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The Cochrane Database of Systematic... May 2018Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with rheumatoid factor activity generated by an expansion of B-cells. The immune complexes formed precipitate mainly in the skin, joints, kidneys or peripheral nerve fibres. Current therapeutic approaches are aimed at elimination of HCV infection, removal of cryoglobulins and also of the B-cell clonal expansions. The optimal treatment for it has not been established.
OBJECTIVES
This review aims to look at the benefits and harms of the currently available treatment options to treat the HCV-associated mixed cryoglobulinaemia with active manifestations of vasculitis (cutaneous or glomerulonephritis).
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Specialised Register to 30 November 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs looking at interventions directed at treatment of HCV-associated cryoglobulinaemic vasculitis (immunosuppressive medications and plasma exchange therapy) have been included.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the retrieved titles and abstracts. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). The planned primary outcomes were kidney disease, skin vasculitis, musculoskeletal symptoms, peripheral joint arthralgia, peripheral neuropathies, liver involvement, interstitial lung involvement, widespread vasculitis and death. Other planned outcomes were: therapy duration, laboratory findings, adverse effects, antiviral therapy failure, B-cell lymphoma, endocrine disorders and costs of treatment.
MAIN RESULTS
Ten studies were included in the review (394 participants). None of them evaluated direct-acting antivirals. Seven studies were single-centre studies and three were multicentre. The duration of the studies varied from six to 36 months. The risk of bias was generally unclear or low. Three different interventions were examined: use of rituximab (3 studies, 118 participants); interferon (IFN) (IFN compared to other strategies (5 studies, 223 participants); six IFN months versus one year (1 study, 36 participants), and immunoadsorption apheresis versus only immunosuppressive therapy (1 study, 17 participants).The use of rituximab may slightly improve skin vasculitis (2 studies, 78 participants: RR 0.57, 95% CI 0.28 to 1.16; moderate certainty evidence) and made little of no difference to kidney disease (moderate certainty evidence). In terms of laboratory data, the effect of rituximab was uncertain for cryocrit (MD -2.01%, 95% CI -10.29% to 6.27%, low certainty evidence) and HCV replication. Rituximab may slightly increase infusion reactions compared to immunosuppressive medication (3 studies, 118 participants: RR 4.33, 95%CI 0.76 to 24.75, moderate certainty evidence) however discontinuations of the treatment due to adverse reactions were similar (3 studies, 118 participants: RR 0.97, 95% CI 0.22 to 4.36, moderate certainty evidence).Effects of lFN on clinical symptoms were evaluated only in narrative results. When laboratory parameters were assessed, IFN made little or no difference in levels of alanine transaminase (ALT) at six months (2 studies, 39 participants: MD -5.89 UI/L, 95%CI -55.77 to 43.99); rheumatoid factor activity at six months (1 study, 13 participants: MD 97.00 UI/mL, 95%CI -187.37 to 381.37), or C4 levels at 18 months (2 studies, 49 participants: MD -0.04 mg/dL, 95%CI -2.74 to 2.67). On the other hand, at 18 months IFN may probably decrease ALT (2 studies, 39 participants: MD -28.28 UI/L, 95%CI -48.03 to -8.54) and Ig M (-595.75 mg/dL, 95%CI -877.2 to -314.3), but all with low certainty evidence. One study reported infusion reactions may be higher in IFN group compared to immunosuppressive therapy (RR 27.82, 95%CI 1.72 to 449.18), and IFN may lead to higher discontinuations of the treatment due to adverse reactions (4 studies, 148 participants: RR 2.32, 95%CI 0.91 to 5.90) with low certainty evidence. Interferon therapy probably improved skin vasculitis (3 studies, 95 participants: RR 0.60, 95% CI 0.36 to 1.00) and proteinuria (2 studies, 49 participants: MD -1.98 g/24 h, 95% CI -2.89 to -1.07), without changing serum creatinine at 18 months (2 studies, 49 participants: MD -30.32 μmol/L, 95%CI -80.59 to 19.95).Six months versus one year treatment with IFN resulted in differences terms of the maintenance of the response, 89% of patients in the six months group presented a relapse and only 11% maintained a long-term response at one year, while in the one year group only 78% relapsed and long-term response was observed in 22%. The one-year therapy was linked to a higher number of side-effects (severe enough to cause the discontinuation of treatment in two cases) than the six-month schedule.One study reported immunoadsorption apheresis had uncertain effects on skin vasculitis (RR 0.44, 95% CI 0.05 to 4.02), peripheral neuropathies (RR 2.70, 95%CI 0.13 to 58.24), and peripheral joint arthralgia (RR 2.70, 95%CI 0.13 to 58.24), cryocrit (MD 0.01%, 95%CI -1.86 to 1.88) at six months, and no infusion reactions were reported. However when clinical scores were evaluated, they reported changes were more favourable in immunoadsorption apheresis with higher remission of severe clinical complications (80% versus 33%, P = 0.05) compared to immunosuppressive treatment alone.In terms of death, it was not possible to present a pooled intervention effect estimate because most of the studies reported no deaths, or did not report death as an outcome.
