Factors Associated with Institutionalization for Treatment of Active Tuberculosis: A Synopsis from In-depth Patient Interviews

To increase the effectiveness of therapeutic regimens for tuberculosis (TB) and to reduce the societal risks for both infected and uninfected individuals, it is beneficial to be able to predict factors associated with non-adherence to treatment. The purpose of this study was to acquire detailed case histories of TB patients admitted to a hospital setting and to gain a better understanding of how patients explain the life events leading up to their admission for treatment. Twenty-one patients with active TB were interviewed concerning their knowledge of TB, diagnosis and treatment history, recent history prior to hospitalization, reactions to and life changes associated with having TB, and future life intentions following treatment. Three situations were identified that contributed to institutionalization: inability to carry out self-care; need for specialized care to address conditions beyond the patient’s control; and failure to follow the therapeutic regimen. Results confirmed known risk factors for acquisition of TB, situations that delay diagnosis and treatment, and variables that influence adherence and defaulting. Coordinated case management of multiple problems co-occurring with TB treatment may contribute to improved adherence. Consideration of psychosocial and economic needs is important to patient care. Improved communication between health care personnel and patients may enhance the likelihood of successful directly observed therapy (DOT) outside of an institutionalized setting. Some circumstances may preclude non- institutionalized care. These findings bring a dimensional richness to understanding of the patient’s view of the disease and institutionalized care

Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis

Pancreatitis is a complex, progressively destructive inflammatory disorder. Alcohol was long thought to be the primary causative agent, but genetic contributions have been of interest since the discovery that rare PRSS1, CFTR, and SPINK1 variants were associated with pancreatitis risk. We now report two significant genome-wide associations identified and replicated at PRSS1-PRSS2 (1×10-12) and x-linked CLDN2 (p < 1×10-21) through a two-stage genome-wide study (Stage 1, 676 cases and 4507 controls; Stage 2, 910 cases and 4170 controls). The PRSS1 variant affects susceptibility by altering expression of the primary trypsinogen gene. The CLDN2 risk allele is associated with atypical localization of claudin-2 in pancreatic acinar cells. The homozygous (or hemizygous male) CLDN2 genotype confers the greatest risk, and its alleles interact with alcohol consumption to amplify risk. These results could partially explain the high frequency of alcohol-related pancreatitis in men – male hemizygous frequency is 0.26, female homozygote is 0.07

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

The Professionalization and Practice of Lactation Consulting: Medicalized Knowledge, Humanistic Care

Breastfeeding support for mothers and their babies historically was the informal work of family and community members. In the United States today, breastfeeding support is embedded in the biomedical system, and is provided by a new allied health professional: the International Board Certified Lactation Consultant (IBCLC). This dissertation explores this professionalization of breastfeeding support and the origins of this new profession. It studies how IBCLCs working in the U.S. cultural context perceive and practice the profession and examines the relationship between the profession of lactation consulting and the medicalization of breastfeeding. Oral history interviews with 17 founders of the profession, which was established in 1985, and a content analysis of the professional journal (the Journal of Human Lactation) from 1985 to 2010, allowed me to build the story of how and why breastfeeding support became professionalized and how experiential breastfeeding knowledge entered the domain of expert knowledge. While constrained by the biomedical system in which they created the profession, the founders exhibited a both agency and creativity in their production and reproduction of professional values and practices. Interviews with 30 currently certified IBCLCs and observations of the clinical practice of 3 IBCLCs provided insight into the daily practice of IBCLCs working in different settings--hospitals, WIC clinics, pediatric offices, and private practice. The data collected from these ethnographic methods demonstrated how the medical knowledge base of IBCLCs translates into clinical practice with patients, and allowed me to understand the relationship between the profession of lactation consulting and the medicalization of breastfeeding. While IBCLCs\u27 draw on medicalized knowledge and evidence about breastfeeding and human lactation, their interactions with clients are best described as empathetic and humanistic, and are derived from nursing and mother-to-mother breastfeeding support models rather than from a technocratic, biomedical approach to care. While the appropriation of certain biomedical values and standards helped to legitimize the professionalization efforts of the founders, in practice, lactation consultants apply their medical knowledge and clinical experience in a way that reflects the compassionate, empowering care approach of mother-to-mother breastfeeding support and that thus resists the overt medicalization of breastfeeding

Rapid Sense Making

This article shares the problem-solving process and resultant rapid sensemaking methodology created by an interdisciplinary research team faced with qualitative “big data.” Confronted with a data set of over half a million free text comments, within an existing data set of 320,500 surveys, our team developed a process to structure the naturally occurring variability within the data, to identify and isolate meaningful analytic units, and to group subsets of our data amenable to automated coding using a template-based process. This allowed a significant portion of the data to be rapidly assessed while still preserving the ability to explore the more complex free text comments with a grounded theory informed emergent process. In this discussion, we focus on strategies useful to other teams interested in fielding open-ended questions as part of large survey efforts and incorporating those findings as part of an integrated analysis