Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.

Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.

Importance: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020). Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods. Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively. Conclusions and Relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers. Trial Registration: ClinicalTrials.gov Identifier: NCT03697096.

Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial.

Importance: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020. Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies. Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups. Conclusions and Relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged. Trial Registration: ClinicalTrials.gov Identifier: NCT03697070.

Geographic information system protocol for mapping areas targeted for mosquito control in North Carolina.

Geographic information systems (GIS) can be used to map mosquito larval and adult habitats and human populations at risk for mosquito exposure and possible arbovirus transmission. Along with traditional methods of surveillance-based targeted mosquito control, GIS can help simplify and target efforts during routine surveillance and post-disaster (e.g., hurricane-related flooding) to protect emergency workers and public health. A practical method for prioritizing areas for emergency mosquito control has been developed and is described here. North Carolina (NC) One Map was used to identify state-level data layers of interest based on human population distribution and mosquito habitat in Brunswick, Columbus, Onslow, and Robeson Counties in eastern NC. Relevant data layers were included to create mosquito control treatment areas for targeted control and an 18-step protocol for map development is discussed. This protocol is expected to help state, territorial, tribal, and/or local public health officials and associated mosquito control programs efficiently create treatment area maps to improve strategic planning in advance of a disaster. This protocol may be applied to any NC county and beyond, thereby increasing local disaster preparedness.

The effect of episodic interprofessional education activities embedded within physical therapy and occupational therapy curricula.

This study aimed to determine the effect of interprofessional education (IPE) activities on professional level occupational and physical therapy student perception of their competency and their actual observed competency in interprofessional collaboration. The effect of three IPE activities embedded within occupational therapy and physical therapy curricula were measured. Significant changes were noted in the students' perception of their interprofessional collaboration using the Interprofessional Collaborative Competencies Attainment Survey (ICCAS) Revised tool, following each of the three activities. Analysis of the Interprofessional Collaborator Assessment Rubric (ICAR)-Modified revealed "expected" proficiency level with no significant difference between occupational and physical therapy students. The study found from a program evaluation perspective that IPE activities generate immediate positive changes, but longitudinal or cumulative development was not detected. This program evaluation also supports the need for an IPE assessment to measure and track longitudinal development of interprofessional collaborative competencies across the curriculum.

The Effectiveness of Ultraviolet-C (UV-C) Irradiation on the Viability of Airborne Pseudomonas aeruginosa.

Pseudomonas aeruginosa (Pa) is the predominant bacterial pathogen in people with cystic fibrosis (CF) and can be transmitted by airborne droplet nuclei. Little is known about the ability of ultraviolet band C (UV-C) irradiation to inactivate Pa at doses and conditions relevant to implementation in indoor clinical settings. We assessed the effectiveness of UV-C (265 nm) at up to seven doses on the decay of nebulized Pa aerosols (clonal Pa strain) under a range of experimental conditions. Experiments were done in a 400 L rotating sampling drum. A six-stage Andersen cascade impactor was used to collect aerosols inside the drum and the particle size distribution was characterized by an optical particle counter. UV-C effectiveness was characterized relative to control tests (no UV-C) of the natural decay of Pa. We performed 112 tests in total across all experimental conditions. The addition of UV-C significantly increased the inactivation of Pa compared with natural decay alone at all but one of the UV-C doses assessed. UV-C doses from 246-1968 µW s/cm2 had an estimated effectiveness of approximately 50-90% for airborne Pa. The effectiveness of doses ≥984 µW s/cm2 were not significantly different from each other (p-values: 0.365 to ~1), consistent with a flattening of effectiveness at higher doses. Modelling showed that delivering the highest dose associated with significant improvement in effectiveness (984 µW s/cm2) to the upper air of three clinical rooms would lead to lower room doses from 37-49% of the 8 h occupational limit. Our results suggest that UV-C can expedite the inactivation of nebulized airborne Pa under controlled conditions, at levels that can be delivered safely in occupied settings. These findings need corroboration, but UV-C may have potential applications in locations where people with CF congregate, coupled with other indoor and administrative infection control measures.

