Impact of lung cancer screening results on participant health-related quality of life and state anxiety in the National Lung Screening Trial

BACKGROUND Low-dose computed tomography (LDCT) lung screening has been associated with a 20% reduction in lung cancer mortality. A major barrier to the adoption of lung screening is the potential negative psychological impact of a false-positive (FP) screen, occurring in 20% to 50% of those screened. The objective of this study was to assess the impact of abnormal findings on health-related quality of life (HRQoL) and anxiety in the American College of Radiology (ACRIN)/National Lung Screening Trial (NLST). METHODS The NLST was a randomized screening trial comparing LDCT with chest X-ray screening (CXR). This study was part of the original protocol. A total of 2812 participants at 16 of 23 ACRIN sites who had baseline HRQoL assessments were asked to complete the Short Form-36 and the State Trait Anxiety Inventory (form Y-1) questionnaires to assess short-term (1 month) and long-term (6 months) effects of screening. FP were lung cancer–free at 1 year, and true-positives (TP) were not. RESULTS Of the total participants, 1024 (36.4%) participants were FP, 63 (2.2%) were TP, 344 (12.2%) had significant incidental findings (SIFs), and 1381 (49.1%) had negative screens. Participants had been randomized to LDCT (n = 1947) and CXR (n = 865). Short-term and long-term HRQoL and state anxiety did not differ across participants with FP, SIF, or negative screens. Short-term and long-term HRQoL were lower and anxiety was higher for TP participants compared to participants with FP, SIF, and negative screens. CONCLUSIONS In a large multicenter lung screening trial, participants receiving a false-positive or SIF screen result experienced no significant difference in HRQoL or state anxiety at 1 or at 6 months after screening relative to those receiving a negative result. Cancer 2014;120:3401–3409. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. In a large multi-center lung screening trial, participants receiving a false positive or significant incidental finding screen result experienced no significant difference in health related quality of life or state anxiety at 1 or at 6 months after screening relative to those receiving a negative result

Use of Practice-Based Research Network Data to Measure Neighborhood Smoking Prevalence

Introduction: Practice-Based Research Networks (PBRNs) and health systems may provide timely, reliable data to guide the development and distribution of public health resources to promote healthy behaviors, such as quitting smoking. The objective of this study was to determine if PBRN data could be used to make neighborhood-level estimates of smoking prevalence. Methods: We estimated the smoking prevalence in 32 greater Boston neighborhoods (population = 877,943 adults) by using the electronic health record data of adults who in 2009 visited one of 26 Partners Primary Care PBRN practices (n = 77,529). We compared PBRN-derived estimates to population-based estimates derived from 1999–2009 Behavioral Risk Factor Surveillance System (BRFSS) data (n = 20,475). Results: The PBRN estimates of neighborhood smoking status ranged from 5% to 22% and averaged 11%. The 2009 neighborhood-level smoking prevalence estimates derived from the BRFSS ranged from 5% to 26% and averaged 13%. The difference in smoking prevalence between the PBRN and the BRFSS averaged −2 percentage points (standard deviation, 3 percentage points). Conclusion: Health behavior data collected during routine clinical care by PBRNs and health systems could supplement or be an alternative to using traditional sources of public health data

Implementation of a web-based tool for patient medication self-management: the Medication Self-titration Evaluation Programme (Med-STEP) for blood pressure control

Background Informatics tools may help support hypertension management.Objective To design, implement and evaluate a web-based system for patient anti-hypertensive medication self-titration.Methods Study stages included: six focus groups (50 patients) to identify barriers/facilitators to patient medication self-titration, software design informed by qualitative analysis of focus group responses and a six-month single-arm pilot study (20 patients) to assess implementation feasibility.Results Focus groups emphasised patient need to feel confident that their own primary care providers were directly involved and approved of the titration protocol. Physicians required 3.3 ± 2.8 minutes/patient to create individualised six-step medication pathways for once-monthly blood pressure evaluations. Pilot participants (mean age of 51.5 ± 11 years, 45% women, mean baseline blood pressure 139/84 ± 12.2/7.5 mmHg) had five medication increases, two non-adherence self-reports, 52months not requiring medication changes, 24 skipped months and 17 months with no evaluations due to technical issues. Four pilot patients dropped out before study completion. From baseline to study completion, blood pressure decreased among the 16 patients remaining in the study (8.0/4.7 mmHg, p = 0.03 for both systolic and diastolic pressures).Conclusions Lessons learned included the benefit of qualitative patient analysis prior to system development and the feasibility of physicians designing individual treatment pathways. Any potential clinical benefits were offset by technical problems, the tendency for patients to skip their monthly self-evaluations and drop outs. To be more widely adopted such systems must effectively generalise to a wider range of patients and be integrated into clinical workflow

