Estimating Post-treatment Recurrence After Multidrug-Resistant Tuberculosis Treatment Among Patients With and Without Human Immunodeficiency Virus: The Impact of Assumptions About Death and Missing Follow-up.

BACKGROUND: Quantification of recurrence risk following successful treatment is crucial to evaluating regimens for multidrug- or rifampicin-resistant (MDR/RR) tuberculosis (TB). However, such analyses are complicated when some patients die or become lost during post-treatment follow-up. METHODS: We analyzed data on 1991 patients who successfully completed a longer MDR/RR-TB regimen containing bedaquiline and/or delamanid between 2015 and 2018 in 16 countries. Using 5 approaches for handling post-treatment deaths, we estimated 6-month post-treatment TB recurrence risk overall and by HIV status. We used inverse-probability weighting to account for patients with missing follow-up and investigated the impact of potential bias from excluding these patients without applying inverse-probability weights. RESULTS: The estimated TB recurrence risk was 7.4/1000 (95% credible interval: 3.3-12.8) when deaths were handled as non-recurrences and 7.6/1000 (3.3-13.0) when deaths were censored and inverse-probability weights were applied to account for the excluded deaths. The estimated risks of composite recurrence outcomes were 25.5 (15.3-38.1), 11.7 (6.4-18.2), and 8.6 (4.1-14.4) per 1000 for recurrence or (1) any death, (2) death with unknown or TB-related cause, or (3) TB-related death, respectively. Corresponding relative risks for HIV status varied in direction and magnitude. Exclusion of patients with missing follow-up without inverse-probability weighting had a small impact on estimates. CONCLUSIONS: The estimated 6-month TB recurrence risk was low, and the association with HIV status was inconclusive due to few recurrence events. Estimation of post-treatment recurrence will be enhanced by explicit assumptions about deaths and appropriate adjustment for missing follow-up data.

Pregnancy and Birth Outcomes in Patients With Multidrug-Resistant Tuberculosis Treated With Regimens That Include New and Repurposed Drugs.

Among 43 pregnant women receiving multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment with bedaquiline and/or delamanid, 98% had favorable treatment outcomes. Of 31 continued pregnancies, 81% had live births with no reported malformations, and 68% of neonates had normal birth weights. Effective MDR/RR-TB treatment during pregnancy can improve maternal outcomes without harming neonates.

Effectiveness of Bedaquiline Use beyond Six Months in Patients with Multidrug-Resistant Tuberculosis.

Rationale: Current recommendations for the treatment of rifampicin- and multidrug-resistant tuberculosis include bedaquiline (BDQ) used for 6 months or longer. Evidence is needed to inform the optimal duration of BDQ. Objectives: We emulated a target trial to estimate the effect of three BDQ duration treatment strategies (6, 7-11, and ⩾12 mo) on the probability of successful treatment among patients receiving a longer individualized regimen for multidrug-resistant tuberculosis. Methods: To estimate the probability of successful treatment, we implemented a three-step approach comprising cloning, censoring, and inverse probability weighting. Measurements and Main Results: The 1,468 eligible individuals received a median of 4 (interquartile range, 4-5) likely effective drugs. In 87.1% and 77.7% of participants, this included linezolid and clofazimine, respectively. The adjusted probability of successful treatment was 0.85 (95% confidence interval [CI], 0.81-0.88) for 6 months of BDQ, 0.77 (95% CI, 0.73-0.81) for 7-11 months, and 0.86 (95% CI, 0.83-0.88) for ⩾12 months. Compared with 6 months of BDQ, the ratio of treatment success was 0.91 (95% CI, 0.85-0.96) for 7-11 months and 1.01 (95% CI, 0.96-1.06) for ⩾12 months. Naive analyses that did not account for bias revealed a higher probability of successful treatment with ⩾12 months (ratio, 1.09 [95% CI, 1.05-1.14]). Conclusions: BDQ use beyond 6 months did not increase the probability of successful treatment among patients receiving longer regimens that commonly included new and repurposed drugs. When not properly accounted for, immortal person-time bias can influence estimates of the effects of treatment duration. Future analyses should explore the effect of treatment duration of BDQ and other drugs in subgroups with advanced disease and/or receiving less potent regimens.

