Improving newborn screening test performance for metachromatic leukodystrophy: Recommendation from a pre-pilot study that identified a late-infantile case for treatment.

Metachromatic leukodystrophy (MLD) is a devastating rare neurodegenerative disease. Typically, loss of motor and cognitive skills precedes early death. The disease is characterised by deficient lysosomal arylsulphatase A (ARSA) activity and an accumulation of undegraded sulphatide due to pathogenic variants in the ARSA gene. Atidarsagene autotemcel (arsa-cel), an ex vivo haematopoietic stem cell gene therapy was approved for use in the UK in 2021 to treat early-onset forms of pre- or early-symptomatic MLD. Optimal outcomes require early diagnosis, but in the absence of family history this is difficult to achieve without newborn screening (NBS). A pre-pilot MLD NBS study was conducted as a feasibility study in Manchester UK using a two-tiered screening test algorithm. Pre-established cutoff values (COV) for the first-tier C16:0 sulphatide (C16:0-S) and the second-tier ARSA tests were evaluated. Before the pre-pilot study, initial test validation using non­neonatal diagnostic bloodspots demonstrated ARSA pseudodeficiency status was associated with normal C16:0-S results for age (n = 43) and hence not expected to cause false positive results in this first-tier test. Instability of ARSA in bloodspot required transfer of NBS bloodspots from ambient temperature to -20°C storage within 7-8 days after heel prick, the earliest possible in this UK pre-pilot study. Eleven of 3687 de-identified NBS samples in the pre-pilot were positive for C16:0-S based on the pre-established COV of ≥170 nmol/l or ≥ 1.8 multiples of median (MoM). All 11 samples were subsequently tested negative determined by the ARSA COV of <20% mean of negative controls. However, two of 20 NBS samples from MLD patients would be missed by this C16:0-S COV. A further suspected false negative case that displayed 4% mean ARSA activity by single ARSA analysis for the initial test validation was confirmed by genotyping of this NBS bloodspot, a severe late infantile MLD phenotype was predicted. This led to urgent assessment of this child by authority approval and timely commencement of arsa-cel gene therapy at 11 months old. Secondary C16:0-S analysis of this NBS bloodspot was 150 nmol/l or 1.67 MoM. This was the lowest result reported thus far, a new COV of 1.65 MoM is recommended for future pilot studies. Furthermore, preliminary data of this study showed C16:1-OH sulphatide is more specific for MLD than C16:0-S. In conclusion, this pre-pilot study adds to the international evidence that recommends newborn screening for MLD, making it possible for patients to benefit fully from treatment through early diagnosis.

Higher precision, first tier newborn screening for metachromatic leukodystrophy using 16:1-OH-sulfatide.

Newborn screening (NBS) for metachromatic leukodystrophy (MLD) is based on first-tier measurement of sulfatides in dried blood spots (DBS) followed by second-tier measurement of arylsulfatase A in the same DBS. This approach is very precise with 0-1 false positives per ∼30,000 newborns tested. Recent data reported here shows that the sulfatide molecular species with an α-hydroxyl, 16­carbon, mono-unsaturated fatty acyl group (16:1-OH-sulfatide) is superior to the original biomarker 16:0-sulfatide in reducing the number of first-tier false positives. This result is consistent across 4 MLD NBS centers. By measuring 16:1-OH-sulfatide alone or together with 16:0-sulfatide, the estimated false positive rate is 0.048% and is reduced essentially to zero with second-tier arylsulfatase A activity assay. The false negative rate is predicted to be extremely low based on the demonstration that 40 out of 40 newborn DBS from clinically-confirmed MLD patients are detected with these methods. The work shows that NBS for MLD is extremely precise and ready for deployment. Furthermore, it can be multiplexed with several other inborn errors of metabolism already tested in NBS centers worldwide.

Piloting a Layperson Prehospital Care System in Rural Uganda.

