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Inflammopharmacology Apr 2024This study is the first to summarize the evidence on how the use of anti-inflammatory drugs during acute pain has an impact on the development of chronic pain. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study is the first to summarize the evidence on how the use of anti-inflammatory drugs during acute pain has an impact on the development of chronic pain.
METHODS
Randomized controlled trials retrieved from nine databases included anti-inflammatory drugs (NSAIDs or steroids) versus non-anti-inflammatory drugs in patients with acute pain and reported the incidence of chronic pain. No specified date, age, sex, or language restrictions. Subgroup analyses were performed according to pain classification, follow-up time, and medication. The GRADE method was used to evaluate quality of evidence.
RESULTS
A total of 29 trials (5220 patients) were included. Steroids or NSAIDs did not reduce the incidence of chronic nociceptive pain. Steroid use in acute phase significantly reduced the incidence of chronic neuropathic pain. In subgroup analysis, benefits were observed for methylprednisolone and dexamethasone, with some adverse effects. Steroids or NSAIDs were statistically significant in reducing pain intensity over 1 year, but the effect size was too small, and whether the long-term effect is clinically relevant needs to be further studied.
CONCLUSION
Quality of the evidence was low to moderate. No drug can be recommended to prevent chronic nociceptive pain. Injections of steroids (methylprednisolone or dexamethasone) during the acute phase reduce the incidence of chronic neuropathic pain, but most included studies also used local anesthetics. The results are indirect and need to be interpreted with caution. The pooled data effect sizes for pain intensity were small, so the clinical relevance was unclear. Study registration PROSPERO (CRD42022367030).
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Acute Pain; Incidence; Steroids; Neuralgia; Methylprednisolone; Nociceptive Pain; Dexamethasone; Randomized Controlled Trials as Topic
PubMed: 38153536
DOI: 10.1007/s10787-023-01405-8 -
Journal of Neuro-oncology Jan 2024Glioblastomas, the most common primary malignant brain tumors in adults, still hold poor prognosis. Corticosteroids, such as dexamethasone, are usually prescribed to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Glioblastomas, the most common primary malignant brain tumors in adults, still hold poor prognosis. Corticosteroids, such as dexamethasone, are usually prescribed to reduce peritumoral edema and limit neurological symptoms, although potential detrimental effects of these drugs have been described. The present meta-analysis aimed to explore the association of dexamethasone with overall survival (OS) and progression free survival (PFS) in patients with newly diagnosed glioblastoma.
METHODS
PubMed, Cochrane Library, Embase, and ClinicalTrials.gov were searched for pertinent studies following the Preferred Reporting Items of Systematic Review and Meta-Analysis checklist. Pooled multivariable-adjusted hazard ratios (HR) for OS and PFS and their associated 95% confidence intervals (CIs) were calculated using the random-effects model and the heterogeneity among studies was assessed using I. The quality of evidence was assessed using the GRADE criteria.
RESULTS
Seven studies were included, pooling data of 1,257 patients, with age varying from 11 to 81 years. Glioblastoma patients on pre- or peri-operative dexamethasone were associated with a significantly poorer overall survival (HR: 1.33, 95% CI: 1.15, 1.55; 7 studies; I: 59.9%) and progression free survival (HR: 1.77, 95% CI: 1.05, 2.97; 3 studies; I: 71.1%) compared to patients not on dexamethasone. The quality of evidence was moderate for overall survival and low for progression free survival.
CONCLUSION
Dexamethasone appeared to be associated with poor survival outcomes of glioblastoma patients.
Topics: Adult; Humans; Child; Adolescent; Young Adult; Middle Aged; Aged; Aged, 80 and over; Glioblastoma; Progression-Free Survival; Dexamethasone; Disease-Free Survival
PubMed: 38151699
DOI: 10.1007/s11060-023-04549-3 -
International Journal of Dermatology Apr 2024Skin is a major site of cortisol bioconversion by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzymes which catalyze intracellular inactive cortisone into... (Review)
Review
Skin is a major site of cortisol bioconversion by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzymes which catalyze intracellular inactive cortisone into physiologically active cortisol. 11β-HSD1 is highly expressed in skin, especially in dermal fibroblasts, epidermal keratinocytes, melanocytes, and hair follicles, and plays important roles in regulating keratinocytes, fibroblast proliferation, and has roles in skin aging. Inhibition of 11β-HSD1 may reverse decreased collagen levels observed in extrinsically and intrinsically aged skin. Inhibitors of 11β-HSD1 may also have the potential to reverse decreased collagen observed in skin atrophy induced by glucocorticoid treatment. This systematic review aimed to summarize the current knowledge of roles for 11β-HSD1 inhibitor in skin physiology and potential for future use in medications. Studies have demonstrated that immediately following experimental insult in an animal model, there is increased expression of 11β-HSD1, and that topical application of an 11β-HSD1 inhibitor increases the rate of healing, increases skin collagen content, increases dermal fibroblasts, and increases dermal thickness. Furthermore, in patients with type 2 diabetes mellitus, 11β-HSD1 inhibitors reduce wound diameter after injury. Further development of 11β-HSD1 inhibitors appears to be a promising area for treating aging skin, aiding wound healing, and mitigating effects of systemic glucocorticoid use. Both topically and orally administered 11β-HSD1 inhibitors appear to be viable avenues for future research.
Topics: Animals; Humans; Aged; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Glucocorticoids; Hydrocortisone; Diabetes Mellitus, Type 2; Collagen; Skin Aging
PubMed: 38146184
DOI: 10.1111/ijd.16967 -
Nutrients Dec 2023Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and... (Review)
Review
BACKGROUND
Withania somnifera (WS), a popular medicinal plant of the Solanaceae family, contains active ingredients with antioxidant, anti-inflammatory, immunomodulatory, and anti-stress activities. However, its precise mechanisms of action and optimal use as a supplement are not yet fully understood. The objective of this systematic review is to assess the impact of WS supplementation on cortisol levels in stressed humans by analyzing clinical trials conducted prior to May 2023.
METHODS
The assessment was carried out following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) by exploring the databases of EMBASE, PubMed, Google Scholar, CENTRAL, and Scopus.
RESULTS
Of the 4788 articles identified, only 9 studies met the selection criteria. The selected studies varied in terms of design, results, formulations, dosages, and treatment duration (30-112 days), and involved subjects with varying degrees of stress. WS supplementation decreases cortisol secretion with no significant adverse effects. Nonetheless, none of the studies evaluated the potential impact of cortisol reduction on adrenal function and long-term effects.
CONCLUSIONS
Brief-term supplementation with WS appears to have a stress-reducing effect in stressed individuals. However, since the long-term effects of WS supplementation are not yet fully understood, WS supplements should be used under medical supervision.
Topics: Humans; Plant Extracts; Withania; Hydrocortisone; Plants, Medicinal; Antioxidants
PubMed: 38140274
DOI: 10.3390/nu15245015 -
Oncology (Williston Park, N.Y.) Dec 2023Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods... (Review)
Review
Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.
Topics: Aged; Female; Humans; Male; Middle Aged; Danazol; Myelodysplastic Syndromes
PubMed: 38133562
DOI: 10.46883/2023.25921009 -
Journal of Critical Care Apr 2024The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP.
METHODS
The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model.
RESULTS
Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty).
CONCLUSIONS
Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.
Topics: Adult; Humans; Adrenal Cortex Hormones; Community-Acquired Infections; Hydrocortisone; Pneumonia; Randomized Controlled Trials as Topic
PubMed: 38128217
DOI: 10.1016/j.jcrc.2023.154507 -
BMC Infectious Diseases Dec 2023Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, some meta-analyses on COVID-19 have suggested that glucocorticoids use can reduce the mortality rate of COVID-19 patients, utilization rate of invasive ventilation, and improve the prognosis of patients. However, optimal regimen and dosages of glucocorticoid remain unclear. Therefore, the purpose of this network meta-analysis is to analyze the efficacy and safety of glucocorticoids in treating COVID-19 at regimens.
METHODS
This meta-analysis retrieved randomized controlled trials from the earliest records to December 30, 2022, published in PubMed, Embase, Cochrane Library, CNKI Database and Wanfang Database, which compared glucocorticoids with placebos for their efficacy and safety in the treatment of COVID-19, Effects of different treatment regimens, types and dosages (high-dose methylprednisolone, very high-dose methylprednisolone, Pulse therapy methylprednisolone, medium-dose hydrocortisone, high-dose hydrocortisone, high-dose dexamethasone, very high-dose dexamethasone and placebo) on 28-day all-caused hospitalization mortality, hospitalization duration, mechanical ventilation requirement, ICU admission and safety outcome were compared.
