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

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study

Background Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. Methods We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. Results Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19–1.94), wheeze (OR 1.37, 95% CI 1.16–1.63) and dyspnoea (OR 1.83, 95% CI 1.53–2.20), but not lower FVC (β=0.02 L, 95% CI −0.02–0.06 L) or lower FEV1/FVC (β=0.04%, 95% CI −0.49–0.58%). Some findings differed by sex and gross national income. Conclusion At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.publishedVersio

Cohort Profile: Burden of Obstructive Lung Disease (BOLD) study

The Burden of Obstructive Lung Disease (BOLD) study was established to assess the prevalence of chronic airflow obstruction, a key characteristic of chronic obstructive pulmonary disease, and its risk factors in adults (≥40 years) from general populations across the world. The baseline study was conducted between 2003 and 2016, in 41 sites across Africa, Asia, Europe, North America, the Caribbean and Oceania, and collected high-quality pre- and post-bronchodilator spirometry from 28 828 participants. The follow-up study was conducted between 2019 and 2021, in 18 sites across Africa, Asia, Europe and the Caribbean. At baseline, there were in these sites 12 502 participants with high-quality spirometry. A total of 6452 were followed up, with 5936 completing the study core questionnaire. Of these, 4044 also provided high-quality pre- and post-bronchodilator spirometry. On both occasions, the core questionnaire covered information on respiratory symptoms, doctor diagnoses, health care use, medication use and ealth status, as well as potential risk factors. Information on occupation, environmental exposures and diet was also collected

Rosuvastatin adjunctive therapy for rifampicin-susceptible pulmonary tuberculosis: a phase 2b, randomised, open-label, multicentre trial

Background: Shorter treatments are needed for drug-susceptible tuberculosis. Adjunctive statins increase bactericidal activity in preclinical tuberculosis models. We investigated the safety and efficacy of adjunctive rosuvastatin in people with tuberculosis. We tested the hypothesis that adjunctive rosuvastatin accelerates sputum culture conversion within the first 8 weeks of treatment of rifampicin-susceptible tuberculosis. Methods: This phase 2b, randomised, open-label, multicentre trial conducted in five hospitals or clinics in three countries with high tuberculosis burden (ie, the Philippines, Viet Nam, and Uganda) enrolled adult participants aged 18–75 years with sputum smear or Xpert MTB/RIF positive, rifampicin-susceptible tuberculosis who had received less than 7 days of previous tuberculosis treatment. Participants were randomly assigned via a web-based system to receive either 10 mg rosuvastatin once per day for 8 weeks plus standard tuberculosis therapy (rifampicin, isoniazid, pyrazinamide, and ethambutol; rosuvastatin group) or standard tuberculosis therapy alone (control group). Randomisation was stratified by trial site, history of diabetes, and HIV co-infection. Laboratory staff and central investigators involved in data cleaning and analysis were masked to treatment allocation, but study participants and site investigators were not. Both groups continued standard treatment to week 24. Sputum samples were collected once per week for the first 8 weeks after randomisation, and then at weeks 10, 12, and 24. The primary efficacy outcome was time to culture conversion (TTCC; days) in liquid culture by week 8, assessed in randomised participants who had microbiological confirmation of tuberculosis, took at least one dose of rosuvastatin, and who did not show resistance to rifampicin (modified intention-to-treat population), for which groups were compared with the Cox proportional hazards model. The main safety outcome was grade 3–5 adverse events by week 24, assessed in the intention-to-treat population, for which groups were compared with Fisher\u27s exact test. All participants completed 24 weeks of follow-up. This trial is registered with ClinicalTrials.gov (NCT04504851). Findings: Between Sept 2, 2020, and Jan 14, 2021, 174 participants were screened and 137 were randomly assigned to the rosuvastatin group (70 participants) or control group (67 participants). In the modified intention-to-treat population of 135 participants, 102 (76%) were men and 33 (24%) were women. Median TTCC in liquid media was 42 days (95% CI 35–49) in the rosuvastatin group (68 participants) and 42 days (36–53) in the control group (67 participants; hazard ratio 1·30 [0·88–1·91], p=0·19). Grade 3–5 adverse events occurred in six (9%) of 70 in the rosuvastatin group (none were considered related to rosuvastatin) and four (6%) of 67 in the control group (p=0·75). There were no serious adverse events that were considered to be related to rosuvastatin. Interpretation: Adjunctive rosuvastatin at 10 mg once per day was safe but did not produce substantive benefits on culture conversion in the overall study population. Future trials could explore the safety and efficacy of higher doses of adjunctive rosuvastatin. Funding: National Medical Research Council, Singapore

Treatment Strategy for Rifampin-Susceptible Tuberculosis

BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points. RESULTS: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups. CONCLUSIONS: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.)

