The effect of medication event reminder monitoring on treatment adherence of TB patients.

BACKGROUND: TB control remains a serious public health problem, compounded by poor treatment adherence, which increases the likelihood of onward transmission. We evaluated the effectiveness of medication event reminder monitoring (MERM) upon treatment adherence in a high TB burden setting.METHODS: We conducted an open-label parallel group randomised controlled trial among pulmonary TB adults. Participants were provided with a MERM device to store their medications. In the intervention arm, the devices were set to provide daily medication intake reminders. Primary outcome was the proportion of patient-months in which at least 6/30 doses were missed. Secondary outcomes included 1) the proportion of patient-months in which at least 14/30 doses were missed, and 2) the proportion of doses missed.RESULTS: Of 2,142 patients screened, 798 (37.3%) met the inclusion criteria and 250 participants were enrolled. The mean ratio (MR) for poor adherence between the intervention and control groups was 0.72 (95% CI 0.55-0.86). The intervention was also associated with a reduction in the proportion of patients missing at least 14/30 doses (MR 0.61, 95% CI 0.54-0.68) and the percentage of total doses missed (MR 0.75, 95% CI 0.68-0.80).CONCLUSION: MERM is effective in improving TB treatment adherence in a resource-limited environment.

A scoping review of interventions to mitigate common non-communicable diseases among people with TB.

BACKGROUND: Recommendations have been made to integrate screening for common non-communicable diseases (NCDs) within TB programs. However, we must ensure screening is tied to evidence-based interventions before scale-up. We aimed to map the existing evidence regarding interventions that address NCDs that most commonly affect people with TB.METHODS: We systematically searched PubMed, Medline, and Embase for studies that evaluated interventions to mitigate respiratory disease, cardiovascular disease, alcohol and substance use disorder, and mental health disorders among people with TB. We excluded studies that only screened for comorbidity but resulted in no further intervention. We also excluded studies focusing on smoking cessation interventions for which evidence-based guidelines are well established.RESULTS: The search identified 20 studies that met our inclusion criteria. The most commonly evaluated intervention was referral for diabetes care (6 studies). Other interventions included pulmonary rehabilitation (5 studies), care programs for alcohol use disorder (4 studies), and psychosocial support or individual counselling (5 studies).CONCLUSION: There is limited robust evidence to support identified interventions in changing individual outcomes, and a significant knowledge gap remains on the long-term durability of the interventions´ clinical benefit, reach, and effectiveness. Implementation research demonstrating feasibility and effectiveness is needed before scaling up.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

Risk factors for TB in Australia and their association with delayed treatment completion.

BACKGROUND: Australia has a low incidence of TB and has committed to eliminating the disease. Identification of risk factors associated with TB is critical to achieving this goal.METHODS: We undertook a prospective cohort study involving persons receiving TB treatment in four Australian jurisdictions. Risk factors and their association with delayed treatment completion (treatment delayed by at least 1 month) were analysed using univariate analyses and multivariate logistic regression.RESULTS: Baseline surveys were completed for 402 persons with TB. Most (86.1%) were born overseas. Exposure to a person with TB was reported by 19.4%. Diabetes mellitus (10.2%), homelessness (9.2%), cigarette smoking (8.7%), excess alcohol consumption (6.0%) and mental illness (6.2%) were other common risk factors. At follow-up, 24.8% of patients had delayed treatment completion, which was associated with adverse events (34.1%, aOR 6.67, 95% CI 3.36-13.27), excess alcohol consumption (6.0%, aOR 21.94, 95% CI 6.03-79.85) and HIV co-infection (2.7%, aOR 8.10, 95% CI 1.16-56.60).CONCLUSIONS: We identified risk factors for TB and their association with delayed treatment completion, not all of which are routinely collected for surveillance purposes. Recognition of these risk factors should facilitate patient-centred care and assist Australia in reaching TB elimination.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Depression, stigma and quality of life in people with drug-susceptible TB and drug-resistant TB in Vietnam.

BACKGROUND: Drug resistance poses a major barrier to global control of TB - a leading infectious cause of death. Depression and stigma occur commonly among people with TB. However, the relationship between drug-resistant forms of TB, depression and stigma are not well understood.OBJECTIVE: To compare depression, stigma and health-related quality of life (HRQoL), among people with drug-susceptible TB (DS-TB) and multidrug-resistant TB (MDR-TB).METHODS: A cross-sectional study of people treated for DS-TB and MDR-TB in four provinces of Vietnam. The survey included a stigma scale (Vietnamese Tuberculosis Stigma Scale), depression scale (9-item Patient Health Questionnaire) and HRQoL scale (Functional Assessment of Chronic Illness Therapy - Tuberculosis). Differences between the two populations were compared using linear regression.RESULTS: Eighty-one people with DS-TB and 315 people with MDR-TB participated in the study. People with MDR-TB had a higher prevalence of depression than those with DS-TB (difference 17.8%, χ² 8.64). The mean depression and stigma scores were higher for people with MDR-TB than those with DS-TB (adjusted difference [AD] 8.6 and 7.6 respectively). People with MDR-TB reported lower HRQoL than those with DS-TB (AD -23.8).CONCLUSION: Depression and stigma are common among people with TB in Vietnam. Strategies to prevent and treat depressive symptoms and stigma in people with TB are critical to a holistic, patient-centred approach to care.