INTRODUCTION: In many low-income countries, basic prehospital Emergency Medical Services (EMS) remain under-developed, resulting in significant delays or the complete inability to access care. STUDY OBJECTIVE: The purpose of this study was to analyze the effectiveness of a layperson EMS training targeting motorcycle taxi (boda) drivers in a rural region of Uganda. METHODS: Fifty (50) adult boda drivers from Masindi, Uganda were selected for a one-day training course including lectures and simulation. Course content covered basic prehospital skills and transport. Participants were given a first responder kit at completion of the course. Understanding of material was assessed prior to training, immediately after course completion, and four months from the initial course using the same ten question test. Test means were analyzed using a standard linear regression model. At the four-month follow up, all 50 boda drivers participated in semi-structured small group qualitative interviews regarding their perception of the course and experiences implementing course skills in the community. Boda drivers were asked to complete a brief form on each patient transported during the study period. For patients transported to Masindi Kitara Medical Center (MKMC), hospital trauma registry data were analyzed. RESULTS: Trainees showed both knowledge acquisition and retention with pre-test scores of 21.8% improving to 48.0% at course completion and 57.7% at the four-month follow up. Overall, participant's scores increased by an average of 35% from the pre-test to the second post-test (P <.001). A total of 69 patient forms were completed on transported patients over the initial four-month period. Ninety-five percent (95%) of these were injured patients, and motorcycle crash was the predominant mechanism of injury (48% of injuries). Eight patients were transported to MKMC, but none of these patients were recorded in the hospital trauma registry. Major barriers identified through semi-structured interviews included harassment by police, poor road conditions, and lack of basic resources for transport. Ninety-four percent (94%) of trainees strongly agreed that the training was useful. Total costs were estimated at $3,489 USD, or $69 per trainee. CONCLUSION: Motorcycle taxi drivers can be trained to provide basic prehospital care in a short time and at a low cost. While there is much enthusiasm for additional training and skill acquisition from this cohort, the sustainability and scalability of such programs is still in question.

Trauma training in low- and middle-income countries: A scoping review of ATLS alternatives.

INTRODUCTION: Trauma training for front-line providers is a critical component of injury mitigation and trauma systems strengthening. Although the Advanced Trauma Life Support (ATLS) course is standard in much of the world, cost and administrative barriers are prohibitive to deploying the course in many low and middle income countries (LMICs). The purpose of this study was to identify alternative trauma training courses used in LMICs by scoping review and compare their effectiveness. METHODS: Several peer-reviewed and grey literature databases were searched for relevant articles describing trauma training courses for front-line medical providers in LMICs. Studies were included if: performed in a LMIC; utilized a general trauma training course other than ATLS; trainees were hospital-based medical providers; study included some type of outcome measure. RESULTS: A total of 34 manuscripts met inclusion criteria. The majority of courses were novel, hospital-initiated courses and ranged in length from 1 day to 1 week. Physicians were the most common target audience, followed by medical students and nurses. Courses were taught in 24 different countries throughout the Middle East, Asia, Latin America and Africa. Comparison of pre- and post-test knowledge was the most common metric used and nearly all courses demonstrated a statistically significant knowledge gain. One study demonstrated a reduction in mortality for injured patients after course implementation. The majority of courses were a collaboration between universities in a high income country and local faculty/practitioners in the LMIC where the course was taught. Reported cost per participant ranged from $10 to $232 USD. CONCLUSIONS: Several trauma courses are currently being utilized in LMICs effectively with increases in knowledge gained and at a lower reported cost than ATLS. More research is needed to link trauma training courses to patient outcomes.

Veterans Hospital Administration Telehealth Utilization for Recreation and Creative Arts Therapies: A Brief Report.

