Publications

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

The movement for research transparency has gained irresistible momentum over the past decade. Although qualitative research is rarely published in the high-impact journals that have adopted, or are most likely to adopt, data sharing policies, qualitative researchers who publish work in these and similar venues will likely encounter questions about data sharing within the next few years. The fundamental ways in which qualitative and quantitative data differ should be considered when assessing the extent to which qualitative and mixed methods researchers should be expected to adhere to data sharing policies developed with quantitative studies in mind. We outline several of the most critical concerns below, while also suggesting possible modifications that may help to reduce the probability of unintended adverse consequences and to ensure that the sharing of qualitative data is consistent with ethical standards in research.

Despite the recognized links between food insecurity, poverty, and the risk of HIV/AIDS, few randomized trials have evaluated the impact of livelihood interventions on HIV risk behaviors. The current study draws upon data collected from a qualitative process evaluation that was embedded into a pilot randomized controlled trial that tested whether a multisectoral agricultural intervention (Shamba Maisha) affected the HIV-related health of HIV-positive adults in rural Kenya. In the current study, we drew upon longitudinal, in-depth interviews with 45 intervention participants and nine control participants (N = 54) in order to examine the impacts of the intervention on gendered power and sexual risk reduction among both women and men. Female and male participants in the intervention described positive changes in sexual practices and gendered power dynamics as a result of intervention participation. Changes included reduced sexual risk behaviors, improved gender-related power dynamics, and enhanced quality of intimate relationships. These findings illuminate how a multisectoral agricultural intervention may affect inequitable gender relations and secondary transmission risk. Further research is needed to explore how to best leverage agricultural interventions to address the important intersections between poverty and inequitable gender relations that shape HIV risks.

The healthy lung maintains a steady state of immune readiness to rapidly respond to injury from invaders. Integrins are important for setting the parameters of this resting state, particularly the epithelial-restricted αVβ6 integrin, which is upregulated during injury. Once expressed, αVβ6 moderates acute lung injury (ALI) through as yet undefined molecular mechanisms. We show that the upregulation of β6 during influenza infection is involved in disease pathogenesis. β6-deficient mice (β6 KO) have increased survival during influenza infection likely due to the limited viral spread into the alveolar spaces leading to reduced ALI. Although the β6 KO have morphologically normal lungs, they harbor constitutively activated lung CD11b+ alveolar macrophages (AM) and elevated type I IFN signaling activity, which we traced to the loss of β6-activated transforming growth factor-β (TGF-β). Administration of exogenous TGF-β to β6 KO mice leads to reduced numbers of CD11b+ AMs, decreased type I IFN signaling activity and loss of the protective phenotype during influenza infection. Protection extended to other respiratory pathogens such as Sendai virus and bacterial pneumonia. Our studies demonstrate that the loss of one epithelial protein, αVβ6 integrin, can alter the lung microenvironment during both homeostasis and respiratory infection leading to reduced lung injury and improved survival.

CONTEXT

Most hip fracture care models are grounded in curative models where the goal is to return the patient to independent function. In many instances, however, hip fractures contribute to continued functional decline and mortality. Although the negative impact of hip fractures is appreciated once they have occurred, what is less understood is what proportion of older adults have high illness burden before experiencing hip fracture and might benefit from geriatric palliative care.

OBJECTIVES

Using data from the Health and Retirement Study linked to Medicare claims (January 1992 through December 2010), we sought to understand the extent of premorbid illness burden before hip fracture.

METHODS

Characteristics were based on the interview before hip fracture. Features used to indicate need for geriatric palliative care included evidence of functional and medical vulnerability, pain, and depression.

RESULTS

Eight hundred fifty-six older adults who experienced a hip fracture were compared to 851 age-, gender-, and race-matched controls. Older adults with hip fractures had significantly more premorbid functional vulnerability (activities of daily living dependent 25.7% vs. 16.1% [P < 0.001]; dementia 16.2% vs. 7.3% (P < 0.001); use of helpers 41.2% vs. 28.7% [P < 0.001]). They also experienced more medical vulnerability (multimorbidity 43% vs. 29.8% [P < 0.001]; high health care utilization 30.0% vs. 20.9% [P < 0.001]; and poor prognosis 36.1% vs. 25.4% [P < 0.001] in controls). There was no difference in premorbid pain and depression between subsequent hip fracture patients and controls.

CONCLUSIONS

A significant proportion of older adults have evidence of functional and medical vulnerability before hip fracture. For these individuals, integration of geriatric palliative care may be particularly important for optimizing quality of life and addressing the high morbidity experienced by this population.

OBJECTIVES

The study sought to examine the safety and performance of transcatheter aortic valve replacement (TAVR) using an all-female registry and to further explore the potential impact of female sex-specific characteristics on clinical outcomes after TAVR.

BACKGROUND

Although women comprise 50% of patients with symptomatic severe aortic stenosis undergoing TAVR, the optimal treatment strategy remains undetermined.

METHODS

The WIN-TAVI (Women's INternational Transcatheter Aortic Valve Implantation) registry is a multinational, prospective, observational registry of women undergoing TAVR for aortic stenosis, conducted without any external funding. The primary endpoint was the Valve Academic Research Consortium (VARC)-2 early safety endpoint at 30 days (composite of mortality, stroke, major vascular complication, life-threatening bleeding, stage 2 or 3 acute kidney injury, coronary artery obstruction, or repeat procedure for valve-related dysfunction).

RESULTS

Between January 2013 and December 2015, 1,019 women were enrolled across 19 European and North American centers. The mean patient age was 82.5 ± 6.3 years, mean EuroSCORE I was 17.8 ± 11.7% and mean Society of Thoracic Surgeons score was 8.3 ± 7.4%. TAVR was performed via transfemoral access in 90.6% and new-generation devices were used in 42.1%. In more than two-thirds of cases, an Edwards SAPIEN 23 mm (Edwards Lifesciences, Irvine, California) or Medtronic CoreValve ≤26 mm (Medtronic Inc., Minneapolis, Minnesota) device was implanted. The 30-day VARC-2 composite endpoint occurred in 14.0% with 3.4% all-cause mortality, 1.3% stroke, 7.7% major vascular complications, and 4.4% VARC life-threatening bleeding. The independent predictors of the primary endpoint were age (odds ratio [OR]: 1.04; 95% confidence interval [CI]: 1.00 to 1.08), prior stroke (OR: 2.02; 95% CI: 1.07 to 3.80), left ventricular ejection fraction <30% (OR: 2.62; 95% CI: 1.07 to 6.40), new device generation (OR: 0.59; 95% CI: 0.38 to 0.91), and history of pregnancy (OR: 0.57; 95% CI: 0.37 to 0.85).

CONCLUSIONS

Women enrolled in this first ever all-female TAVR registry with collection of female sex-specific baseline parameters, were at intermediate-high risk and experienced a 30-day VARC-2 composite safety endpoint of 14.0% with a low incidence of early mortality and stroke. Randomized assessment of TAVR versus surgical aortic valve replacement in intermediate risk women is warranted to determine the optimal strategy.