hydrocortisone possesses enough mineralocorticoid activity to make the use of fludrocortisone unnecessary, and absorption of oral fludrocortisone in a shock state is variable. A total of 499 patients were randomized, and all had a corticotropin test performed at baseline. Patients could be enrolled up to 72 h after the onset of shock. No difference in survival was seen regardless of the response to the ACTH stimulation test. There was also no difference in the proportion of patients with shock reversal, but faster time to reversal of shock was seen in patients who received steroids. Patients treated with hydrocortisone had increased incidence of new infections, hyperglycemia, and hyponatremia.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p7
|
PMC11276593
|
sec[1]/p[4]
|
2. Steroids in Septic Shock
| 4.117188 |
biomedical
|
Study
|
[
0.9970703125,
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[
0.99462890625,
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0.0003139972686767578
] |
In 2018, two larger placebo-controlled studies renewed interest in the use of steroids in septic shock patients. Venkatesh et al. randomized 3658 patients with septic shock requiring mechanical ventilation to 200 mg/day continuous infusion of hydrocortisone or placebo for 7 days . The study showed that hydrocortisone infusion did not result in a statistically significant reduction in 90-day mortality compared to placebo (27.9% vs. 28.8%). Patients in the hydrocortisone group had faster resolution of shock than those in the placebo (median duration of vasopressor use; 3 vs. 4 days, p < 0.001). Although patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation, there was no significant difference in the number of days alive and free of mechanical ventilation). More adverse events were seen in the hydrocortisone group, even though the absolute incidence was low (1.1 vs. 0.3%, p = 0.009).
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p8
|
PMC11276593
|
sec[1]/p[5]
|
2. Steroids in Septic Shock
| 4.125 |
biomedical
|
Study
|
[
0.9765625,
0.0225830078125,
0.0007143020629882812
] |
[
0.94921875,
0.045562744140625,
0.0033321380615234375,
0.001850128173828125
] |
Another placebo-controlled trial was published in 2018 by Annane . Similar to his first study, patients were randomized to receive a combination of hydrocortisone (50 mg IV every 6 h) with fludrocortisone (50 mcg once daily), administered for 7 days. A total of 1241 patients with septic shock for less than 24 h were enrolled. The primary outcome, death from any cause at day 90, was better in the treatment group (43.0 vs. 49.1%, relative risk 0.88, 95% CI 0.78 to 0.99, p = 0.03). Secondary outcomes also favored the use of steroids, including the 180-day mortality, vasopressor-free days, and organ failure-free days to day 28. The study showed more hyperglycemia in the steroids group, but similar rates of gastrointestinal bleeding and superinfections were seen.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p9
|
PMC11276593
|
sec[1]/p[6]
|
2. Steroids in Septic Shock
| 3.419922 |
biomedical
|
Review
|
[
0.9814453125,
0.01561737060546875,
0.0028285980224609375
] |
[
0.017486572265625,
0.3388671875,
0.64013671875,
0.0036106109619140625
] |
Driven by these results, the 2024 SSC guidelines included a conditional recommendation in favor of low-dose corticosteroids in patients with ongoing shock following fluid resuscitation . The debate regarding the association of low-dose corticosteroids with a mortality benefit in patients with septic shock and whether adding fludrocortisone has any additional benefit has yet to be resolved.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276593_p10
|
PMC11276593
|
sec[2]/p[0]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 4.191406 |
biomedical
|
Review
|
[
0.998046875,
0.0017299652099609375,
0.00030493736267089844
] |
[
0.316162109375,
0.1544189453125,
0.5234375,
0.0059356689453125
] |
ARDS is an intense inflammatory process that occurs at the level of the alveoli, alveolar blood membrane, and pulmonary interstitium. The alveolar space fills with fluids, cellular debris, and inflammatory cytokines . This results in severe gas exchange abnormalities with subsequent development of hypoxia, with hypercapnia in severe cases. The inflammation in ARDS is dynamic. The initial stage of the disease, usually occurring during the first week, is characterized by the development of edema and hyaline membranes. The second phase, beginning in the second week, is characterized by the presence of interstitial inflammation and the development of interstitial fibrosis .
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276593_p11
|
PMC11276593
|
sec[2]/p[1]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 4.046875 |
biomedical
|
Study
|
[
0.998046875,
0.0017852783203125,
0.00020623207092285156
] |
[
0.9677734375,
0.00386810302734375,
0.027801513671875,
0.00043010711669921875
] |
The use of steroids in ARDS has been investigated for decades ( Table 2 ), and was proposed as a potential treatment in the original description of ARDS in 1967 . One of the first randomized trials to use steroids in the treatment of ARDS was published by Bernard in 1987. They investigated the use of high-dose (30 mg/kg every six hours) methylprednisolone for 24 h in 99 patients with early ARDS . Patients were enrolled early, within 7 to 11 h after meeting ARDS criteria. The patients were on mechanical ventilation for an average of 2 to 3 days prior to entry into the study. No difference in survival at 45 days was seen between the two groups. The rate of hypoglycemia was increased in the intervention group, but the infectious complications were similar. Importantly, this trial was conducted prior to the widespread use of lung-protective ventilation, which has become the cornerstone of ARDS management. Studies conducted since widespread adoption of lung-protective ventilation strategies have been inconsistent.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p12
|
PMC11276593
|
sec[2]/p[2]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 4.152344 |
biomedical
|
Study
|
[
0.98388671875,
0.0157928466796875,
0.0005211830139160156
] |
[
0.97265625,
0.023162841796875,
0.0027637481689453125,
0.0014476776123046875
] |
A decade later, Meduri evaluated the use of a more prolonged course of methylprednisolone, given to patients with ARDS at a later stage of the disease . They enrolled patients who failed to improve after 7 days of respiratory failure. A total of 24 patients were randomized in a 2:1 ratio to methylprednisolone (loading dose of 2 mg/kg, followed by 2 mg/kg/day then a tapering regimen) or placebo. The treatment was continued for up to 32 days. Bronchioloalveolar lavage (BAL) was carried out on day 5 in order to detect the development of pneumonia. The study’s primary endpoint was the change in the Lung Injury Score (LIS), a combination of criteria including radiographic, gas exchange, positive end expiratory pressure (PEEP), and respiratory system mechanics . Secondary endpoints included mortality and the multiorgan dysfunction score. The study found a significant improvement in the LIS favoring the intervention group. Other findings included improvement in the ICU mortality as well as the in-hospital mortality. The infection rate was similar in the two groups.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p13
|
PMC11276593
|
sec[2]/p[3]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 4.15625 |
biomedical
|
Study
|
[
0.97412109375,
0.025177001953125,
0.0008101463317871094
] |
[
0.9326171875,
0.062042236328125,
0.0029449462890625,
0.00235748291015625
] |
In 2006, and as a result of the encouraging preliminary data, the ARDS network conducted a trial in late ARDS, defined as 7 to 28 days after the onset of disease . The study included patients with moderate-to-severe disease, defined as a PaO 2 /FiO 2 < 200 mm Hg. Methylprednisolone was started with a loading dose of 2 mg/kg of predicted body weight and was then tapered over several weeks. Similar to the Meduri study, BAL was performed at 7 days to evaluate for pneumonia. The primary endpoint was the 60-day mortality, which was found to be similar between the two groups (29.2 vs. 28.6%, p = 1.0). However, a subgroup analysis of patients enrolled beyond 14 days of ARDS onset found an increased risk of death with methylprednisolone (35 vs. 8%, p = 0.02). The number of ventilator-free days at 28 days favored the intervention group (11.2 ± 9.4 vs. 6.8 ± 8.5, p < 0.001). The fact that the improvement in ventilator-free days did not translate into improvement in mortality was thought to be due to a high rate of reintubation, although it is worth noting that the PaO 2 /FiO 2 and plateau pressure both improved in the treatment group. In terms of potential complications, the rate of suspected or probable pneumonia and shock were found to be lower in the intervention group. However, the intervention group had an increased risk of myopathy or neuropathy compared to the placebo group.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p14
|
PMC11276593
|
sec[2]/p[4]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 4.171875 |
biomedical
|
Study
|
[
0.9833984375,
0.0159912109375,
0.0005335807800292969
] |
[
0.966796875,
0.02777099609375,
0.004058837890625,
0.0015993118286132812
] |
A year later, in a placebo-controlled trial enrolling 91 patients, Meduri re-assessed the use of steroids in early severe ARDS, using an infusion of methylprednisolone started within 72 h of disease onset. Starting at a lower dose of 1 mg/kg/day, the infusion was continued for up to 28 days . Serial BALs were performed to monitor for infections. The primary endpoint, the LIS at day 7, improved more rapidly in the intervention group. A similar pattern of improvement was seen with the C-reactive protein (CRP). The duration of mechanical ventilation was significantly lower in the intervention group (5 vs. 9.5 days), as well as the length of ICU stay (7 vs. 14.5 days). A trend toward improved hospital mortality was seen in the steroid group. However, this was potentially confounded by a higher number of patients with shock included in the placebo group (46% vs. 24%). Fewer infections were seen in the treatment group, but an equal number of patients developed neuromuscular weakness. Of note, the study’s protocol called for avoidance of neuromuscular blocking agents, which may explain the differences compared to the ARDS network trial in terms of development of neuromuscular weakness.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276593_p15
|
PMC11276593
|
sec[2]/p[5]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 4.070313 |
biomedical
|
Other
|
[
0.6884765625,
0.30712890625,
0.0045928955078125
] |
[
0.2249755859375,
0.7529296875,
0.00447845458984375,
0.0176849365234375
] |
A 2020 open-label randomized trial by Villar evaluated the use of dexamethasone in 277 patients with early ARDS . Patients with early ARDS, defined as less than 30 h from onset, were enrolled. Dexamethasone was started at 20 mg/day for 5 days, then tapered to 10 mg/day for up to a total of 10 days. The study was stopped early due to low enrollment. The primary outcome was the number of ventilator-free days at 28 days, which was significantly better in the dexamethasone group (12.3 vs. 7.5 days). Additionally, all-cause mortality at 60 days, ICU mortality, and hospital mortality all favored the intervention group. The rate of adverse events was equal between the two groups.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p16
|
PMC11276593
|
sec[2]/p[6]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 3.988281 |
biomedical
|
Study
|
[
0.99951171875,
0.00046539306640625,
0.00023543834686279297
] |
[
0.94580078125,
0.0014219284057617188,
0.05242919921875,
0.0003075599670410156
] |
In 2021, Lin published a meta-analysis assessing the use of steroids in ARDS patients. The analysis included a study with COVID-19 patients . The mortality, ventilator-free days at day 28, and PaO 2 /FiO 2 were all found to be improved in patients who received steroids . A trend toward more hyperglycemia was seen in the steroid group, but the treatment group was again found to have a lower rate of infection.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p17
|
PMC11276593
|
sec[2]/p[7]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 3.804688 |
biomedical
|
Other
|
[
0.7958984375,
0.1983642578125,
0.005779266357421875
] |
[
0.007236480712890625,
0.75,
0.22412109375,
0.0187530517578125
] |
The Society of Critical Care Medicine and the European Society of Intensive Care Medicine’s guidelines suggest the use of corticosteroids in patients with moderate-to-severe ARDS (PaO 2 /FiO 2 < 200) within 14 days of disease onset . However, this recommendation was conditional and was based on moderate quality of evidence. The same guidelines recommended surveillance to ensure identification of any hospital-acquired infection during therapy.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p18
|
PMC11276593
|
sec[2]/p[8]
|
3. Steroids in Acute Respiratory Distress Syndrome
| 3.931641 |
biomedical
|
Review
|
[
0.99169921875,
0.006526947021484375,
0.0017261505126953125
] |
[
0.009613037109375,
0.08489990234375,
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0.002170562744140625
] |
It is important to note that ARDS is a heterogenous process and likely represents a common endpoint for many inflammatory diseases. As such, a variety of diseases present with ARDS, or mimic ARDS, and are known to respond to steroids. These include but are not limited to: COVID pneumonia (discussed further in Section 5 ), vasculitis with diffuse alveolar hemorrhage, acute eosinophilic pneumonia, cryptogenic organizing pneumonia, nonspecific interstitial pneumonitis, acute hypersensitivity pneumonitis, pneumocystis jiroveci pneumonia, and pneumonitis associated with connective tissue disease. Treatment of these processes with steroids is strongly recommended . It is also possible that there is a role for glucocorticoids in other specific conditions .
