Four-Month High-Dose Rifampicin Regimens for Pulmonary Tuberculosis.

BACKGROUND: Shorter but effective tuberculosis treatment regimens would be of value to the tuberculosis treatment community. High-dose rifampicin has been associated with more rapid and secure lung sterilization and may enable shorter tuberculosis treatment regimens. METHODS: We randomly assigned adults who were given a diagnosis of rifampicin-susceptible pulmonary tuberculosis to a 6-month control regimen, a similar 4-month regimen of rifampicin at 1200 mg/d (study regimen 1 [SR1]), or a 4-month regimen of rifampicin at 1800 mg/d (study regimen 2 [SR2]). Sputum specimens were collected at regular intervals. The primary end point was a composite of treatment failure and relapse in participants who were sputum smear positive at baseline. The noninferiority margin was 8 percentage points. Using a sequence of ordered hypotheses, noninferiority of SR2 was tested first. RESULTS: Between January 2017 and December 2020, 672 patients were enrolled in six countries, including 191 in the control group, 192 in the SR1 group, and 195 in the SR2 group. Noninferiority was not shown. Favorable responses rates were 93, 90, and 87% in the control, SR1, and SR2 groups, respectively, for a country-adjusted absolute risk difference of 6.3 percentage points (90% confidence interval, 1.1 to 11.5) comparing SR2 with the control group. The proportions of participants experiencing a grade 3 or 4 adverse event were 4.0, 4.5, and 4.4% in the control, SR1, and SR2 groups, respectively. CONCLUSIONS: Four-month high-dose rifampicin regimens did not have dose-limiting toxicities or side effects but failed to meet noninferiority criteria compared with the standard 6-month control regimen for treatment of pulmonary tuberculosis. (Funded by the MRC/Wellcome Trust/DFID Joint Global Health Trials Scheme; ClinicalTrials.gov number, NCT02581527.)

The Prevalence and Significance of the Early Repolarization Pattern in Sudden Arrhythmic Death Syndrome Families.

BACKGROUND: The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear. METHODS AND RESULTS: We analyzed 12-lead ECGs of 401 first-degree relatives of individuals who had died from SADS. The prevalence of ER patterns was compared with family-clustered controls. ER was more common in SADS family members than in controls (21% versus 8%; odds ratio: 5.14; 95% confidence interval, 3.37-7.84) independent of the presence of a familial cardiac diagnosis. Both ascending and horizontal ER patterns were more common. In addition, ER was investigated for associations with findings from ajmaline provocation (n=332), exercise ECG (n=304), and signal-averaged ECG (n=118) when performed. ER was associated with a trend toward late depolarization, in general was suppressed with exercise and was unaffected by ajmaline. Inferior and horizontal patterns were, however, more likely to persist during exercise. Augmentation of ER with ajmaline was rare. CONCLUSIONS: The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness. The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology. The differing response of ER subtypes to exercise and ajmaline provocation suggests underlying mechanisms of both abnormal repolarization and depolarization.

Cross-Jurisdictional Resource Sharing in Changing Public Health Landscape: Contributory Factors and Theoretical Explanations.

BACKGROUND: Local health departments (LHDs) are striving to meet public health needs within their jurisdictions, amidst fiscal restraints and complex dynamic environment. Resource sharing across jurisdictions is a critical opportunity for LHDs to continue to enhance effectiveness and increase efficiency. PURPOSE: This research examines the extent of cross-jurisdictional resource sharing among LHDs, the programmatic areas and organizational functions for which LHDs share resources, and LHD characteristics associated with resource sharing. METHODS: Data from the National Association of County & City Health Officials' 2013 National Profile of LHDs were used. Descriptive statistics and multinomial logistic regression were performed for the 5 implementation-oriented outcome variables of interest, with 3 levels of implementation. RESULTS: More than 54% of LHDs shared resources such as funding, staff, or equipment with 1 or more other LHDs on a continuous, recurring basis. Results from the multinomial regression analysis indicate that economies of scale (population size and metropolitan status) had significant positive influences (at P ≤ .05) on resource sharing. Engagement in accreditation, community health assessment, community health improvement planning, quality improvement, and use of the Community Guide were associated with lower levels of engagement in resource sharing. Doctoral degree of the top executive and having 1 or more local boards of health carried a positive influence on resource sharing. CONCLUSIONS: Cross-jurisdictional resource sharing is a viable and commonly used process to overcome the challenges of new and emerging public health problems within the constraints of restricted budgets. LHDs, particularly smaller LHDs with limited resources, should consider increased resource sharing to address emerging challenges.

Health and personal resources in older patients with cancer undergoing chemotherapy.

