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Abstract Background Diagnosis of alcohol use disorder (AUD) in primary care is critical for increasing access to alcohol treatment. However, AUD is underdiagnosed and may be inequitably diagnosed due to societal structures that determine access to resources (e.g., structural racism that limits opportunities for some groups and influences interpersonal interactions in and beyond health care). This study described patterns of provider-documented AUD in primary care across intersections of race, ethnicity, sex, and community-level socioeconomic status (SES). Methods This cross-sectional study used EHR data from a regional healthcare system with 35 primary care clinics that included adult patients who completed alcohol screenings between 3/1/2015 and 9/30/2020. The prevalence of provider-documented AUD in primary care based on International Classification of Diseases-9 (ICD-9) and ICD-10 diagnoses was compared across intersections of race, ethnicity, sex, and community-level SES. Results Among 439,375 patients, 6.6% were Latine, 11.0% Asian, 5.4% Black, 1.3% Native Hawaiian/Pacific Islander (NH/PI), 1.5% American Indian/Alaska Native (AI/AN), and 74.2% White, and 58.3% women. The overall prevalence of provider-documented AUD was 1.0% and varied across intersecting identities. Among women, the prevalence was highest for AI/AN women with middle SES, 1.5% (95% CI 1.0–2.3), and lowest for Asian women with middle SES, 0.1% (95% CI 0.1–0.2). Among men, the prevalence was highest for AI/AN men with high and middle SES, 2.0% (95% CI 1.1–3.4) and 2.0% (95% CI 1.2–3.2), respectively, and lowest for Asian men with high SES, 0.5% (95% CI 0.3–0.7). Black and Latine patients tended to have a lower prevalence of AUD than White patients, across all intersections of sex and SES except for Black women with high SES. There were no consistent patterns of the prevalence of AUD diagnosis that emerged across SES. Conclusion The prevalence of provider-documented AUD in primary care was highest in AI/AN men and women and lowest in Asian men and women. Findings of lower prevalence of provider-documented AUD in Black and Hispanic than White patients across most intersections of sex and SES differed from prior studies. Findings may suggest that differences in access to resources, which vary in effects across these identity characteristics and lived experiences, influence the diagnosis of AUD in clinical care.

BackgroundDelivering prescription digital therapeutics (ie, evidence-based interventions designed to treat, manage, or prevent disorders via websites or smartphone apps) in primary care could increase patient access to substance use disorder (SUD) treatments. However, the optimal approach to implementing prescription digital therapeutics in primary care remains unknown. ObjectiveThis pilot study is a precursor to a larger trial designed to test whether implementation strategies (practice facilitation [PF] and health coaching [HC]) improve the delivery of prescription digital therapeutics for SUDs in primary care. This mixed methods study describes outcomes among patients in the 2 pilot clinics and presents qualitative findings on implementation. MethodsFrom February 10 to August 6, 2021, a total of 3 mental health specialists embedded in 2 primary care practices of the same integrated health system were tasked with offering app-based prescription digital therapeutics to patients with SUD. In the first half of the pilot, implementation activities included training and supportive tools. PF (at 1 clinic) and HC (at 2 clinics) were added in the second half. All study analyses relied on secondary data, including electronic health records and digital therapeutic vendor data. Primary outcomes were the proportion of patients reached by the prescription digital therapeutics and fidelity related to ideal use. We used qualitative methods to assess the adherence to planned activities and the barriers and facilitators to implementing prescription digital therapeutics. ResultsOf all 18 patients prescribed the apps, 10 (56%) downloaded the app and activated their prescription, and 8 (44%) completed at least 1 module of content. Patients who activated the app completed 1 module per week on average. Ideal use (fidelity) was defined as completing 4 modules per week and having a monthly SUD-related visit; 1 (6%) patient met these criteria for 10 weeks (of the 12-week prescription period). A total of 5 (28%) patients had prescriptions while HC was available, 2 (11%) were successfully contacted, and both declined coaching. Clinicians reported competing clinical priorities, technical challenges, and logistically complex workflows in part because the apps required a prescription. Some pilot activities were impacted by staff turnover that coincided with the COVID-19 pandemic. The facilitators to implementation were high engagement and the perception that the apps could meet patient needs. ConclusionsThe pilot study encountered the barriers to implementing prescription digital therapeutics in a real-world primary care setting, especially staffing shortages, turnover, and competing priorities for clinic teams. The larger randomized trial will clarify the extent to which PF and HC improve the implementation of digital therapeutics. Trial RegistrationClinicalTrials.gov NCT04907045; https://clinicaltrials.gov/study/NCT04907045

Background:. Body contouring surgery removes excess skin and fat, often after massive weight loss. Some reports suggest that patients who have previously undergone obesity (bariatric) surgery are at excess risk of subsequent bleeding, possibly due to complex nutritional and metabolic sequelae of massive weight loss. Methods:. A retrospective cohort study of intraoperative blood loss and postoperative bleeding indicators were examined for patients who had undergone abdominoplasty. Participants were categorized based on their history of previous obesity surgery, and outcome variables were compared using odds ratio, followed by subgroup comparison between a history of restrictive versus malabsorptive obesity surgery, Results:. The study included 472 patients, of which 171 (36.2 %) had a history of obesity surgery. Mean age was 40.4 years, and 402 (85.1%) participant were women. Fifty-five (11.6%) patients were smokers whereas 65 (13.7%) were hypertensive. Mean body mass index before surgery was 30.2 kg per m2, and average time between obesity and body contouring surgery (if applicable) was 35.8 months. Patients with a history of obesity surgery exhibited greater intraoperative blood loss (162.2 mL versus 132.1 mL; P = 0.001), drainage volume at 24 h (155 mL versus 135 mL; P = 0.001), and total drainage volume (300ml versus 220 mL; P = 0.001). Postoperative hematoma requiring surgical re-exploration was almost three times higher following a history of obesity surgery (4.7% versus 1.7 %; P = 0.05). Conclusions:. History of obesity surgery increases intraoperative blood loss, postoperative serosanguinous drainage volumes, and the risk of postoperative hematoma requiring surgical evacuation after abdominal body contouring procedures.