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276593_p19
|
PMC11276593
|
sec[3]/p[0]
|
4. Steroids in Severe Pneumonia
| 3.933594 |
biomedical
|
Review
|
[
0.99072265625,
0.005733489990234375,
0.0034236907958984375
] |
[
0.003810882568359375,
0.0018520355224609375,
0.99365234375,
0.0005025863647460938
] |
As with the other conditions covered in this review, severe community-acquired pneumonia (CAP) is characterized by inflammation due to increased pulmonary and circulating inflammatory cytokines. For example, a persistent elevation of interluken-6 has been seen in studies of patient who do not survive the infection compared to patients who do . This again provides justification for the use of steroids in treatment of this disease. Table 3 includes 5 randomized trials that addressed the potential use of steroids in severe pneumonia.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p20
|
PMC11276593
|
sec[3]/p[1]
|
4. Steroids in Severe Pneumonia
| 4.144531 |
biomedical
|
Study
|
[
0.9814453125,
0.01806640625,
0.000438690185546875
] |
[
0.98388671875,
0.0131988525390625,
0.0014905929565429688,
0.0014142990112304688
] |
In 2005, Confalonieri published a pilot placebo-controlled study of 46 ICU patients with severe CAP . The severity was based on oxygenation, hemodynamic, and radiographic criteria. Hydrocortisone was started with a 200 mg bolus, followed by an infusion at 10 mg/h for a total of 7 days. At baseline, most patients were on mechanical ventilation, but few were in septic shock. Compared to placebo, the hydrocortisone group had a significant improvement in the PaO 2 /FiO 2 and in the multiorgan dysfunction score at day 8. The CRP was also significantly lower in the steroid group, and the ICU and in-hospital mortality rates were lower in patients treated with hydrocortisone. More adverse events were seen in the placebo group, which suggested that hydrocortisone was safe in these patients.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p21
|
PMC11276593
|
sec[3]/p[2]
|
4. Steroids in Severe Pneumonia
| 4.128906 |
biomedical
|
Study
|
[
0.9931640625,
0.006313323974609375,
0.0003223419189453125
] |
[
0.99609375,
0.0029144287109375,
0.0007381439208984375,
0.0004374980926513672
] |
In 2011, another small study assessed the effect of methylprednisolone in a population of patients with CAP who were not intubated . In this study, 56 patients with respiratory failure (defined as a PaO 2 /FiO 2 < 300) were enrolled. Methylprednisolone was given as a 200 mg bolus prior to the start of antibiotics and was followed by a tapering regimen for 9 days. The need for mechanical ventilation was the primary outcome. There was no difference between the steroid and placebo groups, but the number of events was small (1 and 5 cases, respectively). Initially, the PaO 2 /FiO 2 favored the steroid group, but by day 7, there was virtually no difference between the groups. The decrease in IL-6 and CRP was found to be significantly quicker in the steroid group, and again there were few complications found to be related to their use.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p22
|
PMC11276593
|
sec[3]/p[3]
|
4. Steroids in Severe Pneumonia
| 4.132813 |
biomedical
|
Study
|
[
0.94287109375,
0.0560302734375,
0.0012197494506835938
] |
[
0.88037109375,
0.11181640625,
0.00406646728515625,
0.003997802734375
] |
A larger placebo-controlled trial was published in 2015 by Torres et al., evaluating the use of methylprednisolone in severe CAP . Patients were eligible if they had a CRP greater than 150 mg/L, a level thought to increase the chance of recruiting patients with high inflammatory response. One hundred and twenty patients were enrolled and received methylprednisolone (0.5 mg/kg every 12 h) or placebo for 5 days, started within 36 h of hospital admission. The primary endpoint was defined as treatment failure, a combination of clinical and radiographic criteria. Most patients were admitted to the ICU, but few were on mechanical ventilation. The proportion of patients with septic shock was lower in the steroid group. There was no difference in the rate of early treatment failure (occurring up to 72 h), but the rate of late treatment failure was significantly lower in the methylprednisolone group (3% vs. 25%). However, the difference was primarily driven by a better radiographic progression in the steroid group, and the in-hospital mortality was not different between the groups. This study also identified a more rapid decrease in the level of CRP and IL-10. No association with superinfections or other adverse events was identified in the patients treated with steroids.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276593_p23
|
PMC11276593
|
sec[3]/p[4]
|
4. Steroids in Severe Pneumonia
| 4.082031 |
biomedical
|
Study
|
[
0.89111328125,
0.10711669921875,
0.0017070770263671875
] |
[
0.7958984375,
0.1944580078125,
0.0027179718017578125,
0.006885528564453125
] |
A VA cooperative study published in 2022 assessed the use of a lower-dose methylprednisolone in critically ill patients with severe CAP and healthcare-associated pneumonia (HCAP) . This multicenter placebo-controlled trial enrolled 584 ICU and stepdown patients, within 72 to 96 h of hospital admission. Following a loading dose of 40 mg, methylprednisolone was continued for 20 days. The trial was stopped early due to low recruitment. Thirty-four percent of the patients had HCAP, and thirty-three percent were on mechanical ventilation. The study found no difference in the probability of survival at 60 days. Subgroup analysis found no difference in patients with HCAP. In addition, there was also no difference in the development of shock, ARDS, or ICU stay.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276593_p24
|
PMC11276593
|
sec[3]/p[5]
|
4. Steroids in Severe Pneumonia
| 4.136719 |
biomedical
|
Study
|
[
0.9716796875,
0.027923583984375,
0.0006232261657714844
] |
[
0.9736328125,
0.02294921875,
0.0018568038940429688,
0.0017995834350585938
] |
In early 2023, Dequin published the largest study to date assessing the use of hydrocortisone in 800 patients with severe CAP . ICU patients in need of mechanical ventilation (invasive or noninvasive), a need for oxygen with a PaO 2 /FiO 2 < 300, or a pulmonary severity index greater than 130 were enrolled. Hydrocortisone at 200 mg daily for 4 days was used, tapered for a total of 8 or 14 days based on clinical improvement. The steroids were administered early, with an average time between admission to the ICU and the first administration of less than 15 h. Influenza pneumonia and septic shock patients were excluded. The study was stopped after the second interim analysis. The most common organism isolated in this study was Streptococcus pneumonia. The primary outcome, 28-day mortality, was significantly lower in the hydrocortisone group (6.2 vs. 11.9). Secondary outcomes, including death by day 90, the cumulative incidence of endotracheal intubation in patients not receiving it at baseline, and the cumulative incidence of initiation of vasopressor in patients not on vasopressor at baseline, were also lower in the hydrocortisone group. Steroid use was not associated with an increase in hospital-acquired infections or GI bleeding, but a higher dose of insulin during the first 7 days of treatment was required in the patients treated with steroids.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276593_p25
|
PMC11276593
|
sec[3]/p[6]
|
4. Steroids in Severe Pneumonia
| 3.822266 |
biomedical
|
Review
|
[
0.9951171875,
0.003574371337890625,
0.0013256072998046875
] |
[
0.01377105712890625,
0.0183563232421875,
0.96728515625,
0.0007457733154296875
] |
Thus, the evidence supporting the use of steroids in severe community-acquired pneumonia appears relatively strong when hydrocortisone infusion is administered early. The benefits of methylprednisolone are less clear. However, both agents appear to have a good safety profile in this population. It is worth noting that the data on nosocomial pneumonia are very limited, and the safety of steroids in influenza pneumonia remains in question .
