RESUMO
BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a threat to public health. Shorter regimens have been proposed as potentially valuable treatments for multidrug or rifampicin resistant tuberculosis (MDR/RR-TB). We undertook a systematic review and network meta-analysis to evaluate the efficacy and safety of shorter MDR/RR-TB regimens. METHODS: We searched PubMed/MEDLINE, Cochrane Center for Clinical Trials (CENTRAL), Scopus, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, US Food and Drug Administration, and Chinese Clinical Trial Registry for primary articles published from 2013 to July 2023. Favorable (cured and treatment completed) and unfavorable (treatment failure, death, loss to follow-up, and culture conversion) outcomes were assessed as the main efficacy outcomes, while adverse events were assessed as the safety outcomes. The network meta-analysis was performed using R Studio version 4.3.1 and the Netmeta package. The study protocol adhered to the PRISMA-NMA guidelines and was registered in PROSPERO (CRD42023434050). RESULT: We included 11 eligible studies (4 randomized control trials and 7 cohorts) that enrolled 3,548 patients with MDR/RR-TB. Treatment with a 6-month combination of BdqLzdLfxZTrd/Eto/H had two times more favorable outcomes [RR 2.2 (95% CI 1.22, 4.13), P = 0.0094], followed by a 9-11 month combination of km/CmMfx/LfxPtoCfzZEHh [RR1.67 (95% CI 1.45, 1.92), P < 0.001] and a 6-month BdqPaLzdMfx [RR 1.64 (95% CI 1.24, 2.16), P < 0.0005] compared to the standard longer regimens. Treatment with 6 months of BdqPaLzdMfx [RR 0.33 (95% CI 0.2, 0.55), P < 0.0001] had a low risk of severe adverse events, followed by 6 months of BdqPaLzd [RR 0.36 (95% CI 0.22, 0.59), P ≤ 0.001] and BdqPaLzdCfz [RR 0.54 (95% CI 0.37, 0.80), P < 0.0001] than standard of care. CONCLUSION: Treatment of patients with RR/MDR-TB using shorter regimens of 6 months BdqLzdLfxZTrd/Eto/H, 9-11 months km/CmMfx/LfxPtoCfzZEHh, and 6 months BdqPaLzdMfx provides significantly higher cure and treatment completion rates compared to the standard longer MDR/RR-TB. However, 6BdqPaLzdMfx, 6BdqPaLzd, and 6BdqPaLzdCfz short regimens are significantly associated with decreased severity of adverse events. The findings are in support of the current WHO-recommended 6-month shorter regimens.
Assuntos
Antituberculosos , Metanálise em Rede , Rifampina , Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Rifampina/uso terapêutico , Antituberculosos/uso terapêutico , Antituberculosos/efeitos adversos , Resultado do Tratamento , Mycobacterium tuberculosis/efeitos dos fármacosRESUMO
INTRODUCTION: Understanding the broad aspect of health-related quality of life (HRQoL) is essential to knowing how health problems affect individuals' overall well-being. Evaluating HRQoL is very important in Ethiopia's diverse healthcare setting. This protocol describes a meta-analysis and systematic review that uses the EQ-5D instrument to examine HRQoL in Ethiopia. METHODS: The study will follow Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines, conducting a systematic literature search across PubMed, Web of Science, Embase, Cochrane library and Scopus using keywords like 'quality of life', 'QoL', 'health-related quality of life', 'HRQoL', 'EQ-5D', 'EQ-5D-3L', 'EQ-5D-5L', 'EuroQol', 'five dimensions' and/or 'Ethiopia'. The STATA will be used to pool the mean EQ-5D utility and EQ-VAS scores for a specific disease using the random-effect (Der Simonian-Laird estimator method) and fixed-effect (inverse variance method) models. The quality assessment tool for observational cohort and cross-sectional studies developed by the National Heart, Lung and Blood Institute will be used for quality assessment. ETHICS AND DISSEMINATION: Publicly accessible previously published articles will be included in the research. Therefore, doing this study does not require ethical approval. The protocol offers transparency and adherence to research standards because it is registered on PROSPERO (ID: CRD42024505028). Peer-reviewed publications and conference presentations are dissemination plans. PROSPERO REGISTRATION NUMBER: CRD42024505028.