Introduction: Ventilator-associated pneumonias (VAPs) are a complication of mechanical ventilation in the intensive care unit (ICU) that increase length of stay, morbidity, and mortality. While identifying and treating infections early is paramount to improving patient outcomes, more and more data demonstrate limited courses of antibiotics improve outcomes. Prolonged (10–14 day) courses of antibiotics have remained the standard of care for pneumonia due to gram-negative bacilli (GNR). We aimed to review our GNR VAPs to assess risk factors for recurrent GNR infections. Methods: We reviewed trauma patients who developed VAP from 02/2019 through 05/2022. Demographics, injury characteristics, and outcomes were reviewed with a focus on pneumonia details including the cultured pathogen(s), antibiotic(s) used, treatment duration, and presence of recurrent infections. We then compared single episode VAPs to multiple episode VAPs among patients infected by GNRs. Results: Eleven of the fifty trauma patients admitted to the ICU suffered a VAP caused by a GNR. Of these eleven patients, six experienced a recurrent infection, four of which were caused by Pseudomonas aeruginosa and two of which were caused by Enterobacter aerogenes. Among the patients who received ten days of antibiotic treatment, half suffered a recurrence. Although, there was no difference in the microbiology or antibiotic duration between the recurrences and single episodes. Conclusion: Despite prolonged use of antibiotics, we found that the risk of recurrent or persistent infections was high among patients with VAP due to GNB. Further study is needed to determine optimal treatment to minimize the risk of these recurrences. Key message: Ventilator-associated pneumonia due to gram-negative bacilli is a rare but high morbidity complication in intensive care units. Despite prolonged duration of therapy, these infections still appear to account for many recurrent infections and further study into optimal therapy is warranted.

To contribute to healthcare improvements, qualitative health research must adapt to the demanding pace of constantly changing healthcare practices and policies. To meet this challenge, researchers need methods for rigorous and rapid data analysis. This article introduces the Rapid Group Analysis Process (Rap-GAP), a new approach for rapid qualitative data analysis. This method is more efficient than other rapid qualitative analysis methods. It allows for the direct involvement of diverse participants in the analysis process, including patients or healthcare decision-makers with limited qualitative research experience, while keeping the analysis grounded in the primary data (e.g., transcripts). These attributes make Rap-GAP a unique and valuable alternative to traditional qualitative analysis. This article describes the 5-step Rap-GAP process and 3 case studies that demonstrate how to use the method and adapt it for different analytical goals. Future research will evaluate and describe the outcomes of Rap-GAP compared to traditional qualitative analysis.

Objective. Describe continuous infusion (CI) ketamine practices in pediatric intensive care units (PICUs) and evaluate its effect on pain/sedation scores, exposure to analgesics/sedatives, and adverse effects (AEs). Methods. Multicenter, retrospective, observational study in children

Abstract Background Alcohol use disorders (AUD) are prevalent and often go untreated. Patients are commonly screened for AUD in primary care, but existing treatment programs are failing to meet demand. Digital therapeutics include novel mobile app-based treatment approaches which may be cost-effective treatment options to help fill treatment gaps. The goal of this study was to identify implementation needs and workflow design considerations for integrating digital therapeutics for AUD into primary care. Methods We conducted qualitative interviews with clinicians, care delivery leaders, and implementation staff (n = 16) in an integrated healthcare delivery system in the United States. All participants had experience implementing digital therapeutics for depression or substance use disorders in primary care. Interviews were designed to gain insights into adaptations needed to optimize existing clinical processes, workflows, and implementation strategies for use with alcohol-focused digital therapeutics. Interviews were recorded and transcribed and then analyzed using a rapid analysis process and affinity diagramming. Results Qualitative themes were well represented across health system staff roles. Participants were enthusiastic about digital therapeutics for AUD, anticipated high patient demand for such a resource, and made suggestions for successful implementation. Key insights regarding the implementation of digital therapeutics for AUD and unhealthy alcohol use from our data include: (1) implementation strategy selection must be driven by digital therapeutic design and target population characteristics, (2) implementation strategies should seek to minimize burden on clinicians given the large numbers of patients with AUD who are likely to be interested in and eligible for digital therapeutics, and (3) digital therapeutics should be offered alongside many other treatment options to accommodate individual patients’ AUD severity and treatment goals. Participants also expressed confidence that previous implementation strategies used with other digital therapeutics such as clinician training, electronic health record supports, health coaching, and practice facilitation would be effective for the implementation of digital therapeutics for AUD. Conclusions The implementation of digital therapeutics for AUD would benefit from careful consideration of the target population. Optimal integration requires tailoring workflows to meet anticipated patient volume and designing workflow and implementation strategies to meet the unique needs of patients with varying AUD severity.

Abstract Background Most people with opioid use disorder (OUD) have co-occurring substance use, which is associated with lower receipt of OUD medications (MOUD). Expanding MOUD provision and care linkage outside of substance use disorder (SUD) specialty settings is a key strategy to increase access. Therefore, it is important to understand how MOUD providers in these settings approach care for patients with co-occurring substance use. This qualitative study of Veterans Health Administration (VA) clinicians providing buprenorphine care in primary care, mental health, and pain settings aimed to understand (1) their approach to addressing OUD in patients with co-occurring substance use, (2) perspectives on barriers/facilitators to MOUD receipt for this population, and (3) support needed to increase MOUD receipt for this population. Methods We interviewed a purposive sample of 27 clinicians (12 primary care, 7 mental health, 4 pain, 4 pharmacists) in the VA northwest network. The interview guide assessed domains of the Tailored Implementation for Chronic Diseases Checklist. Interviews were transcribed and qualitatively analyzed using inductive content analysis. Results Participants reported varied approaches to identifying co-occurring substance use and addressing OUD in this patient population. Although they reported that this topic was not clearly addressed in clinical guidelines or training, participants generally felt that patients with co-occurring substance use should receive MOUD. Some viewed their primary role as providing this care, others as facilitating linkage to OUD care in SUD specialty settings. Participants reported multiple barriers and facilitators to providing buprenorphine care to patients with co-occurring substance use and linking them to SUD specialty care, including provider, patient, organizational, and external factors. Conclusions Efforts are needed to support clinicians outside of SUD specialty settings in providing buprenorphine care to patients with co-occurring substance use. These could include clearer guidelines and policies, more specific training, and increased care integration or cross-disciplinary collaboration. Simultaneously, efforts are needed to improve linkage to specialty SUD care for patients who would benefit from and are willing to receive this care, which could include increased service availability and improved referral/hand-off processes. These efforts may increase MOUD receipt and improve OUD care quality for patients with co-occurring substance use.