Effect of a Community Health Worker Intervention on Acute Care Use, Advance Care Planning, and Patient-Reported Outcomes Among Adults With Advanced Stages of Cancer: A Randomized Clinical Trial.

Importance: Deficiencies in advance care planning and symptom management are associated with avoidable acute care use among patients with cancer. Community health worker (CHW)-led approaches may be an approach to reduce acute care use but remain untested in community settings. Objective: To determine whether a CHW-led advance care planning and symptom screening intervention can reduce acute care use more than usual care in a community setting. Design, Setting, and Participants: This randomized clinical trial was conducted among patients with newly diagnosed advanced-stage or recurrent solid and hematologic cancers from August 8, 2017, through November 30, 2021. Data analysis was performed November 30, 2021, through January 1, 2022, by intention to treat. Interventions: Participants were randomized 1:1 to usual care (control group) or usual care with the 6-month CHW-led intervention (intervention group). Main Outcomes and Measures: The primary outcome was acute care use. Secondary outcomes included advance care planning documentation, supportive care use, patient-reported outcomes, survival, and end-of-life care use. Results: Among 128 participants, median (range) age was 67 (19-89) years; 61 (47.7%) were female; and 2 (1.6%) were American Indian or Alaska Native, 11 (8.6%) were Asian, 5 (3.9%) were Black, 23 (18.0%) were Hispanic or Latino, 2 (1.6%) were of mixed race, 2 (1.6%) were Native Hawaiian or other Pacific Islander, 86 (67.2%) were White, and 20 (15.6%) did not report race. Intervention participants had 62% lower risk of acute care use than the control (hazard ratio, 0.38; 95% CI, 0.19-0.76) within 6 months. At 12 months, intervention participants had 17% lower odds of acute care use (odds ratio [OR], 0.83; 95% CI, 0.69-0.98), 8 times the odds of advance care planning documentation (OR, 7.18; 95% CI, 2.85-18.13), 4 times the odds of palliative care (OR, 4.46; 95% CI, 1.88-10.55), nearly double the odds of hospice (OR, 1.83; 95% CI, 1.16-2.88), and nearly double the odds of improved mental and emotional health from enrollment to 6 and 12 months postenrollment (OR, 1.82; 95% CI, 1.03-3.28; and OR, 2.20; 95% CI, 1.04-4.65, respectively) than the control. There were no differences in the death (control, 26 [40.6%] vs intervention, 32 [50.0%]). Fewer intervention participants had acute care use (0 vs 6 [23.1%]) in the month before death than the control. Conclusions and Relevance: In this randomized clinical trial, integration of a CHW-led intervention into cancer care reduced acute care use and is one approach to improve cancer care delivery for patients with advanced stages of disease in community settings. Trial Registration: ClinicalTrials.gov Identifier: NCT03154190.

How Primary School Curriculums in 11 Countries around the World Deliver Food Education and Address Food Literacy: A Policy Analysis.

(1) Background: As one of the biggest drivers of health and climate change, the food system has unrealised potential to influence consumption toward affordable, healthy, sustainable diets. A range of policy levers, including mandating food education, are needed. Schools are considered the best place for food education and childhood is a crucial period when eating habits that persist into adulthood are formed. Food education as part of the curriculum is crucial in generating population shifts in food systems improvements. The purpose of this policy analysis was to analyse mandatory curriculums in different countries to explore the ways in which primary school food education addresses food literacy. (2) Methods: This study analyses how food education within primary school education policy, in 11 countries, addresses Food Literacy (FL). It is the first study of this kind. A case study methodology was employed, and curriculum policy content analysis was conducted using a Food Literacy framework. (3) Results: Each country has a curriculum dedicated to food education, supported by food education in non-food curriculums. There is no standardized approach to primary school food education policy, no consensus in primary food education nomenclature or what curriculums constitute. Curriculums focus on cooking and health topics, but significantly less on social-cultural, equity, and sustainability issues. (4) Conclusion: How primary curriculums around the world deliver food education policy to address FL varies enormously. All 11 countries have dedicated food curriculums, supported by non-food curriculums, but there is no consensus as to what food education is called or constitutes. Countries rarely deal with FL comprehensively. The most comprehensive are single, detailed food curriculums, complemented by non-food curriculums where food knowledge and skills progress clearly and are the intended learning outcome.