Assuntos
Metanálise como Assunto , Qualidade de Vida , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Etiópia , Humanos , Inquéritos e Questionários , Nível de SaúdeRESUMO
BACKGROUND: Tuberculosis (TB) remains a significant global health challenge, especially prevalent in the WHO African region. The WHO's End TB Strategy emphasises effective treatment approaches such as directly observed therapy (DOT), yet the optimal implementation of DOT, whether through health facility-based (HF DOT) or community-based (CB DOT) approaches, remains uncertain. OBJECTIVE: To conduct a systematic comparison of the effectiveness and cost-effectiveness of Community-Based Directly Observed Treatment (CB DOT) versus Health Facility-Based Directly Observed Treatment (HF DOT) for tuberculosis (TB) treatment in African settings. METHODS: We will conduct a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search PubMed, Embase, Web of Science, Scopus and the Cochrane Library for articles published up to 30 March 2023, without date restrictions. Eligible studies must be full economic evaluations conducted in African countries, comparing CB DOT to HF DOT regarding treatment outcomes and costs. Exclusion criteria include non-English, non-peer-reviewed or studies lacking caregiver involvement in CB DOT, health facility-based DOT comparison, direct comparability between CB DOT and HF DOT, significant selection bias or non-economic evaluations. Data extraction will be performed independently by reviewers, and meta-analyses will use STATA software. To pool the data, a random-effect model will be applied, and quality assessment of the studies will be conducted. ETHICS AND DISSEMINATION: Ethical approval is not required as the study will use previously published articles available publicly. Findings will be presented at international and national conferences and published in open-access, peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42023443260.
Assuntos
Análise Custo-Benefício , Terapia Diretamente Observada , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Tuberculose , Humanos , África , Tuberculose/tratamento farmacológico , Tuberculose/economia , Tuberculose/terapia , Instalações de Saúde/economia , Serviços de Saúde Comunitária/economia , Projetos de Pesquisa , Antituberculosos/uso terapêutico , Antituberculosos/economiaRESUMO
Diabetes is a serious threat to global health and among the top 10 causes of death, with nearly half a billion people living with it worldwide. Treating patients with diabetes tend to become more challenging due to the progressive nature of the disease. The role and benefits of combination therapies for the management of type 2 diabetes are well-documented, while the comparative safety and efficacy among the different combination options have not been elucidated. We aimed to systematically synthesize the evidence on the comparative cardiovascular safety and efficacy of combination therapy with metformin-sodium-glucose cotransporter-2 inhibitors versus metformin-sulfonylureas in patients with type 2 diabetes. We searched MEDLINE-PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 15 August 2019 without restriction in the year of publication. We included randomized controlled trials of patients with type 2 diabetes who were on metformin-sodium-glucose cotransporter-2 inhibitors or metformin-sulphonylureas combination therapy at least for a year. The primary endpoints were all-cause mortality and serious adverse events, and the secondary endpoints were cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, hypoglycemia, and changes in glycated hemoglobin A1c (HbA1c), body weight, fasting plasma glucose, blood pressure, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We used a random-effects meta-analysis model to estimate mean differences for continuous outcomes and risk ratio for dichotomous outcomes. We followed PICOS description model for defining eligibility and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for reporting results. Of 3,190 citations, we included nine trials involving 10,974 participants. The pooled analysis showed no significant difference in all-cause mortality (risk ration [RR] = 0.93, 95% CI [0.52, 1.67]), serious adverse events (RR = 0.96, 95% CI [0.79, 1.17]) and adverse events (RR = 1.00, 95% CI [0.99, 1.02]) between the two, but in hypoglycemia (RR = 0.13, 95% CI [0.10, 0.17], P < 0.001). Participants taking metformin-sodium glucose cotransporter-2 inhibitors showed a significantly greater reduction in HbA1c (mean difference [MD] = - 0.10%, 95% CI [- 0.17, - 0.03], body weight (MD = - 4.57 kg, 95% CI [- 4.74, - 4.39], systolic blood pressure (MD = - 4.77 mmHg, 95% CI [- 5.39, - 4.16]), diastolic blood pressure (MD = - 2.07 mmHg, 95% CI [- 2.74, - 1.40], and fasting plasma glucose (MD = - 0.55 mmol/L, 95% CI [- 0.69, - 0.41]), p < 0.001. Combination therapy of metformin and sodium-glucose cotransporter-2 inhibitors is a safe and efficacious alternative to combination therapy of metformin and sulphonylureas for patients with type 2 diabetes who are at risk of cardiovascular comorbidity. However, there remains a need for additional long-term randomized controlled trials as available studies are very limited and heterogeneous.