Abstract Background Experts recommend that treatment for substance use disorder (SUD) be integrated into primary care. The Digital Therapeutics for Opioids and Other SUD (DIGITS) Trial tests strategies for implementing reSET® and reSET-O®, which are prescription digital therapeutics for SUD and opioid use disorder, respectively, that include the community reinforcement approach, contingency management, and fluency training to reinforce concept mastery. This purpose of this trial is to test whether two implementation strategies improve implementation success (Aim 1) and achieve better population-level cost effectiveness (Aim 2) over a standard implementation approach. Methods/Design The DIGITS Trial is a hybrid type III cluster-randomized trial. It examines outcomes of implementation strategies, rather than studying clinical outcomes of a digital therapeutic. It includes 22 primary care clinics from a healthcare system in Washington State and patients with unhealthy substance use who visit clinics during an active implementation period (up to one year). Primary care clinics implemented reSET and reSET-O using a multifaceted implementation strategy previously used by clinical leaders to roll-out smartphone apps (“standard implementation” including discrete strategies such as clinician training, electronic health record tools). Clinics were randomized as 21 sites in a 2x2 factorial design to receive up to two added implementation strategies: (1) practice facilitation, and/or (2) health coaching. Outcome data are derived from electronic health records and logs of digital therapeutic usage. Aim 1’s primary outcomes include reach of the digital therapeutics to patients and fidelity of patients’ use of the digital therapeutics to clinical recommendations. Substance use and engagement in SUD care are additional outcomes. In Aim 2, population-level cost effectiveness analysis will inform the economic benefit of the implementation strategies compared to standard implementation. Implementation is monitored using formative evaluation, and sustainment will be studied for up to one year using qualitative and quantitative research methods. Discussion The DIGITS Trial uses an experimental design to test whether implementation strategies increase and improve the delivery of digital therapeutics for SUDs when embedded in a large healthcare system. It will provide data on the potential benefits and cost-effectiveness of alternative implementation strategies. ClinicalTrials.gov Identifier: NCT05160233 (Submitted 12/3/2021). https://clinicaltrials.gov/ct2/show/NCT05160233

Abstract Background Möbius (Moebius) and Poland’s syndromes are two rare congenital syndromes characterized by non-progressive bilateral (and often asymmetric) dysfunction of the 6th and 7th cranial nerves and hypoplasia of the pectoral muscles associated with chest wall and upper limb anomalies respectively. Manifest simultaneously as Poland-Möbius (Poland-Moebius) syndrome, debate continues as to whether this is a distinct nosological entity or represents phenotypic variation as part of a spectrum of disorders of rhomboencephalic development. Etiological hypotheses implicate both genetic and environmental factors. The PLXND1 gene codes for a protein expressed in the fetal central nervous system and vascular endothelium and is thus involved in embryonic neurogenesis and vasculogenesis. It is located at chromosome region 3q21-q22, a locus of interest for Möbius syndrome. Case presentation We present the first report of a patient with Poland-Möbius syndrome and a mutation in the PLXND1 gene. A child with Poland-Möbius syndrome and a maternally inherited missense variant (NM_015103.2:ex14:c.2890G > Ap.V964M) in the PLXND1 gene is described. In order to contextualize these findings, the literature was examined to identify other confirmed cases of Poland-Möbius syndrome for which genetic data were available. Fourteen additional cases of Poland-Möbius syndrome with genetic studies are described in the literature. None implicated the PLXND1 gene which has previously been implicated in isolated Möbius syndrome. Conclusions This report provides further evidence in support of a role for PLXND1 mutations in Möbius syndrome and reasserts the nosological link between Möbius and Poland’s syndromes. Level of evidence Level V, Descriptive Study.

Abstract Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular disease. While intermittent hypoxia (IH) and catecholamine release play an important role in this increased risk, the mechanisms are incompletely understood. We have recently reported that IH causes endothelial cell (EC) activation, an early phenomenon in the development of cardiovascular disease, via IH-induced catecholamine release. Here, we investigated the effects of IH and epinephrine on gene expression in human aortic ECs using RNA-sequencing. We found a significant overlap between IH and epinephrine-induced differentially expressed genes (DEGs) including enrichment in leukocyte migration, cytokine-cytokine receptor interaction, cell adhesion and angiogenesis. Epinephrine caused higher number of DEGs compared to IH. Interestingly, IH when combined with epinephrine had an inhibitory effect on epinephrine-induced gene expression. Combination of IH and epinephrine induced MT1G (Metallothionein 1G), which has been shown to be highly expressed in ECs from parts of aorta (i.e., aortic arch) where atherosclerosis is more likely to occur. In conclusion, epinephrine has a greater effect than IH on EC gene expression in terms of number of genes and their expression level. IH inhibited the epinephrine-induced transcriptional response. Further investigation of the interaction between IH and epinephrine is needed to better understand how OSA causes cardiovascular disease.

Background Digital interventions, such as smartphone apps, can be effective in treating alcohol use disorders (AUD). However, efforts to integrate digital interventions into primary care have been challenging. To inform successful implementation, we sought to understand how patients and clinicians preferred to use apps in routine primary care. Methods This study combined user-centered design and qualitative research methods, interviewing 18 primary care patients with AUD and nine primary care clinicians on topics such as prior experiences with digital tools, and design preferences regarding approaches for offering apps for AUD in primary care. Interviews were recorded and transcribed for template analysis whereby a priori codes were based on interview topics and refined through iterative coding. New codes and cross-cutting themes emerged from the data. Results Patient participants with AUD indicated they would be more likely to engage in treatment if primary care team members were involved in their use of apps. They also preferred to see clinicians “invested” and recommended that clinicians ask about app use and progress during follow-up appointments or check-ins. Clinician participants valued the opportunity to offer apps to their patients but noted that workflows would need to be tailored to individual patient needs. Time pressures, implementation complexity, and lack of appropriate staffing were cited as barriers. Clinicians proposed concrete solutions (e.g., education, tools, and staffing models) that could improve their ability to use apps within the constraints of primary care and suggested that some patients could potentially use apps without clinician support. Conclusions A user-centered approach to engaging patients in digital alcohol interventions in primary care may require personalized support for both initiation and follow-up. Meeting patients’ needs likely require increased staffing and efficient workflows in primary care. Health systems should consider offering multiple pathways for enrolling patients in apps to accommodate individual preferences and contextual barriers. Plain Language Summary Healthcare systems have begun using app-based treatments to help patients manage their health conditions, including alcohol use disorders. Some apps have been tested in research studies and appear to be effective. However, it is difficult for healthcare teams to offer apps to patients. Clinicians must engage in new activities that they have not done before, such as “teaching” patients to use apps and checking in on their use of the apps. Identifying how to use apps in routine healthcare is critical to their successful implementation. This study interviewed 27 people, including healthcare providers and patients in primary care, to uncover the most optimal ways to offer apps to patients with alcohol use disorders. The interviews combined the use of qualitative research methods and user-centered design. Results suggest that to use to address alcohol use disorders, primary care teams should be prepared to offer personalized support to patients. Both patient and clinician interviewees said that the steps required to use apps must be intuitive and simple. Patients could gain more benefits if clinicians introduced the apps and guided patients to use them, as opposed to making apps available for patients to download and use on their own. However, the exact approach to offering apps would depend on a given patient’s preferences and the extent that staffing was available in the clinic to support patients. Health systems should be prepared to offer and support patients in their use of apps, which should accommodate patient preferences and the constraints of the clinic.