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p26
|
PMC11276593
|
sec[4]/p[0]
|
5. Steroids in COVID-19
| 4.042969 |
biomedical
|
Review
|
[
0.9990234375,
0.0005803108215332031,
0.00029754638671875
] |
[
0.479736328125,
0.00286865234375,
0.5166015625,
0.0008254051208496094
] |
Glucocorticoids were among the first therapies studied in the management of patients with severe SARS-CoV-2 infection (COVID-19). Inflammatory markers and cytokines including CRP, ferritin, IL 1, and IL 6 are elevated in COVID-19 and correlate with the intensity of the disease. While the role of steroids in ARDS at the onset of the COVID-19 pandemic was in question, severe COVID-19 was noted to have distinct radiographic features compared to ARDS from other etiologies. Diffuse ground glass opacities constitute the predominant feature in COVID-19 pneumonia , compared with basilar and lower lobe consolidations, and relatively normal and unaffected anterior and apical areas, which is more traditionally seen in ARDS .
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p27
|
PMC11276593
|
sec[4]/p[1]
|
5. Steroids in COVID-19
| 4.140625 |
biomedical
|
Study
|
[
0.99560546875,
0.004116058349609375,
0.00031304359436035156
] |
[
0.9658203125,
0.006320953369140625,
0.027130126953125,
0.0008034706115722656
] |
Three randomized controlled trials evaluated the use of corticosteroids in COVID-19 ( Table 4 ). The largest and earliest study was the RECOVERY trial . This randomized open-label study evaluated the use of oral or IV dexamethasone at a dose of 6 mg once daily for up to 10 days. It included 6425 patients hospitalized with COVID-19. The primary outcome was the 28-day mortality. Overall, a significant improvement was seen in this endpoint (rate ratio 0.83). However, the effect depended on the severity of the disease. In patients who did not need oxygen therapy at baseline, no improvement was seen with the use of dexamethasone. However, patients who were on oxygen without invasive ventilation saw a significant improvement in mortality with the use of steroids (23.3% vs. 26.2%; rate ratio 0.82). Patients receiving invasive mechanical ventilation saw the most significant benefit from the use of dexamethasone (29.3% vs. 41.4%; rate ratio 0.64). This translated into an absolute reduction in 28-day mortality of 12.3% in patients on invasive mechanical ventilation and 4.2% in those receiving oxygen therapy without invasive ventilation. Therapy with glucocorticoids was safe overall, with only 4 serious adverse reactions deemed related to dexamethasone (2 hyperglycemias, 1 gastrointestinal hemorrhage, and 1 psychosis). Based on this landmark trial, dexamethasone quickly became a standard of care in patients hospitalized with hypoxic respiratory failure due to COVID-19 pneumonia.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p28
|
PMC11276593
|
sec[4]/p[2]
|
5. Steroids in COVID-19
| 4.066406 |
biomedical
|
Study
|
[
0.994140625,
0.005565643310546875,
0.0003399848937988281
] |
[
0.98046875,
0.0117950439453125,
0.00722503662109375,
0.0006566047668457031
] |
Other randomized trials evaluating the use of steroids in COVID-19 were stopped early based on ethical grounds once the RECOVERY trial was published. The first was a placebo-controlled trial conducted in France by Dequin et al., evaluating the use of hydrocortisone infusion (200 mg/day) in patients with COVID-19 requiring ICU admission, who met prespecified severity criteria . A trend toward lower 21-day mortality in the steroid group was seen (14.7 vs. 27.4%). No difference in the incidence of nosocomial pneumonia was seen in this trial.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p29
|
PMC11276593
|
sec[4]/p[3]
|
5. Steroids in COVID-19
| 4.066406 |
biomedical
|
Study
|
[
0.9013671875,
0.0970458984375,
0.0018014907836914062
] |
[
0.7578125,
0.2332763671875,
0.0026645660400390625,
0.0060882568359375
] |
The second was the CODEX randomized trial, conducted in 41 ICUs in Brazil. In this open-label study, Tomazini et al. evaluated a higher dose of dexamethasone (20 mg of IV dexamethasone daily for 5 days, then 10 mg daily for 5 days or until ICU discharge) in patients receiving mechanical ventilation for COVID-19-related ARDS. Patients were enrolled in the first 48 h of meeting moderate-to-severe ARDS criteria (PaO 2 /FiO 2 < 200) . This study was also terminated early based on ethical grounds. The 28-day mortality was not different between the two groups, However, the number of ventilator-free days at 28 days favored the steroid group (6.6 vs. 4.0 days). The incidence of adverse events was again similar between the two groups.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p30
|
PMC11276593
|
sec[4]/p[4]
|
5. Steroids in COVID-19
| 3.90625 |
biomedical
|
Study
|
[
0.9990234375,
0.00054168701171875,
0.0003695487976074219
] |
[
0.8798828125,
0.0021686553955078125,
0.11749267578125,
0.0003533363342285156
] |
Finally, a 2020 meta-analysis evaluating the association between systemic steroids and mortality among critically ill patients with COVID-19 found a significant difference in favor of the use of steroids, with no difference in the risk of serious or adverse events .
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276593_p31
|
PMC11276593
|
sec[4]/p[5]
|
5. Steroids in COVID-19
| 2.550781 |
biomedical
|
Other
|
[
0.91845703125,
0.0775146484375,
0.00409698486328125
] |
[
0.0020656585693359375,
0.98583984375,
0.006404876708984375,
0.005527496337890625
] |
As such, steroids are now considered a mainstay of therapy in patients with severe COVID-19 who require oxygen or ventilatory support.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276593_p32
|
PMC11276593
|
sec[5]/p[0]
|
6. Steroids in Hypercapnic Respiratory Failure Due to Chronic Obstructive Pulmonary Disease
| 4.09375 |
biomedical
|
Study
|
[
0.99755859375,
0.0021381378173828125,
0.00023090839385986328
] |
[
0.99267578125,
0.0022602081298828125,
0.0047454833984375,
0.0003085136413574219
] |
Systemic steroids are used extensively in the treatment of hypercapnic respiratory failure due to COPD. Their use is common based on the idea that airway inflammation underlies the acute exacerbation and results in air trapping that impairs ventilation. Despite the widespread use of steroids in hypercapnic respiratory failure from COPD, there is surprisingly little evidence supporting it. One of the first randomized trials evaluating this population came from a 1999 Veterans Affairs cooperative study . In this trial, methylprednisolone (for 2 or 8 weeks) was compared to placebo in patients admitted for exacerbation of COPD. The study found a shorter initial hospitalization in the combined glucocorticoid group (9.7 vs. 8.5 days), in addition to a lower rate of first treatment failure at 30 days (23% vs. 33%) and 90 days (37% vs. 48%), but not 6 months. Few deaths and intubations were noted in the study. The rate of secondary infections was not different, but increased rates of hypoglycemia requiring treatment were seen in the steroid group.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p33
|
PMC11276593
|
sec[5]/p[1]
|
6. Steroids in Hypercapnic Respiratory Failure Due to Chronic Obstructive Pulmonary Disease
| 3.232422 |
biomedical
|
Study
|
[
0.99853515625,
0.0013589859008789062,
0.0003159046173095703
] |
[
0.96484375,
0.0134429931640625,
0.0206756591796875,
0.0009627342224121094
] |
To date, only two studies have assessed the use of steroids specifically in patients with hypercapnic respiratory failure from COPD ( Table 5 ).
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276593_p34
|
PMC11276593
|
sec[5]/p[2]
|
6. Steroids in Hypercapnic Respiratory Failure Due to Chronic Obstructive Pulmonary Disease
| 4.183594 |
biomedical
|
Study
|
[
0.99462890625,
0.004787445068359375,
0.0003483295440673828
] |
[
0.9912109375,
0.005401611328125,
0.0027599334716796875,
0.0005130767822265625
] |
The first was a 2011 study by Alia, evaluating the effect of methylprednisolone when started within 24 h of ICU admission for acute hypercapnic respiratory failure . This double-blind placebo-controlled trial enrolled 83 patients receiving ventilatory support (invasive or noninvasive) but was stopped early due to low recruitment. Methylprednisolone was started at 0.5 mg/kg every 6 h, and tapered over 10 days. Most patients were men, and exacerbations were mainly related to respiratory infections. Slightly less than half of the population was on noninvasive ventilation at baseline. This study found a significant reduction in the duration of mechanical ventilation in the corticosteroids group (3 vs. 4 days). The rate of noninvasive ventilation failure was significantly lower in the steroid group (0% vs. 37%). There was a trend toward a shorter median length of ICU stay, but no effect on mortality was found. In addition, the study was not able to find a difference in the rate of improvement of intrinsic PEEP (a measure of air trapping). The rate of PaCO 2 decrease favored the steroid group only on days 2 and 3. More cases of hyperglycemia were noted in the steroid group, but there was no difference in other adverse events.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276593_p35
|
PMC11276593
|
sec[5]/p[3]
|
6. Steroids in Hypercapnic Respiratory Failure Due to Chronic Obstructive Pulmonary Disease
| 4.09375 |
biomedical
|
Study
|
[
0.958984375,
0.04022216796875,
0.0008759498596191406
] |
[
0.93017578125,
0.0643310546875,
0.0026645660400390625,
0.0028858184814453125
] |
The second study was published by Abroug in 2014 . This was an open-label randomized trial assessing oral prednisone (1 mg/kg daily for up to 10 days) in patients requiring invasive or noninvasive ventilatory support for acute hypercapnic respiratory failure. A total of 217 patients were enrolled in 2 Tunisian ICUs. The study was also stopped early due to low recruitment. Most patients were men and on home oxygen therapy. Seventy-six percent were on noninvasive ventilation at baseline. The ICU mortality was similar in the groups. Unlike the study by Alia, the rate of noninvasive failure did not differ between the groups. The duration of mechanical ventilation and ICU stay were also similar. More hyperglycemic events were seen with the steroid use.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p36
|
PMC11276593
|
sec[5]/p[4]
|
6. Steroids in Hypercapnic Respiratory Failure Due to Chronic Obstructive Pulmonary Disease
| 3.9375 |
biomedical
|
Review
|
[
0.98779296875,
0.00982666015625,
0.0021991729736328125
] |
[
0.006008148193359375,
0.0167236328125,
0.97607421875,
0.0010652542114257812
] |
Thus, while steroids are often thought of as a mainstay in the treatment of acute exacerbation of COPD with resulting hypercapnic respiratory failure, based on the limited data available, it is difficult to find strong evidence to support this practice. Ongoing studies will hopefully shed more light on this important and common clinical entity. It is important to note that this discussion of steroids in hypercapnic respiratory failure is limited to COPD, where the evidence is less certain. In patients with hypercapnic respiratory failure due to asthma, in particular asthma with a type 2 inflammatory phenotype, the role of steroids is clearer. However, even in the asthma population, management of patients requiring invasive or noninvasive ventilation has not been studied extensively, and much of the current practice is extrapolated from management in a broad emergency department population .