A lived experience co-designed study protocol for a randomised control trial: the Attempted Suicide Short Intervention Program (ASSIP) or Brief Cognitive Behavioural Therapy as additional interventions after a suicide attempt compared to a standard Suicide Prevention Pathway (SPP).

BACKGROUND: Despite being preventable, suicide is a leading cause of death and a major global public health problem. For every death by suicide, many more suicide attempts are undertaken, and this presents as a critical risk factor for suicide. Currently, there are limited treatment options with limited underpinning research for those who present to emergency departments with suicidal behaviour. The aim of this study is to assess if adding one of two structured suicide-specific psychological interventions (Attempted Suicide Short Intervention Program [ASSIP] or Brief Cognitive Behavioural Therapy [CBT] for Suicide Prevention) to a standardised clinical care approach (Suicide Prevention Pathway [SPP]) improves the outcomes for consumers presenting to a Mental Health Service with a suicide attempt. METHODS: This is a randomised controlled trial with blinding of those assessing the outcomes. People who attempt suicide or experience suicidality after a suicide attempt, present to the Gold Coast Mental Health and Specialist Services, are placed on the Suicide Prevention Pathway (SPP), and meet the eligibility criteria, are offered the opportunity to participate. A total of 411 participants will be recruited for the study, with 137 allocated to each cohort (participants are randomised to SPP, ASSIP + SPP, or CBT + SPP). The primary outcomes of this study are re-presentation to hospitals with suicide attempts. Presentations with suicidal ideation will also be examined (in a descriptive analysis) to ascertain whether a rise in suicidal ideation is commensurate with a fall in suicide attempts (which might indicate an increase in help-seeking behaviours). Death by suicide rates will also be examined to ensure that representations with a suicide attempt are not due to participants dying, but due to a potential improvement in mental health. For participants without a subsequent suicide attempt, the total number of days from enrolment to the last assessment (24 months) will be calculated. Self-reported levels of suicidality, depression, anxiety, stress, resilience, problem-solving skills, and self- and therapist-reported level of therapeutic engagement are also being examined. Psychometric data are collected at baseline, end of interventions, and 6,12, and 24 months. DISCUSSION: This project will move both ASSIP and Brief CBT from efficacy to effectiveness research, with clear aims of assessing the addition of two structured psychological interventions to treatment as usual, providing a cost-benefit analysis of the interventions, thus delivering outcomes providing a clear pathway for rapid translation of successful interventions. TRIALS REGISTRATION: ClinicalTrials.gov NCT04072666 . Registered on 28 August 2019.

Preventing abusive head trauma: can educating parents reduce the incidence?

Abusive head trauma (AHT) is the most lethal form of child abuse; preventing AHT should be a national priority, but research into this area is woefully underfunded. Prevention programs have primarily focused on universal parent education during the neonatal period, a time when parents are a captive audience of the health care establishment whose focus is on the needs of their newborn infant, and who will soon be exposed to the frustration and anger of infant crying. Research has suggested a strong causal link between infant crying and AHT, and parents - particularly fathers and father figures - have been identified as the most common perpetrators of AHT. A number of studies have suggested that educating parents during the postnatal period about the normalcy of inconsolable infant crying and its evolution over the first several months of postnatal life improves parental knowledge about infant crying and a number of positive parenting behaviors, and decreases emergency room visits for crying. In 1998, we began a pilot program in Upstate New York near Buffalo that led to a 47% reduction in AHT incidence. Similar studies have demonstrated 35-75% reductions in incidence, which has led to enthusiasm for this approach to preventing AHT. We, as well as another group, have enacted statewide programs in Pennsylvania and North Carolina; unfortunately, these two large statewide replication trials failed to demonstrate any impact of such an intervention on AHT rates. Serial messages for parents, provided repeatedly over the period of greatest risk for AHT, might be another avenue of research.

Seroprevalence of Novel Coronavirus SARS-CoV-2 at a Community Hospital Emergency Department and Outpatient Laboratory in Northern Orange County, California.

INTRODUCTION: The severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) has infected more than 20 million people worldwide, and the spread is most prevalent in the USA, where California had accounted over 240,000 cases in the initial 5 months of the pandemic. To estimate the number of infected persons in our community, we conducted a cross-sectional study to estimate seroprevalence of SARS-CoV-2 infection. METHODS: This cross-sectional study evaluated the presence of immunoglobulin G, antibody for SARS-CoV-2 during the time period of July 15, 2020, to July 27, 2020. Testing was done on serum samples from patients who had visited affiliated outpatient clinics or our emergency department. Additionally, we collected age, gender, ethnicity, race, and location of testing. RESULTS: Eight hundred sixty-five tests were included in the study. The outpatient clinics cohort accounted for 56% of results and emergency department (ED) contributed 44%. The positive percentage of SARS-CoV-2 test was 9.4% (95% CI: 0.08-0.12). The positivity rates of the outpatient (5.6%) and ED (14.2%) setting differed. The prevalence of SARS-CoV-2 IgG was greatest in those that identified as Hispanic/Latino, 18.1% versus 13.4% in other groups. Specifically compared to the non-Hispanic/Latino population, the prevalence was significantly higher, with a relative risk of 2.73 (95% CI: 1.8-4.1), p < 0.0001. CONCLUSION: The low antibody positivity rate in the community indicates the need for a vaccine. The Hispanic/Latino patient population should be considered for increased education on preventing transmission and acquisition of COVID-19 as well as being considered as a priority for vaccination once a vaccine is available.

Fast-track training of temporary healthcare support workers to supplement hospital staff during the COVID-19 pandemic.

In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic, which generated concerns that the NHS could be overwhelmed. The predicted increase in the number of patients requiring hospitalisation prompted the need to increase the number of clinical staff working on hospital wards, particularly healthcare support workers (HCSWs), who play a crucial role in addressing the care needs of older people. This article describes how one health board in Scotland trained and redeployed volunteers among its staff to work as temporary HCSWs in its main hospital during the pandemic. A fast-track, one-day training course was delivered in March and April 2020 to 104 staff from various backgrounds - some non-clinical - by a team of volunteer trainers. Staffing during an emergency, such as the COVID-19 pandemic, presents significant challenges, but the experience at NHS Borders shows that it is possible to develop a training course rapidly and provide additional band 2 staff to supplement the support workforce in a time of crisis.

Process evaluation of the central chronic medicines dispensing and distribution programme in Namakwa district, Northern Cape province protocol: a multimethod approach.

INTRODUCTION: The quadruple burden of disease in South Africa, including the HIV/AIDS epidemic, has placed enormous strains on public healthcare (PHC) facilities. These strains specifically compromised the resources available to deal with high volumes of chronic diseases that contribute to medicine shortages and poor service delivery. In an attempt to address these challenges, the Central Chronic Medicines Dispensing and Distribution (CCMDD) programme, which aimed to provide public sector patients with alternative access to vital antiretroviral and other chronic medication, was implemented. This paper describes the protocol for a process evaluation of the programme compliance at the facility level in Namakwa district, to assess patient experiences and staff expectations of the programme; as well as, identifying factors that may affect the programme implementation so that guidance can be given on which approach to take to achieve programme objectives. METHODS AND ANALYSIS: A multimethod approach will be used in a cross-sectional process evaluation of the CCMDD programme at 11 PHC facilities in Namakwa district. These methods will use checklists to assess programme compliance and subsequently gain an understanding of whether the programme was implemented as planned. Structured questionnaires together with focus group discussions will be conducted with selected patients enrolled in the programme and facility staff to determine patient experiences with and staff expectations of the programme, respectively. Furthermore, in-depth interviews will be conducted with key actors to explore barriers and facilitators of the programme implementation. Descriptive statistics will be conducted to analyse the quantitative data and an inductive interpretive approach will be used to analyse the qualitative data. ETHICS AND DISSEMINATION: The protocol was approved by Stellenbosch University Health Research Ethics Committee (S19/02/047) and the study will be conducted in line with the principles of the Declaration of Helsinki (1964). Findings from the study will be communicated to the study population, and at appropriate local and international conferences, in addition to publishing in peer-reviewed journals.

Use of Mobile Messaging System for Self-Management of Chemotherapy Symptoms in Patients with Advanced Cancer.

The use of an automated text messaging intervention provided a cost-effective option for symptom management for patients experiencing cancer-related symptoms.

The Diagnostic Frame in National Security Evaluations.

In clinical and most forensic evaluations, "diagnosis" connotes the expectation of a DSM-5 or ICD-10 formally labeled mental condition. When the task is to evaluate the security risk a person's psychological makeup presents to an institution, such a molar diagnosis can blind the clinician and elevate the risk to a security agency. When "diagnosis" connotes achieving an understanding of a person's behavior that has raised security concerns, then a different conceptualization of the diagnostic process is required. Unlike the clinical situation, the evaluation is not being performed to benefit the person but for the purpose of assessing risk to an agency. The differences this introduces involve every aspect of the evaluation and changes the type of diagnosis expected. Not appreciating these differences can cause the clinician to fail in the task of assessing psychological tendencies that affect national security.

The PEth Blood Test in the Security Environment: What it is; Why it is Important; and Interpretative Guidelines.

Testing for phosphatidylethanol (PEth) is a relatively new tool for detecting and grossly quantifying a person's use of alcohol in a variety of security, medical, and legal environments. The basic chemistry of PEth is explained with a particular focus on factors that make it highly suitable as a biomarker for alcohol use in such situations. This article meets the need for a literature review that synthesizes PEth laboratory findings and suggests updated guidelines for interpretation. Several ethanol biomarkers have been used for detection or monitoring alcohol use but have significant limitations. Based on this review, the authors propose three guidelines for evaluating PEth values: Light or no Consumption (<20 ng/mL), Significant Consumption (20-199 ng/mL), and Heavy Consumption (>200 ng/mL). These guidelines are important in employment and security environments, but also have applicability in such diverse activities as alcohol treatment programs, organ transplant decisions, and monitoring impaired medical professionals.

Silver Nitrate Grade and Its Effect on Physical Developer Performance-A Validation Study.

Silver nitrate is a critical component of the physical developer (PD) reagent. Significant increases in the cost of silver nitrate in recent years have caused the United States Secret Service's Forensic Laboratory to look for a more economical way to produce physical developer. One possible solution to this dilemma is to use a lower grade of silver nitrate, which typically has a lower cost. This study compared the quality of fingerprints produced on various paper substrates by three physical developer working solutions, each prepared using either the American Chemical Society (ACS), U.S. Pharmacopeia (USP), or technical grade of silver nitrate. It was determined that the less pure grades of silver nitrate produced approximately the same quality of fingerprints as the ACS grade, which is currently used in the authors' laboratory for making PD working solutions. In the experiments comparing PD prepared using the ACS and USP grades of silver nitrate, the ACS grade was superior only 5% of the time, whereas the USP grade was chosen 27% of the time. In the experiments comparing PD prepared using the ACS and technical grades of silver nitrate, the ACS grade was superior only 10% of the time, whereas the technical grade was selected 17% of the time. For the majority of the sample comparisons, no difference in fingerprint quality was observed. The overall conclusion was that either USP or technical grade silver nitrate can be used in place of the current, and more expensive, ACS grade of silver nitrate.

Efficacy, safety, and tolerability of dolutegravir-rilpivirine for the maintenance of virological suppression in adults with HIV-1: phase 3, randomised, non-inferiority SWORD-1 and SWORD-2 studies.

BACKGROUND: Lifelong HIV antiretroviral therapy (ART) has prompted an interest in two-drug regimens to minimise cumulative drug exposure and toxicities. The safety, tolerability, and efficacy of dolutegravir and rilpivirine suggest potential compatibility and effectiveness as a two-drug regimen. We aimed to investigate this two-drug regimen in a phase 3 study. METHODS: We identically designed SWORD-1 and SWORD-2, which were open-label, parallel-group, multicentre, phase 3, randomised, non-inferiority studies in 12 countries evaluating efficacy and safety of once-daily dolutegravir 50 mg plus rilpivirine 25 mg versus current ART regimen (CAR). We included participants aged 18 years or older who were on first or second ART with stable plasma HIV-1 RNA (viral load <50 copies per mL) for 6 months or longer at screening. We randomly assigned participants (1:1) with stratification by third-agent class, age, and planned participation in a bone mineral density substudy. The primary endpoint was proportion of participants with viral load lower than 50 copies per mL at week 48 among those individuals who received one or more doses of study medication. Investigators monitored adverse events to assess safety. These trials are registered with ClinicalTrials.gov, numbers NCT02429791 (SWORD-1) and NCT02422797 (SWORD-2). FINDINGS: We screened for participants from April 14, 2015, to Oct 15, 2015, for SWORD-1 and from April 21, 2015, to Sept 25, 2015, for SWORD-2. We randomly assigned 516 participants to dolutegravir-rilpivirine and 512 to continue with CAR. At week 48 (last patient visit was Nov 22, 2016), in the pooled analysis of the intention-to-treat population, 95% of participants had viral loads lower than 50 copies per mL in each group (486 of 513 in the dolutegravir-rilpivirine group vs 485 of 511 in the CAR group), with an adjusted treatment difference of -0·2% (95% CI -3·0 to 2·5) and showed non-inferiority with a predefined margin of -8%. 395 (77%) of 513 participants in the dolutegravir-rilpivirine group and 364 (71%) of 511 participants in the CAR group reported adverse events. The most common adverse events were nasopharyngitis (49 [10%] for dolutegravir-rilpivirine vs 50 [10%] for CAR) and headache (41 [8%] vs 23 [5%]). More participants taking dolutegravir-rilpivirine (17 [3%]) reported adverse events leading to withdrawal than did participants taking CAR (three [<1%]). INTERPRETATION: Dolutegravir-rilpivirine was non-inferior to CAR over 48 weeks in participants with HIV suppression and showed a safety profile consistent with its components. Results support the use of this two-drug regimen to maintain HIV suppression. FUNDING: ViiV Healthcare and Janssen Pharmaceutica NV.

Sas3 and Ada2(Gcn5)-dependent histone H3 acetylation is required for transcription elongation at the de-repressed FLO1 gene.

The Saccharomyces cerevisiae FLO1 gene encodes a cell wall protein that imparts cell-cell adhesion. FLO1 transcription is regulated via the antagonistic activities of the Tup1-Cyc8 co-repressor and Swi-Snf co-activator complexes. Tup1-Cyc8 represses transcription through the organization of strongly positioned, hypoacetylated nucleosomes across gene promoters. Swi-Snf catalyzes remodeling of these nucleosomes in a mechanism involving histone acetylation that is poorly understood. Here, we show that FLO1 de-repression is accompanied by Swi-Snf recruitment, promoter histone eviction and Sas3 and Ada2(Gcn5)-dependent histone H3K14 acetylation. In the absence of H3K14 acetylation, Swi-Snf recruitment and histone eviction proceed, but transcription is reduced, suggesting these processes, while essential, are not sufficient for de-repression. Further analysis in the absence of H3K14 acetylation reveals RNAP II recruitment at the FLO1 promoter still occurs, but RNAP II is absent from the gene-coding region, demonstrating Sas3 and Ada2-dependent histone H3 acetylation is required for transcription elongation. Analysis of the transcription kinetics at other genes reveals shared mechanisms coupled to a distinct role for histone H3 acetylation, essential at FLO1, downstream of initiation. We propose histone H3 acetylation in the coding region provides rate-limiting control during the transition from initiation to elongation which dictates whether the gene is permissive for transcription.