OBJECTIVES: The purpose of this study was to gather preliminary data on both direct and moderating effects of health status, the social environment, and perceived personal control on the symptom distress and quality of life (QOL) for older patients with cancer during a treatment regimen of chemotherapy. MATERIALS AND METHODS: Participants were patients with cancer aged≥65years being treated with a variety of chemotherapy regimens specific to their particular diagnosis. Using a longitudinal study design, we measured patients at baseline prior to beginning chemotherapy, midpoint in the regimen, and upon discharge (approximately 2weeks after chemotherapy completion). Outcomes of interest were symptom distress and QOL. Multivariate linear regression was used to determine the association between the predictors and outcomes, controlling for demographic and clinical characteristics. RESULTS: Our final sample consisted of 94 patients with cancer (35 males; 59 females; mean age 73.5years). In the health status domain, lower body strength was inversely associated with symptom distress (p=0.025) and positively associated with QOL (p=0.015). In the social environment domain, social support was inversely associated with fatigue (p=0.001) and depression (p<0.001), and positively associated with QOL (p=0.016 and p=0.029 at midpoint and endpoint, respectively). Personal control variables, mastery and self-efficacy, were significantly associated with multiple outcomes of interest. DISCUSSION: Mastery was the best predictor of symptom distress and QOL. Self-efficacy, social support, and lower body functioning are important predictors of these outcomes among older patients with cancer undergoing chemotherapy.

Patterns of care and survival in cancer patients with cognitive impairment.

To address the emerging concern of oncologists who can expect to see an increasing number of older cancer patients with dementia, this retrospective case-control study compared a sample of older cancer patients with cognitive impairment (N=86) to a non-cognitively impaired control group (N=172) as to patterns of care and survival by age, site and stage. Treatment patterns presented much less differences between both groups than in other series. After adjusting for age, sex, performance status, ADLs/IADLs and comorbidity, results showed significantly greater survival (values p<.001) in the non-impaired control group (Mdn=72.6 months) compared to the cognitively impaired cases (Mdn=23.0 months). Similar results were found when we compared these groups according to tumor stage and cancer site (breast versus other). Across tumor types and stages, cognitively impaired patients have approximately one-third the median survival of the control group. This survival can still be a significant number of years.

Gender differences in coping with functional disability in older married couples: the role of personality and social resources.

The present study examines the impact of functional disability on subjective well-being (SWB) and the moderating effects of personal resources on a sample of 144 community-dwelling, older adult couples age 60-84 years, with emphasis on gender differences in both direct and moderating effects. Functional disability in self and in the spouse was associated with poorer well-being in both men and women, but differences were found by gender in the effects of coping resources. While high neuroticism was associated with poorer well-being for both husbands and wives, extraversion and social support had unique benefits in enhancing well-being only in husbands. Husbands were more introverted, and had fewer social resources, and individual differences in social resources may be more critical for older husbands. Results are interpreted in terms of gender differences in coping and their implications for interventions to enhance well-being in older adults.

Individual differences in well-being in older breast cancer survivors.

Older women who survive breast cancer may differ significantly in their long-term well-being. Using a risk and protective factors model, we studied predictors of well-being in 127 women age 70 and above with a history of at least 1 year's survival of breast cancer. Mean post-cancer survivorship was 5.1 years. Using life satisfaction, depression and general health perceptions as outcome variables, we assessed whether demographic variables, cancer-related variables, health status and psychosocial resources predicted variability in well-being using correlational and hierarchical regression analyses. Higher age predicted increased depression but was not associated with life satisfaction or general health perceptions. Cancer-related variables, including duration of survival, and type of cancer treatment, were not significantly associated with survivors' well-being. Poorer health status was associated with poorer well-being in all three dependent variables. After controlling for demographics, cancer-related variables, and health status, higher levels of psychosocial resources including optimism, mastery, spirituality and social support predicted better outcome in all three dependent variables. While many older women survive breast cancer without severe sequelae, there is considerable variability in their well-being after survivorship. Successful intervention with older breast cancer survivors might include greater attention not only to cancer-specific concerns, but also attention to geriatric syndromes and functional impairment, and enhancement of protective psychosocial resources.

Impact of breast cancer survivorship on quality of life in older women.

Quality of life (QOL) is an important outcome for cancer survivors; but although age is a major risk factor, most breast cancer survivorship studies are conducted with younger women. The objective of our study was to compare QOL in a sample of older breast cancer survivors to a sample of older women who were never diagnosed with breast cancer. A sample of 127 older breast cancer survivors as identified by a cancer registry was compared to a demographically equated sample of 87 older women participating in an epidemiological study. Both groups completed a questionnaire and participated in an interview to measure QOL. The older breast cancer survivors scored worse in the Medical Outcomes Study-Short Form, a measure of health-related QOL. Survivors reported no more depressive symptoms or anxious mood than the comparison group, but scored lower in measures of positive psychosocial well-being, including life satisfaction, mastery, and spiritual well-being, and reported more depressed mood and days affected by fatigue. Older breast cancer survivors show multiple indications of decrements in their health-related quality of life, and lower psychosocial well-being than the comparison group. These decrements may represent deficits in reserve capacity that predispose older cancer survivors to functional disability but may not be readily detected in typical clinical evaluations given the multiple impairments common in geriatric populations. Results suggest a need for greater attention to promoting functioning and psychological well-being among older cancer survivors, even when they may not have obvious cancer-related medical complications.