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Journal of the Pediatric Infectious... Aug 2018With the continued high prevalence of chlamydia worldwide and high risk of transfer from mothers to their infant during delivery, a need for safe and effective therapies... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With the continued high prevalence of chlamydia worldwide and high risk of transfer from mothers to their infant during delivery, a need for safe and effective therapies for infants who acquire a chlamydial infection remains. We conducted a systematic review and meta-analysis of antibiotic treatments, including oral erythromycin, azithromycin, and trimethoprim, for neonatal chlamydial conjunctivitis.
METHODS
We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from their inception to July 14, 2017. We included randomized and nonrandomized studies that evaluated the effects of erythromycin, azithromycin, or trimethoprim in neonates with chlamydial conjunctivitis. A meta-analysis using a random-effects generic inverse-variance method was performed, and the certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.
RESULTS
We found 12 studies (n = 292 neonates) and were able to meta-analyze 7 studies that used erythromycin at a dose of 50 mg/kg body weight per day for 14 days. The clinical and microbiological cure were 96% (95% confidence interval [CI], 94%-100%) and 97% (95% CI, 95%-99%), respectively, and adverse gastrointestinal effects occurred in 14% (95% CI, 1%-28%) of the neonates. The microbiological cure in the study that assessed azithromycin at 20 mg/kg per day were 60% (95% CI, 27%-93%) when it was given in a single dose and 86% (95% CI, 61%-100%) when given in a 3-day course. Two studies reported compliance with treatments, and 1 study reported no pyloric stenosis events. Because of the risk of bias and the few neonates included across the studies, the certainty of evidence is low to very low. No studies assessed trimethoprim.
CONCLUSIONS
Although evidence suggests that erythromycin at 50 mg/kg per day for 14 days results in higher numbers of cure than does azithromycin, compliance and risk of pyloric stenosis related to their use for other infections in neonates will factor into treatment recommendations. More data are needed to compare these treatments directly.
Topics: Anti-Bacterial Agents; Azithromycin; Bias; Chlamydia Infections; Chlamydia trachomatis; Conjunctivitis, Bacterial; Drug Administration Schedule; Erythromycin; Female; Gastrointestinal Diseases; Humans; Infant, Newborn; Male; Pyloric Stenosis; Risk Factors; Trimethoprim
PubMed: 30007329
DOI: 10.1093/jpids/piy060 -
Cancer Treatment Reviews Feb 2023The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). (Review)
Review
INTRODUCTION
The aim of this review was to characterize the second- and later-line (≥2L) treatment landscape for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).
METHODS
This systematic literature review (PROSPERO: CRD42021279753) involved searches of MEDLINE® and Embase to identify results from prospective studies of ≥2L treatment options for metastatic pancreatic cancer published from 2016 to 2021. Publications were screened according to predetermined eligibility criteria; population-level data were extracted using standardized data fields. Publication quality was assessed according to Grading of Recommendations Assessment, Development and Evaluation (GRADE). The data were analyzed descriptively, grouped by drug class.
RESULTS
Sixty publications were identified, including 23 relating to comparative trials. GRADE assessment found that, of these 23 trials, 83% reported high or moderate-quality evidence. Of the publications relating to comparative trials, nine (three trials) reported favorable results: the pivotal phase 3 NAPOLI-1 trial for liposomal irinotecan; a phase 3 trial of non-liposomal irinotecan within the FOLFIRINOX regimen; and a phase 2 trial of eryaspase plus chemotherapy.
CONCLUSIONS
The level of unmet need for ≥2L treatment options for mPDAC remains high. Irinotecan-based regimens currently offer the greatest promise. Investigations into paradigm-changing agents and combination approaches continue.
Topics: Humans; Pancreatic Neoplasms; Irinotecan; Fluorouracil; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Leucovorin; Adenocarcinoma; Carcinoma, Pancreatic Ductal
PubMed: 36641880
DOI: 10.1016/j.ctrv.2022.102502 -
Journal of the International AIDS... Jun 2023Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections... (Review)
Review
INTRODUCTION
Co-trimoxazole prophylaxis is recommended for children born to women with HIV to protect those who acquire HIV from opportunistic infections, severe bacterial infections and malaria. With scale-up of maternal antiretroviral therapy, most children remain HIV-exposed uninfected (HEU) and the benefits of universal co-trimoxazole are uncertain. We assessed the effect of co-trimoxazole on mortality and morbidity of children who are HEU.
METHODS
We performed a systematic review (PROSPERO number: CRD42021215059). We systematically searched MEDLINE, Embase, Cochrane CENTRAL, Global Health, CINAHL Plus, Africa-Wide Information, SciELO and WHO Global Index Medicus for peer-reviewed articles from inception to 4th January 2022 without limits. Ongoing randomized controlled trials (RCTs) were identified through registries. We included RCTs reporting mortality or morbidity in children who are HEU receiving co-trimoxazole versus no prophylaxis/placebo. The risk of bias was assessed using the Cochrane 2.0 tool. Data were summarized using narrative synthesis and findings were stratified by malaria endemicity.