Assuntos
Doenças Cardiovasculares/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Compostos de Sulfonilureia/uso terapêutico , Adulto , Idoso , Glicemia , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Feminino , Coração/efeitos dos fármacos , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Transportador 2 de Glucose-Sódio/genética , Transportador 2 de Glucose-Sódio/metabolismo , Compostos de Sulfonilureia/efeitos adversos , Adulto JovemRESUMO
OBJECTIVE: This study aimed to compare glycemic control and risk of cardiovascular outcomes of metformin-insulin versus metformin-sulfonylurea combination therapies in type 2 diabetes mellitus. METHODS: We conducted a comparative cross-sectional study in five tertiary level hospitals in Addis Ababa, Ethiopia. We enrolled 321 patients with type 2 diabetes mellitus who were on continuous treatment follow-up on either metformin-insulin or metformin-sulfonylurea combination therapy. We interviewed the participants and reviewed their medical records to investigate medication efficacy, safety, and adherence. The primary outcome measure was glycemic control and the secondary outcome measures were composite cardiovascular outcomes. RESULTS: Of the total participants enrolled, 50.5% (n = 162) were those who received metformin-insulin and 49.5% (n = 159) metformin-sulfonylurea combination therapies for a median of 48 months follow-up. The reduction of Hb1Ac levels was comparable between the metformin-insulin (-1.04 ± 0.96%) and metformin-sulfonylurea (-1.02 ± 1.03%), p = 0.912. Patients who received metformin-sulfonylurea had 4.3 times more likely to have achieved target HbA1c level compared to those who received metformin-insulin, p < 0.001, adjusted odds ratio (AOR) with 95% CI = 4.31[1.79-10.32]. Risk of composite cardiovascular outcomes was higher in metformin-insulin group (40.5% versus 34.0%), p = 0.021. Co-morbidities, body mass index, systolic blood pressure, and HbA1c had a significant association with composite cardiovascular outcomes. Reductions of bodyweight, HDL-C, LDL-C, triglycerides levels, and microvascular complications were different between the two groups, p < 0.05. CONCLUSION: High proportion of patients who received metformin-sulfonylurea achieved target HbA1c level and had less composite cardiovascular outcomes compared to those who received metformin-insulin. However, these findings have to be confirmed with randomized control trials to determine risks associated with insulin use, while efficacy is maintained as second-line treatment in patients with type 2 diabetes mellitus.
RESUMO
BACKGROUND: Multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) pose major threats to global health. Diagnosis accuracy and delay have been the major drivers for the upsurge of M/XDR-TB. Pyrosequencing (PSQ) is a novel, real-time DNA sequencing for rapid detection of mutations associated with M/XDR-TB. We aimed to systematically synthesize the evidence on the diagnostic accuracy of PSQ for M/XDR-TB. METHODS: We conducted an electronic search of PubMed, Embase, Biosis, Web of Science, and Google Scholar up to March 2020. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the quality of studies, the BRMA (bivariate random-effects meta-analysis) model to synthesize diagnostic accuracies, and the Rev-Man 5.4 software to perform the meta-analyses. We analyzed dichotomous data using the risk ratio (RR) with a 95% confidence interval. PROSPERO Registration ID: CRD42020200817. RESULTS: The analysis included seven studies, with a total sample of 3,165. At 95% confidence interval, the pooled sensitivity and specificity of PSQ were 89.7 (CI: 83.5-93.8) and 97.8 (CI: 94.9-99.1) for Isoniazid, 94.6 (CI: 90.9-96.8) and 98.5 (CI: 96.5-99.3) for Rifampicin, 87.9 (CI: 81.2-92.4) and 98.8 (CI: 97.2-99.5) for Fluoroquinolone, 83.5 (CI: 72.8-90.5) and 99.4 (CI: 98.3-99.8) for Amikacin, 79 (CI: 67-8-87) and 97.9 (CI: 95.5-99) for Capreomycin, and 69.6 (CI: 57-79.8) and 98.2 (CI: 95.9-99.2) for Kanamycin. The overall pooled sensitivity and specificity were 85.8 (CI: 76.7-91.7) and 98.5 (CI: 96.5-99.3), respectively. CONCLUSION: According to the pooled data, PSQ is highly sensitive and specific for detecting M/XDR-TB, both from clinical specimens and culture isolates, and within a shorter turnaround time. We suggest a continued synthesis of the evidence on the cost-effectiveness and technical feasibilities of PSQ in low-income countries context, including sub-Saharan Africa.