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276593_p37
|
PMC11276593
|
sec[6]/p[0]
|
7. Conclusions
| 3.830078 |
biomedical
|
Review
|
[
0.9892578125,
0.0075225830078125,
0.00331878662109375
] |
[
0.0032749176025390625,
0.0187835693359375,
0.97705078125,
0.0007801055908203125
] |
Glucocorticoids are widely used in the treatment of commonly encountered diseases in medical intensive care units. Strong data exist for the use of these medications in the management of certain specific etiologies, such as COVID-19. However, for broader problems that result as a common endpoint from many causes such as septic shock, ARDS, and CAP, the role of steroids is still being debated. The heterogenous nature of these diseases makes a uniform approach difficult. However, based on current data, it does appear that steroids do have a role in management. In hypercapnic respiratory failure from COPD, while steroids are commonly used, there are very few studies to support or refute this approach.
|
[
"Patrick Jenkins",
"Cory Cross",
"Tony Abdo",
"Houssein Youness",
"Jean Keddissi"
] |
https://doi.org/10.3390/diagnostics14141565
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p0
|
PMC11276605
|
sec[0]/p[0]
|
1. Introduction
| 1.842773 |
other
|
Other
|
[
0.28173828125,
0.01322174072265625,
0.705078125
] |
[
0.0020503997802734375,
0.9892578125,
0.0083160400390625,
0.00040268898010253906
] |
The current environment for the delivery of healthcare is hugely complex and politicized. This means, for example, that in many countries across Europe, although the average proportion of gross domestic product spent on healthcare, defined as the final consumption of health goods and services, was over 10.9% in 2022 , which is significant, the demand for and expectations of health services continue to grow. The current models of the delivery and organization of healthcare developed in the Western world are now regularly described as unsustainable , with the largest percentage of funding allocated to hospital-based rather than community-based services.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p1
|
PMC11276605
|
sec[0]/p[1]
|
1. Introduction
| 3.667969 |
biomedical
|
Review
|
[
0.9677734375,
0.0032024383544921875,
0.0290679931640625
] |
[
0.036224365234375,
0.39306640625,
0.5703125,
0.0007419586181640625
] |
The term unsustainable, when related to the delivery of healthcare, is used to describe the consequences of the combination of a complex set of issues, which include an ageing population, an increase in the expectations of patients and their families, and the rising costs from new technologies, procedures and drugs . There is also evidence of wasteful practices and organization of processes within the sector, the lowest available estimates for which exceeded 25% of total healthcare expenditures in the US in 2019 . Current estimates suggest that 15% of the total amount of waste produced in healthcare can be classified as hazardous and can be infectious, toxic or radioactive, which, if not properly treated, forms a potential risk both to human health and to the environment . This continued waste of healthcare resources and generation of healthcare waste affects the ongoing sustainability of the healthcare system.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p2
|
PMC11276605
|
sec[0]/sec[0]/sec[0]/p[0]
|
1.1.1. Defining Sustainability
| 1.407227 |
other
|
Other
|
[
0.00751495361328125,
0.0016012191772460938,
0.99072265625
] |
[
0.0016107559204101562,
0.9794921875,
0.018157958984375,
0.0009431838989257812
] |
In the last two decades, there has been an increase in the number of publications relating to sustainability; however, despite this, sustainability remains an open concept with multiple interpretations and meanings that are often context specific . Sustainability has been elusive to define and has been described as an ideology constituting a set of beliefs and values to establish how life might be better organized . Sustainability is a concept that comprises three fundamental categories: environmental sustainability, economic viability and social equity. These three categories are also known as the three pillars of sustainability or the three pillars of sustainable development. These pillars serve as a framework for defining and evaluating sustainable decisions and issues .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276605_p3
|
PMC11276605
|
sec[0]/sec[0]/sec[0]/p[1]
|
1.1.1. Defining Sustainability
| 3.919922 |
biomedical
|
Study
|
[
0.859375,
0.0012912750244140625,
0.1395263671875
] |
[
0.5361328125,
0.015777587890625,
0.44775390625,
0.00036525726318359375
] |
Environmental sustainability refers to the responsible use and management of natural resources to prevent environmental degradation and contamination . The delivery of healthcare and the provision of services to the healthcare system result in environmental stressors, such as greenhouse gas emissions, particulate matter, and air pollutants and compromise scarce water resources across the globe. Economic sustainability refers to the ability of an economy to maintain and improve its standard of living over time. Social sustainability refers to the ability of a society to meet the needs of its citizens while maintaining social cohesion and equity. It has been acknowledged by Lenzen that those people harmed by the environmental footprint of healthcare often live far away from those who benefit from the healthcare provided. Together, the three pillars of sustainability provide a comprehensive framework for evaluating sustainability issues and making sustainable decisions . Gro Harlem Brundtland’s seminal work is widely acknowledged as bringing the term environmental sustainability into policy discourse, calling for ‘‘a new era of economic growth—growth that is forceful and at the same time socially and environmentally sustainable’’. Regarding environmental sustainability, one of the three pillars that make up the totality of a view of sustainability is , this protocol paper discusses research with a focus on the impact of healthcare institutions on environmental sustainability, recognizing that economic viability and social equity need to be in alignment with environmental sustainability goals to provide a health system, which will be able to provide for future generations.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276605_p4
|
PMC11276605
|
sec[0]/sec[0]/sec[1]/p[0]
|
1.1.2. Environmental Sustainability in Healthcare
| 2.513672 |
other
|
Other
|
[
0.454345703125,
0.0027923583984375,
0.54296875
] |
[
0.0164337158203125,
0.9736328125,
0.00945281982421875,
0.0002944469451904297
] |
Healthcare accounts for approximately 10% of the global economic output, but there is large variability between countries . Compared to many manufacturing sectors, healthcare has a relatively small carbon footprint. However, it still contributes significantly to greenhouse gas emissions, estimated to be approximately 4.4% globally . Healthcare, in particular hospitals, comprises an energy-intensive sector because of the requirement for continuous operation and services, such as lighting, heating, ventilation and cooling required to create a high-performance clinical environment to support healthcare delivery . As a result, the healthcare industry has been identified as a significant contributor to greenhouse gas emissions that are responsible for climate change, along with other pollutants and unsustainable practices that ultimately have negative impacts on human health and well-being. Considering the healthcare industry’s mission to do no harm, it has an inherent responsibility to reduce its environmental footprint .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p5
|
PMC11276605
|
sec[0]/sec[0]/sec[1]/p[1]
|
1.1.2. Environmental Sustainability in Healthcare
| 3.582031 |
biomedical
|
Review
|
[
0.84521484375,
0.037628173828125,
0.116943359375
] |
[
0.0031261444091796875,
0.4267578125,
0.568359375,
0.001644134521484375
] |
The World Health Organization in its description of an environmentally sustainable healthcare system declares it ‘as a health system that improves, maintains or restores health, while minimizing negative impacts on the environment and leveraging opportunities to restore and improve it, to the benefit of the health and well-being of current and future generations’. In its translation of this ambition, the Royal College of Physicians more recently acknowledged the vital role that clinicians and other healthcare professionals in the National Health Service (NHS) can play in improving the sustainability of healthcare through changes to practice and the way that care is delivered , having previously recognized sustainability as an additional domain of quality in healthcare . The inclusion of environmental sustainability seems a natural extension of the current health system’s focus on economic viability and commitment to social equity. Whilst awareness of the importance of environmental protection is increasing, interest remains limited and without coordinated or intentional action.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p6
|
PMC11276605
|
sec[0]/sec[0]/sec[1]/p[2]
|
1.1.2. Environmental Sustainability in Healthcare
| 1.802734 |
other
|
Other
|
[
0.435791015625,
0.015228271484375,
0.548828125
] |
[
0.0021190643310546875,
0.99560546875,
0.0017881393432617188,
0.0003542900085449219
] |
In response to the ongoing challenges of delivering quality, safe and effective care, healthcare staff internationally have been seeking to improve processes through the use of improvement methodologies such as Lean . Lean, a process improvement methodology developed in the Japanese Motor industry , is now considered to be one of the most popular process improvement methodologies used in healthcare internationally .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p7
|
PMC11276605
|
sec[0]/sec[1]/p[0]
|
1.2. Lean
| 1.673828 |
other
|
Other
|
[
0.409912109375,
0.006496429443359375,
0.58349609375
] |
[
0.0031528472900390625,
0.99560546875,
0.0007948875427246094,
0.00034999847412109375
] |
Lean was developed for healthcare as an adaptation of the method of industry pioneers in quality improvement, the Toyota Production System, which differed from the principles of mass manufacturing in the automotive industry through the way that they engaged the workforce to initiate improvements rather than simply responding to problems .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p8
|
PMC11276605
|
sec[0]/sec[1]/p[1]
|
1.2. Lean
| 1.507813 |
other
|
Other
|
[
0.285888671875,
0.01343536376953125,
0.70068359375
] |
[
0.0015287399291992188,
0.99365234375,
0.00434112548828125,
0.0005826950073242188
] |
The approach has been in use in healthcare since 2001 in the UK and since 2002 in the USA and has become one of the most popular process improvement methodologies used in healthcare . This translation and adaptation was successful in some highly effective healthcare organizations with leaders committed to change but has not been successful in all cases.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p9
|
PMC11276605
|
sec[0]/sec[1]/p[2]
|
1.2. Lean
| 3.677734 |
biomedical
|
Review
|
[
0.8359375,
0.027587890625,
0.136474609375
] |
[
0.00527191162109375,
0.11029052734375,
0.8837890625,
0.0007572174072265625
] |
Lean in healthcare can be seen as a set of operating methods and a philosophy, which creates the maximum value as defined by the customer, primarily the patient but also those involved within the delivery or organization of services . Whilst some authors view Lean as simply a toolkit within a methodology other authors disagree with this narrow description , and suggest that Lean should be viewed as a philosophy, which is only successfully implemented if it fully engages people to improve processes . It is this commitment to Lean as a philosophical approach in tandem with a focus on people and processes, particularly in hospital-based settings , that appears to enable an organization to become ‘Lean’. As one of several recognized and practiced quality improvement approaches within healthcare, Lean has been shown to have benefits when applied to this complex system . Healthcare organizations that have adopted Lean give form to the idea of constantly striving for continual improvement , although studies show that implementation may be isolated rather than system-wide .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p10
|
PMC11276605
|
sec[0]/sec[1]/p[3]
|
1.2. Lean
| 1.643555 |
other
|
Other
|
[
0.167236328125,
0.00390625,
0.82861328125
] |
[
0.00261688232421875,
0.99462890625,
0.002536773681640625,
0.0003523826599121094
] |
In acknowledging Lean as an established methodology and philosophy for improvement in healthcare, it is valid to consider it as a potential vehicle for other initiatives, such as engagement around the sustainability agenda to reduce the carbon footprint of the business . The healthcare sector, with its reliance on fossil fuels to energize buildings, was responsible for 4–6% of global greenhouse gas emissions in 2017 and is now taking early but important steps to reduce its emissions. However, it lacks a cohesive and reproducible whole-system approach for engagement. Lean may be a solution to this problem .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p11
|
PMC11276605
|
sec[0]/sec[1]/p[4]
|
1.2. Lean
| 1.711914 |
other
|
Other
|
[
0.30029296875,
0.006801605224609375,
0.69287109375
] |
[
0.0168609619140625,
0.9404296875,
0.04132080078125,
0.001186370849609375
] |
Although uniting the removal of waste from healthcare systems as an improvement methodology together with the active work of the sustainability teams appears intuitively the right thing to do, there is little evidence in the literature of this being a consistent approach across businesses and no evidence of this approach being taken intentionally to scale across healthcare, although there have been some attempts to validate the combination of Lean and organizational sustainability efforts approach at a clinically specific level .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p12
|
PMC11276605
|
sec[0]/sec[2]/p[0]
|
1.3. Sustainability Goals within Lean Interventions
| 2.568359 |
biomedical
|
Other
|
[
0.51513671875,
0.005908966064453125,
0.47900390625
] |
[
0.026947021484375,
0.81884765625,
0.153076171875,
0.0012598037719726562
] |
Hackbarth and Berwick describe six categories of healthcare waste: overtreatment, failures of care coordination, failures in execution of care processes, administrative complexity, pricing failures and fraud and abuse. It has been acknowledged that approximately one-fifth of the cost of healthcare can be described as wasteful, providing no or minimal impact towards good health . Whilst the language of fraud and abuse may not resonate directly with the seven Lean wastes originally developed by Taiichi Ohno, Chief Engineer from Toyota, as defects, overproduction, waiting, transport, inventory, motion and excess processing , it is possible to recognize the overlaps with the six categories previously described by Hackbarth and Berwick .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p13
|
PMC11276605
|
sec[0]/sec[2]/p[1]
|
1.3. Sustainability Goals within Lean Interventions
| 3.681641 |
biomedical
|
Other
|
[
0.87060546875,
0.017181396484375,
0.1124267578125
] |
[
0.0181884765625,
0.5224609375,
0.458251953125,
0.0013227462768554688
] |
Healthcare has adapted Lean tools and techniques from across the most effective businesses to remove these wastes, focusing on both clinical and non-clinical pathways. Quality improvement, and specifically Lean methodology, has been adapted and applied to healthcare by pioneer organizations in North America . Lean is a way to reduce waste or non-value-added activities from processes and add value for stakeholders, in this particular case both patients and staff. It can be described as reducing the overburdening of staff by streamlining the processes to be more efficient. Waste reduction in this context is often measured in terms of time saved, quality improved, better patient and staff experiences of care and financial benefits through the application of rigorous tools and techniques. In addition to the work of Ohno, an eighth important category was included in the 1990s when the Toyota Production System was adopted in the Western world: the waste of human effort. Not having the opportunity to practice to the full scope of their potential or license immediately resonates with many healthcare workers and is a critical element of many Lean initiatives.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p14
|
PMC11276605
|
sec[0]/sec[2]/p[2]
|
1.3. Sustainability Goals within Lean Interventions
| 3.910156 |
biomedical
|
Review
|
[
0.93505859375,
0.005359649658203125,
0.0594482421875
] |
[
0.1785888671875,
0.1373291015625,
0.68310546875,
0.0008435249328613281
] |
To date, in the application of Lean in healthcare, there has been little consideration provided to the development of metrics to measure the waste of natural resources, such as water or energy, nor to the environmental impacts of the redesign and delivery of care pathways. For example, whilst teams may redesign processes to reduce the number of items being used, little attention has been provided, thus far, to the consideration of the manufactured source of the specific item or even the current impact of the disposal of the item. This becomes important when it is recognized that 62% of the total healthcare emissions arise from the supply chain, estates and facilities, pharmaceuticals and medical devices and travel . The removal of waste in healthcare means very different things to different groups, with clinicians involved in pathway improvements looking at efficiencies and streamlining and professional sustainability experts looking at the continuous reduction in the use of natural resources or the disposal of clinical waste. There is a discrete overlap in these two perspectives when both groups consider, for example, the single use of plastic items and packaging. Both approaches would seek to reduce the number of items used, one from a cost and time to utilize perspective and the other from an impact of manufacturing, cost of transportation and disposal perspective.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p15
|
PMC11276605
|
sec[0]/sec[2]/p[3]
|
1.3. Sustainability Goals within Lean Interventions
| 1.397461 |
other
|
Other
|
[
0.123779296875,
0.0033321380615234375,
0.873046875
] |
[
0.002353668212890625,
0.9970703125,
0.0004680156707763672,
0.00023162364959716797
] |
Healthcare, in particular hospitals, along with the consumables that are made and transported for their use in clinical care, is responsible for 5% of the UK’s carbon footprint, with the figure being higher in some countries . Hospital buildings must be heated and ventilated 24 h a day, seven days a week; they are energy-hungry and, if the contribution of the manufacturing that serves the healthcare industry is included, they account for a significant impact on the global environment due to their emissions .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p16
|
PMC11276605
|
sec[0]/sec[2]/p[4]
|
1.3. Sustainability Goals within Lean Interventions
| 1.211914 |
other
|
Other
|
[
0.014404296875,
0.0016889572143554688,
0.98388671875
] |
[
0.0010442733764648438,
0.998046875,
0.0004863739013671875,
0.00029206275939941406
] |
Increasingly, healthcare organizations across Europe are mandated to commit to a reduction in their carbon impact and have environmental sustainability as a key deliverable at the board level . The responsibility for the delivery of this agenda is often undertaken by Estates and Support Service teams who are increasingly expanding their expertise through the appointment of environmental sustainability experts to lead the work.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p17
|
PMC11276605
|
sec[0]/sec[2]/p[5]
|
1.3. Sustainability Goals within Lean Interventions
| 1.118164 |
other
|
Other
|
[
0.003620147705078125,
0.0004470348358154297,
0.99609375
] |
[
0.0355224609375,
0.9501953125,
0.012908935546875,
0.00140380859375
] |
Looking more widely across other business systems, Zokaei et al., argue that there is a “logical fit between economic and environmental waste reduction”, between what they describe as Lean and Green, with “Lean as a descriptor of all forms of quality improvement activities” and “Green to capture all management practices aimed at improving the environmental performance of the firm”. In Lean systems, waste is any activity that does not add value to the customer, while ‘Green’ concerns the inefficient use of natural resources. As Garza-Reyes puts it “For the lean management philosophy, waste refers to any activity that does not add value to the product while for the green concept, waste is related to the wasteful consumption of water, energy or any natural resource.”