Glycyrrhizin, an inhibitor of HMGB1 induces autolysosomal degradation function and inhibits Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori is a key agent for causing gastric complications linked with gastric disorders. In response to infection, host cells stimulate autophagy to maintain cellular homeostasis. However, H. pylori have evolved the ability to usurp the host's autophagic machinery. High mobility group box1 (HMGB1), an alarmin molecule is a regulator of autophagy and its expression is augmented during infection and gastric cancer. Therefore, this study aims to explore the role of glycyrrhizin (a known inhibitor of HMGB1) in autophagy during H. pylori infection. MAIN METHODS: Human gastric cancer (AGS) cells were infected with the H. pylori SS1 strain and further treatment was done with glycyrrhizin. Western blot was used to examine the expression of autophagy proteins. Autophagy and lysosomal activity were monitored by fluorescence assays. A knockdown of HMGB1 was performed to verify the effect of glycyrrhizin. H. pylori infection in in vivo mice model was established and the effect of glycyrrhizin treatment was studied. RESULTS: The autophagy-lysosomal pathway was impaired due to an increase in lysosomal membrane permeabilization during H. pylori infection in AGS cells. Subsequently, glycyrrhizin treatment restored the lysosomal membrane integrity. The recovered lysosomal function enhanced autolysosome formation and concomitantly attenuated the intracellular H. pylori growth by eliminating the pathogenic niche. Additionally, glycyrrhizin treatment inhibited inflammation and improved gastric tissue damage in mice. CONCLUSION: This study showed that inhibiting HMGB1 restored lysosomal activity to ameliorate H. pylori infection. It also demonstrated the potential of glycyrrhizin as an antibacterial agent to address the problem of antimicrobial resistance.

Hepatitis C prevalence and elimination planning in Pakistan, a bottom-up approach accounting for provincial variation.

In Pakistan, substantial changes to hepatitis C virus (HCV) programming and treatment have occurred since the 2008 nationwide serosurvey estimated a 4.8% anti-HCV prevalence. In the absence of an updated national study, this analysis uses provincial data to estimate a national prevalence and the interventions needed to achieve elimination. Using a Delphi process, epidemiologic HCV data for the four provinces of Pakistan (accounting for 97% of the population) were reviewed with 21 subject-matter experts in Pakistan. Province-level estimates were inputted into a mathematical model to estimate the national HCV disease burden in the absence of intervention (Base), and if the World Health Organization (WHO) elimination targets are achieved by 2030 (80% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage, and 65% reduction in mortality: WHO Elimination). An estimated 9,746,000 (7,573,000-10,006,000) Pakistanis were living with viraemic HCV as of January 1, 2021; a viraemic prevalence of 4.3% (3.3-4.4). WHO Elimination would require an annual average of 18.8 million screens, 1.1 million treatments, and 46,700 new infections prevented anually between 2022 and 2030. Elimination would reduce total infections by 7,045,000, save 152,000 lives and prevent 104,000 incident cases of hepatocellular carcinoma from 2015 to 2030. Blood surveys, programmatic data, and expert panel input uncovered more HCV infections and lower treatment numbers in the provinces than estimated using national extrapolations, demonstrating the benefits of a bottom-up approach. Screening and treatment must increase 20 times and 5 times, respectively, to curb the HCV epidemic in Pakistan and achieve elimination by 2030.

Risk-taking propensity as a risk factor for noise-induced hearing loss in the general population.