Background: A brief query was fielded to Veterans Health Administration (VHA) facilities across the United States to provide an initial assessment of recreation therapy (RT) and creative arts therapy (CAT) telehealth utilization. Methods: To develop an understanding of barriers and identify potential solutions for better delivery of services, a cross-sectional survey was deployed to points of contact at 136 VHA facilities. The survey included questions across five areas: staff, infrastructure, barriers to use, training, and interventions being deployed. Descriptive statistics were calculated, and a thematic analysis of qualitative responses was conducted. Results: The most frequent themes from aggregated responses indicated a need for hands-on training, reliable telehealth equipment, and accessible training and tools for Veteran patients who want to use telehealth services. Conclusion: Telehealth delivery of RT/CAT has increased services to Veteran patient populations; however, equipment and training are needed to expand consistent delivery to enhance patient reach across a national health care system.

Analytical Evaluation of the Ideal Strategy for High-Throughput Flow Injection Analysis by Tandem Mass Spectrometry in Routine Newborn Screening.

The introduction of tandem mass spectrometry (MS/MS) to clinical laboratories and the advent of expanded newborn screening (NBS) were crucial changes to public health programs worldwide. Speed, robustness, accuracy, selectivity, and specificity of analysis are all requirements of expanded NBS and are needed to minimize false positive results risks, to possibly eliminate false negatives, and to improve the positive predictive value of NBS. In this study, we firstly evaluated the analytical performances of the RenataDX Screening System, a fully integrated flow-injection MS/MS (FIA-MS/MS) IVD system for high-throughput dried blood spot (DBS) analysis in a routine NBS laboratory. Since a choice of several commercial NBS kits is available, we sought to compare NeoBaseTM 2 (PerkinElmer®) and MassChrom® (Chromsystems) non-derivatized kits on the RenataDX platform by evaluating their analytical performances. Moreover, we verified the degree of correlation between data obtained by the two different NBS MS/MS kits by FIA-MS/MS of over 500 samples. Our data suggest that both methods correlate well with clinically insignificant differences that do not impact the NBS result. Finally, while NeoBase™ 2 offers an easier and faster sample preparation, MassChrom® provides a cleaner sample extract which empirically should improve instrument reliability.

Impact of point-of-care ultrasound on the diagnosis and treatment of patients in rural Uganda.

Œ: Ultrasound is increasingly used by physicians at the bedside to diagnose and treat a variety of conditions and is particularly useful in the resource-limited setting. The purpose of this study was to determine whether point-of-care ultrasound (POCUS) performed by physicians changed the diagnosis or treatment of patients in mobile clinics in rural Uganda. Patients presenting to mobile clinics in Uganda were assessed by physicians and, when appropriate, POCUS was performed. When available, a radiologist reviewed ultrasound images in real time. A de-identified questionnaire was completed for each ultrasound and reviewed retrospectively. A total of 177 ultrasounds were performed. A radiologist reviewed 50% of the ultrasounds. In 73% of patients, the findings either confirmed (50%) or changed (23%) a diagnosis. In 53% of patients, the ultrasound findings changed the treatment plan. POCUS positively impacted patient care in rural Ugandan clinics by improving diagnostic capabilities and influencing treatment plans.

Magnetic resonance imaging (MRI) of pharmacological ascorbate-induced iron redox state as a biomarker in subjects undergoing radio-chemotherapy.