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p18
|
PMC11276605
|
sec[0]/sec[2]/p[6]
|
1.3. Sustainability Goals within Lean Interventions
| 1.595703 |
other
|
Other
|
[
0.10125732421875,
0.00147247314453125,
0.8974609375
] |
[
0.037384033203125,
0.94677734375,
0.0150146484375,
0.0008220672607421875
] |
Salvador et al. adapted the work of Dües to illustrate the relationship between a Lean and Green approach in business, which can be further explored in healthcare. They purport that an integrated approach seems to be an easier and better option on the path to Leaner and greener business practices. The overlap with the organization and delivery of healthcare in some areas of product planning and design, supply chain and quality management, organizational culture and performance and logistics gives rise to an opportunity that could be adapted to be more specific to healthcare. It is this opportunity that will be explored in this research.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p19
|
PMC11276605
|
sec[0]/sec[3]/p[0]
|
1.4. Methodology
| 1.942383 |
other
|
Other
|
[
0.2470703125,
0.002857208251953125,
0.75
] |
[
0.12164306640625,
0.77099609375,
0.10552978515625,
0.001888275146484375
] |
The degree to which environmental sustainability is integrated into Lean improvement interventions may vary, and the field is evolving . The inclusion of organizational environmental sustainability goals specifically into Lean healthcare is under-reported in the literature . There is no clear understanding of the contexts in which Lean interventions that include environmental sustainability outcomes occur, nor of the mechanisms that encourage engagement in those interventions that lead to specific anticipated environmental sustainability outcomes. A realist approach can be used to examine these contexts, mechanisms and outcomes.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p20
|
PMC11276605
|
sec[0]/sec[3]/p[1]
|
1.4. Methodology
| 2.546875 |
biomedical
|
Other
|
[
0.55322265625,
0.00362396240234375,
0.443115234375
] |
[
0.0133209228515625,
0.96630859375,
0.0198822021484375,
0.0003948211669921875
] |
Realist inquiry is a research approach that includes two main methods: realist review and realist evaluation. Realist review is also known as realist synthesis and involves analyzing already existing data, including stakeholders’ views and opinions . Realist evaluation is used for primary research and involves collecting data directly from the source . The focus of realist inquiry is on interventions and there is a growing body of work that uses realist inquiry to analyze interventions in healthcare organizations , such as those using Lean methodology .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276605_p21
|
PMC11276605
|
sec[0]/sec[3]/p[2]
|
1.4. Methodology
| 3.769531 |
biomedical
|
Review
|
[
0.75048828125,
0.003627777099609375,
0.245849609375
] |
[
0.043853759765625,
0.130859375,
0.82470703125,
0.0006246566772460938
] |
Research strategies such as systematic reviews look for the answer to the question ‘what works?’. In a realist inquiry, there is a focus not only on ‘what works’ but also on ‘what works for whom, why it works and in what circumstances’ . Realist review goes beyond traditional systematic reviews by focusing on the underlying theories and mechanisms that explain how interventions work in specific contexts. It is a robust approach that recognizes and embraces the complexity of social systems . Realist review acknowledges that theories cannot and do not always offer explanations or predict outcomes in every context, for example, in patient safety programs . A realist review encompasses reviews of existing studies that use a wide range of research and evaluation approaches and have no particular bias towards either quantitative or qualitative methods. Wong, et al. see realist reviews in the context of the ‘what works, for whom, in what circumstances’ approach as being non-judgmental and explanatory and, whilst borrowing some ideas from traditional systematic reviews, they are more iterative, testing and building theory.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p22
|
PMC11276605
|
sec[0]/sec[3]/p[3]
|
1.4. Methodology
| 3.546875 |
other
|
Study
|
[
0.33251953125,
0.0020771026611328125,
0.66552734375
] |
[
0.53515625,
0.0158843994140625,
0.447998046875,
0.0008616447448730469
] |
The underlying focus of a realist review recognizes the explanatory power and contribution to the knowledge of ‘generative causation’ through the first principles of Context Mechanism Outcome configurations CMOcs . CMOcs comprise the Context (C) that denotes a wide range of conditions that affect any programme. The variation in response of individuals to the program will be dependent on factors such as their understanding of what they can do and what they need to contribute ; this is an example of a Mechanism (M). The hypothesis as to a program’s Outcomes (Os) concerns the program’s results. The Context, Mechanism and Outcome are often expressed in the formula C + M = O (CMO), with configurations (c) of multiple CMOs generating the term CMOcs. A realist review will facilitate an understanding of how Lean interventions that include environmental sustainability outcomes in their design interact with specific contexts to trigger particular mechanisms that lead to observable anticipated outcomes. We now elaborate on the use of realist review to address the research questions posed by this study.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p23
|
PMC11276605
|
sec[1]/sec[0]/p[0]
|
2.1. Aim
| 3.763672 |
biomedical
|
Review
|
[
0.916015625,
0.015838623046875,
0.06829833984375
] |
[
0.005146026611328125,
0.005336761474609375,
0.9892578125,
0.0004050731658935547
] |
The realist review outlined in this protocol aims to understand the use of the term environmental sustainability in a healthcare context and to develop a clear narrative regarding the specific relationship between Lean healthcare improvement interventions and environmental sustainability. It aims to explore, describe and understand barriers to achieving environmental sustainability and the contexts and mechanisms that may support and enable local teams to deliver more environmentally sustainable outcomes from their Lean improvement interventions.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p24
|
PMC11276605
|
sec[1]/sec[1]/p[0]
|
2.2. Research Questions
| 3.824219 |
biomedical
|
Review
|
[
0.93017578125,
0.00725555419921875,
0.0625
] |
[
0.040374755859375,
0.0899658203125,
0.869140625,
0.0007033348083496094
] |
A realist review protocol does not provide answers to the research questions; rather, it serves as a guide for conducting a subsequent realist review of the literature. This approach enables the research questions to be systematically addressed through an iterative and theory-driven process . The purpose of the protocol is to structure the review, ensuring that it explores how and why interventions work in specific contexts, thus facilitating the eventual answering of the research questions . The realist review described in this protocol will be guided by these research questions: What contextual factors facilitate the design of Lean healthcare improvement interventions that include environmental sustainability outcomes, and what mechanisms enable their inclusion? What contextual factors facilitate the deployment of Lean healthcare improvement interventions that include environmental sustainability outcomes in their design, and what mechanisms enable the engagement of stakeholders with these interventions, resulting in the achievement of the anticipated outcomes?
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p25
|
PMC11276605
|
sec[1]/sec[2]/p[0]
|
2.3. Stages of the Realist Review
| 3.933594 |
biomedical
|
Review
|
[
0.89404296875,
0.005565643310546875,
0.10028076171875
] |
[
0.019134521484375,
0.125732421875,
0.8544921875,
0.0008740425109863281
] |
A realist review involves the analysis and interpretation of existing data. In essence, it is the application of the realist approach to retrospective literature reviews , acknowledging that theories do not and cannot always offer explanations or predict outcomes in every context . Based on Pawson’s work, and the interpretation of that work by Velonis et al. , we can identify a five-step approach to a realist review as follows: Agree on the scope of the review and identify hypotheses that will explain mechanisms that are causative factors in change. Identify a starting point to search for evidence. Review primary studies and retrieve data. Synthesize evidence and develop conclusions. Refine theory iteratively and disseminate findings.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p26
|
PMC11276605
|
sec[1]/sec[2]/p[1]
|
2.3. Stages of the Realist Review
| 2.794922 |
biomedical
|
Other
|
[
0.96826171875,
0.004161834716796875,
0.0278167724609375
] |
[
0.166748046875,
0.7119140625,
0.1197509765625,
0.0014829635620117188
] |
These steps are congruent with RAMESES (Realist And Meta-narrative Evidence Syntheses: Evolving Standards) . The RAMESES guidelines are widely regarded as the benchmark for conducting realist reviews, providing comprehensive standards and resources. They offer structured guidance on methodology and reporting practices essential for ensuring rigor and transparency in realist reviews . Figure 1 outlines the steps we will undertake to complete the realist review according to the RAMESES guidelines. Steps 1–3 have already been completed to inform this realist review protocol.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p27
|
PMC11276605
|
sec[1]/sec[2]/sec[0]/p[0]
|
2.3.1. Scope of the Review and Expert Panel Formation
| 3.701172 |
biomedical
|
Review
|
[
0.72021484375,
0.006816864013671875,
0.27294921875
] |
[
0.0178985595703125,
0.00893402099609375,
0.97265625,
0.0003399848937988281
] |
Defining the scope of any realist review question can prove challenging, given the application of this methodology to complex systems like healthcare . The scope of this review concerns the inclusion of environmental sustainability outcomes in Lean improvement interventions in healthcare settings. Given the limited research into Lean interventions with environmental sustainability goals in healthcare , the scope of the review will consider the inclusion of such goals in the design of Lean improvement initiatives in non-healthcare settings. This will allow for the realist review to take account of the transferability of relevant review findings from sectors other than healthcare to health and social care settings. Generally, realist reviews commence with the development of one or more candidate program theories (CPTs) (hypotheses) and end with a more developed theory . The first step in conducting a realist review is therefore to develop CPTs that seek to explain how the designers and implementers of Lean improvement interventions with stated environmental sustainability outcomes expect them to work, and why . CPTs do this by describing the context, mechanism, and outcomes at play .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p28
|
PMC11276605
|
sec[1]/sec[2]/sec[0]/p[1]
|
2.3.1. Scope of the Review and Expert Panel Formation
| 1.681641 |
other
|
Other
|
[
0.09130859375,
0.00344085693359375,
0.9052734375
] |
[
0.0272064208984375,
0.72607421875,
0.24462890625,
0.0018863677978515625
] |
A realist review is theory-led because it consults the literature and relevant stakeholders to develop and test theories. The inclusion of stakeholders and explicit, extensive, iterative engagement with them grounds the review in local contexts to facilitate theory refinement . To inform CPT development for this review protocol, a stakeholder consultation was undertaken with leadership teams and improvement specialists within organizations that had or were in the process of including environmental sustainability outcomes in their Lean improvement training and interventions .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p29
|
PMC11276605
|
sec[1]/sec[2]/sec[0]/p[2]
|
2.3.1. Scope of the Review and Expert Panel Formation
| 3.996094 |
biomedical
|
Study
|
[
0.99609375,
0.0005521774291992188,
0.003322601318359375
] |
[
0.9970703125,
0.00228118896484375,
0.0004718303680419922,
0.00005525350570678711
] |
The use of expert panels, a group of individuals who are judged to possess expertise and experience relevant to the research topic or intervention under investigation, guides the development of the initial program theory and assists in iterative theory development . An engaged expert panel provides expertise and validates program theories iteratively, ensuring rigor . For this study, a panel has been convened consisting of acknowledged subject experts with a particular interest in the application of Lean methods in healthcare , the environmental effect of healthcare through its organization and delivery, and the impact on the engagement and practice of individuals . The panel’s role is to provide feedback, challenge findings, identify gaps in current knowledge and provide further insights into the information already collected to determine whether and which theories merit further development and testing. In addition, the ability of the expert panel to interpret realist review results and develop additional lines of inquiry as program theories are recognized as an additional value of their engagement .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p30
|
PMC11276605
|
sec[1]/sec[2]/sec[1]/p[0]
|
2.3.2. Literature Search to Develop Candidate Program Theories (CPTs)
| 3.845703 |
biomedical
|
Review
|
[
0.97607421875,
0.0011339187622070312,
0.022918701171875
] |
[
0.430908203125,
0.007808685302734375,
0.56103515625,
0.00039839744567871094
] |
Pawson and Tilley emphasize the importance of CPT generation at the outset of the evaluation . Before undertaking a realist review, it is necessary to conduct an initial scoping of the literature . A preliminary background search in key databases was undertaken searching article titles, abstracts, keywords, and subject headings to guide the development of the CPTs. The databases CINAHL, EBSCOhost, ProQuest, MEDLINE, PubMed, BMJ best practice, EMBASE, Web of Science, Green FILE, Scopus, ScienceDirect Journals, CAB Direct, JSTOR and Google Scholar were used to identify studies that were relevant to the review questions and involved Lean and environmental sustainability outcomes in healthcare. The searches included combinations of the keywords Health, Healthcare, Lean, Lean Methodology, Green, Environmental Sustainability, and Sustainability. The studies encompassed both empirical and conceptual work. As the theories to be developed were at this stage candidate or ‘rough’ , sources of grey literature, editorials, reports, and the websites of relevant organizations, such as The Health Foundation, Healthcare without Harm, the Institute for Healthcare Improvement and Toyota Environmental Challenge 2050 were also included.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p31
|
PMC11276605
|
sec[1]/sec[2]/sec[1]/p[1]
|
2.3.2. Literature Search to Develop Candidate Program Theories (CPTs)
| 2.212891 |
biomedical
|
Study
|
[
0.73388671875,
0.0016622543334960938,
0.2646484375
] |
[
0.9501953125,
0.047454833984375,
0.0017137527465820312,
0.00042319297790527344
] |
Searches yielded a small number of articles ( n = 7) directly and fully related to the research questions. The expert panel suggested further areas for consideration for inclusion, specifically websites. An expert panel can provide valuable expertise in relation to sources, including the grey literature (e.g., government documents, reports and websites) that may be relevant to program theory development . From the consultations with stakeholders and the exploratory review of the literature, six CPTs were developed, which were further refined after discussion among members of the research team. This resulted in the development of seven CPTs to be discussed with the expert panel ( Supplementary File S1 ).
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p32
|
PMC11276605
|
sec[1]/sec[2]/sec[2]/p[0]
|
2.3.3. Refine CPTs with the Expert Panel
| 2.269531 |
biomedical
|
Other
|
[
0.56103515625,
0.004512786865234375,
0.434326171875
] |
[
0.037261962890625,
0.65234375,
0.308837890625,
0.0014495849609375
] |
Within realist review, much of the time and effort needed is spent on developing program theory and developing, confirming, refuting or refining aspects of it . The convened expert panel was adjudicated upon the program theories being investigated. This facilitated an emerging understanding of how and why particular interventions work or do not work in specific contexts by examining the underlying mechanisms activated in those contexts that influence the interventions’ outcomes .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p33
|
PMC11276605
|
sec[1]/sec[2]/sec[2]/p[1]
|
2.3.3. Refine CPTs with the Expert Panel
| 2.626953 |
biomedical
|
Study
|
[
0.9365234375,
0.0021724700927734375,
0.06121826171875
] |
[
0.87744140625,
0.1134033203125,
0.0084991455078125,
0.0006241798400878906
] |
In relation to the seven CPTs presented to them ( Supplementary File S1 ), the panel’s adjudication and deliberation led to the following: Two CPTs (numbers 4 and 5) were deemed as being aligned with the available evidence and existing understanding in the field and therefore, required no refinement (CPTs confirmed). Four CPTs (numbers 1, 3, 6 and 7) were seen as valid in their candidate form but were identified as having incomplete elements of theory, and additional mechanisms, contexts and potential outcomes were identified (CPTs refined). One CPT (number 2) was seen as not relevant to the research (CPT refuted).
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p34
|
PMC11276605
|
sec[1]/sec[2]/sec[2]/p[2]
|
2.3.3. Refine CPTs with the Expert Panel
| 1.826172 |
biomedical
|
Other
|
[
0.681640625,
0.0031414031982421875,
0.3154296875
] |
[
0.405517578125,
0.58740234375,
0.00612640380859375,
0.0011739730834960938
] |
This consultation and feedback on the CPTs ensures that they have wider validity and consistency with the panel members’ experiences and that nothing crucial was missed . The expert panel review, through adjudication of the presented CPTs, facilitated the development of eight Initial Program Theories ( Supplementary File S2 ).
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p35
|
PMC11276605
|
sec[1]/sec[2]/sec[2]/p[3]
|
2.3.3. Refine CPTs with the Expert Panel
| 1.333008 |
other
|
Other
|
[
0.46337890625,
0.005374908447265625,
0.53125
] |
[
0.03143310546875,
0.943359375,
0.0236663818359375,
0.0013322830200195312
] |
The expert panel, throughout the research process, will continue to provide ongoing input, expertise and guidance in adjudicating upon the iteratively developed program theory. Having completed steps 1–3 to inform this realist review protocol, we now set out our planned next steps.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p36
|
PMC11276605
|
sec[1]/sec[2]/sec[3]/p[0]
|
2.3.4. Evidence Search
| 4.136719 |
biomedical
|
Study
|
[
0.99853515625,
0.0004696846008300781,
0.0008292198181152344
] |
[
0.998046875,
0.0008831024169921875,
0.0009908676147460938,
0.00005841255187988281
] |
The next step will be an evidence search based on keywords derived from the Initial Programme Theories (IPTs) elicited from steps 1 to 3 . PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines are specifically designed for systematic reviews and meta-analyses, providing a structured approach to synthesizing evidence from various study designs, including observational and interventional trials . Realist reviews, which aim to understand complex interventions and contexts rather than evaluate efficacy through controlled trials, benefit from PRISMA’s flexibility in reporting diverse types of evidence and its emphasis on transparency and reproducibility in data synthesis . Searches will be reported in line with PRISMA guidelines for systematic reviews and congruent with RAMESES guidelines . The internet search engines and electronic databases used to develop the CPT ( Section 2.3.2 ) will be used to carry out an evidence search using keywords based on the IPTs identified in steps 1–3 ( Supplementary File S2 ). This search will be augmented by a search of: Any literature citing the included papers; The literature cited in the reference lists of included papers; Grey literature and websites of relevant organizations; Any further suggestions from the expert panel.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p37
|
PMC11276605
|
sec[1]/sec[2]/sec[3]/p[1]
|
2.3.4. Evidence Search
| 3.947266 |
biomedical
|
Review
|
[
0.99658203125,
0.0011005401611328125,
0.002529144287109375
] |
[
0.294921875,
0.00804901123046875,
0.6962890625,
0.0005636215209960938
] |
We will make use of the population-intervention-comparison-outcome-context (PICOC) tool, commonly used in literature reviews, to outline inclusion and exclusion criteria . The PICOC ( Table 1 ) outlines the current inclusion and exclusion criteria, generated following the development of the IPTs, that will inform the realist review. We recognize that the inclusion and exclusion criteria may be refined and further iterative searches may be needed as the review progresses . The PICOC has been shown to ensure that the selection of items for inclusion is systematic, consistent, and independent of factors such as sample size or funding source that may affect the direction of the inquiry or the interpretation of results .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999995 |
PMC11276605_p38
|
PMC11276605
|
sec[1]/sec[2]/sec[3]/p[2]
|
2.3.4. Evidence Search
| 3.048828 |
biomedical
|
Review
|
[
0.93505859375,
0.003162384033203125,
0.061737060546875
] |
[
0.191162109375,
0.1448974609375,
0.66259765625,
0.0013103485107421875
] |
The search strategy reflects a realist review methodology that does not exclude gray literature, which can illuminate causal factors . In line with the realist review methodology, iterative and purposive searches may be necessitated by the need to gather more supporting evidence to develop and test the developing IPTs. This may be to search for further evidence or wider theories that may explain findings and assist in theory refinement . The need for further searches, search terms and strategies will be identified as the review progresses. Search results from electronic databases and other sources will be imported into reference management software and duplicates removed.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p39
|
PMC11276605
|
sec[1]/sec[2]/sec[4]/p[0]
|
2.3.5. Evidence Selection and Appraisal
| 3.171875 |
biomedical
|
Study
|
[
0.9091796875,
0.001087188720703125,
0.08978271484375
] |
[
0.90966796875,
0.046783447265625,
0.04327392578125,
0.0002777576446533203
] |
Retrieved documents will be selected based on their relevance to the research questions ( Section 2.2 ) and on their contribution to the development of IPTs . Brennan et al. advise that when seeking to inform the program theory, the reviewer should be cognizant that even small sections of a primary study may be relevant and contribute to testing a specific hypothesis about the relationships between context, mechanisms and outcomes. Retrieved documents will contribute to a high-quality collection of papers for a theory-driven realist review that will further inform and refine the developed IPTs ( Supplementary File S2 ).
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999999 |
PMC11276605_p40
|
PMC11276605
|
sec[1]/sec[2]/sec[4]/p[1]
|
2.3.5. Evidence Selection and Appraisal
| 3.164063 |
biomedical
|
Study
|
[
0.87060546875,
0.0015039443969726562,
0.1278076171875
] |
[
0.7666015625,
0.1419677734375,
0.09075927734375,
0.0005125999450683594
] |
The selection of studies for analysis and synthesis will depend on their relevance and rigor. For a realist review, relevance refers to whether a study can contribute to building or testing a program theory, while rigor refers to the credibility and trustworthiness of the methods used to collect the relevant data . These criteria will be used to determine whether the literature contributes to testing or developing the IPT and to inform its inclusion or exclusion in the realist review .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p41
|
PMC11276605
|
sec[1]/sec[2]/sec[5]/p[0]
|
2.3.6. Data Extraction
| 4.011719 |
biomedical
|
Study
|
[
0.9970703125,
0.0015621185302734375,
0.0012264251708984375
] |
[
0.9951171875,
0.003620147705078125,
0.00140380859375,
0.00009709596633911133
] |
Data extraction will be a three-step process. Firstly, an initial screening of identified papers by title and abstract, followed by a full-text retrieval and finally appraisal. Initial screening by title and abstract will be undertaken in duplicate by authors 1 and 2. Each title and abstract retrieved from the searches will be reviewed using the inclusion and exclusion criteria ( Table 1 ) to determine suitability. Authors 1 and 2 will screen documents for initial relevance, while Author 3 will further assess the included documents for richness and rigor. Any queries or disparities will be discussed by all three authors. Throughout the entire process, the authors will continue to adhere to the criteria outlined in the RAMESES guidelines .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p42
|
PMC11276605
|
sec[1]/sec[2]/sec[5]/p[1]
|
2.3.6. Data Extraction
| 3.285156 |
biomedical
|
Study
|
[
0.89453125,
0.001972198486328125,
0.10333251953125
] |
[
0.880859375,
0.1158447265625,
0.0031147003173828125,
0.00026535987854003906
] |
To facilitate the data extraction process, congruent with realist review guidelines, the IPT being ‘tested’ through the realist review will first be rendered apparent through the development and use of bespoke data extraction forms . The bespoke nature of the data extraction forms recognizes that data extraction forms in realist reviews will vary based on the underlying theoretical framework, making each form unique to the specific realist review . Given the theoretical framework, standardized data extraction forms may be unsuitable, and this is reflected in the design of tailored forms within realist review . These data extraction forms will be used to extract and review information relevant to IPT refinement through the identification of contextual factors, mechanisms and outcomes relating to the research questions.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p43
|
PMC11276605
|
sec[1]/sec[2]/sec[6]/p[0]
|
2.3.7. Data Analysis
| 3.740234 |
biomedical
|
Study
|
[
0.97705078125,
0.0009245872497558594,
0.02215576171875
] |
[
0.9453125,
0.035552978515625,
0.0189666748046875,
0.00022268295288085938
] |
Following data extraction, we will import the selected papers into the specialized qualitative software NVivo version 14 (Mac), which has been used in realist reviews to facilitate coding and thematic analysis of the data to identify CMOcs. NVivo is highly regarded for its ability to efficiently manage and analyze qualitative data, making it an excellent choice for realist reviews. It supports systematic coding and thematic analysis, crucial for identifying patterns and refining theories iteratively throughout the review process . Where relevant, stakeholders will help us improve the final theoretical framework by sharing their knowledge and expertise in the field. The authors will revisit any stage of the review process as necessary to ensure that we have gathered enough data and reached a state of ‘theory saturation’ .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
PMC11276605_p44
|
PMC11276605
|
sec[1]/sec[2]/sec[7]/p[0]
|
2.3.8. Further Refine IPTs
| 2.023438 |
biomedical
|
Other
|
[
0.91015625,
0.00975799560546875,
0.08026123046875
] |
[
0.41748046875,
0.564453125,
0.01654052734375,
0.0012617111206054688
] |
The refined IPTs from the realist review will be presented to and adjudicated by the expert panel, which will provide further feedback on the IPTs to ensure an appropriate interpretation of results . The involvement of the expert panel at this stage will contribute to ensuring that the refined IPTs are robust, contextually sensitive, and reflective of the complexities inherent in the intervention’s implementation and outcomes .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p45
|
PMC11276605
|
sec[2]/p[0]
|
3. Dissemination of Findings
| 1.742188 |
biomedical
|
Other
|
[
0.85546875,
0.022979736328125,
0.12158203125
] |
[
0.082275390625,
0.91259765625,
0.004161834716796875,
0.0008082389831542969
] |
The dissemination of the results of the realist review outlined in this protocol will be consistent with the RAMESES reporting guidelines . The intention is to disseminate the findings through the publication of the realist review in a peer-reviewed journal, through relevant conference presentations attended by healthcare, industry, and academic audiences, and for further dissemination to take place through stakeholder involvement in further theory refinement. The realist review will also constitute part of a PhD thesis. The findings of the realist review will inform the next stage of this research, which will be a realist evaluation of the findings with stakeholders involved in Lean healthcare interventions that include sustainability outcomes in their design. This realist review protocol will be registered with PROSPERO.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p46
|
PMC11276605
|
sec[3]/p[0]
|
4. Discussion
| 3.738281 |
biomedical
|
Study
|
[
0.96044921875,
0.0013780593872070312,
0.0380859375
] |
[
0.7734375,
0.131103515625,
0.09490966796875,
0.0004012584686279297
] |
The integration of environmental sustainability outcomes into Lean interventions in healthcare requires a conscious effort to align environmental, social, and economic considerations with the primary goals of efficiency and quality improvement . Whilst this research seeks to consider environmental sustainability in healthcare settings , a more comprehensive and integrated approach can contribute to a healthcare system that not only operates efficiently but also considers its long-term impact on the well-being of the community and the environment. Measuring and quantifying environmental sustainability outcomes can be complex, as they extend beyond immediate efficiency gains to include environmental impact, social responsibility, and long-term economic considerations .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p47
|
PMC11276605
|
sec[3]/p[1]
|
4. Discussion
| 3.873047 |
biomedical
|
Study
|
[
0.9853515625,
0.0015192031860351562,
0.01319122314453125
] |
[
0.810546875,
0.00909423828125,
0.1798095703125,
0.0003609657287597656
] |
The realist review outlined in this protocol will facilitate the identification of the specific contextual factors in which certain mechanisms trigger anticipated outcomes from Lean interventions that include environmental sustainability outcomes in their design. We purport that the realist review will identify the available literature and case studies that facilitate further iteration of the developed IPTs and highlight where there may be instances of successful Lean projects with a focus on environmental sustainability that has not been widely published or otherwise highlighted in the literature. Our study aims to improve the understanding of the inclusion of environmental sustainability outcomes in the design of Lean interventions, what works or does not work, for whom and in what contexts. We contend that this study will make an important and timely contribution with implications for healthcare policy, research and practice.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
PMC11276605_p48
|
PMC11276605
|
sec[4]/p[0]
|
5. Conclusions
| 4.101563 |
biomedical
|
Review
|
[
0.98876953125,
0.003955841064453125,
0.007080078125
] |
[
0.018829345703125,
0.0100860595703125,
0.97021484375,
0.0007066726684570312
] |
This realist review protocol is designed to ensure transparency and facilitate study replication by other investigators. It begins by clearly defining research questions to focus the inquiry and establishes a comprehensive theoretical framework detailing mechanisms, contexts, and anticipated outcomes . Detailed documentation of the search strategy, including databases, search terms, and criteria for inclusion and exclusion, ensures replicability . The protocol systematically outlines data extraction and analysis procedures, including coding methods and evidence synthesis and emphasizes an iterative approach allowing for continuous theory refinement and testing with emerging data . Stakeholder involvement, such as reference and expert groups, are clearly emphasized for their contribution to iterative theory development .
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999997 |
PMC11276605_p49
|
PMC11276605
|
sec[4]/p[1]
|
5. Conclusions
| 3.894531 |
biomedical
|
Review
|
[
0.9638671875,
0.005077362060546875,
0.0308380126953125
] |
[
0.050018310546875,
0.016876220703125,
0.9326171875,
0.0004420280456542969
] |
The realist review outlined in this protocol will comply with the evidence-based practice for the conduct of a realist review in a systematic manner . The findings of the review will facilitate an understanding of the barriers and facilitators to the inclusion of environmental sustainability goals in Lean healthcare interventions and will inform the methods that the authors use to further evaluate program theories in a realist evaluation. Whilst there is a wide body of research on Lean demonstrating its impact on effectiveness and efficiency, there is little known about the outcomes of the inclusion of environmental sustainability outcomes in Lean healthcare interventions. The realist review will provide internationally relevant findings, representing a departure from traditional systematic review methodologies and will provide a robust platform for the realist evaluation.
|
[
"Elaine Shelford Mead",
"Seán Paul Teeling",
"Martin McNamara"
] |
https://doi.org/10.3390/ijerph21070868
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
39057576_p0
|
39057576
|
sec[0]/p[0]
|
1. Introduction
| 3.980469 |
biomedical
|
Review
|
[
0.99365234375,
0.0025959014892578125,
0.00365447998046875
] |
[
0.01374053955078125,
0.0085906982421875,
0.97705078125,
0.00038933753967285156
] |
Over 12.2 million strokes occur globally every year, resulting in more than 101 million stroke survivors. Population statistics show a 70% increase in the incidence of strokes between 1990 and 2019, which translates to an estimated doubling to more than 200 million stroke survivors by 2050 if the current trends continue. Stroke remains the second highest cause of mortality worldwide with 6.55 million deaths in 2019 alone . As the largest cause of complex and chronic disability, with greater than half of all stroke patients being affected, stroke constitutes a major public health priority . In the UK, around 100,000 people have a stroke every year, and approximately 1.3 million people have survived a stroke . In 2017, European figures postulated that 7.06 million disability-adjusted life years have been lost due to stroke. The European continent is predicted to have a 27% increase in demand for rehabilitation and long-term care over the next 3 decades .
|
[
"Daniel O’Flaherty",
"Khalid Ali"
] |
https://doi.org/10.3390/healthcare12141433
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999996 |
39057576_p1
|
39057576
|
sec[0]/sec[0]/p[0]
|
1.1. Pathophysiology of Motor Deficit after Stroke
| 4.320313 |
biomedical
|
Study
|
[
0.99853515625,
0.0009179115295410156,
0.0003581047058105469
] |
[
0.79931640625,
0.1585693359375,
0.03936767578125,
0.00262451171875
] |
Motor activity is largely controlled by the primary motor cortex, located within the precentral gyrus. This cortex is organised topographically, where the medial aspects represent the lower limbs and trunk while the more lateral aspects control upper limb and facial movements . Cerebral circulation is primarily provided by the anterior, middle and posterior cerebral arteries. Upon ischaemic insult to the central nervous system (CNS), the affected region infarcts, which results in corticospinal tract (CST) disruption and reduced innervation to the muscle groups in the affected territory. Blood supply to the upper limb motor cortex is delivered by the middle cerebral artery, and hence disruption to this vascular territory results in upper limb motor impairment .
|
[
"Daniel O’Flaherty",
"Khalid Ali"
] |
https://doi.org/10.3390/healthcare12141433
|
N/A
|
https://creativecommons.org/licenses/by/4.0/
|
en
| 0.999998 |
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