RESUMO
BACKGROUND: Despite global containment measures to fight the coronavirus disease 2019 (COVID-19), the pandemic continued to rise, rapidly spread across the world, and resulting in 2.6 million confirmed cases and 185 061 deaths worldwide as of 23 April 2020. Yet, there are no approved vaccines or drugs to make the disease less deadly, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy of remdesivir in patients with COVID-19. METHOD AND ANALYSIS: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Google scholar databases for articles published as of 30 June 2020 and we will complete the study on 30 August 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We will include RCTs that assessed the efficacy of remdesivir versus placebo or standard of care. The primary endpoint will be time to clinical recovery. The secondary endpoints will be proportion of participants relieved from clinical symptoms defined at the time (in hours) from initiation of the study treatment, all-cause mortality, discharged date, frequency of respiratory progression and treatment-emergent adverse events. RevMan V.5.3 software will be used for statistical analysis. Random effects model will be carried out to calculate mean differences for continuous outcome data and risk ratio for dichotomous outcome data between remdesivir and placebo or standard of care. ETHICS AND DISSEMINATION: There are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open-access peer-reviewed journals and present at international and national conferences. PROSPERO REGISTRATION NUMBER: CRD42020177953.
Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Betacoronavirus , Infecções por Coronavirus , Controle de Infecções/métodos , Pandemias , Pneumonia Viral , Projetos de Pesquisa , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Alanina/administração & dosagem , Alanina/efeitos adversos , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/isolamento & purificação , COVID-19 , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Humanos , Metanálise como Assunto , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Revisões Sistemáticas como Assunto , Resultado do TratamentoRESUMO
Coronavirus disease 2019 (COVID-19), an infectious disease that primarily attacks the human pulmonary system, is caused by a viral strain called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak emerged from Wuhan, China, and later spread throughout the world. Until the first week of May 2020, over 3.7 million cases had been reported worldwide and more than 258,000 had died due to the disease. So far, off label use of various drugs has been tried in many clinical settings, however, at present, there is no vaccine or antiviral treatment for human and animal coronaviruses. Therefore, repurposing of the available drugs may be promising to control emerging infections of SARS-COV2; however, new interventions are likely to require months to years to develop. Glycopeptides, which are active against gram-positive bacteria, have demonstrated significant activity against viral infections including SARS-COV and MERS-COV and have a high resemblance of sequence homology with SARS-COV2. Recent in vitro studies have also shown promising activities of aglycon derivative of glycopeptides and teicoplanin against SARS-COV2. Hydrophobic aglycon derivatives and teicoplanin, with minimal toxicity to human cell lines, inhibit entry and replication of SARS-COV2. These drugs block proteolysis of polyprotein a/b with replicase and transcription domains. Teicoplanin use was associated with complete viral clearance in a cohort of patients with severe COVID-19 symptoms. This review attempts to describe the activity, elucidate the possible mechanisms and potential clinical applications of existing glycopeptides against corona viruses, specifically SARS-COV2.
RESUMO
INTRODUCTION: Adverse drug interaction is a major cause of morbidity and mortality. Its occurrence is influenced by a multitude of factors. The influences of drug-drug interactions (DDIs) can be minimized through creation of awareness to health care professionals. OBJECTIVE: The objective of this study was to assess DDIs in Ayder Comprehensive Specialized Hospital (ACSH). METHODOLOGY: A retrospective study design was employed on patient prescriptions available in the outpatient department of pharmacy and filled from September 2016 to February 2017 in ACSH. RESULT: From the 600 prescription records assessed, the average number of drugs on single prescription was 2.73. Regarding the interaction observed 34 (9.63%) prescriptions with major drug-drug interaction, 210 (59.5%) moderate, 87 (24.65%) minor, and 22 (6.22%) unknown were identified. Age category showed significant association to affect the occurrence of DDIs and polypharmacy had statistically significant association with DDIs in bivariate analysis which was lost in adjusted OR. CONCLUSION: From the current study it can be concluded that nearly half of the prescription ordered in ACSH contained DDIs and from the prescription with interacting medications majority of them had moderate DDIs.