Perinatal diesel exhaust exposure causes persistent changes in the brains of aged mice: An assessment of behavioral and biochemical endpoints related to neurodegenerative disease.

Epidemiological studies support an association between air pollution exposure, specifically particulate matter (PM), and neurodegenerative disease. Diesel exhaust (DE) is a principal component of ambient air pollution and a major contributor of PM. Our study aimed to examine whether early-life perinatal DE exposure is sufficient to affect behavioral and biochemical endpoints related to Alzheimer's disease later in life. To achieve this, mice were perinatally exposed (embryonic day 0-postnatal day 21) to DE (250-300 µg/m3 ) or filtered air (FA), and allowed to reach aged status (>18 months). Mice underwent behavioral assessment at 6 and 20 months of age, with tissue collected at 22 months for biochemical endpoints. At 6 months, minimal changes were noted in home-cage behavior of DE treated animals. At 20 months, an alternation deficit was noted with the T-maze, although no difference was seen in the object location task or any home-cage metrics. DE exposure did not alter the expression of Aß42, phosphorylated tau S199, or total tau. However, IBA-1 protein, a microglial activation marker, was significantly higher in DE exposed animals. Further, lipid peroxidation levels were significantly higher in the DE exposed animals compared to FA controls. Cytokine levels were largely unchanged with DE exposure, suggesting a lack of inflammation despite persistent lipid peroxidation. Taken together, the findings of this study support that perinatal exposure alone is sufficient to cause lasting changes in the brain, although the effects appear to be less striking than those previously reported in younger animals, suggesting some effects do not persist over time. These findings are encouraging from a public health standpoint and support the aggressive reduction of DE emissions to reduce lifetime exposure and potentially reduce disease outcome.

A Longitudinal Observational Study of Multimorbidity and Partner Support for Physical Activity Among People with Osteoarthritis.

BACKGROUND: Physical activity can improve osteoarthritis-related symptoms; however, many people with osteoarthritis (PWOA) are insufficiently active. Social support for physical activity from an intimate partner can help PWOA increase activity, but managing multiple, chronic physical or mental health conditions (i.e., multimorbidity) may influence provision and receipt of that support. METHOD: Data from a 1-year longitudinal observational study was used to examine associations between multimorbidity and three dimensions of partner support for physical activity-companionship partner support (doing activity together), enacted partner support, and social support effectiveness-in 169 insufficiently active PWOA and their partners. RESULTS: Multivariable-adjusted multi-level models indicated baseline differences in support by multimorbidity status: when partners had multimorbidity, PWOA reported receiving less companionship support and less effective support from partners; when PWOA had multimorbidity, partners reported providing less enacted support and both partners and PWOA reported less effective partner support. Broad trends (p < .05) indicate initial increases and subsequent decreases in companionship and enacted partner support when PWOA had multimorbidity, and among partners with and without multimorbidity. When PWOA had multimorbidity, an initial increase in support effectiveness was followed by no significant change; a similar trend was seen among partners with and without multimorbidity. CONCLUSION: Multimorbidity may generally contribute to less partner support for physical activity or less effective support, although influences on support over time are less clear. Physical activity interventions for couples experiencing multimorbidity would likely benefit from attention to the impact of multiple chronic health conditions on physical activity and physical activity-related partner support.

The Role of Cohabitating Partner and Relationship Characteristics on Physical Activity among Individuals with Osteoarthritis.