Mental health, social connectedness, and fear during the COVID-19 pandemic: a qualitative perspective from older women with HIV.

Older women with HIV (WWH) confront significant biopsychosocial challenges that may be exacerbated by the COVID-19 pandemic. Between May 2020 and April 2021, following a resiliency intervention conducted as part of a randomized parent trial, 24 cisgender WWH (M = 58 years old) completed quantitative assessments and qualitative interviews exploring the impact of COVID-19 on mental health. Qualitative data were analyzed via rapid analysis. Most participants were Black (62.5%) and non-Hispanic or Latina (87.5%). Emergent themes included (1) increased anxiety and depression; (2) a loss of social connectedness; (3) fear of unknown interactions among COVID-19, HIV, and other comorbidities; and (4) the use of largely adaptive strategies to cope with these issues. Findings suggest that older WWH face significant COVID-19-related mental health challenges, compounding existing stressors. As the pandemic persists, it will be important to assess the impact of these stressors on wellbeing, identify effective coping strategies, and provide increased support to mitigate COVID-19-related mental health issues over time. Trial Registration: ClinicalTrials.gov identifier: NCT03071887.R34 AT009170 - NCCIH NIH HHS; T32 MH116140 - NIMH NIH HHS; 5R34AT009170 - NCCIH NIH HHSAccepted manuscrip

Personalized Genetic Risk Counseling to Motivate Diabetes Prevention: A randomized trial

OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors. RESEARCH DESIGN AND METHODS We conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top and bottom score quartiles received individual genetic counseling before being enrolled with untested control participants in a 12-week, validated, diabetes prevention program. Middle-risk quartile participants were not studied further. We examined the effect of this genetic counseling intervention on patient self-reported attitudes, program attendance, and weight loss, separately comparing higher-risk and lower-risk result recipients with control participants. RESULTS The 108 participants enrolled in the diabetes prevention program included 42 participants at higher diabetes genetic risk, 32 at lower diabetes genetic risk, and 34 untested control subjects. Mean age was 57.9 ± 10.6 years, 61% were men, and average BMI was 34.8 kg/m2, with no differences among randomization groups. Participants attended 6.8 ± 4.3 group sessions and lost 8.5 ± 10.1 pounds, with 33 of 108 (30.6%) losing ≥5% body weight. There were few statistically significant differences in self-reported motivation, program attendance, or mean weight loss when higher-risk recipients and lower-risk recipients were compared with control subjects (P > 0.05 for all but one comparison). CONCLUSIONS Diabetes genetic risk counseling with currently available variants does not significantly alter self-reported motivation or prevention program adherence for overweight individuals at risk for diabetes

Evolution and Spread of Ebola Virus in Liberia, 2014–2015

The 2013–present Western African Ebola virus disease (EVD) outbreak is the largest ever recorded with >28,000 reported cases. Ebola virus (EBOV) genome sequencing has played an important role throughout this outbreak; however, relatively few sequences have been determined from patients in Liberia, the second worst-affected country. Here, we report 140 EBOV genome sequences from the second wave of the Liberian outbreak and analyze them in combination with 782 previously published sequences from throughout the Western African outbreak. While multiple early introductions of EBOV to Liberia are evident, the majority of Liberian EVD cases are consistent with a single introduction, followed by spread and diversification within the country. Movement of the virus within Liberia was widespread and reintroductions from Liberia served as an important source for the continuation of the already ongoing EVD outbreak in Guinea. Overall, little evidence was found for incremental adaptation of EBOV to the human host.Organismic and Evolutionary Biolog

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.</p

Genomic epidemiology reveals multiple introductions of Zika virus into the United States

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism