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Antimicrobial Agents and Chemotherapy May 2024The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and...
The prevalence of obesity has increased considerably in the last few decades. Pathophysiological changes in obese patients lead to pharmacokinetic (PK) and pharmacodynamic (PD) alterations that can condition the correct exposure to antimicrobials if standard dosages are used. Inadequate dosing in obese patients can lead to toxicity or therapeutic failure. In recent years, additional antimicrobial PK/PD data, extended infusion strategies, and studies in critically ill patients have made it possible to obtain data to provide a better dosage in obese patients. Despite this, it is usually difficult to find information on drug dosing in this population, which is sometimes contradictory. This is a comprehensive review of the dosing of different types of antimicrobials (antibiotics, antifungals, antivirals, and antituberculosis drugs) in obese patients, where the literature on PK and possible dosing strategies in obese adults was critically assessed.
Topics: Humans; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Antitubercular Agents; Antiviral Agents; Critical Illness; Obesity
PubMed: 38526051
DOI: 10.1128/aac.01719-23 -
The Journal of Manual & Manipulative... Oct 2023Adhesive capsulitis (AC) affects approximately 1% of the general population. Current research lacks clear guidance on the dosage of manual therapy and exercise... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adhesive capsulitis (AC) affects approximately 1% of the general population. Current research lacks clear guidance on the dosage of manual therapy and exercise interventions.
OBJECTIVE
The purpose of this systematic review was to assess the effectiveness of manual therapy and exercise in the management of AC, with a secondary aim of describing the available literature present on the dosage of interventions.
METHODS
Eligible studies were randomized clinical/quasi-experimental trials with complete data analysis and no limits on date of publication, published in English, recruited participants >18 years of age with primary adhesive capsulitis, that had at least two groups with one group receiving manual therapy (MT) alone, exercise alone, or MT and exercise, that included at least one outcome measure of pain, disability, or external rotation range of motion, and that had dosage of visits clearly defined. An electronic search was conducted using PubMed, Embase, Cochrane, Pedro, and clinicaltrials.gov. Risk of bias was assessed using the Cochrane Collaboration Risk of Bias 2 Tool. The Grading of Recommendations Assessment, Development, and Evaluation was used to provide an overall assessment of the quality of evidence. Meta-analyses were conducted when possible, and dosage was discussed in narrative form.
RESULTS
Sixteen studies were included. All meta-analyses revealed non-significant effects of pain, disability, and external rotation range of motion at short- and long-term follow-up, with an overall level of evidence ranging from very low to low.
CONCLUSION
Non-significant findings with low-to-very-low-quality of evidence were found across meta-analyses, preventing seamless transition of research evidence to clinical practice. Lack of consistency in study designs, manual therapy techniques, dosing parameters, and duration of care impedes the ability to make strong recommendations regarding optimal dosage of physical therapy for individuals with AC.
Topics: Humans; Exercise; Musculoskeletal Manipulations; Physical Therapy Modalities; Shoulder Pain; Bursitis; Randomized Controlled Trials as Topic
PubMed: 36861780
DOI: 10.1080/10669817.2023.2180702 -
American Journal of Respiratory and... May 2024The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. To... (Meta-Analysis)
Meta-Analysis Comparative Study
Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.
Topics: Humans; Fludrocortisone; Hydrocortisone; Shock, Septic; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Anti-Inflammatory Agents; Network Meta-Analysis; Treatment Outcome; Male; Bayes Theorem; Female; Adult; Middle Aged
PubMed: 38271488
DOI: 10.1164/rccm.202310-1785OC -
Heart (British Cardiac Society) Apr 2024In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly...
OBJECTIVE
In clinical practice, patients with eosinophilic myocarditis (EM) may forgo the gold standard diagnostic procedure, endomyocardial biopsy (EMB), although it is highly recommended in guidelines. This systematic review aims to summarise current approaches in diagnosing and treating EM with a particular emphasis on the utilisation and value of alternative diagnostic methods.
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we searched MEDLINE and EMBASE for all peer-reviewed articles using the keywords "eosinophilic myocarditis" from their inception to 10 September 2022.
RESULTS
We included 239 articles, including 8 observational studies and 274 cases, in this review. The median patient age was 45 years. Initial presentations were non-specific, including dyspnoea (50.0%) and chest pain (39.4%). The aetiologies of EM were variable with the most common being idiopathic (28.8%) and eosinophilic granulomatosis polyangiitis (19.3%); others included drug-induced (13.1%) and hypereosinophilic syndrome (12.8%). 82.4% received an EM diagnosis by EMB while 17.6% were diagnosed based on clinical reasoning and cardiac MRI (CMR). CMR-diagnosed patients exhibited a better risk profile at diagnosis, particularly higher left ventricular ejection fraction and less need for inotropic or mechanical circulatory supports. Glucocorticoids were the primary treatment with variability in dosages and regimens.
CONCLUSION
EMB is the mainstay for diagnostic testing for EM. CMR is potentially helpful for screening in appropriate clinical scenarios. Regarding treatment, there is no consensus regarding the optimal dosage of corticosteroids. Large clinical trials are warranted to further explore the utility of CMR in the diagnosis of EM and steroid regimen in treating EM.
Topics: Humans; Myocarditis; Eosinophilia; Biopsy; Myocardium
PubMed: 37963727
DOI: 10.1136/heartjnl-2023-323225 -
Cardiovascular Diabetology Nov 2023Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia.
METHODS
PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867).
RESULTS
Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79-0.95), myocardial infarction (OR 0.76, 95% CI 0.64-0.88) and unstable angina (OR 0.69, 95% CI 0.54-0.88) compared to control, over a median follow up of 87 (15-162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]-22.42,95% CI - 24.02% to - 20.82%), total cholesterol (- 16.50%,95% - 19.21% to - 13.79%), Apo-B lipoprotein (- 19.55%, - 22.68% to - 16.42%) and high-sensitivity CRP (- 27.83%, - 31.71% to - 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27-1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy.
CONCLUSIONS
The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cholesterol, LDL; Cholesterol; Myocardial Infarction; Gout; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38017541
DOI: 10.1186/s12933-023-02022-z -
Nutrients Aug 2023Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and... (Review)
Review
INTRODUCTION
Studies indicate a high prevalence of vitamin D deficiency in both the general population and at-risk groups. Given the association between vitamin D deficiency and various diseases, addressing this concern becomes crucial, especially in situations where routine monitoring is challenging.
MATERIALS AND METHODS
A systematic literature review of the current knowledge on vitamin D dosing in diverse at-risk populations and the application of the findings to a broader clinical perspective.
RESULTS
The reviewed studies revealed a high prevalence of vitamin D deficiency among patients with musculoskeletal disorders, systemic connective tissue diseases, corticosteroid use, endocrine and metabolic conditions, malabsorption syndromes, obesity, chronic kidney disease, cancer, and central nervous system diseases. Vitamin D deficiency was often more severe compared to the general population. Higher dosages of vitamin D beyond the recommended levels for the general population were shown to be effective in improving vitamin D status in these at-risk individuals. Additionally, some studies suggested a potential link between intermittent vitamin D administration and improved adherence.
CONCLUSION
Simplified dosing could empower clinicians to address vitamin D deficiency, particularly in high-risk populations, even without routine monitoring. Further research is needed to establish the optimal dosing regimens for specific at-risk populations.
Topics: Humans; Vitamin D; Vitamins; Vitamin D Deficiency; Knowledge; Malabsorption Syndromes
PubMed: 37686757
DOI: 10.3390/nu15173725 -
Journal of Research in Medical Sciences... 2023Calcitonin gene-related peptides (CGRP) have been considered a new effective means to prevent and treat migraine. Eptinezumab is a new class of CGRP antagonists that has... (Review)
Review
BACKGROUND
Calcitonin gene-related peptides (CGRP) have been considered a new effective means to prevent and treat migraine. Eptinezumab is a new class of CGRP antagonists that has been ratified for clinical treatment. The purpose of this systematic review was to assess and contrast the therapeutic effect and safety of eptinezumab in the management of migraine in comparison with a placebo.
MATERIALS AND METHODS
We systematically searched PubMed, Embase, Cochrane Library, and the US National Institutes of Health Clinical Trials Registry from the earliest date to February 16, 2023, for randomized controlled trials (RCTs). The mean difference (MD) and risk ratio (RR) were chosen to assess clinical indicators.
RESULTS
In total, there were 2, 739 patients in four RCTs, who were ultimately included. Our summarized results showed that eptinezumab had better healing efficacy compared to placebo with respect to monthly migraine days (MD = -1.56, 95% confidence interval [CI]: -2.32, -0.79, < 0.001), improving ≥75% migraine responder rate (RR = 1.80, 95% CI: 1.40, 2.33, < 0.001), ≥50% migraine responder rate (RR = 1.46, 95% CI: 1.33, 1.61, < 0.001), and 100% migraine responder rate (RR = 2.41, 95% CI: 1.08, 5.38, < 0.001). Furthermore, compared with placebo, there was no significant increase for treatment-related adverse events (RR = 1.01, 95% CI 0.94, 1.10, = 0.71) and serious AEs (RR = 0.93, 95% CI 0.46, 1.90, = 0.84). It was found that all dosages except for 10 mg had significant efficacy compared with placebo, especially 300 mg ( < 0.001).
CONCLUSION
Eptinezumab has good healing efficacy and insignificant adverse effects in treating migraine, particularly the dosage of 300 mg.
PubMed: 38292336
DOI: 10.4103/jrms.jrms_306_22 -
JAMA Network Open Aug 2023Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.
OBJECTIVE
To evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.
DATA SOURCES
PubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.
STUDY SELECTION
Randomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently performed data extraction following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.
RESULTS
Twenty-seven randomized clinical trials with 1861 patients (median age, 45.99 years [range, 20.00-70.00 years]; 759 women [40.8%]) were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of -22.07% (95% CI, -33.22% to -10.92%) for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events (nausea, vomiting, and dizziness) among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.
CONCLUSIONS AND RELEVANCE
These findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments.
Topics: Humans; Female; Middle Aged; Gabapentin; Pregabalin; Analgesics; Analgesics, Opioid; Network Meta-Analysis; Pain, Postoperative
PubMed: 37556139
DOI: 10.1001/jamanetworkopen.2023.28121 -
Pathogens (Basel, Switzerland) Jul 2023Biological pest control is an environmentally friendly alternative to synthetic pesticides, using organisms such as viruses, bacteria, fungi, and parasitoids. However,... (Review)
Review
Biological pest control is an environmentally friendly alternative to synthetic pesticides, using organisms such as viruses, bacteria, fungi, and parasitoids. However, efficacy is variable and combining different biocontrol agents could improve success rates. We conducted a systematic review of studies combining a parasitoid with an entomopathogenic microorganism, the first of its kind. We searched in Web of Science and extracted data from 49 publications matching the pre-defined inclusion criteria. Combinations of 36 hymenopteran parasitoids with 17 entomopathogenic microorganisms used to control 31 target pests were found. and were the most frequently studied parasitoids, while , , , var. , the Spodoptera exigua multiple nucleopolyhedrovirus, and the Spodoptera frugiperda multiple nucleopolyhedrovirus were the main microbial agents assessed. Out of 49 parasitoid-microorganism combinations assessed in the laboratory experiments, thirty-eight were reported as compatible and six as incompatible. Timing and dosage of biopesticides played a crucial role, with later application and appropriate dosage minimizing adverse effects on parasitoid development. More research is needed to assess compatibility and efficacy under real-world conditions. Our review provides valuable insights for researchers and practitioners to optimize the combined use of micro- and macroorganisms for effective pest control.
PubMed: 37513804
DOI: 10.3390/pathogens12070957 -
Journal of Perinatal Medicine Nov 2023Dexamethasone administration can reduce bronchopulmonary dysplasia, our objective was to identify long term adverse effects. (Review)
Review
BACKGROUND
Dexamethasone administration can reduce bronchopulmonary dysplasia, our objective was to identify long term adverse effects.
CONTENT
A systematic review was performed to determine the childhood and adolescent cardiopulmonary and cognitive effects of dexamethasone systemically administered to preterm infants during neonatal intensive care. Relevant studies were identified by searching two electronic health databases and the grey literature. Spirometry assessments were used as respiratory outcomes, blood pressure and echocardiography assessments as cardiovascular outcomes and cognitive and motor function as cognitive outcomes. From 1,479 articles initially identified, 18 studies (overall 1,609 patients) were included (respiratory n=8, cardiovascular n=2, cognitive n=10); all were observational cohort studies. Dexamethasone exposure was associated with worse pulmonary outcomes in children and adolescents (more abnormal FVC and FEV1:FVC z scores). Dexamethasone exposure was associated in one study with lower IQ scores compared to preterm controls (mean 78.2 [SD 15.0] vs. 84.4 [12.6], [p=0.008]) and in two others was associated with lower total and performance IQ when compared to term controls (p<0.001).
SUMMARY AND OUTLOOK
Postnatal dexamethasone exposure has a negative influence on pulmonary and cognitive outcomes in childhood and adolescence. Medications with a better benefit to risk profile need to be identified.
Topics: Adolescent; Child; Humans; Infant; Infant, Newborn; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Bronchopulmonary Dysplasia; Chronic Disease; Dexamethasone; Glucocorticoids; Infant, Premature
PubMed: 37606507
DOI: 10.1515/jpm-2023-0297