OBJECTIVES: To examine general risk propensity in relation to perceptions of noise, risk behaviour, and hearing loss in the general population. DESIGN: Participants completed an online survey using the Amazon Mechanical Turk crowdsourcing platform. STUDY SAMPLE: The sample comprised 1274 adults from the United States. RESULTS: Higher general risk propensity was associated with an increased likelihood to engage in noise-risk behaviours. Lower general risk propensity was associated with increased knowledge of noise risks and an increased perception of noise as risky. The frequency of self-reported exposures to hazardous noise resulted in estimated annual noise doses exceeding standard hazard limits in 40% of the surveyed population. CONCLUSIONS: Results revealed limited knowledge of the risks and associated health consequences of noise exposure in the general population Results of this study suggest a high rate of self-exposure to hazardous noise by the general population. Those with higher general risk propensity are more likely to engage in risky noise behaviour. Risky noise behaviour is associated with age, gender, race, ethnicity, and general risk propensity. Intervention programs to modify risky noise behaviour in the general population should focus on both increasing knowledge and establishing accurate perceptions of risk.

Predicting suicide attempts among people with diabetes using a large multicenter electronic health records dataset.

OBJECTIVE: People with diabetes have a higher risk of suicidal behaviors than the general population. However, few studies have focused on understanding this relationship. We investigated risk factors and predicted suicide attempts in people with diabetes using Least Absolute Shrinkage and Selection Operator (LASSO) regression. METHOD: Data was retrieved from Cerner Real-World Data and included over 3 million diabetes patients in the study. LASSO regression was applied to identify associated factors. Gender, diabetes-type, and depression-specific LASSO regression models were analyzed. RESULTS: There were 7764 subjects diagnosed with suicide attempts with an average age of 45. Risk factors for suicide attempts in diabetes patients were American Indian or Alaska Native race (ß = 0.637), receiving atypical antipsychotic agents (ß = 0.704), benzodiazepines (ß = 0.784), or antihistamines (ß = 0.528). Amyotrophy was negatively associated with suicide attempts in males (ß = 2.025); in contrast, amyotrophy significantly increased the risk in females (ß = 3.339). Using a MAOI was negatively related to suicide attempts in T1DM patients (ß = 7.304). Age less than 20 was positively associated with suicide attempts in depressed (ß = 2.093) and non-depressed patients (ß = 1.497). The LASSO model achieved a 94.4% AUC and 87.4% F1 score. CONCLUSIONS: To our knowledge, this is the first study to use LASSO regression to identify risk factors for suicide attempts in patients with diabetes. The shrinkage technique successfully reduced the number of variables in the model to improve the fit. Further research is needed to determine cause-and-effect relationships. The results may help providers to identify high-risk groups for suicide attempt among diabetic patients.

Correlates of poor clinical outcomes related to COVID-19 among older people with psychiatric illness - a mixed methods study.

OBJECTIVE: COVID-19 may lead to a range of clinical outcomes among older people with psychiatric and medical conditions. Evidence guiding management of future outbreaks among this vulnerable population in psychiatric hospital settings are sparse. In this study, we examined the correlates of poor clinical outcomes related to COVID-19 and explored the perspectives of COVID-19 survivors hospitalized in psychiatry settings. METHOD: The correlates of poor clinical outcomes related to COVID-19 were examined using a retrospective chart review of 81 older people hospitalized in psychiatry settings. Correlates of clinical outcomes related to COVID-19 were assessed by multiple logistic regression models. In addition, the perspectives of 10 COVID-19 survivors were explored by qualitative interviews. The qualitative data was subject to thematic analysis. RESULTS: Although 25.9% (n = 21) participants were asymptomatic, there was high COVID-19 related mortality (14.8%; n = 12). Vitamin-D deficiency, anticholinergic burden, and isolation policies within psychiatric wards were significantly (p < 0.05) related to COVID-19 related deaths. In qualitative interviews, participants emphasized the importance of strengthening local support networks and making vaccination centers more accessible. CONCLUSIONS: Reducing anticholinergic prescriptions and improving isolation policies may help to mitigate poor clinical outcomes. Future research investigating the impact of vitamin-D supplementation on COVID-19 related outcomes is warranted.

Improvement in the diagnosis and practices of emergency healthcare providers for heat emergencies after HEAT (heat emergency awareness & treatment) an educational intervention: a multicenter quasi-experimental study.