BACKGROUND: Most individuals with knee or hip osteoarthritis do not meet recommendations for physical activity. The Social Cognitive Theory suggests that the social environment (e.g., spouses/partners) may influence the physical activity of individuals with osteoarthritis. The purpose of this study was to examine whether the physical activity of insufficiently active, coupled adults with osteoarthritis was associated with received partner support for physical activity, partner's engagement in physical activity, and relationship satisfaction. METHODS: Cross-sectional data from 169 couples were collected. Accelerometers estimated moderate-to-vigorous physical activity and daily steps for participants with osteoarthritis and their partners. Participants with osteoarthritis reported total received partner support for physical activity and relationship satisfaction. RESULTS: Participants with osteoarthritis were on average 65 years old, 65% female, 86% non-Hispanic white, and 47% retired. Receiving total partner support more frequently was associated with more minutes of moderate-to-vigorous physical activity but not with steps. Relationship satisfaction moderated the association of partner's physical activity on the daily steps of individuals with osteoarthritis such that having a partner who accomplished more daily steps was associated with participants with osteoarthritis accomplishing more daily steps themselves when they reported greater relationship satisfaction. CONCLUSIONS: Partners and relationship satisfaction may play an important role in the physical activity of individuals with osteoarthritis. Interventions seeking to increase physical activity in this population may be enhanced by promoting partner support. Additional research is needed to further explain these associations within the context of relationship satisfaction.

Mycobacterium syngnathidarum sp. nov., a rapidly growing mycobacterium identified in syngnathid fish.

Two closely related isolates, 27335T and 24999, of rapidly growing, non-pigmented mycobacteria, were cultured from two clinically ill fish of the family Syngnathidae. Whole genome sequencing of the two isolates revealed low sequence homology to documented mycobacteria within public databases such as the NCBI. Evaluation of targeted housekeeping genes, including 16S rRNA, ITS, rpoB and hsp65, related the two bacteria distantly to Mycobacterium senegalense CK2 M4421 and Mycobacterium farcinogenes DSM 43637. Phenotypic, biochemical and dDNA-DNA hybridization tests demonstrated that Mycobacterium syngnathidarum is a new species distinct from other recognized rapidly growing mycobacterial species. Phenotypic, chemotaxonomic and phylogenetic data evaluation provided evidence that the two strains represent one novel species. We propose the formal recognition of Mycobacterium syngnathidarum sp. nov., with isolate 27335T as the type strain (=ATCC TSD-89T,=DSM 105112T).

Amphotericin B concentrations in healthy mallard ducks (Anas platyrhynchos) following a single intratracheal dose of liposomal amphotericin B using an atomizer.

Aspergillosis is a fungal infection that primarily affects the respiratory tract. Amphotericin B has broad antifungal activity and is commonly used to treat aspergillosis, a fungal pneumonia that is a common sequela in oiled waterfowl as well as other birds in wildlife rehabilitation. Pharmacokinetic parameters of nebulized amphotericin B in an avian model have been reported, but those of direct intratracheal delivery have yet to be established. The objective of this study was to evaluate if a single 3 mg/kg dose of liposomal amphotericin B delivered intratracheally using a commercial atomizer would achieve plasma and lung tissue concentrations exceeding targeted minimum inhibitory concentrations (MIC) for Aspergillus species in adult mallard ducks (Anas platyrhynchos). Following intratracheal delivery, amphotericin B was present in lung parenchyma at concentrations above the targeted MIC of 1 µg/g for up to 9 days post-administration; however, distribution of the drug was uneven, with the majority of the drug concentrated in one lung lobe. Concentrations in the contralateral lung lobe and the kidneys were above the targeted MIC 1 day after administration but declined exponentially with a half-life of approximately 2 days. Plasma concentrations were never above the targeted MIC. Histological examination of the trachea, bronchi, lungs, heart, liver, and kidneys did not reveal any toxic changes. Using a commercial atomizer, intratracheal delivery of amphotericin B at 3 mg/kg resulted in lung parenchyma concentrations above 1 µg/ml with no discernable systemic effects. Further studies to establish a system of drug delivery to both sides of the pulmonary parenchyma need to be performed, and the efficacy of this treatment for disease prevention remains to be determined.

Rutin suppresses human-amylin/hIAPP misfolding and oligomer formation in-vitro, and ameliorates diabetes and its impacts in human-amylin/hIAPP transgenic mice.