RESULTS
We screened 1257 records and included seven reports from four RCTs. Two trials from Botswana and South Africa of 4067 children who are HEU found no difference in mortality or infectious morbidity in children randomized to co-trimoxazole prophylaxis started at 2-6 weeks of age compared to those randomized to placebo or no treatment, although event rates were low. Sub-studies found that antimicrobial resistance was higher in infants receiving co-trimoxazole. Two trials in Uganda investigating prolonged co-trimoxazole after breastfeeding cessation showed protection against malaria but no other morbidity or mortality differences. All trials had some concerns or a high risk of bias, which limited the certainty of evidence.
DISCUSSION
Studies show no clinical benefit of co-trimoxazole prophylaxis in children who are HEU, except to prevent malaria. Potential harms were identified for co-trimoxazole prophylaxis leading to antimicrobial resistance. The trials in non-malarial regions were conducted in populations with low mortality potentially reducing generalizability to other settings.
CONCLUSIONS
In low-mortality settings with few HIV transmissions and well-performing early infant diagnosis and treatment programmes, universal co-trimoxazole may not be required.
Topics: Infant; Female; Child; Humans; Trimethoprim, Sulfamethoxazole Drug Combination; HIV Infections; Malaria; Uganda; Anti-Infective Agents; World Health Organization; Randomized Controlled Trials as Topic
PubMed: 37292018
DOI: 10.1002/jia2.26079 -
Global Heart 2023This systematic review and meta-analysis aimed to determine the efficacy of macitentan in patients with pulmonary hypertension (PH). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to determine the efficacy of macitentan in patients with pulmonary hypertension (PH).
METHODS
A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of PH with macitentan, compared with placebo or blank, were reviewed. Studies were pooled to weighted mean differences (WMDs) and risk ratios (RRs), with 95% confidence intervals (CIs).
RESULTS
Six RCTs (enrolling 1,003 participants) met the inclusion criteria. Macitentan showed significant effects on 6-min walk distance (6MWD) (WMD 12.06 m, 95% CI 2.12 to 21.99 m), pulmonary vascular resistance (PVR) (WMD -186.51 dyn·s/cm, 95% CI -232.72 to -140.29 dyn·s/cm), mean pulmonary artery pressure (mPAP) (WMD -3.20 mmHg, 95% CI -5.93 to -0.47 mmHg), N-terminal pro-brain natriuretic peptide (NT-proBNP) (WMD -232.47 ng/L, 95% wCI -318.22 to -146.72 ng/L), and cardiac index (WMD 0.39 L/min/m, 95% CI 0.20 to 0.58 L/min/m).
CONCLUSION
Macitentan significantly improved 6MWD, PVR, mPAP, NT-proBNP, and cardiac index in patients with PH. Macitentan should be further validated in patients with PH.
Topics: Humans; Hypertension, Pulmonary; Treatment Outcome; Randomized Controlled Trials as Topic; Pyrimidines
PubMed: 37901601
DOI: 10.5334/gh.1274 -
Journal of Renal Nutrition : the... Mar 2024Thiamine (vitamin B1) deficiency is relatively common in patients with kidney disease. Wernicke's encephalopathy (WE) is caused by vitamin B1 deficiency. Our aim was to... (Review)
Review
Thiamine (vitamin B1) deficiency is relatively common in patients with kidney disease. Wernicke's encephalopathy (WE) is caused by vitamin B1 deficiency. Our aim was to systematically review the signs and symptoms of WE in patients with kidney disease. We conducted a systematic literature review on WE in kidney disease and recorded clinical and radiographic characteristics, treatment and outcome. In total 323 manuscripts were reviewed, which yielded 46 cases diagnosed with acute and chronic kidney disease and WE published in 37 reports. Prodromal characteristics of WE were loss of appetite, vomiting, weight loss, abdominal pain, and diarrhea. Parenteral thiamine 500 mg 3 times per day often led to full recovery, while Korsakoff's syndrome was found in those receiving low doses. To prevent WE in kidney failure, we suggest administering high doses of parenteral thiamine in patients with kidney disease who present with severe malnutrition and (prodromal) signs of thiamine deficiency.
Topics: Humans; Wernicke Encephalopathy; Thiamine Deficiency; Thiamine; Renal Insufficiency, Chronic
PubMed: 37838073
DOI: 10.1053/j.jrn.2023.10.003 -
European Urology Oncology Apr 2022Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH)... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients.
OBJECTIVE
This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix.