BACKGROUND: The incidence of heat emergencies, including heat stroke and heat exhaustion, have increased recently due to climate change. This has affected global health and has become an issue of consideration for human health and well-being. Due to overlapping clinical manifestations with other diseases, and most of these emergencies occurring in an elderly patient, patients with a comorbid condition, or patients on poly medicine, diagnosing and managing them in the emergency department can be challenging. This study assessed whether an educational training on heat emergencies, defined as heat intervention in our study, could improve the diagnosis and management practices of ED healthcare providers in the ED setting. METHODS: A quasi-experimental study was conducted in the EDs of four hospitals in Karachi, Pakistan. Eight thousand two hundred three (8203) patients were enrolled at the ED triage based on symptoms of heat emergencies. The pre-intervention data were collected from May to July 2017, while the post-intervention data were collected from May to July 2018. The HEAT intervention, consisting of educational activities targeted toward ED healthcare providers, was implemented in April 2018. The outcomes assessed were improved recognition-measured by increased frequency of diagnosing heat emergencies and improved management-measured by increased temperature monitoring, external cooling measures, and intravenous fluids in the post-intervention period compared to pre-intervention. RESULTS: Four thousand one hundred eighty-two patients were enrolled in the pre-intervention period and 4022 in the post-intervention period, with at least one symptom falling under the criteria for diagnosis of a heat emergency. The diagnosis rate improved from 3% (n = 125/4181) to 7.5% (n = 7.5/4022) (p-value < 0.001), temperature monitoring improved from 0.9% (n = 41/4181) to 13% (n = 496/4022) (p-value < 0.001) and external cooling measure (water sponging) improved from 1.3% (n = 89/4181) to 3.4% (n = 210/4022) (p-value < 0.001) after the administration of the HEAT intervention. CONCLUSION: The HEAT intervention in our study improved ED healthcare providers' approach towards diagnosis and management practices of patients presenting with health emergencies (heat stroke or heat exhaustion) in the ED setting. The findings support the case of training ED healthcare providers to address emerging health issues due to rising temperatures/ climate change using standardized treatment algorithms.

Brand loyalty in the face of stockouts.

An important managerial challenge is understanding consumers' reactions to stockouts of a desired product-will they stay brand loyal or switch to competing brands? We posit that consumers are more likely to prefer substitutes from the same brand when a stockout is unexpected (vs. expected). This tendency arises as consumers feel greater negative affect upon encountering an unexpected stockout, which leads them to choose alternatives that provide greater affective value to ameliorate their negative feelings. Since the brand is a relatively affect-rich attribute compared to common non-brand attributes (e.g., price and quantity), consumers facing an unexpected stockout are more likely to choose a same-brand substitute. Five studies illustrate the effect and support the process by demonstrating that unexpected stockouts do not result in brand loyalty when non-brand attributes offer greater affective value than the brand. We further show that managers systematically mispredict how consumers' expectations of stockouts relate to brand loyalty. Supplementary Information: The online version contains supplementary material available at 10.1007/s11747-023-00924-8.

Workplace Violence and Bullying Faced by Health Care Personnel at the Emergency Department of a Tertiary Care Hospital of Karachi, Pakistan: A Cross-Sectional Study.

INTRODUCTION: The emergency department is the most affected by physical and verbal abuse and bullying in health care. Violence against health care workers not only affects their safety, but also their performance and motivation. This study aimed to determine the prevalence and associated determinants of violence against health care personnel. METHODS: A cross-sectional study design was used with 182 health care personnel at the emergency department tertiary care hospital of Karachi, Pakistan. Data were collected through a questionnaire comprised of 2 sections: (1) demographic questions and (2) statements to identify the prevalence of workplace violence and bullying among health care personnel. Nonprobability purposive sampling was used for recruitment. Binary logistic regression was used to identify the prevalence and determinants of violence and bullying. RESULTS: Most participants were younger than 40 years of age (n = 106, 58.2%). Participants were mainly nurses (n = 105, 57.7%) and physicians (n = 31, 17.0%). Participants reported experiencing sexual abuse (n = 5, 2.7%), physical violence (n = 30, 16.50%), verbal abuse (n = 107, 58.8%), and bullying (n = 49, 26.9%). The odds of experiencing physical violence were 3.7 times greater (confidence interval = 1.6-9.2) when there was not a procedure for reporting workplace violence compared to when there was a procedure. DISCUSSION: Attention is required to identify the prevalence of workplace violence. Creating effective policies and procedures for a reporting system would potentially lead to lowering violence rates and positively impacting health care workers' well-being.