Pharmacological ascorbate (P-AscH-) combined with standard of care (SOC) radiation and temozolomide is being evaluated in a phase 2 clinical trial (NCT02344355) in the treatment of glioblastoma (GBM). Previously published data demonstrated that paramagnetic iron (Fe3+) catalyzes ascorbate's oxidation to form diamagnetic iron (Fe2+). Because paramagnetic Fe3+ may influence relaxation times observed in MR imaging, quantitative MR imaging of P-AscH--induced changes in redox-active Fe was assessed as a biomarker for therapy response. Gel phantoms containing either Fe3+ or Fe2+ were imaged with T2* and quantitative susceptibility mapping (QSM). Fifteen subjects receiving P-AscH- plus SOC underwent T2* and QSM imaging four weeks into treatment. Subjects were scanned: pre-P-AscH- infusion, post-P-AscH- infusion, and post-radiation (3-4 h between scans). Changes in T2* and QSM relaxation times in tumor and normal tissue were calculated and compared to changes in Fe3+ and Fe2+ gel phantoms. A GBM mouse model was used to study the relationship between the imaging findings and the labile iron pool. Phantoms containing Fe3+ demonstrated detectable changes in T2* and QSM relaxation times relative to Fe2+ phantoms. Compared to pre-P-AscH-, GBM T2* and QSM imaging were significantly changed post-P-AscH- infusion consistent with conversion of Fe3+ to Fe2+. No significant changes in T2* or QSM were observed in normal brain tissue. There was moderate concordance between T2* and QSM changes in both progression free survival and overall survival. The GBM mouse model showed similar results with P-AscH- inducing greater changes in tumor labile iron pools compared to the normal tissue. CONCLUSIONS: T2* and QSM MR-imaging responses are consistent with P-AscH- reducing Fe3+ to Fe2+, selectively in GBM tumor volumes and represent a potential biomarker of response. This study is the first application using MR imaging in humans to measure P-AscH--induced changes in redox-active iron.

Injury patterns of patients presenting to a non-governmental hospital in Western Uganda.

INTRODUCTION: Injury is a leading cause of morbidity and mortality globally and disproportionately affects low-income countries. While most injury data comes from tertiary care centers in urban settings, the purpose of this study was to describe the characteristics and severity of injury in rural Uganda and the associated treatment patterns and delays in care. METHODS: This is a retrospective cohort study of a trauma registry that was implemented at Masindi-Kitara Medical Center (MKMC), a rural hospital in Western Uganda. Demographic information, injury characteristics, modified Kampala Trauma Scores (M-KTS), and treatment modalities over a 12 month period were retrospectively collected from paper-based registry forms completed for all injury patients presenting to MKMC. RESULTS: A total of 350 patients were entered into the trauma registry. Most patients were male (71.2%) with a median age of 26.5 years. Motorcycle crashes were the most prevalent mechanism of injury (42.3%) with the majority being unhelmeted (83.3%). Soft tissue injury was the most common diagnosis (44.9%). Patients were frequently treated in the outpatient department and then discharged (54.8%). Patients requiring admission or transfer (M-KTS = 11.57 or 11.67) tended to have a lower M-KTS than discharged patients (M-KTS = 12.75). Analgesics (74.6%) and antibiotics (52.9%) were the most common treatments administered. For those patients requiring admission (29.4%), only one in-hospital death was documented. Thirty-nine percent of patients reported a delay in seeking care, most frequently due to lack of transportation (31.5%) with a median time of delay of 11 h. CONCLUSION: Road traffic injuries were the leading cause of injury in Masindi, with a high proportion of injuries associated with unhelmeted motorcycle crashes. Future opportunities to prevent injury and improve care may be seen through improved prehospital care, enforcement of helmet laws, increased access to neurosurgical services, and enactment of hospital quality improvement measures.

Injury patterns of patients presenting to a non-governmental hospital in Western Uganda