Pancreatic islet ß-cells secrete the hormones insulin and amylin, and defective ß-cell function plays a central role in the pathogenesis of type-2 diabetes (T2D). Human amylin (hA, also termed hIAPP) misfolds and forms amyloid aggregates whereas orthologous mouse amylin does neither. Furthermore, hA elicits apoptosis in cultured ß-cells and ß-cell death in ex-vivo islets. In addition, hA-transgenic mice that selectively express hA in their ß-cells, manifest ß-cell apoptosis and progressive islet damage that leads to diabetes closely resembling that in patients with T2D. Aggregation of hA is thus linked to the causation of diabetes. We employed time-dependent thioflavin-T spectroscopy and ion-mobility mass spectrometry to screen potential suppressors of hA misfolding for anti-diabetic activity. We identified the dietary flavonol rutin as an inhibitor of hA-misfolding and measured its anti-diabetic efficacy in hA-transgenic mice. In vitro, rutin bound hA, suppressed misfolding, disaggregated oligomers and reverted hA-conformation towards the physiological. In hA-transgenic mice, measurements of glucose, fluid-intake, and body-weight showed that rutin-treatment slowed diabetes-progression by lowering of rates of elevation in blood glucose (P = 0.030), retarding deterioration from symptomatic diabetes to death (P = 0.014) and stabilizing body-weight (P < 0.0001). In conclusion, rutin treatment suppressed hA-aggregation in vitro and doubled the lifespan of diabetic mice (P = 0.011) by a median of 69 days compared with vehicle-treated control-diabetic hA-transgenic mice.

Trauma-Informed HIV Prevention and Treatment.

The high prevalence of trauma and its negative impact on health and health-promoting behaviors underscore the need for multi-level interventions to address trauma and its associated sequelae to improve physical and mental well-being in both HIV-infected and HIV-uninfected populations. Growing global awareness of the intersection of trauma and HIV has resulted in development and testing of interventions to address trauma in the context of HIV treatment and HIV prevention in the USA and globally. Despite increasing recognition of the widespread nature of trauma and the importance of trauma to HIV transmission around the globe, several gaps remain. Through a survey of the literature, we identified eight studies (published in the past 5 years) describing interventions to address the effects of trauma on HIV-related outcomes. In particular, this study focused on the levels of intervention, populations the interventions were designed to benefit, and types of trauma addressed in the interventions in the context of both HIV prevention and treatment. Remarkably absent from the HIV prevention, interventions reviewed were interventions designed to address violence experienced by men or transgender individuals, in the USA or globally. Given the pervasive nature of trauma experienced generally, but especially among individuals at heightened risk for HIV, future HIV prevention interventions universally should consider becoming trauma-informed. Widespread acknowledgement of the pervasive impact of gender-based violence on HIV outcomes among women has led to multiple calls for trauma-informed care (TIC) approaches to improve the effectiveness of HIV services for HIV-infected women. TIC approaches may be relevant for and should also be tested among men and all groups with high co-occurring epidemics of HIV and trauma (e.g., men who have sex with men (MSM), transgendered populations, injection drug users, sex workers), regardless of type of trauma experience.

Relating gas phase to solution conformations: Lessons from disordered proteins.

In recent years both mass spectrometry (MS) and ion mobility mass spectrometry (IM-MS) have been developed as techniques with which to study proteins that lack a fixed tertiary structure but may contain regions that form secondary structure elements transiently, namely intrinsically disordered proteins (IDPs). IM-MS is a suitable method for the study of IDPs which provides an insight to conformations that are present in solution, potentially enabling the analysis of lowly populated structural forms. Here, we describe the IM-MS data of two IDPs; α-Synuclein (α-Syn) which is implicated in Parkinson's disease, and Apolipoprotein C-II (ApoC-II) which is involved in cardiovascular diseases. We report an apparent discrepancy in the way that ApoC-II behaves in the gas phase. While most IDPs, including α-Syn, present in many charge states and a wide range of rotationally averaged collision cross sections (CCSs), ApoC-II presents in just four charge states and a very narrow range of CCSs, independent of solution conditions. Here, we compare MS and IM-MS data of both proteins, and rationalise the differences between the proteins in terms of different ionisation processes which they may adhere to.

Insertion of apoLp-III into a lipid monolayer is more favorable for saturated, more ordered, acyl-chains.

Neutral lipid transport in mammals is complicated involving many types of apolipoprotein. The exchangeable apolipoproteins mediate the transfer of hydrophobic lipids between tissues and particles, and bind to cell surface receptors. Amphipathic α-helices form a common structural motif that facilitates their lipid binding and exchangeability. ApoLp-III, the only exchangeable apolipoprotein found in insects, is a model amphipathic α-helix bundle protein and its three dimensional structure and function mimics that of the mammalian proteins apoE and apoAI. Even the intracellular exchangeable lipid droplet protein TIP47/perilipin 3 contains an α-helix bundle domain with high structural similarity to that of apoE and apoLp-III. Here, we investigated the interaction of apoLp-III from Locusta migratoria with lipid monolayers. Consistent with earlier work we find that insertion of apoLp-III into fluid lipid monolayers is highest for diacylglycerol. We observe a preference for saturated and more highly ordered lipids, suggesting a new mode of interaction for amphipathic α-helix bundles. X-ray reflectivity shows that apoLp-III unfolds at a hydrophobic interface and flexible loops connecting the amphipathic α-helices stay in solution. X-ray diffraction indicates that apoLp-III insertion into diacylglycerol monolayers induces additional ordering of saturated acyl-chains. These results thus shed important new insight into the protein-lipid interactions of a model exchangeable apolipoprotein with significant implications for its mammalian counterparts.

Conformational dynamics of α-synuclein: insights from mass spectrometry.

The aggregation and deposition of α-synuclein in Lewy bodies is associated with the progression of Parkinson's disease. Here, Mass Spectrometry (MS) is used in combination with Ion Mobility (IM), chemical crosslinking and Electron Capture Dissociation (ECD) to probe transient structural elements of α-synuclein and its oligomers. Each of these reveals different aspects of the conformational heterogeneity of this 14 kDa protein. IM-MS analysis indicates that this protein is highly disordered, presenting in positive ionisation mode with a charge state range of 5 ≤z≤ 21 for the monomer, along with a collision cross section range of ∼1600 Å(2). Chemical crosslinking applied in conjunction with IM-MS captures solution phase conformational families enabling comparison with those exhibited in the gas phase. Crosslinking IM-MS identifies 3 distinct conformational families, Compact (∼1200 Å(2)), Extended (∼1500 Å(2)) and Unfolded (∼2350 Å(2)) which correlate with those observed in solution. ECD-Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry (ECD-FT-ICR MS) highlights the effect of pH on α-synuclein structure, identifying the conformational flexibility of the N and C termini as well as providing evidence for structure in the core and at times the C terminus. A hypothesis is proposed for the variability displayed in the structural rearrangement of α-synuclein following changes in solution pH. Following a 120 h aggregation time course, we observe an increase in the ratio of dimer to monomer, but no gross conformational changes in either, beyond the significant variations that are observed day-to-day from this conformationally dynamic protein.

Using text messages to improve patient-doctor communication among racial and ethnic minority adults: an innovative solution to increase influenza vaccinations.

Despite the 2010 CDC recommendation that all adults receive influenza vaccinations, in the 2013-2014 influenza season, only 35% of Blacks and 37% of Hispanics were vaccinated, compared to 40% of Whites. This disparity could be due to poor patient-doctor communication, among other barriers. Doctors provide more health information to active communicators; unfortunately, they perceive minority patients to be poor communicators. A novel way to prompt minority patients to better communicate with their doctors is through mHealth. Text messaging is a simple, low cost, mHealth platform widely-used among racial and ethnic minorities. A text message campaign could be effective in providing vaccine education and prompting patients to converse with their doctors about influenza vaccinations. Text prompts could improve patient communication, thus increasing their likelihood of vaccination. This campaign could accomplish Healthy People 2020 goals: increase influenza vaccination, improve patient-doctor communication, increase use of mHealth, and reduce health disparities.