AUTHORS' CONCLUSIONS
To treat HCV-associated mixed cryoglobulinaemia, it may be beneficial to eliminate HCV infection by using antiviral treatment and to stop the immune response by using rituximab. For skin vasculitis and for some laboratory findings, it may be appropriate to combine antiviral treatment with deletion of B-cell clonal expansions by using of rituximab. The applicability of evidence reviewed here is limited by the absence of any studies with direct-acting antivirals, which are urgently needed to guide therapy.
Topics: Antiviral Agents; Blood Component Removal; Cryoglobulinemia; Hepacivirus; Hepatitis C; Humans; Immunologic Factors; Immunosorbent Techniques; Immunosuppressive Agents; Interferons; Randomized Controlled Trials as Topic; Rituximab; Skin Diseases; Vasculitis
PubMed: 29734473
DOI: 10.1002/14651858.CD011403.pub2 -
Tropical Medicine & International... Apr 2017The retention of patients on antiretroviral therapy (ART) is key to achieving global targets in response to the HIV epidemic. Loss to follow-up (LTFU) can be... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The retention of patients on antiretroviral therapy (ART) is key to achieving global targets in response to the HIV epidemic. Loss to follow-up (LTFU) can be substantial, with unknown outcomes for patients lost to ART programmes. We examined changes in outcomes of patients LTFU over calendar time, assessed associations with other study and programme characteristics and investigated the relative success of different tracing methods.
METHODS
We performed a systematic review and logistic random-effects meta-regression analysis of studies that traced adults or children who started ART and were LTFU in sub-Saharan African treatment programmes. The primary outcome was mortality, and secondary outcomes were undocumented transfer to another programme, treatment interruption and the success of tracing attempts.
RESULTS
We included 32 eligible studies from 12 countries in sub-Saharan Africa: 20 365 patients LTFU were traced, and 15 708 patients (77.1%) were found. Compared to telephone calls, tracing that included home visits increased the probability of success: the adjusted odds ratio (aOR) was 9.35 (95% confidence interval [CI] 1.85-47.31). The risk of death declined over calendar time (aOR per 1-year increase 0.86, 95% CI 0.78-0.95), whereas undocumented transfers (aOR 1.13, 95% CI 0.96-1.34) and treatment interruptions (aOR 1.31, 95% CI 1.18-1.45) tended to increase. Mortality was lower in urban than in rural areas (aOR 0.59, 95% CI 0.36-0.98), but there was no difference in mortality between adults and children. The CD4 cell count at the start of ART increased over time.
CONCLUSIONS
Mortality among HIV-positive patients who started ART in sub-Saharan Africa, were lost to programmes and were successfully traced has declined substantially during the scale-up of ART, probably driven by less severe immunodeficiency at the start of therapy.
Topics: Adult; Africa South of the Sahara; Anti-HIV Agents; Child; Delivery of Health Care; HIV Infections; Humans; Lost to Follow-Up
PubMed: 28102610
DOI: 10.1111/tmi.12843 -
Scientific Reports Mar 2023In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review... (Meta-Analysis)
Meta-Analysis
Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies.
In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. We conducted a systematic review and meta-analysis of published studies evaluating patient response to antiviral therapy for chronic hepatitis C on the risk of HCC occurrence in Japan. Articles were searched using terms determined a priori through PubMed, screened by title and abstract, and selected by full-text assessment according to criteria determined a priori, including HCC occurrence in response to interferon (IFN)-based or IFN-free therapy, Japanese study, and 2 or more years of follow-up. We excluded studies on HCC recurrence. We calculated the pooled estimate of the crude incidence rate ratio with data from the selected studies using the person-years method with Poisson regression model and pooled estimate of the hazard ratio adjusted for potential confounders reported by the studies using a random effects model. A total of 26 studies were identified, all of which examined only IFN-based therapy as a result of the selection process. The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.33-0.43) for sustained virologic response (SVR) and 1.70 (1.61-1.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.19-0.26) for the incidence rate ratio (SVR vs. non-SVR). The pooled estimate of the hazard ratio (95% CI) of HCC incidence adjusted for potential confounders of 8 studies was 0.25 (0.19-0.34). SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence.
