Reminder systems to improve patient adherence to tuberculosis clinic appointments for diagnosis and treatment

Background People with active tuberculosis (TB) require six months of treatment. Some people find it difficult to complete treatment, and there are several approaches to help ensure completion. One such system relies on reminders, where the health system prompts patients to attend for appointments on time, or re-engages people who have missed or defaulted on a scheduled appointment. Objectives To assess the effects of reminder systems on improving attendance at TB diagnosis, prophylaxis, and treatment clinic appointments, and their effects on TB treatment outcomes. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, Cochrane Effective Practice and Organization of Care Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, CINAHL, SCI-EXPANDED, SSCI, mRCT, and the Indian Journal of Tuberculosis without language restriction up to 29 August 2014. We also checked reference lists and contacted researchers working in the field. Selection criteria Randomized controlled trials (RCTs), including cluster RCTs and quasi-RCTs, and controlled before-and-after studies comparing reminder systems with no reminders or an alternative reminder system for people with scheduled appointments for TB diagnosis, prophylaxis, or treatment. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in the included trials. We compared the effects of interventions by using risk ratios (RR) and presented RRs with 95% confidence intervals (CIs). Also we assessed the quality of evidence using the GRADE approach. Main results Nine trials, including 4654 participants, met our inclusion criteria. Five trials evaluated appointment reminders for people on treatment for active TB, two for people on prophylaxis for latent TB, and four for people undergoing TB screening using skin tests. We classified the interventions into 'pre-appointment' reminders (telephone calls or letters prior to a scheduled appointment) or 'default' reminders (telephone calls, letters, or home visits to people who had missed an appointment). For people being treated for active TB, clinic attendance and TB treatment completion were higher in people receiving pre-appointment reminder phone-calls (clinic attendance: 66% versus 50%; RR 1.32, 95% CI 1.10 to 1.59, one trial (USA), 615 participants, low quality evidence; TB treatment completion: 100% versus 88%; RR 1.14, 95% CI 1.02 to 1.27, one trial (Thailand), 92 participants, low quality evidence). Clinic attendance and TB treatment completion were also higher with default reminders (letters or home visits) (clinic attendance: 52% versus 10%; RR 5.04, 95% CI 1.61 to 15.78, one trial (India), 52 participants, low quality evidence; treatment completion: RR 1.17, 95% CI 1.11 to 1.24, two trials (Iraq and India), 680 participants, moderate quality evidence). For people on TB prophylaxis, clinic attendance was higher with a policy of pre-appointment phone-calls (63% versus 48%; RR 1.30, 95% CI 1.07 to 1.59, one trial (USA), 536 participants); and attendance at the final clinic was higher with regular three-monthly phone-calls or nurse visits (93% versus 65%, one trial (Spain), 318 participants). For people undergoing screening for TB, three trials of pre-appointment phone-calls found little or no effect on the proportion of people returning to clinic for the result of their skin test (three trials, 1189 participants, low quality evidence), and two trials found little or no effect with take home reminder cards (two trials, 711 participants). All four trials were conducted among healthy volunteers in the USA. Authors' conclusions Policies of sending reminders to people pre-appointment, and contacting people who miss appointments, seem sensible additions to any TB programme, and the limited evidence available suggests they have small but potentially important benefits. Future studies of modern technologies such as short message service (SMS) reminders would be useful, particularly in low-resource settings

Durability and extent of protection of SARS-CoV-2 antibodies among patients with COVID-19 in Metro Manila, Philippines

IntroductionInformation on the magnitude and durability of humoral immunity against COVID-19 among specific populations can guide policies on vaccination, return from isolation and physical distancing measures. The study determined the durability of SARS-CoV-2 antibodies after an initial infection among Filipinos in Metro Manila, Philippines, and the extent of protection SARS-CoV-2 antibodies confer against reinfection.MethodsWe conducted a cohort study to monitor the antibody levels of patients diagnosed with COVID-19. Receptor-binding domain (RBD)-specific antibodies were measured at Days 21, 90, 180, 270 and 360. Antibody levels were reported as geometric mean titers (GMT) with geometric standard deviation (GSD). Differences in GMT were tested using Friedman test and Kruskal Wallis test, with Bonferroni multiple comparisons procedure. Adjusted hazard ratios on the development of probable reinfection were estimated using Cox proportional models.ResultsThere were 307 study participants included in the study, with 13 dropouts. Study participants received SARS-CoV-2 vaccines at varying times, with 278 participants (90.5%) fully vaccinated by the end of study. The GMT of the study cohort increased over time, from 19.7 U/mL (GSD 11) at Day 21; to 284.5 U/mL (GSD 9.6) at Day 90; 1,061 U/mL (GSD 5.3) at Day 180; 2,003 U/mL (GSD 6.7) at Day 270; and 8,403 U/mL (GSD 3.1) at Day 360. The increase was statistically significant from Day 21 to Day 90 (p<0.0001), Day 90 to Day 180 (p=0.0005), and Day 270 to Day 360 (p<0.0001). Participants with more severe initial infection demonstrated significantly higher antibody levels compared to those with milder infection at Day 21. Sixty-four patients had probable COVID-19 reinfection (incidence of 20.8%, 95% CI 16.4, 25.8%). The GMT of these 64 patients was 411.8 U/mL (GSD 6.9) prior to the occurrence of the probable reinfection. Majority (87.5%) were fully vaccinated. Antibody titers significantly affected the risk of developing reinfection, with adjusted hazard ratio of 0.994, 95% CI 0.992-0.996, p<0.001.ConclusionAntibody levels against SARS-CoV-2 increased over a one-year follow-up. Higher antibody levels were observed among those with more severe initial infection and those vaccinated. Higher antibody levels are associated with a lower risk of probable reinfection

Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses.

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

Funder: laura and john arnold foundationBACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care

Reinfection rates, change in antibody titers and adverse events after COVID-19 vaccination among patients previously infected with COVID-19 in Metro Manila, Philippines: a secondary analysis of a completed cohort study

Abstract Background Variation in immune response to COVID-19 vaccines is observed among different ethnicities. We aimed to describe the reinfection rates, change in antibody titers, and adverse events among Filipinos. Methods This is a secondary analysis of a cohort study of 307 participants within one year of having COVID-19 infection. We measured COVID-19 antibody levels at pre-determined timepoints (Days 21, 90, 180, 270, and 360 from initial infection). We monitored for COVID-19 symptoms and obtained details on COVID-19 vaccination. An adjudication committee classified the participants as probable, possible, or unlikely COVID-19 reinfection. We determined the probable reinfection rate, adverse events, and the geometric mean titer (GMT) ratio of pre- and post-vaccination antibody levels according to type and brand of COVID-19 vaccine. Results At the end of the follow-up period, 287 (93.5%) out of 307 study participants were fully vaccinated, 1 was partially vaccinated (0.3%), and 19 were unvaccinated (6.2%). Among the fully vaccinated participants, those given mRNA vaccines had the lowest reinfection rate (19.2 cases/100 person-years, 95% CI 9.6, 38.4), followed by viral vector vaccines (29.8 cases/100 person-years, 95% CI 16.9, 52.4). We observed the highest reinfection rate among those given inactivated virus vaccines (32.7 cases/100 person-years, 95% CI 23.6, 45.3). The reinfection rate was 8.6 cases/100 person-years (95% CI 4.1, 17.9) for unvaccinated participants and 3.6 cases/100 person-years (95% CI 0.5, 25.3) for partially vaccinated participants. We observed the largest rise in antibody titers among those given mRNA vaccines (GMT ratio 288.5), and the smallest rise among those given inactivated virus vaccines (GMT ratio 16.7). We observed the highest percentage of adverse events following immunization with viral vector vaccines (63.8%), followed by mRNA vaccines (62.7%), and the lowest for inactivated virus vaccines (34.7%). No serious adverse events were reported. Conclusion Vaccinees given the mRNA vaccines had the lowest reinfection rate and the highest rise in antibody titers. Vaccinees given inactivated virus vaccines had the highest reinfection rate, smallest rise in antibody titers, and lowest percentage of adverse events. The small sample size and imbalanced distribution of the type of vaccines received limits the external generalizability of our results. Study Registration The cohort study was registered at the Philippine Health Research Registry on December 14, 2020 (PHRR201214-003199)

Association between convalescent plasma treatment and mortality in COVID-19: a collaborative systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX ). METHODS: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung-Knapp-Sidik-Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. RESULTS: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of the weight in the meta-analysis. CONCLUSIONS: Convalescent plasma treatment of patients with COVID-19 did not reduce all-cause mortality. These results provide strong evidence that convalescent plasma treatment for patients with COVID-19 should not be used outside of randomized trials. Evidence synthesis from collaborations among trial investigators can inform both evidence generation and evidence application in patient care. [Liste complète des auteurs - voir article en document joint

Repurposed Antiviral Drugs for Covid-19 : Interim WHO Solidarity Trial Results

BACKGROUND World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs — remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a — in patients hospitalized with coronavirus disease 2019 (Covid-19). METHODS We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry. RESULTS At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan–Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration. CONCLUSIONS These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.)Medicine, Faculty ofNon UBCPediatrics, Department ofReviewedFacultyResearche