Accurate estimates of long-term mortality following tuberculosis treatment are scarce. This systematic review and meta-analysis aimed to estimate the post-treatment mortality among tuberculosis ...survivors, and examine differences in mortality risk by demographic and clinical characteristics.
We systematically searched Embase, MEDLINE, and the Cochrane Database of Systematic Reviews for cohort studies published in English between Jan 1, 1997, and May 31, 2018. We included research papers that used a cohort study design, included bacteriological or clinical confirmation of tuberculosis disease for all participants, and reported, or provided enough data to calculate, mortality estimates for people with tuberculosis and a valid control group representative of the general population. We excluded studies that reported duplicate data, had a study population of fewer than 50 people overall, had a follow-up period shorter than 12 months after treatment completion, or had a loss to follow-up of more than 30%. From eligible studies, we extracted standardised mortality ratios (SMRs), or calculated them when the data were sufficient, by dividing the sum of the observed deaths by the sum of the expected deaths. For studies that did not report SMR as their mortality estimate, either mortality hazard ratios or mortality rate ratios were extracted and pooled with SMRs. Random-effects meta-analysis was used to obtain pooled SMRs. Between-study heterogeneity was estimated with I2. This study was prospectively registered in PROSPERO (CRD42018092592).
Of the 7283 unique studies identified, data from ten studies, reporting on 40 781 individuals and 6922 deaths, were included. The pooled SMR for all-cause mortality among people with tuberculosis, compared with the control group, was 2·91 (95% CI 2·21–3·84; I2=99%, pheterogeneity<0·0001). When restricted to people with confirmed treatment completion or cure, the pooled SMR was 3·76 (95% CI 3·04–4·66; I2=95%). Effect estimates were similar when stratified by tuberculosis type, sex, age, and country income category. Causes of mortality were extracted for 4226 deaths that occurred post-treatment, with most deaths attributable to cardiovascular disease (20% 95% CI 15–26; I2=92%).
People treated for tuberculosis have significantly increased mortality following treatment compared with the general population or matched controls. These findings support the need for further research to understand and address the biomedical and social factors that affect the long-term prognosis of this population.
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Abstract
Background
Transmission of Mycobacterium tuberculosis in healthcare settings is a preventable driver of the global tuberculosis epidemic. We aimed to assess the evidence for infection ...control interventions, including cough etiquette, engineering and personal respiratory protection measures, to prevent transmission of M. tuberculosis in healthcare settings.
Methods
Three independent systematic reviews were performed using 6 databases and clinical trials websites. Randomized trials, cohort studies, before-after studies, and case-control studies were included. Searches were performed for controlled studies evaluating respiratory hygiene, engineering, and personal respiratory protection measures. Outcome measures included the incidence of tuberculosis infection and disease. Studies involving transmission to either humans or animals were included.
Results
Evaluation of respiratory hygiene and cough etiquette interventions identified 4 human studies, with 22 855 participants, and 1 guinea pig study. Studies in humans evaluated the effects of multiple concurrent interventions. Patient use of surgical masks reduced infection by 14.8%, and tuberculosis disease was reduced by between 0.5% and 28.9%. Engineering and environmental interventions were evaluated in 10 studies of humans, including 31 776 human participants, and 2 guinea pig studies. Mechanical ventilation was associated with between 2.9% and 14% less infection. Nine studies of personal respiratory protection were included, including 33 913 participants. Infection was reduced by between 0% and 14.8% in studies where particulate respirators were used. The quality of included studies was assessed as low.
Conclusions
Respiratory hygiene, engineering, and environmental infection controls and personal respiratory protection interventions were associated with reduced transmission of M. tuberculosis and reduced tuberculosis disease in healthcare settings.
Respiratory hygiene, engineering, and environmental infection controls and personal respiratory protection interventions are associated with reduced transmission of M. tuberculosis and reduced tuberculosis disease in healthcare settings. Most studies included in this systematic review evaluated the effect of multiple concurrent interventions.
Early childhood poverty is a risk factor for lower school achievement, reduced earnings, and poorer health, and has been associated with differences in brain structure and function. Whether poverty ...causes differences in neurodevelopment, or is merely associated with factors that cause such differences, remains unclear. Here, we report estimates of the causal impact of a poverty reduction intervention on brain activity in the first year of life. We draw data from a subsample of the Baby's First Years study, which recruited 1,000 diverse low-income mother-infant dyads. Shortly after giving birth, mothers were randomized to receive either a large or nominal monthly unconditional cash gift. Infant brain activity was assessed at approximately 1 y of age in the child's home, using resting electroencephalography (EEG;
= 435). We hypothesized that infants in the high-cash gift group would have greater EEG power in the mid- to high-frequency bands and reduced power in a low-frequency band compared with infants in the low-cash gift group. Indeed, infants in the high-cash gift group showed more power in high-frequency bands. Effect sizes were similar in magnitude to many scalable education interventions, although the significance of estimates varied with the analytic specification. In sum, using a rigorous randomized design, we provide evidence that giving monthly unconditional cash transfers to mothers experiencing poverty in the first year of their children's lives may change infant brain activity. Such changes reflect neuroplasticity and environmental adaptation and display a pattern that has been associated with the development of subsequent cognitive skills.