Active case-finding in contacts of people with TB.

BACKGROUND: Exposure to people with TB substantially elevates a person's risk of tuberculous infection and TB disease. Systematic screening of TB contacts enables the early detection and treatment of co-prevalent disease, and the opportunity to prevent future TB disease. However, scale-up of contact investigation in high TB transmission settings remains limited.METHODS: We undertook a narrative review to evaluate the evidence for contact investigation and identify strategies that TB programmes may consider when introducing contact investigation and management.RESULTS: Selection of contacts for priority screening depends upon their proximity and duration of exposure, along with their susceptibility to develop TB. Screening algorithms can be tailored to the target population, the availability of diagnostic tests and preventive therapy, and healthcare worker expertise. Contact investigation may be performed in the household or at communal locations. Local contact investigation policies should support vulnerable patients, and ensure that drop-out during screening can be mitigated. Ethical issues should be anticipated and addressed in each setting.CONCLUSION: Contact investigation is an important strategy for TB elimination. While its epidemiological impact will be greatest in lower-transmission settings, the early detection and prevention of TB have important benefits for contacts and their communities.

Determining the value of TB active case-finding: current evidence and methodological considerations.

Active case-finding (ACF) is an important component of the End TB Strategy. However, ACF is resource-intensive, and the economics of ACF are not well-understood. Data on the costs of ACF are limited, with little consistency in the units and methods used to estimate and report costs. Mathematical models to forecast the long-term effects of ACF require empirical measurements of the yield, timing and costs of case detection. Pragmatic trials offer an opportunity to assess the cost-effectiveness of ACF interventions within a 'real-world´ context. However, such analyses generally require early introduction of economic evaluations to enable prospective data collection on resource requirements. Closing the global case-detection gap will require substantial additional resources, including continued investment in innovative technologies. Research is essential to the optimal implementation, cost-effectiveness, and affordability of ACF in high-burden settings. To assess the value of ACF, we must prioritize the collection of high-quality data regarding costs and effectiveness, and link those data to analytical models that are adapted to local settings.

No Venous Thromboembolism Increase Among Transgender Female Patients Remaining on Estrogen for Gender-Affirming Surgery.

BACKGROUND: Both surgery and exogenous estrogen use are associated with increased risk of venous thromboembolism (VTE). However, it is not known whether estrogen hormone therapy (HT) exacerbates the surgery-associated risk among transgender and gender nonbinary (TGNB) individuals. The lack of published data has contributed to heterogeneity in perioperative protocols regarding estrogen HT administration for TGNB patients undergoing gender-affirming surgery. METHODS: A single-center retrospective chart review was performed on all TGNB patients who underwent gender-affirming surgery between November 2015 and August 2019. Surgery type, preoperative HT regimen, perioperative HT regimen, VTE prophylaxis management, outcomes, and demographic data were recorded. RESULTS: A total of 919 TGNB patients underwent 1858 surgical procedures representing 1396 unique cases, of which 407 cases were transfeminine patients undergoing primary vaginoplasty. Of the latter, 190 cases were performed with estrogen suspended for 1 week prior to surgery, and 212 cases were performed with HT continued throughout. Of all cases, 1 patient presented with VTE, from the cohort of transfeminine patients whose estrogen HT was suspended prior to surgery. No VTE events were noted among those who continued HT. Mean postoperative follow-up was 285 days. CONCLUSIONS: Perioperative VTE was not a significant risk in a large, homogenously treated cohort of TGNB patients independent of whether HT was suspended or not prior to surgery.

Ototoxicity among multidrug-resistant TB patients: a systematic review and meta-analysis.

BACKGROUND: The use of injectable antibiotics to treat multidrug-resistant TB (MDR-TB) is associated with substantial morbidity due to long-term hearing loss. This systematic review evaluates the incidence of ototoxicity among patients treated for MDR-TB, and the evidence for routine audiometric monitoring to mitigate its severity.METHODS: Studies of ototoxicity among patients with MDR-TB were identified from six databases: PubMed, MEDLINE, Web of Science, Embase, SCOPUS and the Cochrane Library. Meta-analyses were performed to determine the overall incidence of hearing loss, tinnitus and vertigo. The incidence of hearing loss was further stratified by country income status and the injectable agent used during treatment.RESULTS: Among 64 studies from 25 countries including 12 793 patients, 28.3% (95%CI 23.4-33.1) of patients treated with injectables reported hearing loss. Tinnitus and vertigo were experienced by respectively 14.5% (95%CI 10.3-18.7) and 8.1% (95%CI 4.7-11.6) of patients. The incidence of hearing loss was highest among patients treated with amikacin (33.4%, 95%CI 18.2-48.6), and lowest among those treated with capreomycin (2.0%, 95%CI 0-5.5). We found that audiometry was widely used as a method of evaluating hearing loss, and was feasible in a wide range of settings.CONCLUSION: Injectable antibiotics contribute to significant morbidity in patients with MDR-TB. In settings where they are used, routine audiometric monitoring is recommended to prevent irreversible damage.