Topics: Humans; Hepatitis C, Chronic; Carcinoma, Hepatocellular; Japan; Liver Neoplasms; Interferons; Antiviral Agents
PubMed: 36859564
DOI: 10.1038/s41598-023-30467-5 -
The Cochrane Database of Systematic... Feb 2018Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed.
OBJECTIVES
To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma.
SEARCH METHODS
We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials.
SELECTION CRITERIA
All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials.
MAIN RESULTS
Eighteen studies met our criteria and were included in the meta-analysis, with a total of 2625 participants. We found evidence of an increase of objective response rates in people treated with chemoimmunotherapy, in comparison with people treated with chemotherapy. Nevertheless, the impact of these increased response rates was not translated into a survival benefit. We found no difference in survival to support the addition of immunotherapy to chemotherapy in the systemic treatment of metastatic melanoma, with a hazard ratio of 0.89 (95% CI 0.72 to 1.11, P = 0.31). Additionally, we found increased hematological and non-hematological toxicities in people treated with chemoimmunotherapy.
AUTHORS' CONCLUSIONS
We failed to find any clear evidence that the addition of immunotherapy to chemotherapy increases survival of people with metastatic melanoma. Further use of combined immunotherapy and chemotherapy should only be done in the context of clinical trials.
Topics: Antineoplastic Agents; Combined Modality Therapy; Humans; Immunotherapy; Interferon-alpha; Interleukin-2; Melanoma; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 29409139
DOI: 10.1002/14651858.CD005413.pub3 -
The Cochrane Database of Systematic... Jun 2017Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Millions of people worldwide suffer from hepatitis C, which can lead to severe liver disease, liver cancer, and death. Direct-acting antivirals (DAAs) are relatively new and expensive interventions for chronic hepatitis C, and preliminary results suggest that DAAs may eradicate hepatitis C virus (HCV) from the blood (sustained virological response). However, it is still questionable if eradication of hepatitis C virus in the blood eliminates hepatitis C in the body, and improves survival and leads to fewer complications.
OBJECTIVES
To assess the benefits and harms of DAAs in people with chronic HCV.
SEARCH METHODS
We searched for all published and unpublished trials in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, LILACS, and BIOSIS; the Chinese Biomedical Literature Database (CBM), China Network Knowledge Information (CNKI), the Chinese Science Journal Database (VIP), Google Scholar, The Turning Research into Practice (TRIP) Database, ClinicalTrials.gov, European Medicines Agency (EMA) (www.ema.europa.eu/ema/), WHO International Clinical Trials Registry Platform (www.who.int/ictrp), the Food and Drug Administration (FDA) (www.fda.gov), and pharmaceutical company sources for ongoing or unpublished trials. Searches were last run in October 2016.
SELECTION CRITERIA
Randomised clinical trials comparing DAAs versus no intervention or placebo, alone or with co-interventions, in adults with chronic HCV. We included trials irrespective of publication type, publication status, and language.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were hepatitis C-related morbidity, serious adverse events, and quality of life. Our secondary outcomes were all-cause mortality, ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, hepatocellular carcinoma, non-serious adverse events (each reported separately), and sustained virological response. We systematically assessed risks of bias, performed Trial Sequential Analysis, and followed an eight-step procedure to assess thresholds for statistical and clinical significance. The overall quality of the evidence was evaluated using GRADE.