RESULTS
In this network meta-analysis, a total of 10,544 patients from 19 randomized controlled trials were finally included, involving a total of 9 glucocorticoid treatment regimens of different types and dosages. According to the analysis results, the 28-day all-cause mortality rate was the lowest in the treatment with pulse therapy methylprednisolone (OR 0.08, 95% CI 0.02, 0.42), but the use of high-dose methylprednisolone (OR 0.85, 95% CI 0.59, 1.22), very high-dose dexamethasone (OR 0.95, 95% CI 0.67, 1.35), high-dose hydrocortisone (OR 0.64, 95% CI 0.34, 1.22), medium-dose hydrocortisone (OR 0.80, 95% CI 0.49, 1.31) showed no benefit in prolonging the 28-day survival of patient. Compared with placebo, the treatment with very high-dose methylprednisolone (MD = -3.09;95%CI: -4.10, -2.08) had the shortest length of hospital stay, while high-dose dexamethasone (MD = -1.55;95%CI: -3.13,0.03) and very high-dose dexamethasone (MD = -1.06;95%CI: -2.78,0.67) did not benefit patients in terms of length of stay.
CONCLUSIONS
Considering the available evidence, this network meta‑analysis suggests that the prognostic impact of glucocorticoids in patients with COVID-19 may depend on the regimens of glucocorticoids. It is suggested that pulse therapy methylprednisolone is associated with lower 28-day all-cause mortality, very high-dose methylprednisolone had the shortest length of hospital stay in patients with COVID-19.
TRIAL REGISTRATION
PROSPERO CRD42022350407 (22/08/2022).
Topics: Humans; Glucocorticoids; COVID-19; Hydrocortisone; Network Meta-Analysis; Methylprednisolone; Dexamethasone
PubMed: 38124031
DOI: 10.1186/s12879-023-08874-w -
Sports Medicine (Auckland, N.Z.) Apr 2024Professional rugby union is a high-intensity contact sport with position-specific high training and match volumes across a season that may lead to periods of fatigue if... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Professional rugby union is a high-intensity contact sport with position-specific high training and match volumes across a season that may lead to periods of fatigue if above a typically experienced threshold. This study assesses the influence of match play and/or training on fatigue levels in rugby union players.
OBJECTIVE
We aimed to perform a systematic review and meta-analysis of measures used to assess fatigue status in male professional rugby union players.
METHODS
Using electronic databases (PubMed, SPORTDiscus, Web of Science, Cochrane Library, EMBASE, and MEDLINE), a systematic review of fatigue testing in rugby union was conducted on (1) neuromuscular, (2) subjective self-report, (3) biochemical, and (4) heart rate-derived measures.
RESULTS
Thirty-seven articles were included in this systematic review, of which 14 were further included in a meta-analysis. The results of the meta-analysis revealed small, yet not significant, decreases in countermovement jump height immediately after (effect size [ES] = - 0.29; 95% confidence interval [CI] - 0.64 to 0.06), 24 h (ES = - 0.43; 95% CI - 3.99 to 3.21), and 48 h (ES = - 0.22; 95% CI - 0.47 to 0.02) after exposure to rugby union match play or training. Reported wellness (ES = - 0.33; 95% CI - 1.70 to 1.04) and tiredness (ES = - 0.14; 95% CI - 1.30 to 1.03) declined over a period of a few weeks (however, the results were not-statistically significant), meanwhile muscle soreness increased (ES = 0.91; 95% CI 0.06 to 1.75) within the 96 h after the exposure to rugby union match play or training. Finally, while cortisol levels (ES = 1.87; 95% CI - 1.54 to 5.29) increased, testosterone declined (ES = - 1.54; 95% CI - 7.16 to 4.08) within the 24 h after the exposure. However, these results were not statistically significant.
CONCLUSIONS
Subjective measures of muscle soreness can be used to assess fatigue after match play and training in rugby union players. Within-study and between-study variability for countermovement jump height, biochemical markers, and heart rate-derived measures means the utility (practical application) of these measures to assess fatigue in professional rugby union players after matches and training is unclear.
CLINICAL TRIAL REGISTRATION
PROSPERO ID: CRD42020216706.
Topics: Humans; Football; Fatigue; Male; Heart Rate; Physical Conditioning, Human; Muscle Fatigue; Exercise Test; Hydrocortisone; Myalgia; Testosterone
PubMed: 38114782
DOI: 10.1007/s40279-023-01973-3 -
Infection Feb 2024Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if... (Review)
Review
PURPOSE
Preliminary evidence suggests a potential effect of antiviral medication used during the acute COVID-19 phase for preventing long-COVID. This review investigates if having received pharmacological treatment during acute SARS-CoV-2 infection may reduce the risk of long-COVID.