Chlorine gas hazardous material incident in Karachi, Pakistan: A clinical experience from an emergency department of a tertiary care hospital.

OBJECTIVE: To determine the clinical characteristics, management and outcomes of patients presenting with chlorine gas exposure in an emergency setting. METHODS: The single-centre, retrospective cross-sectional study was conducted at the emergency department of Aga Khan University Hospital, Karachi, and comprised data of all patients who presented on March 06, 2020, due to acute chlorine gas exposure after a specific industrial accident. Demographic and clinical data was recorded from the medical record files. The association between risk factors and complications was explored. Data was analysed using SPSS 20. RESULTS: There were 51 male patients with a mean age of 33.10±8.37 years. The most commonly affected organ system was respiratory 49(96%), with 43(84.3) having shortness of breath. Eye irritation was found in 44(86.3%) cases and the central nervous system was involved in 14(27.4%). Most of the patients were admitted from the emergency department 36(70%). Regarding treatment, 1(1.9%) patient each required invasive and non-invasive mechanical ventilation. Complications included toxic pneumonitis 3(5.9%) and pneumomediastinum 1(1.7%). No correlation was found between smoking and complications (p>0.05). CONCLUSIONS: Most patients showed complete resolution of symptoms after receiving supportive treatment, while complications were rare and there was no mortality.

Safety of Treatment Regimens Containing Bedaquiline and Delamanid in the endTB Cohort.

BACKGROUND: Safety of treatment for multidrug-resistant tuberculosis (MDR/RR-TB) can be an obstacle to treatment completion. Evaluate safety of longer MDR/RR-TB regimens containing bedaquiline and/or delamanid. METHODS: Multicentre (16 countries), prospective, observational study reporting incidence and frequency of clinically relevant adverse events of special interest (AESIs) among patients who received MDR/RR-TB treatment containing bedaquiline and/or delamanid. The AESIs were defined a priori as important events caused by bedaquiline, delamanid, linezolid, injectables, and other commonly used drugs. Occurrence of these events was also reported by exposure to the likely causative agent. RESULTS: Among 2296 patients, the most common clinically relevant AESIs were peripheral neuropathy (26.4%), electrolyte depletion (26.0%), and hearing loss (13.2%) with an incidence per 1000 person months of treatment, 1000 person-months of treatment 21.5 (95% confidence interval [CI]: 19.8-23.2), 20.7 (95% CI: 19.1-22.4), and 9.7 (95% CI: 8.6-10.8), respectively. QT interval was prolonged in 2.7% or 1.8 (95% CI: 1.4-2.3)/1000 person-months of treatment. Patients receiving injectables (N = 925) and linezolid (N = 1826) were most likely to experience events during exposure. Hearing loss, acute renal failure, or electrolyte depletion occurred in 36.8% or 72.8 (95% CI: 66.0-80.0) times/1000 person-months of injectable drug exposure. Peripheral neuropathy, optic neuritis, and/or myelosuppression occurred in 27.8% or 22.8 (95% CI: 20.9-24.8) times/1000 patient-months of linezolid exposure. CONCLUSIONS: AEs often related to linezolid and injectable drugs were more common than those frequently attributed to bedaquiline and delamanid. MDR-TB treatment monitoring and drug durations should reflect expected safety profiles of drug combinations. CLINICAL TRIALS REGISTRATION: NCT02754765.

Safety and Effectiveness Outcomes From a 14-Country Cohort of Patients With Multi-Drug Resistant Tuberculosis Treated Concomitantly With Bedaquiline, Delamanid, and Other Second-Line Drugs.

BACKGROUND: Concomitant use of bedaquiline (Bdq) and delamanid (Dlm) for multi-drug/rifampicin resistant tuberculosis (MDR/RR-TB) has raised concerns about a potentially poor risk-benefit ratio. Yet this combination is an important alternative for patients infected with strains of TB with complex drug resistance profiles or who cannot tolerate other therapies. We assessed safety and treatment outcomes of MDR/RR-TB patients receiving concomitant Bdq and Dlm, along with other second-line anti-TB drugs. METHODS: We conducted a multi-centric, prospective observational cohort study across 14 countries among patients receiving concomitant Bdq-Dlm treatment. Patients were recruited between April 2015 and September 2018 and were followed until the end of treatment. All serious adverse events and adverse events of special interest (AESI), leading to a treatment change, or judged significant by a clinician, were systematically monitored and documented. RESULTS: Overall, 472 patients received Bdq and Dlm concomitantly. A large majority also received linezolid (89.6%) and clofazimine (84.5%). Nearly all (90.3%) had extensive disease; most (74.2%) had resistance to fluoroquinolones. The most common AESI were peripheral neuropathy (134, 28.4%) and electrolyte depletion (94, 19.9%). Acute kidney injury and myelosuppression were seen in 40 (8.5%) and 24 (5.1%) of patients, respectively. QT prolongation occurred in 7 patients (1.5%). Overall, 78.0% (358/458) had successful treatment outcomes, 8.9% died, and 7.2% experienced treatment failure. CONCLUSIONS: Concomitant use of Bdq and Dlm, along with linezolid and clofazimine, is safe and effective for MDR/RR-TB patients with extensive disease. Using these drugs concomitantly is a good therapeutic option for patients with resistance to many anti-TB drugs.

All-oral longer regimens are effective for the management of multidrug-resistant tuberculosis in high-burden settings.

BACKGROUND: Recent World Health Organization guidance on drug-resistant tuberculosis treatment de-prioritised injectable agents, in use for decades, and endorsed all-oral longer regimens. However, questions remain about the role of the injectable agent, particularly in the context of regimens using new and repurposed drugs. We compared the effectiveness of an injectable-containing regimen to that of an all-oral regimen among patients with drug-resistant tuberculosis who received bedaquiline and/or delamanid as part of their multidrug regimen. METHODS: Patients with a positive baseline culture were included. 6-month culture conversion was defined as two consecutive negative cultures collected >15 days apart. We derived predicted probabilities of culture conversion and relative risk using marginal standardisation methods. RESULTS: Culture conversion was observed in 83.8% (526 out of 628) of patients receiving an all-oral regimen and 85.5% (425 out of 497) of those receiving an injectable-containing regimen. The adjusted relative risk comparing injectable-containing regimens to all-oral regimens was 0.96 (95% CI 0.88-1.04). We found very weak evidence of effect modification by HIV status: among patients living with HIV, there was a small increase in the frequency of conversion among those receiving an injectable-containing regimen, relative to an all-oral regimen, which was not apparent in HIV-negative patients. CONCLUSIONS: Among individuals receiving bedaquiline and/or delamanid as part of a multidrug regimen for drug-resistant tuberculosis, there was no significant difference between those who received an injectable and those who did not regarding culture conversion within 6 months. The potential contribution of injectable agents in the treatment of drug-resistant tuberculosis among those who were HIV positive requires further study.

Barriers to breast cancer screening in Atlanta, GA: results from the Pink Panel survey at faith-based institutions.

PURPOSE: Our research sought to describe barriers to mammography screening among a sample of predominantly Black women in metropolitan Atlanta, Georgia. METHODS: The Pink Panel project convened community leaders from faith-based institutions to administer an offline survey to women via convenience sampling at fourteen churches in Atlanta in late 2019 and early 2020. With the COVID-19 pandemic, the research team switched to an online survey. The survey included seven questions about breast cancer awareness, barriers to breast cancer screening, and screening status. We used residence information to attain the 9-digit zip code to link to the Area Deprivation Index at the Census Block Group neighborhood level. We report results as descriptive statistics of the barriers to mammography screening. RESULTS: The 643 women represented 21 counties in Georgia, predominantly from metropolitan Atlanta, and 86% identified as Black. Among women aged 40 and older, 90% have ever had a mammogram. Among all women, 79% have ever had a mammogram, and 86% indicated that they would get a mammogram if offered in their neighborhood. The top barriers to mammography screening were lack of health insurance and high cost. Barriers to mammography screening did not differ substantially by Area Deprivation Index. CONCLUSION: Among metropolitan Atlanta women aged 40+ , nearly all reported ever having a mammogram. However, addressing the barriers, including lack of health insurance and high cost, that women reported may further improve mammography screening rates.

Culture Conversion in Patients Treated with Bedaquiline and/or Delamanid. A Prospective Multicountry Study.

Rationale: Bedaquiline and delamanid offer the possibility of more effective and less toxic treatment for multidrug-resistant (MDR) tuberculosis (TB). With this treatment, however, some patients remain at high risk for an unfavorable treatment outcome. The endTB Observational Study is the largest multicountry cohort of patients with rifampin-resistant TB or MDR-TB treated in routine care with delamanid- and/or bedaquiline-containing regimens according to World Health Organization guidance.Objectives: We report the frequency of sputum culture conversion within 6 months of treatment initiation and the risk factors for nonconversion.Methods: We included patients with a positive baseline culture who initiated a first endTB regimen before April 2018. Two consecutive negative cultures collected 15 days or more apart constituted culture conversion. We used generalized mixed models to derive marginal predictions for the probability of culture conversion in key subgroups.Measurements and Main Results: A total of 1,109 patients initiated a multidrug treatment containing bedaquiline (63%), delamanid (27%), or both (10%). Of these, 939 (85%) experienced culture conversion within 6 months. In adjusted analyses, patients with HIV had a lower probability of conversion (0.73; 95% confidence interval [CI], 0.62-0.84) than patients without HIV (0.84; 95% CI, 0.79-0.90; P = 0.03). Patients with both cavitary disease and highly positive sputum smear had a lower probability of conversion (0.68; 95% CI, 0.57-0.79) relative to patients without either (0.89; 95% CI, 0.84-0.95; P = 0.0004). Hepatitis C infection, diabetes mellitus or glucose intolerance, and baseline resistance were not associated with conversion.Conclusions: Frequent sputum conversion in patients with rifampin-resistant TB or MDR-TB who were treated with bedaquiline and/or delamanid underscores the need for urgent expanded access to these drugs. There is a need to optimize treatment for patients with HIV and extensive disease.

Out of hospital cardiac arrest: experience of a bystander CPR training program in Karachi, Pakistan.