MAIN RESULTS
We included a total of 138 trials randomising a total of 25,232 participants. The 138 trials assessed the effects of 51 different DAAs. Of these, 128 trials employed matching placebo in the control group. All included trials were at high risk of bias. Eighty-four trials involved DAAs on the market or under development (13,466 participants). Fifty-seven trials administered withdrawn or discontinued DAAs. Trial participants were treatment-naive (95 trials), treatment-experienced (17 trials), or both treatment-naive and treatment-experienced (24 trials). The HCV genotypes were genotype 1 (119 trials), genotype 2 (eight trials), genotype 3 (six trials), genotype 4 (nine trials), and genotype 6 (one trial). We identified two ongoing trials.Meta-analysis of the effects of all DAAs on the market or under development showed no evidence of a difference when assessing hepatitis C-related morbidity or all-cause mortality (OR 3.72, 95% CI 0.53 to 26.18, P = 0.19, I² = 0%, 2,996 participants, 11 trials, very low-quality evidence). As there were no data on hepatitis C-related morbidity and very few data on mortality (DAA 15/2377 (0.63%) versus control 1/617 (0.16%)), it was not possible to perform Trial Sequential Analysis on hepatitis C-related morbidity or all-cause mortality.Meta-analysis of all DAAs on the market or under development showed no evidence of a difference when assessing serious adverse events (OR 0.93, 95% CI 0.75 to 1.15, P = 0.52, I² = 0%, 15,817 participants, 43 trials, very low-quality evidence). The Trial Sequential Analysis showed that the cumulative Z-score crossed the trial sequential boundary for futility, showing that there was sufficient information to rule out that DAAs compared with placebo reduced the relative risk of a serious adverse event by 20%. The only DAA that showed a significant difference on risk of serious adverse events when meta-analysed separately was simeprevir (OR 0.62, 95% CI 0.45 to 0.86). However, Trial Sequential Analysis showed that there was not enough information to confirm or reject a relative risk reduction of 20%, and when one trial with an extreme result was excluded, then the meta-analysis result showed no evidence of a difference.DAAs on the market or under development seemed to reduce the risk of no sustained virological response (RR 0.44, 95% CI 0.37 to 0.52, P < 0.00001, I² = 77%, 6886 participants, 32 trials, very low-quality evidence) and Trial Sequential Analysis confirmed this meta-analysis result.Only 1/84 trials on the market or under development assessed the effects of DAAs on health-related quality of life (SF-36 mental score and SF-36 physical score).Withdrawn or discontinued DAAs had no evidence of a difference when assessing hepatitis C-related morbidity and all-cause mortality (OR 0.64, 95% CI 0.23 to 1.79, P = 0.40, I² = 0%; 5 trials, very low-quality evidence). However, withdrawn DAAs seemed to increase the risk of serious adverse events (OR 1.45, 95% CI 1.22 to 1.73, P = 0.001, I² = 0%, 29 trials, very low-quality evidence), and Trial Sequential Analysis confirmed this meta-analysis result.Most of all outcome results were short-term results; therefore, we could neither confirm nor reject any long-term effects of DAAs. None of the 138 trials provided useful data to assess the effects of DAAs on the remaining secondary outcomes (ascites, variceal bleeding, hepato-renal syndrome, hepatic encephalopathy, and hepatocellular carcinoma).
AUTHORS' CONCLUSIONS
Overall, DAAs on the market or under development do not seem to have any effects on risk of serious adverse events. Simeprevir may have beneficial effects on risk of serious adverse event. In all remaining analyses, we could neither confirm nor reject that DAAs had any clinical effects. DAAs seemed to reduce the risk of no sustained virological response. The clinical relevance of the effects of DAAs on no sustained virological response is questionable, as it is a non-validated surrogate outcome. All trials and outcome results were at high risk of bias, so our results presumably overestimate benefit and underestimate harm. The quality of the evidence was very low.
Topics: Antiviral Agents; Cause of Death; Hepacivirus; Hepatitis C, Chronic; Humans; Nucleic Acid Synthesis Inhibitors; Placebos; Protease Inhibitors; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Simeprevir
PubMed: 28585310
DOI: 10.1002/14651858.CD012143.pub2 -
Systematic Reviews Aug 2019Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic hepatitis B (CHB) infection poses a significant burden to public health worldwide. Most cases are clinically silent until late in the disease course. The main goal of current therapy is to improve survival and quality of life by preventing disease progression to cirrhosis and liver failure, and consequently hepatocellular carcinoma development. The objective of this review is to provide a contemporary and comprehensive evaluation of the effectiveness of treatment options.
METHODS
We performed a systematic review of peer-reviewed literature for randomized controlled trials involving treatment-naïve CHB adult population who received antiviral therapy. The endpoints were virologic response (VR), normalization of alanine aminotransferase (ALT norm), HBeAg loss, HBeAg seroconversion, and HBsAg loss for the HBeAg-positive population; and VR and ALT norm for the HBeAg-negative population. Network meta-analysis (NMA) was performed to synthesize evidence on the efficacy of treatment.