Treatment Strategy for Rifampin-Susceptible Tuberculosis

BACKGROUND: Tuberculosis is usually treated with a 6-month rifampin-based regimen. Whether a strategy involving shorter initial treatment may lead to similar outcomes is unclear. METHODS: In this adaptive, open-label, noninferiority trial, we randomly assigned participants with rifampin-susceptible pulmonary tuberculosis to undergo either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or a strategy involving initial treatment with an 8-week regimen, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse. There were four strategy groups with different initial regimens; noninferiority was assessed in the two strategy groups with complete enrollment, which had initial regimens of high-dose rifampin-linezolid and bedaquiline-linezolid (each with isoniazid, pyrazinamide, and ethambutol). The primary outcome was a composite of death, ongoing treatment, or active disease at week 96. The noninferiority margin was 12 percentage points. RESULTS: Of the 674 participants in the intention-to-treat population, 4 (0.6%) withdrew consent or were lost to follow-up. A primary-outcome event occurred in 7 of the 181 participants (3.9%) in the standard-treatment group, as compared with 21 of the 184 participants (11.4%) in the strategy group with an initial rifampin-linezolid regimen (adjusted difference, 7.4 percentage points; 97.5% confidence interval [CI], 1.7 to 13.2; noninferiority not met) and 11 of the 189 participants (5.8%) in the strategy group with an initial bedaquiline-linezolid regimen (adjusted difference, 0.8 percentage points; 97.5% CI, -3.4 to 5.1; noninferiority met). The mean total duration of treatment was 180 days in the standard-treatment group, 106 days in the rifampin-linezolid strategy group, and 85 days in the bedaquiline-linezolid strategy group. The incidences of grade 3 or 4 adverse events and serious adverse events were similar in the three groups. CONCLUSIONS: A strategy involving initial treatment with an 8-week bedaquiline-linezolid regimen was noninferior to standard treatment for tuberculosis with respect to clinical outcomes. The strategy was associated with a shorter total duration of treatment and with no evident safety concerns. (Funded by the Singapore National Medical Research Council and others; TRUNCATE-TB ClinicalTrials.gov number, NCT03474198.)

Overdiagnosis of COPD in subjects with unobstructed spirometry

Background: There are several reports on the underdiagnosis of COPD, while little is known about COPD overdiagnosis and overtreatment. We describe the overdiagnosis and the prevalence of spirometrically defined false-positive COPD, as well as their relationship with overtreatment across 23 population samples in 20 countries participating in the BOLD Study between 2003 and 2012. Methods: A false-positive diagnosis of COPD was considered when participants reported a doctor's diagnosis of COPD, but postbronchodilator spirometry was unobstructed (FEV1/FVC > LLN). Additional analyses were performed using the fixed ratio criterion (FEV1/FVC < 0.7). Results: Among 16,177 participants, 919 (5.7%) reported a previous medical diagnosis of COPD. Postbronchodilator spirometry was unobstructed in 569 subjects (61.9%): false-positive COPD. A similar rate of overdiagnosis was seen when using the fixed ratio criterion (55.3%). In a subgroup analysis excluding participants who reported a diagnosis of "chronic bronchitis" or "emphysema" (n = 220), 37.7% had no airflow limitation. The site-specific prevalence of false-positive COPD varied greatly, from 1.9% in low- to middle-income countries to 4.9% in high-income countries. In multivariate analysis, overdiagnosis was more common among women, and was associated with higher education; former and current smoking; the presence of wheeze, cough, and phlegm; and concomitant medical diagnosis of asthma or heart disease. Among the subjects with false-positive COPD, 45.7% reported current use of respiratory medication. Excluding patients with reported asthma, 34.4% of those with normal spirometry still used a respiratory medication. Conclusions: False-positive COPD is frequent. This might expose nonobstructed subjects to possible adverse effects of respiratory medication.info:eu-repo/semantics/publishedVersio

COPD: should diagnosis match physiology?

We are very grateful to Dr. Vanfleteren and colleagues for commenting on our data regarding overdiagnosed COPD2 and for putting this evidence into the framework of the current understanding of the disease. Based on the data presented on overdiagnosis, and on prior Burden of Obstructive Lung Disease (BOLD) observations on underdiagnosis,3 we truly believe that our worldwide community of pulmonary specialists could do much better in caring for this extremely prevalent and devastating disease. Overall, our data indicate that for one patient with a “matched” COPD diagnosis (ie, the presence of postbronchodilator airways obstruction and a positive recall of such a diagnosis), there is always another “mismatched,” false-positive patient with COPD. This patient possibly experiences all the untoward consequences, such as receiving expensive and possibly harmful medication, and missing chances for treatment of cardiac disease or asthma. On the contrary, for each “known” patient with COPD who has a poorly reversible airway obstruction, there are four to five other patients out there with yet undetected airways obstruction. Again, we are missing opportunities in these patients for smoking intervention, symptom relief, and prolongation of their lives.info:eu-repo/semantics/publishedVersio