Introduction: Injury is a leading cause of morbidity and mortality globally and disproportionately affects low-income countries. While most injury data comes from tertiary care centers in urban settings, the purpose of this study was to describe the characteristics and severity of injury in rural Uganda and the associated treatment patterns and delays in care. Methods: This is a retrospective cohort study of a trauma registry that was implemented at Masindi-Kitara Medical Center (MKMC), a rural hospital in Western Uganda. Demographic information, injury characteristics, modified Kampala Trauma Scores (M-KTS), and treatment modalities over a 12 month period were retrospectively collected from paper-based registry forms completed for all injury patients presenting to MKMC. Results: A total of 350 patients were entered into the trauma registry. Most patients were male (71.2%) with a median age of 26.5 years. Motorcycle crashes were the most prevalent mechanism of injury (42.3%) with the majority being unhelmeted (83.3%). Soft tissue injury was the most common diagnosis (44.9%). Patients were frequently treated in the outpatient department and then discharged (54.8%). Patients requiring admission or transfer (M-KTS = 11.57 or 11.67) tended to have a lower M-KTS than discharged patients (M-KTS = 12.75). Analgesics (74.6%) and antibiotics (52.9%) were the most common treatments administered. For those patients requiring admission (29.4%), only one in-hospital death was documented. Thirty-nine percent of patients reported a delay in seeking care, most frequently due to lack of transportation (31.5%) with a median time of delay of 11 h. Conclusion: Road traffic injuries were the leading cause of injury in Masindi, with a high proportion of injuries associated with unhelmeted motorcycle crashes. Future opportunities to prevent injury and improve care may be seen through improved prehospital care, enforcement of helmet laws, increased access to neurosurgical services, and enactment of hospital quality improvement measures

Solar-Powered Point-of-Care Sonography: Our Himalayan Experience.

The benefits of sonography utilization in low-resource communities has been thoroughly demonstrated in the literature.1-3 As ultrasound units have become smaller and more portable, the feasibility of bringing these imaging devices into more remote areas is becoming a reality. One factor that limits ultrasound use in austere environments is battery life. Although solar power has been used for oxygen delivery5,6 in resource-limited settings, its use in sonography has not been previously described. This report describes the use of a Lumify (Philips; Amsterdam, Netherlands) for a month-long trip into a remote Himalayan region of India powered exclusively with an Anker (Shenzhen, China) solar panel for the entirety of the trip. According to the Palmetto Health Institutional Review Board, this does not qualify as "research" as defined by the US Department of Health and Human Services and therefore does not meet the requirements for institutional review board review.

Using Future Employers' Expectations to Inform Global Health Fellowship Curricula.

BACKGROUND: Fellowships in global health are increasingly popular and seek to equip physicians with the skills necessary to be effective global health practitioners. Little objective guidance exists on which skills make graduates competitive applicants from the perspective of potential global health employers. OBJECTIVE: We sought to provide objective evidence for the qualifications that make applicants competitive for global health positions by analyzing the listed qualifications for current job openings in large global health organizations. METHODS: The websites of 48 global health employers were systematically searched for current job postings between May and August 2017. Jobs were included for analysis if a medical degree was listed among the primary degrees accepted, and the job was based primarily in a low- or middle-income country. RESULTS: A total of 5849 employment opportunities were posted during the search period, and 81 (1.4%) of these met inclusion criteria. Twenty-two (27%) jobs required and 35 (43%) preferred a relevant master's degree. Few jobs requested a candidate with a PhD and none mentioned tropical medicine training as a requirement or preference. Twenty-three jobs (28%) required and 19 (23%) preferred candidates to speak another language. Most jobs (69%, 56 of 81) required more than 5 years of relevant experience. Only 11 (13%) jobs were primarily clinical positions. CONCLUSIONS: For physicians pursuing a career in global health, most publicly searchable jobs require substantial previous experience and involvement in global health activities beyond clinical practice. Master's degree and language skills are frequently requested candidate qualifications.

Pharmacologic Ascorbate Reduces Radiation-Induced Normal Tissue Toxicity and Enhances Tumor Radiosensitization in Pancreatic Cancer.