METHODS
MEDLINE, CINAHL, PubMed, EMBASE, Web of Science databases, as well as medRxiv/bioRxiv preprint servers were searched up to July 15th, 2023. Articles comparing the presence of long-COVID symptoms between individuals who received or not a specific medication, particularly antivirals, during the acute phase of SARS-CoV-2 infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale or Cochrane's Risk of Bias (Rob) tool.
RESULTS
From 517 studies identified, 6 peer-reviewed studies and one preprint met all inclusion criteria. The sample included 2683 (n = 4) hospitalized COVID-19 survivors and 307,409 (n = 3) non-hospitalized patients. The methodological quality was high in 71% of studies (n = 5/7). Two studies investigating the effects of Nirmaltrevir/Ritonavir and three studies the effect of Remdesivir reported conflicting results on effectiveness for preventing long-COVID. Three studies investigating the effects of other medication such as Dexamethasone (n = 2) or Metformin (n = 1) found positive results of these medications for preventing long-COVID.
CONCLUSION
Available evidence about the effect of medication treatment with antivirals during acute COVID-19 and reduced risk of developing long-COVID is conflicting. Heterogeneous evidence suggests that Remdesivir or Nirmaltrevir/Ritonavir could have a potential protective effect for long-COVID. A limited number of studies demonstrated a potential benefit of other medications such as Dexamethasone or Metformin, but more studies are needed.
Topics: Humans; COVID-19; Post-Acute COVID-19 Syndrome; Ritonavir; SARS-CoV-2; Antiviral Agents; Dexamethasone; Metformin
PubMed: 38113020
DOI: 10.1007/s15010-023-02154-0 -
Neurology(R) Neuroimmunology &... Jan 2024We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE).
BACKGROUND AND OBJECTIVES
We characterize clinical and neuroimaging features of SARS-CoV-2-related acute necrotizing encephalopathy (ANE).
METHODS
Systematic review of English language publications in PubMed and reference lists between January 1, 2020, and June 30, 2023, in accordance with PRISMA guidelines. Patients with SARS-CoV-2 infection who fulfilled diagnostic criteria for sporadic and genetic ANE were included.
RESULTS
From 899 articles, 20 cases (17 single case reports and 3 additional cases) were curated for review (50% female; 8 were children). Associated COVID-19 illnesses were febrile upper respiratory tract infections in children while adults had pneumonia (45.6%) and myocarditis (8.2%). Children had early neurologic deterioration (median day 2 in children vs day 4 in adults), seizures (5 (62.5%) children vs 3 of 9 (33.3%) adults), and motor abnormalities (6 of 7 (85.7%) children vs 3 of 7 (42.9%) adults). Eight of 12 (66.7%) adults and 4 (50.0%) children had high-risk ANE scores. Five (62.5%) children and 12 (66.7%) adults had brain lesions bilaterally and symmetrically in the putamina, external capsules, insula cortex, or medial temporal lobes, in addition to typical thalamic lesions of ANE. Hypotension was only seen in adults (30%). Hematologic derangements were common: lymphopenia (66.7%), coagulopathy (60.0%), or elevated D-dimers (100%), C-reactive protein (91.7%), and ferritin (62.5%). A pathogenic heterozygous c/.1754 C>T variant in was present in 2 children: one known to have this before SARS-CoV-2 infection, and a patient tested because the SARS-CoV-2 infection was the second encephalopathic illness. Three other children with no prior encephalopathy or family history of encephalopathy were negative for this variant. Fifteen (75%) received immunotherapy (with IV methylprednisolone, immunoglobulins, tocilizumab, or plasma exchange): 6 (40.0%) with monotherapy and 9 (60.0%) had combination therapy. Deaths were in 8 of 17 with data (47.1%): a 2-month-old male infant and 7 adults (87.5%) of median age 56 years (33-70 years), 4 of whom did not receive immunotherapy.
DISCUSSION
Children and adults with SARS-CoV-2 ANE have similar clinical features and neuroimaging characteristics. Mortality is high, predominantly in patients not receiving immunotherapy and at the extremes of age.
Topics: Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Brain Diseases; COVID-19; Methylprednisolone; SARS-CoV-2; Seizures; Aged
PubMed: 38086061
DOI: 10.1212/NXI.0000000000200186