Abstract. Objective:. To explore patient and treatment factors explaining the association between spine injury and opioid misuse. Design:. Prospective cohort study. Setting:. Level I trauma center in a Midwestern city. Participants:. English speaking patients aged 18 to 75 on Trauma and Orthopedic Surgical Services receiving opioids during hospitalization and prescribed at discharge. Exposure:. Spine injury on the Abbreviated Injury Scale. Main outcome measures:. Opioid misuse was defined by using opioids: in a larger dose, more often, or longer than prescribed; via a non-prescribed route; from someone other than a prescriber; and/or use of heroin or opium. Exploratory factor groups included demographic, psychiatric, pain, and treatment factors. Multivariable logistic regression estimated the association between spine injury and opioid misuse when adjusting for each factor group. Results:. Two hundred eighty-five eligible participants consented of which 258 had baseline injury location data and 224 had follow up opioid misuse data. Most participants were male (67.8%), white (85.3%) and on average 43.1 years old. One-quarter had a spine injury (25.2%). Of those completing follow-up measures, 14 (6.3%) developed misuse. Treatment factors (injury severity, intubation, and hospital length of stay) were significantly associated with spine injury. Spine injury significantly predicted opioid misuse [odds ratio [OR] 3.20, 95% confidence interval [CI] (1.05, 9.78)]. In multivariable models, adjusting for treatment factors attenuated the association between spine injury and opioid misuse, primarily explained by length of stay. Conclusion:. Spine injury exhibits a complex association with opioid misuse that predominantly operates through treatment factors. Spine injury patients may represent a subpopulation requiring early intervention to prevent opioid misuse.

Hantaviral diseases have been recognized as ‘place diseases’ from their earliest identification and, epidemiologically, are tied to single host species with transmission occurring from infectious hosts to humans. As such, human populations are most at risk when they are in physical proximity to suitable habitats for reservoir populations, when numbers of infectious hosts are greatest. Because of the lags between improving habitat conditions and increasing infectious host abundance and spillover to humans, it should be possible to anticipate (forecast) where and when outbreaks will most likely occur. Most mammalian hosts are associated with specific habitat requirements, so identifying these habitats and the ecological drivers that impact population growth and the dispersal of viral hosts should be markers of the increased risk for disease outbreaks. These regions could be targeted for public health and medical education. This paper outlines the rationale for forecasting zoonotic outbreaks, and the information that needs to be clarified at various levels of biological organization to make the forecasting of orthohantaviruses successful. Major challenges reflect the transdisciplinary nature of forecasting zoonoses, with needs to better understand the implications of the data collected, how collections are designed, and how chosen methods impact the interpretation of results.

The Costa Rican pygmy rice rat (Oligoryzomys costaricensis) is the primary reservoir of Choclo orthohantavirus (CHOV), the causal agent of hantavirus disease, pulmonary syndrome, and fever in humans in Panama. Since the emergence of CHOV in early 2000, we have systematically sampled and archived rodents from >150 sites across Panama to establish a baseline understanding of the host and virus, producing a permanent archive of holistic specimens that we are now probing in greater detail. We summarize these collections and explore preliminary habitat/virus associations to guide future wildlife surveillance and public health efforts related to CHOV and other zoonotic pathogens. Host sequences of the mitochondrial cytochrome b gene form a single monophyletic clade in Panama, despite wide distribution across Panama. Seropositive samples were concentrated in the central region of western Panama, consistent with the ecology of this agricultural commensal and the higher incidence of CHOV in humans in that region. Hantavirus seroprevalence in the pygmy rice rat was >15% overall, with the highest prevalence in agricultural areas (21%) and the lowest prevalence in shrublands (11%). Host–pathogen distribution, transmission dynamics, genomic evolution, and habitat affinities can be derived from the preserved samples, which include frozen tissues, and now provide a foundation for expanded investigations of orthohantaviruses in Panama.

Abstract Purpose Little is known about prevalence and treatment of OUD among youth engaged in primary care (PC). Medications are the recommended treatment of opioid use disorder (OUD) for adolescents and young adults (youth). This study describes the prevalence of OUD, the prevalence of medication treatment for OUD, and patient characteristics associated with OUD treatment among youth engaged in PC. Methods This cross-sectional study includes youth aged 16–25 years engaged in PC. Eligible patients had ≥ 1 PC visit during fiscal years (FY) 2014–2016 in one of 6 health systems across 6 states. Data from electronic health records and insurance claims were used to identify OUD diagnoses, office-based OUD medication treatment, and patient demographic and clinical characteristics in the FY of the first PC visit during the study period. Descriptive analyses were conducted in all youth, and stratified by age (16–17, 18–21, 22–25 years). Results Among 303,262 eligible youth, 2131 (0.7%) had a documented OUD diagnosis. The prevalence of OUD increased by ascending age groups. About half of youth with OUD had documented depression or anxiety and one third had co-occurring substance use disorders. Receipt of medication for OUD was lowest among youth 16–17 years old (14%) and highest among those aged 22–25 (39%). Conclusions In this study of youth engaged in 6 health systems across 6 states, there was low receipt of medication treatment, and high prevalence of other substance use disorders and mental health disorders. These findings indicate an urgent need to increase medication treatment for OUD and to integrate treatment for other substance use and mental health disorders.