: Chemoradiation therapy is the mainstay for treatment of locally advanced, borderline resectable pancreatic cancer. Pharmacologic ascorbate (P-AscH-, i.e., intravenous infusions of ascorbic acid, vitamin C), but not oral ascorbate, produces high plasma concentrations capable of selective cytotoxicity to tumor cells. In doses achievable in humans, P-AscH- decreases the viability and proliferative capacity of pancreatic cancer via a hydrogen peroxide (H2O2)-mediated mechanism. In this study, we demonstrate that P-AscH- radiosensitizes pancreatic cancer cells but inhibits radiation-induced damage to normal cells. Specifically, radiation-induced decreases in clonogenic survival and double-stranded DNA breaks in tumor cells, but not in normal cells, were enhanced by P-AscH-, while radiation-induced intestinal damage, collagen deposition, and oxidative stress were also reduced with P-AscH- in normal tissue. We also report on our first-in-human phase I trial that infused P-AscH- during the radiotherapy "beam on." Specifically, treatment with P-AscH- increased median overall survival compared with our institutional average (21.7 vs. 12.7 months, P = 0.08) and the E4201 trial (21.7 vs. 11.1 months). Progression-free survival in P-AscH--treated subjects was also greater than our institutional average (13.7 vs. 4.6 months, P < 0.05) and the E4201 trial (6.0 months). Results indicated that P-AscH- in combination with gemcitabine and radiotherapy for locally advanced pancreatic adenocarcinoma is safe and well tolerated with suggestions of efficacy. Because of the potential effect size and minimal toxicity, our findings suggest that investigation of P-AscH- efficacy is warranted in a phase II clinical trial. SIGNIFICANCE: These findings demonstrate that pharmacologic ascorbate enhances pancreatic tumor cell radiation cytotoxicity in addition to offering potential protection from radiation damage in normal surrounding tissue, making it an optimal agent for improving treatment of locally advanced pancreatic adenocarcinoma.

Utilization of Mobile Integrated Health Providers During a Flood Disaster in South Carolina (USA).

As health care systems in the United States have become pressured to provide greater value, they have embraced the adoption of innovative population health solutions. One of these initiatives utilizes prehospital personnel in the community as an extension of the traditional health care system. These programs have been labeled as Community Paramedicine (CP) and Mobile Integrated Health (MIH). While variation exists amongst these programs, generally efforts are targeted at individuals with high rates of health care utilization. By assisting with chronic disease management and addressing the social determinants of health care, these programs have been effective in decreasing Emergency Medical Services (EMS) utilization, emergency department visits, and hospital admissions for enrolled patients.The actual training, roles, and structure of these programs vary according to state oversight and community needs, and while numerous reports describe the novel role these teams play in population health, their utilization during a disaster response has not been previously described. This report describes a major flooding event in October 2015 in Columbia, South Carolina (USA). While typical disaster mitigation and response efforts were employed, it became clear during the response that the MIH providers were well-equipped to assist with unique patient and public health needs. Given their already well-established connections with various community health providers and social assistance resources, the MIH team was able to reconnect patients with lost medications and durable medical equipment, connect patients with alternative housing options, and arrange access to outpatient resources for management of chronic illness.Mobile integrated health teams are a potentially effective resource in a disaster response, given their connections with a variety of community resources along with a unique combination of training in both disease management and social determinants of health. As roles for these providers are more clearly defined and training curricula become more developed, there appears to be a unique role for these providers in mitigating morbidity and decreasing costs in the post-disaster response. Training in basic disaster response needs should be incorporated into the curricula and community disaster planning should identify how these providers may be able to benefit their local communities.Gainey CE, Brown HA, Gerard WC. Utilization of mobile integrated health providers during a flood disaster in South Carolina (USA). Prehosp Disaster Med. 2018;33(4):432-435.

Consuming a Ketogenic Diet while Receiving Radiation and Chemotherapy for Locally Advanced Lung Cancer and Pancreatic Cancer: The University of Iowa Experience of Two Phase 1 Clinical Trials.

Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a ketogenic diet or standard rodent chow, treated with conventionally fractionated radiation (2 Gy/fraction), and tumor growth rates were assessed daily. Tumors were assessed for immunoreactive 4-hydroxy-2-nonenal-(4HNE)-modfied proteins as a marker of oxidative stress. Based on this and another previously published preclinical study, phase 1 clinical trials in locally advanced NSCLC and pancreatic cancer were initiated, combining standard radiation and chemotherapy with a ketogenic diet for six weeks (NSCLC) or five weeks (pancreatic cancer). The xenograft experiments demonstrated prolonged survival and increased 4HNE-modfied proteins in animals consuming a ketogenic diet combined with radiation compared to radiation alone. In the phase 1 clinical trial, over a period of three years, seven NSCLC patients enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study and one was withdrawn due to a dose-limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose-limiting toxicity. The preclinical experiments demonstrate that a ketogenic diet increases radiation sensitivity in a pancreatic cancer xenograft model. However, patients with locally advanced NSCLC and pancreatic cancer receiving concurrent radiotherapy and chemotherapy had suboptimal compliance to the oral ketogenic diet and thus, poor tolerance.

Evaluation of a Short-term Training Program in Bedside Emergency Ultrasound in Southwestern Tanzania.

OBJECTIVES: To evaluate the effect of a short-term training program in emergency ultrasound on physician skills and attitudes in southwestern Tanzania. METHODS: Eight registrar physicians at Mbeya Zonal Referral Hospital (Mbeya, Tanzania) underwent a 5-day course in bedside emergency ultrasound, focusing primarily on the focused assessment with sonography for trauma examination, including didactic sessions, practical sessions, and on-job training. The impact on ultrasound knowledge was assessed by pretest and posttest evaluations. Provider skill was evaluated by a standardized observed simulated patient encounter. Attitudes toward ultrasound training, utility, and self-confidence were assessed by a post-training questionnaire. RESULTS: All 8 physicians who began the training completed the course and successfully passed their objective structured clinical examination. There was a statistically significant improvement in written ultrasound test scores from 31% to 66% (P < .01) after the course. Most trainees felt confident performing and interpreting a basic focused assessment with sonography for trauma examination at the end of the course, and 7 of 8 stated that they would consider paying tuition for similar courses in the future. Main concerns with the course revolved around insufficient time dedicated to practicing under supervision. CONCLUSIONS: Registrar physicians in Tanzania can effectively learn basic emergency ultrasound skills in a short-term training program. Similar future programs may consider heavier emphasis on practical hands-on training with experts. Ongoing data collection is required to understand the true impact of such training on long-term ultrasound use and patient outcomes.

Development and Implementation of a Novel Prehospital Care System in the State of Kerala, India.

Most low- and middle-income countries (LMICs) have struggled to find a system for prehospital care that can provide adequate patient care and geographical coverage while maintaining a feasible price tag. The emergency medical systems of the Western world are not necessarily relevant in developing economic systems, given the lack of strict legislation, the scarcity of resources, and the limited number of trained personnel. Meanwhile, most efforts to provide prehospital care in India have taken the form of adapting Western models to the Indian context with limited success. Described here is a novel approach to prehospital care designed for and implemented in the State of Kerala, India. The Active Network Group of Emergency Life Savers (ANGELS) was launched in 2011 in Calicut City, the third largest city in the Indian State of Kerala. The ANGELS integrated an existing fleet of private and state-owned ambulances into a single network utilizing Global Positioning System (GPS) technology and a single statewide call number. A total of 85 volunteer emergency medical certified technicians (EMCTs) were trained in basic first aid and trauma care principles. Public awareness campaigns accompanied all activities to raise awareness amongst community members. Funding was provided via public-private partnership, aimed to minimize costs to patients for service utilization. Over a two-year period from March 2011 to April 2013, 8,336 calls were recorded, of which 54.8% (4,569) were converted into actual ambulance run sheets. The majority of calls were for medical emergencies and most patients were transported to Medical College Hospital in Calicut. This unique public-private partnership has been responsive to the needs of the population while sustaining low operational costs. This system may provide a relevant template for Emergency Medical Services (EMS) development in other resource-limited settings. Brown HA , Douglass KA , Ejas S , Poovathumparambil V . Development and implementation of a novel prehospital care system in the State of Kerala, India. Prehosp Disaster Med. 2016;31(6):663-666.