Design and development of a combined calcium-iron-folic acid prenatal supplement to support implementation of the new World Health Organization recommendations for calcium supplementation during pregnancy.

BACKGROUND: Hypertensive diseases of pregnancy are important causes of maternal and perinatal mortality. Based on meta-analyses of efficacy trials of prenatal calcium supplementation to reduce the risk of hypertensive diseases of pregnancy, the World Health Organization recommends 1.5 to 2.0 g of elemental calcium per day for pregnant women with low dietary calcium intakes (as well as 60 mg of iron and 400 microg of folic acid). However, implementation of this recommendation is challenged by the size and number of calcium tablets required and the need to avoid concurrent ingestion of calcium and iron due to intraintestinal interactions. OBJECTIVE: We developed a novel micronutrient powder containing microencapsulated pH-sensitive calcium in addition to iron and folic acid, designed to facilitate early intestinal iron release and delayed calcium release. METHODS: Two pharmaceutical companies were contracted to develop a prototype, one of which was chosen for clinical testing. Calcium carbonate granules were coated with a trilayer pH-sensitive enteric coating using a fluid-bed spray coater. Iron and folic acid granules were encapsulated with a time-release coating. Iron and calcium dissolution profiles were assessed during exposure to acidic (pH 1.2) and/or basic (pH 5.8) media using a modified USP apparatus 1 (basket) method. RESULTS: At pH 1.2, calcium and iron release was < or = 10% and > 90% after 120 minutes, respectively. At pH 5.8, > 80% of total calcium was released after 90 minutes. CONCLUSIONS: Based on in vitro criteria, the supplement may be a promising approach for delivering calcium, iron, and folic acid as a single daily dose to pregnant women in settings of low dietary intake of calcium.

Development of culturally-appropriate text message booster content to follow a brief intervention focused on reducing alcohol related harms for injury patients in Moshi, Tanzania.

Alcohol use is a risk factor for death and disability and is attributed to almost one-third of injury deaths globally. This highlights the need for interventions aimed at alcohol reduction, especially in areas with high rates of injury with concurrent alcohol use, such as Tanzania. The aim of this study is to create a culturally appropriate text messages as a booster to a brief negotiational intervention (BNI), to in the Emergency Department of the Kilimanjaro Christian Medical Centre, Moshi, Tanzania. Creation of text message boosters for an ED-based intervention expands the window of opportunity for alcohol use reduction in this high-risk population. The study followed a two-step approach to create the text message content in English and then translate and culturally adapt to Tanzanian Swahili. The culturalization process followed the World Health Organization's process of translation and adaptation of instruments. Translation, back translation, and qualitative focus groups were used for quality control to ensure text message content accuracy and cultural appropriateness. In total, nearly 50 text messages were initially developed in English, yet only 29 text messages were successfully translated and adapted; they were focused on the themes of Self-awareness, Goal setting and Motivation. We developed culturally appropriate text message boosters in Swahili for injury patients in Tanzania coupled with a BNI for alcohol use reduction. We found it important to evaluate content validation for interventions and measurement tools because the intended text message can often be lost in translation. The process of culturalization is critical in order to create interventions that are applicable and beneficial to the target population. Trial registration: Clinical Trials Registration Number: NCT02828267, NCT04535011.

Single-day protein LC-MS bioanalysis: can next-generation trypsins cut it?

Aims: The drive toward more sensitive LC-MS assays has resulted in long, complex methods. We assessed next-generation trypsins to identify a suitable candidate to integrate into protein LC-MS method development strategies, to simplify methods and increase throughput. Materials & methods: The performance of commercially available next-generation trypsins was assessed based on the digestion of protein standards in buffer and complex matrix by LC-high-resolution MS. Results: The performance of all next-generation trypsins assessed exceeded that of an overnight tryptic digest in a fraction of the time. Performing reduction and alkylation prior to digestion with heat-stable trypsins may be beneficial and should be investigated. Conclusion: Promega Rapid-Digestion Trypsin is the best-performing next-generation trypsin, surpassing an overnight tryptic digestion.