EVIDENCE ACQUISITION
A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis.
EVIDENCE SYNTHESIS
Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses.
CONCLUSIONS
We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available.
PATIENT SUMMARY
We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.
Topics: Bayes Theorem; Gonadotropin-Releasing Hormone; Humans; Male; Network Meta-Analysis; Oligopeptides; Phenylurea Compounds; Prostatic Neoplasms; Pyrimidinones; Randomized Controlled Trials as Topic; United States
PubMed: 34301529
DOI: 10.1016/j.euo.2021.07.002 -
Palliative & Supportive Care Feb 2016Akathisia is a neuropsychiatric syndrome characterized by subjective and objective restlessness. It is a common side effect in patients taking antipsychotics and other... (Review)
Review
OBJECTIVE
Akathisia is a neuropsychiatric syndrome characterized by subjective and objective restlessness. It is a common side effect in patients taking antipsychotics and other psychotropics. Patients with delirium are frequently treated with antipsychotic medications that are well known to induce akathisia as a side effect. However, the prevalence, phenomenology, and management of akathisia in patients with delirium remain largely unknown. The purpose of this review was to examine the medical literature in order to establish the current state of knowledge regarding the prevalence of antipsychotic-induced akathisia in patients with delirium.
METHOD
A systematic review of the literature was conducted using the EMBASE, MEDLINE, PsycINFO, and CINAHL databases. Ten studies addressing the incidence of akathisia in patients taking antipsychotic medication for delirium were identified and included in our review.
RESULTS
The included studies reported a variable prevalence of antipsychotic-induced akathisia. A higher prevalence was found in patients taking haloperidol. Among atypical antipsychotics, paliperidone and ziprasidone were associated with a higher risk of akathisia. The risk for akathisia appeared to be a dose-related phenomenon.
SIGNIFICANCE OF RESULTS
Studies using specific scales for evaluation of akathisia in delirium are lacking. Some populations, such as patients with cancer or terminally ill patients in palliative care settings taking antipsychotics for the treatment of delirium, could be at higher risk for development of akathisia as a side effect.
Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Delirium; Haloperidol; Humans; Prevalence; Risperidone
PubMed: 26087817
DOI: 10.1017/S1478951515000784 -
BMC Psychiatry Oct 2023We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of blonanserin and risperidone for the treatment of schizophrenia and to provide reliable pharmacotherapeutic evidence for in the clinical treatment of schizophrenia.
METHODS
We systematically searched the PubMed, Cochrane Library, Embase, Chinese Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI) databases for head-to-head randomized controlled trials that compared blonanserin with risperidone for the treatment of schizophrenia. We extracted the following data: author, year, country, diagnostic criteria, sample size, course of treatment, dosage and outcomes. Our main endpoint was the changes in the Positive and Negative Syndrome Scale (PANSS) total scores. Meta-analysis of the included data was conducted by RevMan 5.3 software. We used the GRADE criteria to evaluate the certainty of the evidence.
RESULTS
A total of 411 studies were initially; 8 trials were eligible and were included in our analysis (N = 1386 participants). Regarding efficacy, there was no difference in changes in the PANSS total scores between the two groups (P > 0.05). In terms of safety, compared to risperidone, the incidence of serum prolactin increases and weight gain in the blonanserin group was lower (P<0.05), but the incidence of extrapyramidal symptoms (EPS) was higher (P<0.05).
CONCLUSION
The efficacy of blonanserin is similar to that of risperidone, but it is unclear whether blonanserin is more effective than risperidone at improving cognitive and social function. More high-quality studies are needed to verify the efficacy and safety of blonanserin in the future.
Topics: Humans; Risperidone; Schizophrenia; Antipsychotic Agents; Randomized Controlled Trials as Topic
PubMed: 37821875
DOI: 10.1186/s12888-023-05240-7 -
The Cochrane Database of Systematic... Jul 2022Whilst antipsychotics are the mainstay of treatment for schizophrenia spectrum disorders, there have been numerous attempts to identify biomarkers that can predict... (Review)
Review
BACKGROUND
Whilst antipsychotics are the mainstay of treatment for schizophrenia spectrum disorders, there have been numerous attempts to identify biomarkers that can predict treatment response. One potential marker may be psychomotor abnormalities, including catatonic symptoms. Early studies suggested that catatonic symptoms predict poor treatment response, whilst anecdotal reports of rare adverse events have been invoked against antipsychotics. The efficacy and safety of antipsychotics in the treatment of this subtype of schizophrenia have rarely been studied in randomised controlled trials (RCTs).
OBJECTIVES
To compare the effects of any single antipsychotic medication with another antipsychotic or with other pharmacological agents, electroconvulsive therapy (ECT), other non-pharmacological neuromodulation therapies (e.g. transcranial magnetic stimulation), or placebo for treating positive, negative, and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, the ISRCTN registry, and WHO ICTRP, on 19 September 2021. There were no language, date, document type, or publication status limitations for inclusion of records in the register. We also manually searched reference lists from the included studies, and contacted study authors when relevant.