Oral Health Status of Older Adults Attending Senior Centers and Congregate Meal Sites in New Hampshire.

PURPOSE: This study assessed the oral health status of older adults in randomly selected New Hampshire senior centers and congregate meal sites for the purpose of future planning, implementation and evaluation of targeted public health programs. METHODS: A cross-sectional surveillance project was developed. Registered dental hygienists visually assessed denture use, number of natural teeth, teeth mobility, untreated caries, root fragments, gingivitis, need for care and treatment urgency among randomly selected active older adults living within New Hampshire communities. RESULTS: Altogether, 610 adults 60 years old and older attending 25 senior centers and congregate meal sites participated. Sixteen percent were edentulous and 42% reported having a removable upper or lower denture. Among edentulous adults, 5% had no dentures at all. Among 513 dentate participants, 22% had untreated caries, 14% had root fragments, 9% had gingivitis and 7% presented with obviously mobile teeth. Overall, 19% required early or urgent dental care. Differences were detected by sex, age group, urban versus rural location of the site and by the participation in a federal nutritional program for older adults. CONCLUSION: Baseline information about oral health needs of older adults in New Hampshire was gathered. Overall needs as well as existing oral health disparities will be addressed through the collaboration of public and private partners.

Confirmation of congenital adrenal hyperplasia by adrenal steroid profiling of filter paper dried blood samples using ultra-performance liquid chromatography-tandem mass spectrometry.

BACKGROUND: The specificity of screening for congenital adrenal hyperplasia by direct measurement of 17-hydroxyprogesterone in filter paper dried blood spot samples by immunoassay is low and has a high false-positive rate. In order to reduce the false-positive rate of this test, we developed a rapid, robust, specific confirmatory procedure in which cortisol, 4-androstene-3,17-dione and 17-hydroxyprogesterone were measured simultaneously by ultra-performance liquid chromatography-tandem mass spectrometry. METHODS: After extraction, samples were analysed by ultra-performance liquid chromatography-tandem mass spectrometry and 17-hydroxyprogesterone was quantified accurately. Other steroids were determined using stable deuterated internal standards. In total, 25 patient blood spot samples and 92 control samples were analysed. RESULTS: The assay was linear for 17-hydroxyprogesterone, with a coefficient of determination >0.997 and imprecision ≤ 6.5%. An upper limit of normal for 17-hydroxyprogester-one of 4.45 nmol/L was established by analysing a cohort of samples from unaffected newborns. In addition, a cut-off of 3.5 for the peak areas ratio (17-hydroxyprogesterone+4-androstene-3,17-dione)/cortisol, allows confirmation of the affected steroidogenic enzyme. CONCLUSIONS: A high throughput method for the detection of steroids related to congenital adrenal hyperplasia has been developed, allowing the false-positive rate associated with screening for 17-hydroxyprogesterone by immunoassay to be determined.

Serum steroid profiling for congenital adrenal hyperplasia using liquid chromatography-tandem mass spectrometry.

BACKGROUND: Diagnosis of Congenital Adrenal Hyperplasia (CAH) is based on the quantification of 17-hydroxyprogesterone (17-OHP), usually by immunoassay. During the neonatal period the specificity of screening for CAH by blood spot 17-OHP immunoassay is low. High false-positive rates result in a relatively high demand for a second-tier serum confirmation test. A robust, specific and selective method for measurement of cortisol, 21-deoxycortisol, 11-deoxycortisol, 4-androstene-3,17-dione (A4) and 17-OHP in serum has been developed. The method involves a simple extraction procedure and a fast analysis using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS). METHODS: The steroids were extracted from 50microl of serum using methyl-tert-butyl-ether. Analysis was performed on a UPLC tandem quadrupole mass spectrometer system in positive mode electrospray ionization and multiple reaction monitoring acquisition. RESULTS: The assay was linear over each analyte concentration range with all correlation coefficients (r(2))>0.996. Inter- and intra-day CVs were