A comparison of digital chest radiography and Xpert® MTB/RIF in active case finding for tuberculosis.

OBJECTIVE: To compare two community screening tests for TB: sputum examination using Xpert® MTB/RIF and chest radiography (CXR).METHOD: Men aged ≥15 years and women aged >45 years living in 96 sub-communes in Ca Mau, Viet Nam, were invited to provide a single sputum specimen that was tested using Xpert. Participants were also invited to attend a nearby location for digital radiography. Participants whose sputum was Xpert MTB-positive or whose CXR was reported as 'consistent with TB´ were requested to provide two further sputum specimens for culture. The sensitivities of the two tests for detecting TB (defined as sputum culture-positive for Mycobacterium tuberculosis) were compared.RESULTS: There were 72 985 eligible participants, of whom 57 597 (78.9%) participated in Xpert screening, 12 752 (17.5%) had CXR and 11 235 (15.4%) had both tests. We estimated that there were 59 cases of TB, of whom 20 were Xpert MTB-positive (programmatic sensitivity 34.0%) and 47 had CXR reported as 'consistent with TB´ (sensitivity 80.0%, P < 0.0001).CONCLUSION: In community-wide screening for TB, CXR is more sensitive than a single spontaneously expectorated sputum sample tested using Xpert, but it has a substantially lower participation rate.

Resource implications of the latent tuberculosis cascade of care: a time and motion study in five countries.

BACKGROUND: The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients. METHODS: We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step. RESULTS: A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6-16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2-9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana. CONCLUSIONS: Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.

An assessment of current tuberculosis patient care and support policies in high-burden countries.

CONTEXT: Adherence to treatment for tuberculosis (TB) is an important predictor of treatment outcomes. The World Health Organization guidelines recommend a patient-centred approach to adherence support; however, the extent to which policies in high-burden countries facilitate this approach remains uncertain.DESIGN: A cross-sectional survey of current national patient care and support policies in high TB burden countries was performed.RESULT: Responses were provided by TB care programmes in 23 of the 30 high TB burden countries, comprising 77.4% of TB cases globally. Clinic-based and household adherence support and patient education were recommended in all countries, while policies for digital technologies and social supports have been adopted in a small minority of countries. Financial or material support (such as reimbursement for transportation) and psychological support to patients-if included in the policies-was mainly recommended only for specific sub-groups of patients.CONCLUSION: National policies in many countries have not yet fully adopted global recommendations for patient care and support. Further scale-up of evidence-based approaches to care is required to improve quality of care for patients in high TB burden settings.

PROMIS Physical Function 10-Item Short Form for Older Adults in an Emergency Setting.

BACKGROUND: Functional status in older adults predicts hospital use and mortality, and offers insight into independence and quality of life. The Patient-Reported Outcome Measurement Information System (PROMIS) was developed to improve and standardize patient-reported outcomes measurements. The PROMIS Physical Function (PROMIS PF) 10-Item Short Form was not created specifically for older adults. By comparing PROMIS with the Katz Index of Activities of Daily Living (Katz), we evaluated PROMIS for measurement of physical function versus general function in an older adult population seen in the ED. METHODS: A prospective, convenience sample of ED patients 65 years and older (from January 1, 2015 to June 30, 2015) completed Katz and PROMIS PF. Both were compared for scoring distributions and conventional scoring thresholds for severity of impairment (eg, minimal, moderate, severe). We assessed convergence through Spearman correlations, equivalents of conventional thresholds and ranges of physical function, and item-response frequencies. RESULTS: A total of 357 completed both function surveys. PROMIS PF and Katz have a modest positive correlation (r = .50, p < .01). Mean PROMIS PF scores within Katz scoring ranges for minimal (43, SD = 10), moderate (32, SD = 7), and severe (24, SD = 7) impairment fell within respective PROMIS PF scoring ranges (severe = 14-29, moderate = 30-39, mild = 40-45), indicating convergence. PROMIS identified impairment in 3× as many patients as did Katz, as PROMIS assesses vigorous physical function (eg, running, heavy lifting) not queried by Katz. However, PROMIS does not assess select activities of daily living (ADLs; eg, feeding, continence) important for assessment of function in older adults. CONCLUSIONS: There is a modest correlation between PROMIS and Katz. PROMIS may better assess physical function than Katz, but is not an adequate replacement for assessment of general functional status in older adults.