Abstract Background Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. Methods PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16–90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be > 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims (“electronic health records,” [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. Discussion The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings. Trial registration # NCT03407638 (February 28, 2018); CTN-0074 https://clinicaltrials.gov/ct2/show/NCT03407638?term=CTN-0074&draw=2&rank=1

Abstract Background Acceptability is a critical requisite in establishing feasibility when planning a larger effectiveness trial. This study assessed the acceptability of conducting a feasibility randomized clinical trial of a 20-week microenterprise intervention for economically-vulnerable African-American young adults, aged 18 to 24, in Baltimore, Maryland. Engaging MicroenterprisE for Resource Generation and Health Empowerment (EMERGE) aimed to reduce sexual risk behaviors and increase employment and uptake of HIV preventive behaviors. Methods Thirty-eight participants were randomized to experimental (n = 19) or comparison group (n = 19). The experimental group received text messages on job openings plus educational sessions, mentoring, a start-up grant, and business and HIV prevention text messages. The comparison group received text messages on job openings only. Qualitative and quantitative post-intervention, in-person interviews were used in addition to process documentation of study methods. Results Our results found that the study design and interventions showed promise for being acceptable to economically-vulnerable African-American young adults. The largely positive endorsement suggested that factors contributing to acceptability included perceived economic potential, sexual health education, convenience, incentives, and encouraging, personalized feedback to participants. Barriers to acceptability for some participants included low cell phone connectivity, perceived payment delays, small cohort size, and disappointment with one’s randomization assignment to comparison group. Use of peer referral, network, or wait-list designs, in addition to online options may enhance acceptability in a future definitive trial. Expanding administrative and mentoring support may improve overall experience. Conclusion Microenterprise interventions are acceptable ways of providing young adults with important financial and sexual health content to address HIV risks associated with economic vulnerability. Trial registration ClinicalTrials.gov. NCT03766165 . Registered 04 December 2018.

De novo and acquired resistance are major impediments to the efficacy of conventional and targeted cancer therapy. In unselected gastric cancer (GC) patients with advanced disease, trials combining chemotherapy and an anti-EGFR monoclonal antibody have been largely unsuccessful. In an effort to identify biomarkers of resistance so as to better select patients for such trials, we screened the secretome of chemotherapy-treated human GC cell lines. We found that levels of CGA, the α-subunit of glycoprotein hormones, were markedly increased in the conditioned media of chemoresistant GC cells, and CGA immunoreactivity was enhanced in GC tissues that progressed on chemotherapy. CGA levels in plasma increased in GC patients who received chemotherapy, and this increase was correlated with reduced responsiveness to chemotherapy and poor survival. Mechanistically, secreted CGA was found to bind to EGFR and activate EGFR signaling, thereby conferring a survival advantage to GC cells. N-glycosylation of CGA at Asn52 and Asn78 is required for its stability, secretion, and interaction with EGFR. GATA2 was found to activate CGA transcription, whose increase, in turn, induced the expression and phosphorylation of GATA2 in an EGFR-dependent manner, forming a positive feedback circuit that was initiated by GATA2 autoregulation upon sublethal exposure to chemotherapy. Based on this circuit, combination strategies involving anti-EGFR therapies or targeting CGA with microRNAs (miR-708-3p and miR-761) restored chemotherapy sensitivity. These findings identify a clinically actionable CGA/EGFR/GATA2 circuit and highlight CGA as a predictive biomarker and therapeutic target in chemoresistant GC.

BackgroundDigital interventions, such as websites and smartphone apps, can be effective in treating drug use disorders (DUDs). However, their implementation in primary care is hindered, in part, by a lack of knowledge on how patients might like these treatments delivered to them. ObjectiveThis study aims to increase the understanding of how patients with DUDs prefer to receive app-based treatments to inform the implementation of these treatments in primary care. MethodsThe methods of user-centered design were combined with qualitative research methods to inform the design of workflows for offering app-based treatments in primary care. Adult patients (n=14) with past-year cannabis, stimulant, or opioid use disorder from 5 primary care clinics of Kaiser Permanente Washington in the Seattle area participated in this study. Semistructured interviews were recorded, transcribed, and analyzed using qualitative template analysis. The coding scheme included deductive codes based on interview topics, which primarily focused on workflow design. Inductive codes emerged from the data. ResultsParticipants wanted to learn about apps during visits where drug use was discussed and felt that app-related conversations should be incorporated into the existing care whenever possible, as opposed to creating new health care visits to facilitate the use of the app. Nearly all participants preferred receiving clinician support for using apps over using them without support. They desired a trusting, supportive relationship with a clinician who could guide them as they used the app. Participants wanted follow-up support via phone calls or secure messaging because these modes of communication were perceived as a convenient and low burden (eg, no copays or appointment travel). ConclusionsA user-centered implementation of treatment apps for DUDs in primary care will require health systems to design workflows that account for patients’ needs for structure, support in and outside of visits, and desire for convenience.

Abstract Background Economic vulnerability, such as homelessness and unemployment, contributes to the HIV risk among racial minorities in the U.S., who are disproportionately infected. Yet, few economic-strengthening interventions have been adapted for HIV prevention in economically-vulnerable African-American young adults. Engaging Microenterprise for Resource Generation and Health Empowerment (EMERGE) is a feasibility randomized clinical trial of an HIV prevention microenterprise intervention with integrated text messages (“nudges”) that are informed by behavioral economic principles. The trial aims to reduce sexual risk behaviors and increase employment and uptake of HIV preventive behaviors. Methods/design In total, 40 young adults who are African-American, aged 18–24, live in Baltimore City, have experienced at least one episode of homelessness in the last 12 months, are unemployed or underemployed (fewer than 10 h per week), are not enrolled in school, own a cell phone with text messaging, and report at least one episode of unprotected or unsafe sex in the prior 12 months will be recruited from two community-based organizations providing residential supportive services to urban youth. Participants will undergo a 3-week run-in period and thereafter be randomly assigned to one of two groups with active interventions for 20 weeks. The first group (“comparison”) will receive text messages with information on job openings. The second group (“experimental”) will receive text messages with information on job openings plus information on HIV prevention and business educational sessions, a mentored apprenticeship, and a start-up grant, and business and HIV prevention text messages based on principles from behavioral economics. The two primary outcomes relate to the feasibility of conducting a larger trial. Secondary outcomes relate to employment, sexual risk behaviors, and HIV preventive practices. All participants will be assessed using an in-person questionnaire at pre-intervention (prior to randomization) and at 3 weeks post-intervention. To obtain repeated, longitudinal measures, participants will be assessed weekly using text message surveys from pre-intervention up to 3 weeks post-intervention. Discussion This study will be one of the first U.S.-based feasibility randomized clinical trials of an HIV prevention microenterprise intervention for economically-vulnerable African-American young adults. The findings will inform whether and how to conduct a larger efficacy trial for HIV risk reduction in this population. Trial registration ClinicalTrials.gov, NCT03766165. Registered on 4 December 2018.