BACKGROUND: Nearly 90% of out-of-hospital cardiac arrest (OHCA) patients are witnessed, yet only 2.3% received bystander cardiopulmonary resuscitation (CPR) in Pakistan. This study aimed to determine retention of knowledge and skills of Hands-Only CPR among community participants in early recognition of OHCA and initiation of CPR in Karachi, Pakistan. METHODS: Pre and post-tests were conducted among CPR training participants from diverse non-health-related backgrounds from July 2018 to October 2019. Participants were tested for knowledge and skills of CPR before training (pre-test), immediately after training (post-test), and 6 months after training (re-test). All the participants received CPR training through video and scenario-based demonstration using manikins. Post-training CPR skills of the participants were assessed using a pre-defined performance checklist. The facilitator read out numerous case scenarios to the participants, such as drowning, poisoning, and road traffic injuries, etc., and then asked them to perform the critical steps of CPR identified in the scenario on manikins. The primary outcome was the mean difference in the knowledge score and skills of the participants related to the recognition of OHCA and initiation of CPR. RESULTS: The pre and post-tests were completed by 652 participants, whereas the retention test after 6 months was completed by 322 participants. The mean knowledge score related to the recognition of OHCA, and initiation of CPR improved significantly (p < 0.001) from pre-test [47.8/100, Standard Deviation (SD) ±13.4] to post-test (70.2/100, SD ±12.1). Mean CPR knowledge after 6 months (retention) reduced slightly from (70.2/100, ±12.1) to (66.5/100, ±10.8). CPR skill retention for various components (check for scene safety, check for response, check for breathing and correct placement of the heel of hands) deteriorated significantly (p < 0.001) from 77.9% in the post-test to 72.8% in re-test. Participants performed slightly better on achieving an adequate rate of chest compressions from 73.1% in post-test to 76.7% in re-test (p 0.27). CONCLUSION: Community members with non-health backgrounds can learn and retain CPR skills, allowing them to be effective bystander CPR providers in OHCA situations. We recommend mass population training in Pakistan for CPR to increase survival from OHCA.

Acceptability of telephone-cardiopulmonary resuscitation (T-CPR) practice in a resource-limited country- a cross-sectional study.

BACKGROUND: T-CPR has been shown to increase bystander CPR rates dramatically and is associated with improved patient survival. OBJECTIVE: To evaluate the acceptability of T-CPR by the bystanders and identify baseline quality measures of T-CPR in Karachi, Pakistan. METHODS: A cross-sectional study was conducted from January to December 2018 at the Aman foundation command and control center. Data was collected from audiotaped phone calls of patients who required assistance from the Aman ambulance and on whom the EMS telecommunicator recognized the need for CPR and provided instructions. Information was recorded using a structured questionnaire on demographics, the status of the patient, and different time variables involved in CPR performance. A One-way ANOVA was used to compare different time variables with recommended AHA guidelines. P-value ≤ 0.05 was considered significant. RESULTS: There were 481 audiotaped calls in which CPR instruction was given, listened to, and recorded data. Out of which in 459(95.4%) of cases CPR was attempted Majority of the patients were males (n = 278; 57.8%) and most had witnessed cardiac arrest (n = 470; 97.7%) at home (n = 430; 89.3%). The mean time to recognize the need for CPR by an EMS telecommunicator was 4:59 ± 1:59(min), while the mean time to start CPR instruction by a bystander was 5:28 ± 2:24(min). The mean time to start chest compression was 6:04 ± 1:52(min.). CONCLUSION: Our results show the high acceptability of T-CPR by bystanders. We also found considerable delays in recognizing cardiac arrest and initiation of CPR by telecommunicators. Further training of telecommunicators could reduce these delays.

Asymmetric and long-run impact of political stability on consumption-based carbon dioxide emissions in Finland: Evidence from nonlinear and Fourier-based approaches.

The study investigates the asymmetric and long-run impact of political stability on consumption-based carbon dioxide (CCO2) emissions in Finland. In this context, the study examines the impact of political stability, economic growth, renewable energy consumption, and trade openness; includes quarterly data between 1990/Q1 and 2019/Q4, and applies nonlinear and Fourier-based approaches. The empirical outcomes reveal that (i) there is a long-run cointegration between CCO2 emissions and political stability as well as other controlling variables; (ii) positive changes in political stability have statistically significant impacts on CCO2 emissions, whereas negative shocks in political stability are not statistically significant. Also, positive shocks are more powerful than negative shocks; (iii) positive shocks in economic growth have significantly increasing impacts; (iv) positive and negative shocks in renewable energy have decreasing impacts on CCO2 emissions, while positive shocks are more powerful; (v) positive (negative) shocks in trade openness have decreasing (increasing) impacts on CCO2 emissions. Overall, the empirical results highlight the role of political stability on CCO2 emissions. Thus, consideration of political stability by policymakers of Finland in the policy development and implementation processes is highly recommended to achieve a carbon-neutrality target by 2035.