RESULTS
Forty-two publications were selected. Twenty-three evaluated HBeAg-positive population, 13 evaluated HBeAg-negative population, and six evaluated both. We applied NMA to the efficacy outcomes of the two populations separately. Treatment strategies were ranked by the probability of achieving outcomes, and pairwise comparisons calculated from NMA were reported in odds ratios (OR). For HBeAg-positive population, tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) were the best for VR; OR vs adefovir = 14.29, 95% CI 7.69-25 and 12.5, 95% CI 4.35-33.33 respectively. TAF was the best for achieving ALT norm (OR vs placebo = 12.5, 95% CI 4.55-33.33), HBeAg loss, and seroconversion (OR vs entecavir/TDF combination = 3.03, 95% CI 1.04-8.84 and 3.33, 95% CI 1.16-10 respectively). In the HBeAg-negative population, TDF and TAF were the best for VR (OR vs adefovir = 9.79, 95% CI 2.38-42.7 and 11.71, 95% CI 1.03-150.48 respectively). Telbivudine and TAF were the best for ALT norm. Certain nucleos(t)ide combinations also had high probability of achieving positive outcomes.
CONCLUSIONS
Our results are consonant with current clinical guidelines and other evidence reviews. For both HBeAg-positive and HBeAg-negative populations, TDF and TAF are the most effective agents for virologic suppression, and TAF is effective across all outcomes.
Topics: Antiviral Agents; Hepatitis B, Chronic; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31426837
DOI: 10.1186/s13643-019-1126-1 -
Systematic Reviews May 2022In an unparalleled global response, during the COVID-19 pandemic, 90 countries asked 3.9 billion people to stay home. Yet other countries avoided lockdowns and focused... (Review)
Review
BACKGROUND
In an unparalleled global response, during the COVID-19 pandemic, 90 countries asked 3.9 billion people to stay home. Yet other countries avoided lockdowns and focused on other strategies, like contact tracing. How effective and cost-effective are these strategies? We aimed to provide a comprehensive summary of the evidence on past pandemic controls, with a focus on cost-effectiveness.
METHODS
Following PRISMA guidelines, MEDLINE (1946 to April week 2, 2020) and EMBASE (1974 to April 17, 2020) were searched using a range of terms related to pandemic control. Articles reporting on the effectiveness or cost-effectiveness of at least one intervention were included.
RESULTS
We found 1653 papers; 62 were included. The effectiveness of hand-washing and face masks was supported by randomized trials. These measures were highly cost-effective. For other interventions, only observational and modelling studies were found. They suggested that (1) the most cost-effective interventions are swift contact tracing and case isolation, surveillance networks, protective equipment for healthcare workers, and early vaccination (when available); (2) home quarantines and stockpiling antivirals are less cost-effective; (3) social distancing measures like workplace and school closures are effective but costly, making them the least cost-effective options; (4) combinations are more cost-effective than single interventions; and (5) interventions are more cost-effective when adopted early. For 2009 H1N1 influenza, contact tracing was estimated to be 4363 times more cost-effective than school closure ($2260 vs. $9,860,000 per death prevented).
CONCLUSIONS AND CONTRIBUTIONS
For COVID-19, a cautious interpretation suggests that (1) workplace and school closures are effective but costly, especially when adopted late, and (2) scaling up as early as possible a combination of interventions that includes hand-washing, face masks, ample protective equipment for healthcare workers, and swift contact tracing and case isolation is likely to be the most cost-effective strategy.
