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JAMA Network Open Apr 2023Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Calciphylaxis is a rare disease with high mortality mainly involving patients with chronic kidney disease (CKD). Sodium thiosulphate (STS) has been used as an off-label therapeutic in calciphylaxis, but there is a lack of clinical trials and studies that demonstrate its effect compared with those without STS treatment.
OBJECTIVE
To perform a meta-analysis of the cohort studies that provided data comparing outcomes among patients with calciphylaxis treated with and without intravenous STS.
DATA SOURCES
PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using relevant terms and synonyms including sodium thiosulphate and calci* without language restriction.
STUDY SELECTION
The initial search was for cohort studies published before August 31, 2021, that included adult patients diagnosed with CKD experiencing calciphylaxis and could provide a comparison between patients treated with and without intravenous STS. Studies were excluded if they reported outcomes only from nonintravenous administration of STS or if the outcomes for CKD patients were not provided.
DATA EXTRACTION AND SYNTHESIS
Random-effects models were performed. The Egger test was used to measure publication bias. Heterogeneity was assessed using the I2 test.
MAIN OUTCOMES AND MEASURES
Skin lesion improvement and survival, synthesized as ratio data by a random-effects empirical Bayes model.
RESULTS
Among the 5601 publications retrieved from the targeted databases, 19 retrospective cohort studies including 422 patients (mean age, 57 years; 37.3% male) met the eligibility criteria. No difference was observed in skin lesion improvement (12 studies with 110 patients; risk ratio, 1.23; 95% CI, 0.85-1.78) between the STS and the comparator groups. No difference was noted for the risk of death (15 studies with 158 patients; risk ratio, 0.88; 95% CI, 0.70-1.10) and overall survival using time-to-event data (3 studies with 269 participants; hazard ratio, 0.82; 95% CI, 0.57-1.18). In meta-regression, lesion improvement associated with STS negatively correlated with publication year, implying that recent studies are more likely to report a null association compared with past studies (coefficient = -0.14; P = .008).
CONCLUSIONS AND RELEVANCE
Intravenous STS was not associated with skin lesion improvement or survival benefit in patients with CKD experiencing calciphylaxis. Future investigations are warranted to examine the efficacy and safety of therapies for patients with calciphylaxis.
Topics: Adult; Humans; Male; Middle Aged; Female; Calciphylaxis; Retrospective Studies; Bayes Theorem; Renal Insufficiency, Chronic
PubMed: 37099293
DOI: 10.1001/jamanetworkopen.2023.10068 -
International Journal of Infectious... Jul 2023To estimate the pooled proportion of extensively drug-resistant tuberculosis (XDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) in patients with... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To estimate the pooled proportion of extensively drug-resistant tuberculosis (XDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) in patients with multidrug-resistant TB (MDR-TB).
METHODS
We systematically searched articles from electronic databases: MEDLINE (PubMed), ScienceDirect, and Google Scholar. We also searched gray literature from the different literature sources main outcome of the review was either XDR-TB or pre-XDR-TB in patients with MDR-TB. We used the random-effects model, considering the substantial heterogeneity among studies. Heterogeneity was assessed by subgroup analyses. STATA version 14 was used for analysis.
RESULTS
A total of 64 studies that reported on 12,711 patients with MDR-TB from 22 countries were retrieved. The pooled proportion of pre-XDR-TB was 26% (95% confidence interval [CI]: 22-31%), whereas XDR-TB in MDR-TB cases was 9% (95% CI: 7-11%) in patients treated for MDR-TB. The pooled proportion of resistance to fluoroquinolones was 27% (95% CI: 22-33%) and second-line injectable drugs was 11% (95% CI: 9-13%). Whereas the pooled resistance proportions to bedaquiline, clofazimine, delamanid, and linezolid were 5% (95% CI: 1-8%), 4% (95% CI: 0-10%), 5% (95% CI; 2-8%), and 4% (95% CI: 2-10%), respectively.
CONCLUSION
The burden of pre-XDR-TB and XDR-TB in MDR-TB were considerable. The high burdens of pre-XDR-TB and XDR-TB in patients treated for MDR-TB suggests the need to strengthen TB programs and drug resistance surveillance.