Ensembles of Species Distribution Models (SDMs) represent the geographic ranges of pathogen vectors by combining alternative analytical approaches and merging information on vector occurrences with more extensive environmental data. Biased collection data impact SDMs, regardless of the target species, but no studies have compared the differences in the distributions predicted by the ensemble models when different sampling frameworks are used for the same species. We compared Ensemble SDMs for two important Ixodid tick vectors, Amblyomma americanum and Ixodes scapularis in mainland Florida, USA, when inputs were either convenience samples of ticks, or collections obtained using the standard protocols promulgated by the U.S. Centers for Disease Control and Prevention. The Ensemble SDMs for the convenience samples and standard surveys showed only a slight agreement (Kappa = 0.060, A. americanum; 0.053, I. scapularis). Convenience sample SDMs indicated A. americanum and I. scapularis should be absent from nearly one third (34.5% and 30.9%, respectively) of the state where standard surveys predicted the highest likelihood of occurrence. Ensemble models from standard surveys predicted 81.4% and 72.5% (A. americanum and I. scapularis) of convenience sample sites. Omission errors by standard survey SDMs of the convenience collections were associated almost exclusively with either adjacency to at least one SDM, or errors in geocoding algorithms that failed to correctly locate geographic locations of convenience samples. These errors emphasize commonly overlooked needs to explicitly evaluate and improve data quality for arthropod survey data that are applied to spatial models.

Florida faces the challenge of repeated introduction and autochthonous transmission of arboviruses transmitted by Aedes aegypti and Aedes albopictus. Empirically-based predictive models of the spatial distribution of these species would aid surveillance and vector control efforts. To predict the occurrence and abundance of these species, we fit a mixed-effects zero-inflated negative binomial regression to a mosquito surveillance dataset with records from more than 200,000 trap days, representative of 53% of the land area and ranging from 2004 to 2018 in Florida. We found an asymmetrical competitive interaction between adult populations of Aedes aegypti and Aedes albopictus for the sampled sites. Wind speed was negatively associated with the occurrence and abundance of both vectors. Our model predictions show high accuracy (72.9% to 94.5%) in validation tests leaving out a random 10% subset of sites and data since 2017, suggesting a potential for predicting the distribution of the two Aedes vectors.

Effective mentoring is a key mechanism propelling successful research and academic careers, particularly for early career scholars. Most mentoring programs focus on models pairing senior and early career researchers, with limited focus on peer mentoring. Peer mentoring may be especially advantageous within emerging areas such as implementation science (IS) where challenges to traditional mentoring may be more prevalent. This special communication highlights the value of peer mentoring by describing a case study of an early career IS peer mentoring group. We delineate our curriculum and structure; support and processes; and products and outcomes. We highlight important group member characteristics to consider during group formation and continuation. The group’s long-term (6 years) success was attributed to the balance of similarities and differences among group members. Members were in a similar career phase and used similar methodologies but studied different health topics at different institutions. Group members gave and received instrumental and psychosocial support and shared resources and knowledge. Peer mentoring can serve an important function to provide emotional, logistical, and professional development support for early career scholars. Our case study highlights strategies to foster peer mentoring groups that provide a generalizable blueprint and opportunity for improved outcomes for early career professionals.

In Ukraine, a retrospective review of clinical case reports by public health officials suggest that human cases of febrile illnesses associated with hemorrhage may be due to infections of Crimean-Congo hemorrhagic fever virus (CCHFV) and Old World hantaviruses. In a serosurvey of 966 healthy individuals in the Lviv Oblast, Ukraine, bordering Poland, we found that 1.6% showed cross-reactivity to hantaviral antigens by an immunofluorescence assay (IFA) and 1.7% of the study participants had antibodies cross-reactive to CCHFV by enzyme-linked immunosorbent assay (ELISA). Demographic variables and history of exposures obtained through questionnaires were assessed by logistic regression models for association with seroprevalence for both viruses with no significant risk factors found. Analysis of spatial distribution identified two clusters of samples positive for antibodies to both hantaviruses and CCHFV, which, however, were not statistically significant (p > 0.05). In general, the study results suggest that the population of the study area is exposed to hantaviruses and CCHFV. Further surveillance for respective pathogens in Ukraine is warranted and prospective surveillance of febrile patients with unidentified febrile illness.

BackgroundRespondent-driven sampling (RDS) is a peer-referral sampling methodology used to estimate characteristics of underserved groups that cannot be randomly sampled. RDS has been implemented in several settings to identify hidden populations at risk for HIV, but few studies have reported the methodological lessons learned on RDS design and implementation for assessing sexual risk behaviors in marginalized youth.MethodsWe used RDS to recruit N = 350 young adults, aged 18 to 22, who were living in urban slum settlements in Nairobi, Kenya. A structured survey was used to assess sexual risk behaviors. Twenty seeds were selected and asked to recruit up to three eligible peers. We used small monetary incentives and a three-day recruitment coupon with sequential numbers linking recruiters to their recruits.ResultsData collection was completed in 8 days with a maximum chain length of 6 waves. Each seed yielded 16 to 21 eligible recruits. Three (15%) seeds were unproductive and were replaced. RDS benefits were high identification rates (90% coupons returned per coupons given), high eligibility rates (100% eligible recruits per coupons returned), and high efficiency (~39 eligible recruits per day). 44% of the sample was female. Most recruits (74%) reported being "friends" for 7+ years with their recruiter. RDS overcame feasibility concerns of household-, clinic-, and school-based sampling methodologies in that underserved youth who were unemployed (68%), out of school (48%), ethnic minorities (26%), and having prior residential instability (≥2 moves in the past year) (20%) were successfully recruited, based on weighted analyses. Youth reporting HIV risk behaviors, including unprotected sex (38%), sex while high/drunk (35%), and sex exchange for pay (14%), were also enrolled. However, 28% were not sexually active within the last 6 months. Challenges included managing wait times during peaks and participant referral expectations. Community engagement, use of study-stamped coupons, broad inclusion criteria, incentives, and study sites within walking distances all contributed to the successful implementation of the sampling methodology.ConclusionRDS is an important tool in reaching a diverse sample of underserved and at-risk young adults for study participation. Implications for optimizing RDS for behavioral studies in this population are discussed.