Feasibility of a pragmatic randomized adaptive clinical trial to evaluate a brief negotiational interview for harmful and hazardous alcohol use in Moshi, Tanzania.

INTRODUCTION: Low-resourced settings often lack personnel and infrastructure for alcohol use disorder treatment. We culturally adapted a Brief Negotiational Interview (BNI) for Emergency Department injury patients, the "Punguza Pombe Kwa Afya Yako (PPKAY)" ("Reduce Alcohol For Your Health") in Tanzania. This study aimed to evaluate the feasibility of a pragmatic randomized adaptive controlled trial of the PPKAY intervention. MATERIALS AND METHODS: This feasibility trial piloted a single-blind, parallel, adaptive, and multi-stage, block-randomized controlled trial, which will subsequently be used to determine the most effective intervention, with or without text message booster, to reduce alcohol use among injury patients. We reported our feasibility pilot study using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework, with recruitment and retention rates being our primary and secondary outcomes. We enrolled adult patients seeking care for an acute injury at the Kilimanjaro Christian Medical Center in Tanzania if they (1) exhibited an Alcohol Use Disorder Identification Test (AUDIT) ≥8, (2) disclosed alcohol use prior to injury, or (3) had a breathalyzer ≥0.0 on arrival. Intervention arms were usual care (UC), PPKAY, PPKAY with standard text booster, or a PPKAY with a personalized text booster. RESULTS: Overall, 181 patients were screened and 75 enrolled with 80% 6-week, 82.7% 3-month and 84% 6-month follow-up rates showing appropriate Reach and retention. Adoption measures showed an overwhelmingly positive patient acceptance with 100% of patients perceiving a positive impact on their behavior. The Implementation and trial processes were performed with high rates of PPKAY fidelity (76%) and SMS delivery (74%). Intervention nurses believed Maintenance and sustainability of this 30-minute, low-cost intervention and adaptive clinical trial were feasible. CONCLUSIONS: Our intervention and trial design are feasible and acceptable, have evidence of good fidelity, and did not show problematic deviations in protocol. Results suggest support for undertaking a full trial to evaluate the effectiveness of the PPKAY, a nurse-driven BNI in a low-income country. TRIAL REGISTRATION: Trial registration number NCT02828267. https://classic.clinicaltrials.gov/ct2/show/NCT02828267.

Perspectives on snakebite envenoming care needs across different sociocultural contexts and health systems: A comparative qualitative analysis among US and Brazilian health providers.

With the advancements in therapeutics and available treatment options, almost all deaths and permanent disabilities from snakebite envenoming (SBE) are preventable. The challenge lies in implementing these evidence-based treatments and practices across different settings and populations. This study aims to compare data on provider perceptions of SBE care across health systems and cultural contexts to inform potential implementation science approaches. We hypothesize different health systems and cultural contexts will influence specific perceived needs to provide adequate snakebite care within central tenets of care delivery (e.g., cost, access, human resources). We previously conducted exploratory descriptive studies in the US and Brazil in order to understand the experience, knowledge, and perceptions of health professionals treating SBE. In the US, in-depth interviews were performed with emergency physicians from January 2020 to March 2020. In BR, focus group discussions were conducted with health professionals from community health centers at the end of June 2021. The focus group discussions (BR) were originally analyzed through an inductive thematic analysis approach. We conducted a secondary qualitative analysis in which this codebook was then applied to the interviews (US) in a deductive content analysis. The analysis concluded in August 2022. Brazil participants were physicians (n=5) or nurses (n=20) from three municipalities in the State of Amazonas with an average of three years of professional experience. US participants were emergency physicians (n=16) with an average of 15 years of professional experience. Four main themes emerged: 1) barriers to adequate care on the patient and/or community side and 2) on the health system side, 3) perceived considerations for how to address SBE, and 4) identified needs for improving care. There were 25 subthemes within the four themes. These subthemes were largely the same across the Brazil and US data, but the rationale and content within each shared subtheme varied significantly. For example, the subtheme "role of health professionals in improving care" extended across Brazil and the US. Brazil emphasized the need for task-shifting and -sharing amongst health care disciplines, whereas the US suggested specialized approaches geared toward increasing access to toxicologists and other referral resources. Despite similar core barriers to adequate snakebite envenoming care and factors to consider when trying to improve care delivery, health professionals in different health systems and sociocultural contexts identified different needs. Accounting for, and understanding, these differences is crucial to the success of initiatives intended to strengthen snakebite envenoming care. Implementation science efforts, with explicit health professional input, should be applied to develop new and/or adapt existing evidence-based treatments and practices for SBE.