Topics: Humans; Extensively Drug-Resistant Tuberculosis; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Fluoroquinolones; Clofazimine; Microbial Sensitivity Tests; Mycobacterium tuberculosis
PubMed: 37072053
DOI: 10.1016/j.ijid.2023.04.392 -
Clinical Pharmacokinetics Mar 2023Understanding the pharmacokinetics (PK) of antimicrobial drugs in pregnant women is crucial to provide effective and safe treatment. This study is part of a series that...
INTRODUCTION
Understanding the pharmacokinetics (PK) of antimicrobial drugs in pregnant women is crucial to provide effective and safe treatment. This study is part of a series that systematically reviews literature on the PK and analyzes if, based on the changed PK, evidence-based dosing regimens have been developed for adequate target attainment in pregnant women. This part focusses on antimicrobials other than penicillins and cephalosporins.
METHODS
A literature search was conducted in PubMed according to the PRISMA guidelines. Search strategy, study selection, and data extraction were independently performed by two investigators. Studies were labeled as relevant when information on the PK of antimicrobial drugs in pregnant women was available. Extracted parameters included bioavailability for oral drugs, volume of distribution (Vd) and clearance (CL), trough and peak drug concentrations, time of maximum concentration, area under the curve and half-life, probability of target attainment, and minimal inhibitory concentration (MIC). In addition, if developed, evidence-based dosing regimens were also extracted.
RESULTS
Of the 62 antimicrobials included in the search strategy, concentrations or PK data during pregnancy of 18 drugs were reported. Twenty-nine studies were included, of which three discussed aminoglycosides, one carbapenem, six quinolones, four glycopeptides, two rifamycines, one sulfonamide, five tuberculostatic drugs, and six others. Eleven out of 29 studies included information on both Vd and CL. For linezolid, gentamicin, tobramycin, and moxifloxacin, altered PK throughout pregnancy, especially in second and third trimester, has been reported. However, no target attainment was studied and no evidence-based dosing developed. On the other hand, the ability to reach adequate targets was assessed for vancomycin, clindamycin, rifampicin, rifapentine, ethambutol, pyrazinamide, and isoniazid. For the first six mentioned drugs, no dosage adaptations during pregnancy seem to be needed. Studies on isoniazid provide contradictory results.
CONCLUSION
This systematic literature review shows that a very limited number of studies have been performed on the PK of antimicrobials drugs-other than cephalosporins and penicillins-in pregnant women.
Topics: Female; Humans; Pregnancy; Cephalosporins; Penicillins; Isoniazid; Anti-Bacterial Agents; Clindamycin
PubMed: 36940039
DOI: 10.1007/s40262-023-01226-6 -
International Journal of... 2023Drug-resistant tuberculosis (DR-TB) is a public health concern that is difficult to treat, requiring long and complex treatment with highly effective drugs. Bedaquiline... (Review)
Review
BACKGROUND
Drug-resistant tuberculosis (DR-TB) is a public health concern that is difficult to treat, requiring long and complex treatment with highly effective drugs. Bedaquiline and/or delamanid have already shown promising outcomes in patients with DR-TB, increasing the rate of culture conversion and lowering TB-related mortality.
METHODS
We comprehensively searched and evaluated the effectiveness of individual regimens containing bedaquiline and delamanid on culture conversion and treatment success. We assessed for quality either observational or experimental studies.
RESULTS
We identified 14 studies that met the inclusion criteria using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart with 12 observational and 2 experimental studies. Of 1691 DR-TB patients enrolled in the included studies, 1407 of them concomitantly received regimens containing bedaquiline and delamanid. Overall multidrug resistant (MDR), preextensively drug resistant (XDR), and XDR-TB were seen in 21.4%, 44.1%, and 34.5%, respectively. Of 14 studies, 8 of them reported favorable outcomes including sputum culture conversion and cure rate at the end of treatment, meanwhile 6 studies only reported sputum culture conversion. Sputum culture conversion at the end of the 6 month was 63.6%-94.7% for observational studies, and 87.6%-95.0% for experimental studies. The favorable outcome at the end of treatment was 67.5%-91.4%. With high pre-XDR and XDR cases among DR-TB patients with limited treatment options, regimens containing bedaquiline and delamanid provide successful treatment.