Abstract Background Opioid addiction and overdose are epidemic in the U.S. Victims of traumatic injury are at greater than average risk for opioid misuse and related complications. Potential risk screens and preventive interventions in this clinical population remain under-investigated. The current project seeks to develop and pilot the implementation of a screening tool for opioid risk at American College of Surgeons (ACS) Level I and Level II trauma centers. Methods The project began with an online survey, which was sent to Wisconsin trauma center medical directors and trauma coordinators for the purpose of gathering information on current substance use screening practices. Next, a focus group of trauma center staff was convened to discuss barriers and facilitators to screening, resources available and needed to support trauma patients with opioid use disorders, and measurable clinical observations that could indicate a patient’s potential risk for opioid misuse. Data from the surveys and focus group were combined to inform the data collection instruments that are currently being administered to patients recruited from the University of Wisconsin Hospital Trauma Inpatient and Orthopedic Surgery Services. Eligible and consenting patients complete standardized measures of socio-demographics, substance use history, opioid misuse risk, mental health, medical history, and injury and pain severity. Follow up visits at weeks 4, 12, and 24 after hospital discharge assess hypothesized risk factors for opioid addiction and opioid use disorder diagnosis. At the completion of patient data collection, a forward stepwise regression will identify factors of most significant risk of the development of opioid use disorder after traumatic injury. This modeling will inform the development of a novel opioid risk screening tool, which will undergo pilot implementation at 4 Wisconsin ACS Level I and Level II trauma centers, using an evidence-based implementation strategy with roots in systems engineering. Discussion Positive findings from the proposed work would lead to improved, standardized opioid risk screening practices among victims of traumatic injury. The ultimate goal of this and future work is to reduce the likelihood of opioid misuse, addiction, and related complications, such as overdose and death. Trial registration Clinicaltrials.gov registration number: NCT02861976. Date of registration: Feb 9, 2016

In Europe, two species of hantaviruses, Puumala orthohantavirus (PUUV) and Dobrava orthohantavirus (DOBV), cause hemorrhagic fever with renal syndrome in humans. The rodent reservoirs for these viruses are common throughout Ukraine, and hence, the goal of this study was to identify the species and strains of hantaviruses circulating in this region. We conducted surveillance of small rodent populations in a rural region in northwestern Ukraine approximately 30 km from Poland. From the 424 small mammals captured, we identified nine species, of which the most abundant were Myodes glareolus, the bank vole (45%); Apodemus flavicollis, the yellow-necked mouse (29%); and Apodemus agrarius, the striped field mouse (14.6%) Using an indirect immunofluorescence assay, 15.7%, 20.5%, and 33.9% of the sera from M. glareolus, A. glareolus, and A. flavicollis were positive for hantaviral antibodies, respectively. Additionally, we detected antibodies to the hantaviral antigen in one Microtus arvalis, one Mus musculus, and one Sorex minutus. We screened the lung tissue for hantaviral RNA using next-generation sequencing and identified PUUV sequences in 25 small mammals, including 23 M. glareolus, 1 M. musculus, and 1 A. flavicollis, but we were unable to detect DOBV sequences in any of our A. agrarius specimens. The percent identity matrix and Bayesian phylogenetic analyses of the S-segment of PUUV from 14 M. glareolus lungs suggest the highest similarity (92–95% nucleotide or 99–100% amino acid) with the Latvian lineage. This new genetic information will contribute to future molecular surveillance of human cases in Ukraine.

Abstract In 2016, the International Network on Brief Interventions for Alcohol & Other Drugs convened a meeting titled “Rethinking alcohol interventions in health care”. The aims of the meeting were to synthesize recent evidence about screening and brief intervention and to set directions for research, practice, and policy in light of this evidence. Screening and brief intervention is efficacious in reducing self-reported alcohol consumption for some with unhealthy alcohol use, but there are gaps in evidence for its effectiveness. Because screening and brief intervention is not known to be efficacious for individuals with more severe unhealthy alcohol use, recent data showing the lack of evidence for referral to treatment as part of screening and brief intervention are alarming. While screening and brief intervention was designed to be a population-based approach, its reach is limited. Implementation in real world care also remains a challenge. This report summarizes practice, research, and policy recommendations and key research developments from our meeting. In order to move the field forward, a research agenda was proposed to (1) address evidence gaps in screening, brief intervention, and referral to treatment, (2) develop innovations to address severe unhealthy alcohol use within primary care, (3) describe the stigma of unhealthy alcohol use, which obstructs progress in prevention and treatment, (4) reconsider existing conceptualizations of unhealthy alcohol use that may influence health care, and (5) identify efforts needed to improve the capacity for addressing unhealthy alcohol consumption in all world regions.

Two Old World rodents, house mice (Mus musculus) and Norway rats (Rattus norvegicus), were introduced into and established populations on every continent, save Antarctica. With their travels, they concomitantly introduced several zoonotic agents capable of causing human diseases. Two viruses—Lymphocytic choriomeningitis virus (LCMV; genus Arenavirus with mice) and Seoul virus (SEOV; genus Hantavirus with rats)—can cause chronic infections within their respective rodent hosts, resulting in persistent or life-long sporadic shedding of virus through secreta and excreta. Although the prevalence of infection within their wild rodent hosts can exceed 25% among mice infected with LCMV and 50% among rats infected with SEOV, acute human disease resulting from direct transmission from wild rodents is rarely reported even though both species live in close coexistence with humans. The usual “classic” zoonotic cycle of transmission from wild rodent reservoirs to humans now includes multiple unusual/unexpected routes. The largest described outbreaks of human disease caused by these viruses are linked to pet rodents. A novel reservoir host, the golden hamster, has supplanted house mice as the major source of LCMV infection, and SEOV outbreaks are linked to fancy rats kept as pets. Following LCMV, and to a lesser extent SEOV, outbreaks or infections associated with lab animals and/or cultured tissues derived from mice and hamsters have led to hundreds of cases of LCMV among laboratory workers, and SEOV has been detected among cell-cultured tissues. Additionally, LCMV is now a recognized source of severe congenital disease and is the unexpected source of severe and often fatal disease among solid organ recipients. Although the extensive usual and unusual routes of LCMV infection are exceptional there are many parallels with SEOV emergence.