Topics: COVID-19; Communicable Disease Control; Cost-Benefit Analysis; Humans; Influenza A Virus, H1N1 Subtype; Pandemics; SARS-CoV-2
PubMed: 35550674
DOI: 10.1186/s13643-022-01958-9 -
Medicina (Kaunas, Lithuania) Aug 2022: Probiotic supplementation can prevent and alleviate gastrointestinal and respiratory tract infections in healthy individuals. Markers released from the site of... (Review)
Review
: Probiotic supplementation can prevent and alleviate gastrointestinal and respiratory tract infections in healthy individuals. Markers released from the site of inflammation are involved in the response to infection or tissue injury. Therefore, we measured the pre-exercise and postexercise levels of inflammation-related markers-tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-10, interferon (IFN)-γ, salivary immunoglobulin A (IgA), IL-1β, IL-2, IL-4, and C-reactive protein (CRP)-in probiotic versus placebo groups to investigate the effects of probiotics on these markers in athletes. Probiotics contained multiple species (e.g., , etc.). : We performed a systematic search for studies published until May 2022 and included nine randomized clinical trials. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Fixed-effects meta-analyses and sensitivity analyses were performed. Subgroup analyses were conducted on the basis of the period of probiotic intervention and timing of postassessment blood sampling. : The levels of IFN-γ and salivary IgA exhibited a significant positive change, whereas those of TNF-α and IL-10 demonstrated a negative change in the probiotic group. The subgroup analysis revealed that the probiotic group exhibited significant negative changes in TNF-α and IL-10 levels in the shorter intervention period. For the subgroup based on the timing of postassessment blood sampling, the subgroup whose blood sample collection was delayed to at least the next day of exercise exhibited significant negative changes in their TNF-α and IL-10 levels. The subgroups whose blood samples were collected immediately after exercise demonstrated negative changes in their TNF-α, IL-8, and IL-10 levels. : Probiotic supplementation resulted in significant positive changes in the IFN-γ and salivary IgA levels and negative changes in the IL-10 and TNF-α levels. No significant changes in the IL-1β, IL-2, IL-4, IL-6, IL-8, or CRP levels were observed after probiotic use in athletes.
Topics: Athletes; Biomarkers; C-Reactive Protein; Humans; Immunoglobulin A; Inflammation; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Probiotics; Randomized Controlled Trials as Topic; Tumor Necrosis Factor-alpha
PubMed: 36143865
DOI: 10.3390/medicina58091188 -
Medicine Mar 2016All possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However,... (Meta-Analysis)
Meta-Analysis Review
Systematic Review and Network Meta-Analysis of Randomized Controlled Trials: Comparative Effectiveness and Safety of Direct-Acting Antiviral Agents for Treatment-Naive Hepatitis C Genotype 1.
All possible direct-acting antiviral agent (DAA) regimens for treatment-naive hepatitis C genotype 1 were evaluated by many randomized controlled trials (RCTs). However, the optimum regimen remains inconclusive. We aim to compare interventions in terms of sustained virological response at 12 (SVR12) and 24 (SVR24) weeks after the end of treatment and adverse effects (AEs) (fatigue, headache, nausea, insomnia). PubMed, Embase, and the Cochrane Library were searched for RCTs until July 31, 2015. We estimated odds ratios (ORs) between treatments on clinical outcomes. Twenty-two eligible RCTs were included. Compared with peginterferon-ribavirin (PR), daclatasvir plus PR (OR 8.90, P < 0.001), faldaprevir plus PR (OR 3.72, P < 0.001), simeprevir plus PR (OR 3.59, P < 0.001), sofosbuvir plus PR (OR 4.69, P < 0.001) yield a significant effect in improving SVR12. Consistently, simeprevir plus PR (OR 3.49, P < 0.001), sofosbuvir plus PR (OR 4.51, P < 0.001), daclatasvir plus PR (OR 4.77, P < 0.001) also improved the rates of SVR24 significantly compared with PR. With respect to AEs, compared with PR, ledipasvir plus sofosbuvir plus PR (OR 2.13, P < 0.001) confer a significant AE in nausea, whereas daclatasvir plus PR (OR 0.20, P < 0.001 and OR 0.18, P < 0.001, respectively) lowered the incidence of fatigue and nausea significantly when compared with ledipasvir plus sofosbuvir plus PR. Daclatasvir plus PR was the most effective in SVR12 and SVR24, but caused an increased AEs profile (headache and insomnia). Combined ledipasvir with sofosbuvir or combination of PR was associated with higher incidence of fatigue and nausea.
Topics: Antiviral Agents; Comparative Effectiveness Research; Drug Therapy, Combination; Genotype; Hepacivirus; Hepatitis C, Chronic; Humans; Odds Ratio; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26945424
DOI: 10.1097/MD.0000000000003004 -
PloS One 2014We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.
METHODS
We systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran's Q test and I2 statistic).
RESULTS
39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%-48%, I2 = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%-94%, I2 = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%-81%, I2 = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%-11%, I2 = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%-83%, I2 = 36%, 4 studies), and 57% (95% CI: 46%-68%, I2 = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm3 (4 studies).
CONCLUSIONS
Despite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.
Topics: Anti-HIV Agents; Female; HIV Infections; Humans; Patient Compliance; Sex Work
PubMed: 25265158
DOI: 10.1371/journal.pone.0105645