CONCLUSION
In DR-TB patients receiving regimens containing bedaquiline and delamanid, favorable outcomes were high including sputum conversion and cure rate.
Topics: Humans; Antitubercular Agents; Tuberculosis, Multidrug-Resistant; Diarylquinolines; Treatment Outcome
PubMed: 36926755
DOI: 10.4103/ijmy.ijmy_217_22 -
International Journal of Antimicrobial... May 2023A milestone in the development of novel antituberculosis drugs is the demonstration of early bactericidal activity (EBA) in a phase IIa clinical trial. The significant... (Review)
Review
A milestone in the development of novel antituberculosis drugs is the demonstration of early bactericidal activity (EBA) in a phase IIa clinical trial. The significant variability in measurements of bacterial load complicates data analysis in these trials. A systematic review and evaluation of methods for determination of EBA in pulmonary tuberculosis studies was undertaken. Bacterial load quantification biomarkers, reporting intervals, calculation methods, statistical testing, and handling of negative culture results were extracted. In total, 79 studies were identified in which EBA was determined. Colony-forming units on solid culture media and/or time-to-positivity in liquid media were the biomarkers used most often, reported in 72 (91%) and 34 (43%) studies, respectively. Twenty-two different reporting intervals were presented, and 12 different calculation methods for EBA were identified. Statistical testing for a significant EBA compared with no change was performed in 54 (68%) studies, and between-group testing was performed in 32 (41%) studies. Negative culture result handling was discussed in 34 (43%) studies. Notable variation was found in the analysis methods and reporting of EBA studies. A standardized and clearly reported analysis method, accounting for different levels of variability in the data, could aid the generalization of study results and facilitate comparison between drugs/regimens.
Topics: Humans; Mycobacterium tuberculosis; Time Factors; Tuberculosis, Pulmonary; Antitubercular Agents; Tuberculosis; Sputum
PubMed: 36893811
DOI: 10.1016/j.ijantimicag.2023.106775 -
Polish Archives of Internal Medicine Sep 2023Although it is well established that 2 doses of COVID‑19 vaccines are associated with reduced immune responses in liver transplant recipients (LTRs), studies regarding... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although it is well established that 2 doses of COVID‑19 vaccines are associated with reduced immune responses in liver transplant recipients (LTRs), studies regarding their immunogenicity and tolerability after a booster dose are limited.
OBJECTIVES
We aimed to review the available literature data regarding antibody responses and safety of the third dose of COVID‑19 vaccines in LTRs.
METHODS
We searched PubMed and Google Scholar for eligible studies. The primary outcome was to compare the rates of seroconversion after the second and third dose of COVID‑19 vaccine in LTRs. This meta‑analysis was performed using a generalized linear mixed model and the Clopper and Pearson method was employed to calculate the 2‑sided CIs.
RESULTS
Six prospective studies involving 596 LTRs met the inclusion criteria. The pooled rate of antibody response before the third dose was 71% (95% CI, 56%-83%; heterogeneity, I2 = 90%; P <0.001), while after the third dose it was 94% (95% CI, 91%-96%; heterogeneity, I2 = 17%; P = 0.31). There was no difference in antibody responses after the third dose in relation to the use of calcineurin inhibitors (P = 0.44) or mammalian target of rapamycin inhibitors (P = 0.33), while the pooled rate of antibody responses in the patients on mycophenolate mofetil (MMF) was 88% (95% CI, 83%-92%; heterogeneity, I2 = 0%; P = 0.57). It was significantly lower (P <0.001), as compared with those on MMF‑free immunosuppression (pooled rate, 97%; 95% CI, 95%-98%; heterogeneity, I2 = 30%; P = 0.22). No safety concerns were reported for the booster dose.
CONCLUSIONS
Our meta‑analysis demonstrated that the third dose of COVID‑19 vaccines induced adequate humoral and cellular immune responses in LTRs, while MMF remained a negative predictor of immunologic responses.
Topics: Humans; COVID-19 Vaccines; Seroconversion; COVID-19; Liver Transplantation; Prospective Studies; Mycophenolic Acid
PubMed: 36876925
DOI: 10.20452/pamw.16455 -
Indian Journal of Ophthalmology Mar 2023The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating... (Review)
Review
The extended use of ethambutol beyond 2 months for treating tuberculosis has increased risk of optic neuropathy. We performed a systematic review of studies evaluating optic neuropathy in extended ethambutol use since 2010 and compared the outcome with a similar systematic review (1965-2010) by Ezer et al. Literature search was conducted in PubMed, Medline, EMBASE, and Cochrane databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Main outcome measures were visual acuity, color vision, visual field defects, optical coherence tomography (OCT), and visual evoked potential (VEP). The JBI Critical Appraisal Checklists were used for quality assessment. Twelve studies were selected (out of 639 studies) for analysis of ethambutol optic neuropathy. Visual acuity improvement after stopping ethambutol was statistically significant. Similar improvement was not noted for other outcome measures. On comparing the results of this review with those by Ezer et al., significant improvement was noted in visual acuity, color vision, and visual field defects. Moreover, more patients reported increased optic nerve toxicity, color vision defects, and visual field defects in the present review. Hence, we conclude that the extended use of ethambutol beyond 2 months results in significant optic nerve toxicity. Further randomized controlled trials with different populations are needed to understand the magnitude of this issue.
Topics: Humans; Ethambutol; Evoked Potentials, Visual; Optic Nerve Diseases; Optic Nerve; Checklist; Rare Diseases
PubMed: 36872667
DOI: 10.4103/ijo.IJO_1920_22 -
Antimicrobial Resistance and Infection... Mar 2023Antimicrobial resistance (AMR) is widely acknowledged as a global health problem, yet its extent is not well evaluated, especially in low-middle income countries. It is... (Review)
Review
BACKGROUND
Antimicrobial resistance (AMR) is widely acknowledged as a global health problem, yet its extent is not well evaluated, especially in low-middle income countries. It is challenging to promote policies without focusing on healthcare systems at a local level, therefore a baseline assessment of the AMR occurrence is a priority. This study aimed to look at published papers relating to the availability of AMR data in Zambia as a means of establishing an overview of the situation, to help inform future decisions.
METHODS
PubMed, Cochrane Libraries, Medical Journal of Zambia and African Journals Online databases were searched from inception to April 2021 for articles published in English in accordance with the PRISMA guidelines. Retrieval and screening of article was done using a structured search protocol with strict inclusion/exclusion criteria.
RESULTS
A total of 716 articles were retrieved, of which 25 articles met inclusion criteria for final analysis. AMR data was not available for six of the ten provinces of Zambia. Twenty-one different isolates from the human health, animal health and environmental health sectors were tested against 36 antimicrobial agents, across 13 classes of antibiotics. All the studies showed a degree of resistance to more than one class of antimicrobials. Majority of the studies focused on antibiotics, with only three studies (12%) highlighting antiretroviral resistance. Antitubercular drugs were addressed in only five studies (20%). No studies focused on antifungals. The most common organisms tested, across all three sectors, were Staphylococcus aureus, with a diverse range of resistance patterns found; followed by Escherichia coli with a high resistance rate found to cephalosporins (24-100%) and fluoroquinolones (20-100%).
CONCLUSIONS
This review highlights three important findings. Firstly, AMR is understudied in Zambia. Secondly, the level of resistance to commonly prescribed antibiotics is significant across the human, animal, and environmental sectors. Thirdly, this review suggests that improved standardization of antimicrobial susceptibility testing in Zambia could help to better delineate AMR patterns, allow comparisons across different locations and tracking of AMR evolution over time.
Topics: Animals; Humans; Zambia; Drug Resistance, Bacterial; One Health; Antitubercular Agents; Anti-Retroviral Agents; Escherichia coli
PubMed: 36869351
DOI: 10.1186/s13756-023-01224-0 -
Clinical Pharmacokinetics Mar 2023Quantifying exposure to drugs for personalized dose adjustment is of critical importance in patients with tuberculosis who may be at risk of treatment failure or...
BACKGROUND AND OBJECTIVE
Quantifying exposure to drugs for personalized dose adjustment is of critical importance in patients with tuberculosis who may be at risk of treatment failure or toxicity due to individual variability in pharmacokinetics. Traditionally, serum or plasma samples have been used for drug monitoring, which only poses collection and logistical challenges in high-tuberculosis burden/low-resourced areas. Less invasive and lower cost tests using alternative biomatrices other than serum or plasma may improve the feasibility of therapeutic drug monitoring.
METHODS
A systematic review was conducted to include studies reporting anti-tuberculosis drug concentration measurements in dried blood spots, urine, saliva, and hair. Reports were screened to include study design, population, analytical methods, relevant pharmacokinetic parameters, and risk of bias.
RESULTS
A total of 75 reports encompassing all four biomatrices were included. Dried blood spots reduced the sample volume requirement and cut shipping costs whereas simpler laboratory methods to test the presence of drug in urine can allow point-of-care testing in high-burden settings. Minimal pre-processing requirements with saliva samples may further increase acceptability for laboratory staff. Multi-analyte panels have been tested in hair with the capacity to test a wide range of drugs and some of their metabolites.
CONCLUSIONS
Reported data were mostly from small-scale studies and alternative biomatrices need to be qualified in large and diverse populations for the demonstration of feasibility in operational settings. High-quality interventional studies will improve the uptake of alternative biomatrices in guidelines and accelerate implementation in programmatic tuberculosis treatment.
Topics: Humans; Drug Monitoring; Antitubercular Agents; Tuberculosis
PubMed: 36869170
DOI: 10.1007/s40262-023-01220-y -
BMC Gastroenterology Feb 2023Gastrointestinal strictures impact clinical presentation in abdominal tuberculosis and are associated with significant morbidity. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Gastrointestinal strictures impact clinical presentation in abdominal tuberculosis and are associated with significant morbidity.
AIM
To conduct a systematic review of the prevalence of stricturing disease in abdominal and gastrointestinal tuberculosis and response to antitubercular therapy (ATT).
METHODS
We searched Pubmed and Embase on 13th January 2022, for papers reporting on the frequency and outcomes of stricturing gastrointestinal tuberculosis. The data were extracted, and pooled prevalence of stricturing disease was estimated in abdominal tuberculosis and gastrointestinal (intestinal) tuberculosis. The pooled clinical response and stricture resolution (endoscopic or radiologic) rates were also estimated. Publication bias was assessed using the Funnel plot and Egger test. The risk of bias assessment was done using a modified Newcastle Ottawa Scale.
RESULTS
Thirty-three studies reporting about 1969 patients were included. The pooled prevalence of intestinal strictures in abdominal tuberculosis and gastrointestinal TB was 0.12 (95%CI 0.07-0.20, I = 89%) and 0.27 (95% CI 0.21-0.33, I = 85%), respectively. The pooled clinical response of stricturing gastrointestinal tuberculosis to antitubercular therapy was 0.77 (95%CI 0.65-0.86, I = 74%). The pooled stricture response rate (endoscopic or radiological) was 0.66 (95%CI 0.40-0.85, I = 91%). The pooled rate of need for surgical intervention was 0.21 (95%CI 0.13-0.32, I = 70%), while endoscopic dilatation was 0.14 (95%CI 0.09-0.21, I = 0%).
CONCLUSION
Stricturing gastrointestinal tuberculosis occurs in around a quarter of patients with gastrointestinal tuberculosis, and around two-thirds of patients have a clinical response with antitubercular therapy. A subset of patients may need endoscopic or surgical intervention. The estimates for the pooled prevalence of stricturing disease and response to ATT had significant heterogeneity.
Topics: Humans; Constriction, Pathologic; Tuberculosis, Gastrointestinal; Antitubercular Agents; Intestinal Obstruction; Abdomen
PubMed: 36814249
DOI: 10.1186/s12876-023-02682-x