Abstract Current World Health Organisation targets calling for an end to the global tuberculosis (TB) epidemic by 2035 require a dramatic improvement in current case-detection strategies. A reliance ...on passive case finding (PCF) has resulted consistently, in over three million infectious TB cases per year, being missed by the health system, leading to ongoing transmission of infection within families and communities. Active case finding (ACF) for TB has been recognized as an important complementary strategy to PCF, in order to diagnose and treat patients earlier, reducing the period of infectiousness and therefore transmission. ACF may also achieve substantial population-level TB control. Local TB epidemiology and the resources available in each setting will influence which populations should be screened, and the types of ACF interventions to use for maximal impact. TB control programs should begin with the highest risk groups and broaden their activities as resources allow. Mathematical models can help to predict the population-level effects and the cost-effectiveness of a variety of ACF strategies on different risk populations.
The global drive to vaccinate against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) began in December 2020 with countries in Europe, Middle East, and North America leading the roll out ...of a mass-vaccination program. This systematic review synthesised all available English-language guidelines and research regarding mass-vaccination for COVID-19 until 1 March 2021-the first three months of the global mass-vaccination effort. Data were extracted from national websites, PubMed, Embase, Medline and medRxiv, including peer and non-peer review research findings. A total of 15 national policy documents were included. Policies were summarised according to the World Health Organisation (WHO) framework for mass vaccination. All included policies prioritised front-line health care workers and the elderly. Limited information was available regarding staffing, cold chain, communication strategies and infrastructure requirements for effective vaccine delivery. A total of 26 research studies were identified, reporting roll-out strategies, vaccine uptake and reasons for refusal, adverse effects, and real-life estimates of efficacy. Early data showed a reduction in SARS-CoV-2 cases, hospitalisation and deaths in settings with good coverage. Very low rates of vaccine-related serious adverse events were observed. These findings provide an overview of current practice and early outcomes of COVID-19 mass-vaccination, guiding countries where roll-out is yet to commence.
Tuberculosis preventive treatment (TPT) is an essential component for TB elimination. In order to be successfully implemented on a large scale, TPT needs to be safe, affordable and widely available ...in all settings. Short TPT regimens, that are less burdensome than longer regimens, to patients and health systems, are needed. Doses of rifampin higher than the standard 10mg/kg/day were tolerated in studies to reduce duration of treatment for tuberculosis disease (TBD). The objective of this trial is to test the safety of high dose rifampin monotherapy to shorten the duration of the currently recommended TPT of 4 months rifampin.
This is a phase 2b, randomised, controlled, parallel group, superiority, partially-blind trial. Primary outcomes are completion of treatment (as a proxy measure of tolerability) and safety. The two experimental arms comprise 60 days of (i) 20mg/kg/day or (ii) 30mg/kg/day rifampin; the control arm comprises 120 days of 10mg/kg/day rifampin as TPT. Participants are adults and children 10 years or older, eligible for TPT. Completion is the primary outcome, measured by pill count and is defined as taking minimum of 80% of treatment in 120% of allowed time; it will be tested for superiority by logistic regression. Safety outcome comprises proportion of grade 3-5 adverse events and grade 1-2 rash, adjudicated related to study drug, and resulting in permanent drug discontinuation; compared for non-inferiority between each of the two high dose arms and the standard arm, using Poisson regression. A sample size of 1,359 participants will give 80% power to detect a 10% difference in completion rates and a 1% difference in the safety outcome. The study is conducted in Canada, Indonesia and Vietnam. Enrolment is ongoing at all sites.
Approvals from a local research ethics board (REB) have been obtained at all participating sites and by the trial coordinating centre. Approval has been given by drug regulatory agencies in Canada and Indonesia and by Ministry of Health in Vietnam; participants give written informed consent before participation. All data collected are non-nominal. Primary results will be submitted for publication in a peer-reviewed journal when all participants have completed treatment; results of secondary outcomes will be submitted for publication at the end of study; all sites will receive the final data of participants from their sites.
Trial registered in ClinicalTrials.gov (Identifier: NCT03988933). Coordinating center is the study team working at McGill University Health Center-Research Institute (MUHC-RI); sponsor is the MUHC-RI; funding has been granted by Canadian Institute of Health Research (FDN-143350).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Childhood economic disadvantage is associated with lower cognitive and social-emotional skills, reduced educational attainment, and lower earnings in adulthood. Despite these robust correlations, it ...is unclear whether family income is the cause of differences observed between children growing up in poverty and their more fortunate peers or whether these differences are merely due to the many other aspects of family life that co-occur with poverty. Baby's First Years is the first randomized controlled trial in the United States designed to identify the causal impact of poverty reduction on children's early development. A total of 1000 low-income mothers of newborns were enrolled in the study and began receiving a monthly unconditional cash gift for the first several years of their children's lives. Mothers were randomly assigned to receive either a large monthly cash gift or a nominal monthly cash gift. All monthly gifts are administered via debit card and can be freely spent with no restrictions. Baby's First Years aims to answer whether poverty reduction in early childhood (1) improves children's developmental outcomes and promotes healthier brain functioning, and (2) improves family functioning and better enables parents to support child development. Here we present the rationale and design of the study as well as potential implications for science and policy.
Tuberculosis continues to be a global health challenge. In this report, active case finding was more than twice as likely as standard passive case finding to identify tuberculosis among household ...contacts of index patients with smear-positive disease.
While the safety and efficacy of inhaled budesonide-formoterol, used as-needed for symptoms, has been established for patients with asthma, it has not been trialed in undifferentiated patients with ...chronic respiratory diseases. We aimed to assess the feasibility of a pragmatic intervention that entails a stepped algorithm using inhaled budesonide-formoterol (dry powder inhaler, 160mug/4.5mug per dose) for patients presenting with chronic respiratory diseases to three rural district hospitals in Hanoi, Vietnam. We recruited patients with evidence of airflow obstruction on spirometry and/or symptoms consistent with asthma. The algorithm consisted of three steps: 1. as-needed inhaled budesonide-formoterol for symptoms, 2. maintenance plus as-needed inhaled budesonide-formoterol, and 3. referral to a higher-level healthcare facility. All participants started at step 1, with escalation to the next step at review visits if there had been exacerbation(s) or inadequate symptom control. Patients were followed for 12 months. Among 313 participants who started the treatment algorithm, 47.2% had greater than or equal to 1 episode of acute respiratory symptoms requiring a visit to hospital or clinic and 35.4% were diagnosed with an exacerbation. Twelve months after enrolment, 50.7% still adhered to inhaled budesonide-formoterol at the recommended treatment step. The mean and median number of doses per day was 1.5 (standard deviation 1.2) doses and 1.3 (interquartile range 0.7-2.3) doses, respectively. The proportion of patients taking more than 800mug budesonide per day was 3.8%. This novel therapeutic algorithm is feasible for patients with chronic respiratory diseases in a rural setting in Vietnam. Further studies are required to establish the effectiveness, safety and cost-effectiveness of similar approaches in different settings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Despite the criticality of adherence to tuberculosis treatment, there is paucity of rigorous experimental research exploring the efficacy of interventions to promote adherence and a greater lack of ...inquiry addressing the integral role of adherence behaviour. The aim of this formative study was to examine the way in which the Wisepill evriMED Medication Event Reminder Monitor (MERM) was used among outpatients with drug susceptible pulmonary tuberculosis.
In depth interviews were conducted with 20 outpatients receiving treatment from two public healthcare facilities in Thanh Hoa, a rural province in northern Viet Nam. Patients had been enrolled in a randomized controlled trial evaluating the effect of using the MERM device upon adherence for between 1-3 months. The control group used the device without an alert, while the intervention group used the device with a daily alert and scheduled dosing history review.
All 20 patients interviewed were supportive of using the MERM device. Those able to be at home at the time that their treatment was due (50%) used the device as intended. Patients who worked all reported separating the time when the box was opened from the time at which they ingested their medication. Patients expressed fidelity to the prescribed medication taking time and concerns regarding the portability of the device. Limitations of the study surround the inclusion of a small sample population that did not experience factors that further compromise adherence.
Data recorded by the box did not always accurately reflect usage patterns. The alert in the intervention arm was able to support adherence only in patients who did not work while completing their treatment. MERM implementation can be improved by better aligning prescriber instructions with patients' daily routines, and increasing the use of adherence data to guide adherence support practices. Healthcare staff need to be aware of potential barriers to optimal use of MERM devices. A rigorous qualitative approach to formative assessment is essential to inform the scale up of new digital technologies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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