BITES study: A qualitative analysis among emergency medicine physicians on snake envenomation management practices.

INTRODUCTION: Antivenom is currently considered standard treatment across the full spectrum of severity for snake envenomation in the United States. Although safe and effective antivenoms exist, their use in clinical practice is not universal. OBJECTIVE: This study explored physicians' perceptions of antivenom use and experience with snake envenomation treatment in order to identify factors that influence treatment decisions and willingness to administer. METHODS: We conducted a qualitative study including in-depth interviews via online video conferencing with physicians practicing in emergency departments across the United States. Participants were selected based on purposive sampling methods. Data analysis followed inductive strategies, conducted by two researchers. The codebook and findings were discussed within the research team. FINDINGS: Sixteen in-depth interviews with physicians from nine states across the US were conducted. The participants' specialties include emergency medicine (EM), pediatric EM, and toxicology. The experience of treating snakebites ranged from only didactic education to having treated over 100 cases. Emergent themes for this manuscript from the interview data included perceptions of antivenom, willingness to administer antivenom and influencing factors to antivenom usage. Overall, cost-related concerns were a major barrier to antivenom administration, especially in cases where the indications and effectiveness did not clearly outweigh the potential financial burden on the patient in non-life- or limb-threatening cases. The potential to decrease recovery time and long-term functional impairments was not commonly reported by participants as an indication for antivenom. In addition, level of exposure and perceived competence, based on prior education and clinical experience, further impacted the decision to treat. Resources such as Poison Center Call lines were well received and commonly used to guide the treatment plan. The need for better clinical guidelines and updated treatment algorithms with clinical and measurable indicators was stated to help the decision-making process, especially among those with low exposure to snake envenomation patients. CONCLUSIONS: A major barrier to physician use of antivenom is a concern about cost, cost transparency and cost-benefit for the patients. Those concerns, in addition to the varying degrees of awareness of potential long-term benefits, further influence inconsistent clinical treatment practices.

Feasibility of SMS booster for alcohol reduction in injury patients in Tanzania.

Alcohol use is associated with 3 million annual deaths globally. Harmful alcohol use, which is associated with a high burden of disease in low- and middle-income countries (LMICs), often increases the probability of traumatic injury. Treatments for harmful alcohol use in LMICs, such as Tanzania, lack trained personnel and adequate infrastructure. The aim of this study was to assess the feasibility of using SMS boosters to augment a hospital based brief negotiational intervention (BNI) in this low resourced setting. We conducted a three stage, four arm feasibility trial of a culturally adapted BNI for injury patients with harmful and hazardous drinking admitted to Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania. Post hospital discharge, two of the four arms included patients receiving either a standard or personalized short message service (SMS) booster to enhance and or perpetuate the effect of the in-hospital BNI. Text messages were sent weekly throughout a 3-month follow-up period. SMS feasibility was assessed according to the TIDier checklist evaluating what, when, how much, tailoring processes, modifications and how well (intervention fidelity). Data was collected with SMS logs and short answer surveys to participants. A total of 41 study participants were assigned to each receive 12 SMS over a three-month period; 38 received messages correctly, 3 did not receive intended messages, and 1 received a message who was not intended to. Of the 258 attempted texts, 73% were successfully sent through the messaging system. Of the messages that failed delivery, the majority were not able to be sent due to participants traveling out of cellular service range or turning off their phones. Participants interviewed in both booster arms reported that messages were appropriate, and that they would appreciate the continuation of such reminders. At 6-month follow-up, 100% (n = 11) of participants interviewed believed that the boosters had a positive impact on their behavior, with 90% reporting a large impact. This study demonstrated feasibility and acceptability of the integration of SMS mobile health technology to supplement this type of nurse-led BNI. SMS booster is a practical tool that can potentially prolong the impact of a brief hospital based intervention to enact behavioral change in injury patients with AUD.