Abstract The mechanism by which trauma initiates healing remains unclear. Precise understanding of these events may define interventions for accelerating healing that could be translated to the clinical arena. We previously reported that addition of low‐dose recombinant human TNF (rhTNF) at the fracture site augmented fracture repair in a murine tibial fracture model. Here, we show that local rhTNF treatment is only effective when administered within 24 h of injury, when neutrophils are the major inflammatory cell infiltrate. Systemic administration of anti‐TNF impaired fracture healing. Addition of rhTNF enhanced neutrophil recruitment and promoted recruitment of monocytes through CCL2 production. Conversely, depletion of neutrophils or inhibition of the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility, or osteoporotic, fractures represent a major medical problem as they are associated with permanent disability and premature death. Using a murine model of fragility fractures, we found that local rhTNF treatment improved fracture healing during the early phase of repair. If translated clinically, this promotion of fracture healing would reduce the morbidity and mortality associated with delayed patient mobilization.

Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses and transmitted by rodents is a significant public health problem in China, and occurs more frequently in selenium-deficient regions. To study the role of selenium concentration in HFRS incidence we used a multidisciplinary approach combining ecological analysis with preliminary experimental data. The incidence of HFRS in humans was about six times higher in severe selenium-deficient and double in moderate deficient areas compared to non-deficient areas. This association became statistically stronger after correction for other significant environment-related factors (low elevation, few grasslands, or an abundance of forests) and was independent of geographical scale by separate analyses for different climate regions. A case-control study of HFRS patients admitted to the hospital revealed increased activity and plasma levels of selenium binding proteins while selenium supplementation in vitro decreased viral replication in an endothelial cell model after infection with a low multiplicity of infection (MOI). Viral replication with a higher MOI was not affected by selenium supplementation. Our findings indicate that selenium deficiency may contribute to an increased prevalence of hantavirus infections in both humans and rodents. Future studies are needed to further examine the exact mechanism behind this observation before selenium supplementation in deficient areas could be implemented for HFRS prevention.

Despite efforts to control Lyme disease in Connecticut, USA, it remains endemic in many towns, posing a heavy burden. We examined changes in the spatial distribution of significant spatial clusters of Lyme disease incidence rates at the town level from 1991 to 2014 as an approach for targeted interventions. Lyme disease data were grouped into four discrete time periods and incidence rates were smoothed with Empirical Bayes estimation in GeoDa. Local clustering was measured using a local indicator of spatial autocorrelation (LISA). Elliptic spatial scan statistics (SSS) in different shapes and directions were also performed in SaTScan. The accuracy of these two cluster detection methods was assessed and compared for sensitivity, specificity, and overall accuracy. There was significant clustering during each period and significant clusters persisted predominantly in western and eastern parts of the state. Generally, the SSS method was more sensitive, while LISA was more specific with higher overall accuracy in identifying clusters. Even though the location of clusters changed over time, some towns were persistently (across all four periods) identified as clusters in LISA and their neighbouring towns (three of four periods) in SSS suggesting these regions should be prioritized for targeted interventions.

A statewide survey of questing ixodid ticks in mainland Florida was developed consistent with U.S. CDC standards to maximize the amount of epidemiologic and environmental data gathered. Survey sites were stratified by climatic zones and proportional to recognized land cover categories. A total of 560 transects on 41 sites within the state were sampled repeatedly by flagging between 2015 and 2018. Four tick species were collected; Amblyomma americanum, Amblyomma maculatum, Ixodes scapularis and Dermacentor variabilis. All species were more commonly found in northern and central regions of the state than in southern and western regions. Adult I. scapularis were active from autumn through spring and complementary to adult A. americanum and D. variabilis. Standardized survey methods help reduce sampling biases and better characterize risk from the species surveyed. However, differences in the attractiveness of collection methods for different tick species makes cross-species comparisons a continuing challenge.

Objective: To identify opportunities to reduce overuse of antibiotics for prevention of perinatal group B streptococcal (GBS) disease and management of preterm premature rupture of membranes (pPROM).

Objective: To identify opportunities to reduce overuse of antibiotics for prevention of perinatal group B streptococcal (GBS) disease and management of preterm premature rupture of membranes (pPROM).

Background: Malaria is endemic in 13 of 64 districts in Bangladesh. About 14 million people are at risk. Some evidence suggests that the prevalence of malaria in Bangladesh has decreased since the the Global Fund to Fight AIDS, Tuberculosis and Malaria started to support the National Malaria Control Program (NMCP) in 2007. We did an epidemiological and economic assessment of malaria control in Bangladesh. Methods: We obtained annually reported, district-level aggregated malaria case data and information about disbursed funds from the NMCP. We used a Poisson regression model to examine the associations between total malaria, severe malaria, malaria-attributable mortality, and insecticide-treated net coverage. We identified and mapped malaria hotspots using the Getis-Ord Gi* statistic. We estimated the cost-effectiveness of the NMCP by estimating the cost per confirmed case, cost per treated case, and cost per person of insecticide-treated net coverage. Findings: During the study period (from Jan 1, 2008, to Dec 31, 2012) there were 285 731 confirmed malaria cases. Malaria decreased from 6·2 cases per 1000 population in 2008, to 2·1 cases per 1000 population in 2012. Prevalence of all malaria decreased by 65% (95% CI 65–66), severe malaria decreased by 79% (78–80), and malaria-associated mortality decreased by 91% (83–95). By 2012, there was one insecticide-treated net for every 2·6 individuals (SD 0·20). Districts with more than 0·5 insecticide-treated nets per person had a decrease in prevalence of 21% (95% CI 19–23) for all malaria, 25% (17–32) for severe malaria, and 76% (35–91) for malaria-associated mortality among all age groups. Malaria hotspots remained in the highly endemic districts in the Chittagong Hill Tracts. The cost per diagnosed case was US$0·39 (SD 0·02) and per treated case was $0·51 (0·27); $0·05 (0·04) was invested per person per year for health education and $0·68 (0·30) was spent per person per year for insecticide-treated net coverage. Interpretation: Malaria elimination is an achievable prospect in Bangladesh and failure to push for elimination nearly ensures a resurgence of disease. Consistent financing is needed to avoid resurgence and maintain elimination goals. Funding: None.

This text provides the philosophic, conceptual, and pragmatic orientation for conducting action research within one's organization. Beginning with a review of the origins of action research, the authors detail the methodology and its relevance to organizational growth and progress. The text is divided into two main sections. The first provides the theoretical foundations for the use of action research within an organizational setting. The second section furnishes an in-depth discussion of the implementation process including potential pitfalls and challenges. Although one can glean all that is necessary to implement such an endeavor from the text, this would not be an approach for a first-time researcher to undertake without comprehensive assistance from a more seasoned researcher. URN: urn:nbn:de:0114-fqs0204446