SELECTION CRITERIA
All RCTs comparing any single antipsychotic medication with another antipsychotic or with other pharmacological agents, ECT, other non-pharmacological neuromodulation therapies, or placebo for people who have schizophrenia spectrum disorders with catatonic symptoms.
DATA COLLECTION AND ANALYSIS
two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we planned to calculate risk ratios and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous outcomes, we planned to calculate mean differences between groups and their 95% CI. We assessed risk of bias for the included studies, and created a summary of findings table; however, we did not assess the certainty of the evidence using the GRADE approach because there was no quantitative evidence in the included study.
MAIN RESULTS
Out of 53 identified reports, one RCT including 14 hospitalised adults with schizophrenia and catatonic symptoms met the inclusion criteria of the review. The study, which was conducted in India and lasted only three weeks, compared risperidone with ECT in people who did not respond to an initial lorazepam trial. There were no usable data reported on the primary efficacy outcomes of clinically important changes in positive, negative, or catatonic symptoms. Whilst both study groups improved in catatonia scores on the Bush-Francis Catatonia Rating Scale (BFCRS), the ECT group showed significantly greater improvement at week 3 endpoint (mean +/- estimated standard deviation; 0.68 +/- 4.58; N = 8) than the risperidone group (6.04 +/- 4.58; N = 6; P = 0.035 of a two-way analysis of variance (ANOVA) for repeated measures originally conducted in the trial). Similarly, both groups improved on the Positive and Negative Syndrome Scale (PANSS) scores by week 3, but ECT showed significantly greater improvement in positive symptoms scores compared with risperidone (P = 0.04). However, data on BFCRS scores in the ECT group appeared to be skewed, and mean PANSS scores were not reported, thereby precluding further analyses of both BFCRS and PANSS data according to the protocol. Although no cases of neuroleptic malignant syndrome were reported, extrapyramidal symptoms as a primary safety outcome were reported in three cases in the risperidone group. Conversely, headache (N = 6), memory loss (N = 4), and a prolonged seizure were reported in people receiving ECT. These adverse effects, which were assessed as specific for antipsychotics and ECT, respectively, were the only adverse effects reported in the study. However, the exact number of participants with adverse events was not clearly reported in both groups, precluding further analysis. Our results were based only on a single study with a very small sample size, short duration of treatment, unclear or high risk of bias due to unclear randomisation methods, possible imbalance in baseline characteristics, skewed data, and selective reporting. Data on outcomes of general functioning, global state, quality of life, and service use, as well as data on specific phenomenology and duration of catatonic symptoms, were not reported.
AUTHORS' CONCLUSIONS
We found only one small, short-term trial suggesting that risperidone may improve catatonic and positive symptoms scale scores amongst people with schizophrenia spectrum disorders and catatonic symptoms, but that ECT may result in greater improvement in the first three weeks of treatment. Due to small sample size, methodological shortcomings and brief duration of the study, as well as risk of bias, the evidence from this review is of very low quality. We are uncertain if these are true effects, limiting any conclusions that can be drawn from the evidence. No cases of neuroleptic malignant syndrome were reported, but we cannot rule out the risk of this or other rare adverse events in larger population samples. High-quality trials continue to be necessary to differentiate treatments for people with symptoms of catatonia in schizophrenia spectrum disorders. The lack of consensus on the psychopathology of catatonia remains a barrier to defining treatments for people with schizophrenia. Better understanding of the efficacy and safety of antipsychotics may clarify treatment for this unique subtype of schizophrenia.
Topics: Adult; Antipsychotic Agents; Catatonia; Humans; Neuroleptic Malignant Syndrome; Risperidone; Schizophrenia
PubMed: 35844143
DOI: 10.1002/14651858.CD013100.pub2 -
PloS One 2016In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/OBJECTIVES
In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR), progression-free survival (PFS), overall survival (OS) and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET.
METHODS
Randomised controlled trials (RCTs) from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling.
RESULTS
Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU) chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN) were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI) 0.72-1.27], PFS (RR 0.95; CI 0.81-1.13), or OS (RR 1.03; CI 0.77-1.39). IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04-1.13), but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27-0.82) and lower overall renal toxicity (RR 3.61; CI 1.24-10.51).
CONCLUSION
Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET.
Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Fluorouracil; Humans; Interferons; Neoplasm Metastasis; Neuroendocrine Tumors; Randomized Controlled Trials as Topic; Somatostatin; Streptozocin; Treatment Outcome
PubMed: 27362760
DOI: 10.1371/journal.pone.0158140