PRACT: a pragmatic randomized adaptive clinical trial protocol to investigate a culturally adapted brief negotiational intervention for alcohol use in the emergency department in Tanzania.

BACKGROUND: Alcohol use in resource-limited settings results in significant morbidity and mortality. These settings lack the necessary specialty-trained personnel and infrastructure. Therefore, implementing evidence-based interventions from high-income settings, like a brief negotiational intervention (BNI) for alcohol, will require rapid production of evidence of effectiveness to guide implementation priorities. Thus, this study describes a clinical trial protocol to rapidly optimize and evaluate the impact of a culturally adapted BNI to reduce alcohol-related harms and alcohol consumption among injury patients. METHODS: Our pragmatic, adaptive, randomized controlled trial (PRACT) is designed to determine the most effective intervention approach to reduce hazardous alcohol use among adult (≥18 years old) in acute (< 24 h) injury patients. Our culturally adapted, nurse-delivered, intervention (PPKAY) has been augmented with evidence-based, culturally appropriate standards and will be evaluated as follows. Stage 1 of the trial will determine if PPKAY, either with a standard short-message-service (SMS) booster or with a personalized SMS booster is more effective than usual care (UC). While optimizing statistical efficiency, Stage 2 drops the UC arm to compare the PPKAY with a standard SMS booster to PPKAY with a personalized SMS booster. Finally, in Stage 3, the more effective arm in Stage 2 is compared to PPKAY without an SMS booster. The study population is acute injury patients who present to Kilimanjaro Christian Medical Centre, Tanzania, who (1) test alcohol positive by breathalyzer upon arrival; (2) have an Alcohol Use Disorder Identification Test of 8 or above; and/or (3) have reported drinking alcohol prior to their injury. Outcome measures will be evaluated for all arms at 3, 6, 9, 12, and 24 months. The primary outcome for the study is the reduction of the number of binge drinking days in the 4 weeks prior to follow-up. Secondary outcomes include alcohol-related consequences, measured by the Drinker Inventory of Consequences. DISCUSSION: The findings from this study will be critically important to identify alcohol harm reduction strategies where alcohol research and interventions are scarce. Our innovative and adaptive trial design can transform behavior change research and identify the most effective nurse-driven intervention to be targeted for integration into standard care. TRIAL REGISTRATION: ClinicalTrials.gov NCT04535011 . Registered on September 1, 2020.

Contextualizing the Impact of Snakebite Envenoming on Patients: A Qualitative Content Analysis of Patient-Specific Functional Scale Activities Using the International Classification of Functioning, Disability and Health.

To categorize the Patient-specific Functional Scale (PSFS) activities in snakebite envenoming (SBE) using the International Classification of Function (ICF) model in order to describe the impact of SBE on patients' activities and daily lives and to develop a theoretical SBE model of functioning, we performed a post-hoc analysis of two multi-center, prospective studies, conducted at 14 clinical sites in the United States with consecutive SBE patients presenting to the emergency department. Qualitative content analysis and natural language processing were used to categorize activities reported in the PSFS using the ICF model. Our sample included 93 patients. The mean age was 43.0 (SD 17.9) years, most had lower extremity injuries (59%). A total of 99 unique activities representing eight domains came within the Activity and Participation component of the ICF model, with the majority in the Mobility and General Tasks and Demands domains. The main concerns of SBE patients are the ability to perform daily activities and to engage within their social environment. Applying the ICF model to SBE can facilitate the creation of a patient-centered treatment approach, moving beyond body-structural impairments towards a function-based treatment approach and facilitate early integration of rehabilitation services.