Progression of ECG in hydroxychloroquine overdose.

Hydroxychloroquine overdose is associated with myocardial toxicity and conduction disorders. We report a case of hydroxychloroquine overdose that demonstrated a rapid progressive intraventricular conduction delay and QT prolongation resulting in significant bradycardia and shock despite aggressive treatment. We describe the rare capture of abrupt abnormalities of this overdose in sequential electrocardiograms in the immediate hours post-ingestion.

Baseline characteristics of people experiencing homelessness with a recent drug overdose in the PHOENIx pilot randomised controlled trial.

BACKGROUND: Drug-related deaths in Scotland are the highest in Europe. Half of all deaths in people experiencing homelessness are drug related, yet we know little about the unmet health needs of people experiencing homelessness with recent non-fatal overdose, limiting a tailored practice and policy response to a public health crisis. METHODS: People experiencing homelessness with at least one non-fatal street drug overdose in the previous 6 months were recruited from 20 venues in Glasgow, Scotland, and randomised into PHOENIx plus usual care, or usual care. PHOENIx is a collaborative assertive outreach intervention by independent prescriber NHS Pharmacists and third sector homelessness workers, offering repeated integrated, holistic physical, mental and addictions health and social care support including prescribing. We describe comprehensive baseline characteristics of randomised participants. RESULTS: One hundred and twenty-eight participants had a mean age of 42 years (SD 8.4); 71% male, homelessness for a median of 24 years (IQR 12-30). One hundred and eighteen (92%) lived in large, congregate city centre temporary accommodation. A quarter (25%) were not registered with a General Practitioner. Participants had overdosed a mean of 3.2 (SD 3.2) times in the preceding 6 months, using a median of 3 (IQR 2-4) non-prescription drugs concurrently: 112 (87.5%) street valium (benzodiazepine-type new psychoactive substances); 77 (60%) heroin; and 76 (59%) cocaine. Half (50%) were injecting, 50% into their groins. 90% were receiving care from Alcohol and Drug Recovery Services (ADRS), and in addition to using street drugs, 90% received opioid substitution therapy (OST), 10% diazepam for street valium use and one participant received heroin-assisted treatment. Participants had a mean of 2.2 (SD 1.3) mental health problems and 5.4 (SD 2.5) physical health problems; 50% received treatment for physical or mental health problems. Ninety-one per cent had at least one mental health problem; 66% had no specialist mental health support. Participants were frail (70%) or pre-frail (28%), with maximal levels of psychological distress, 44% received one or no daily meal, and 58% had previously attempted suicide. CONCLUSIONS: People at high risk of drug-related death continue to overdose repeatedly despite receiving OST. High levels of frailty, multimorbidity, unsuitable accommodation and unmet mental and physical health care needs require a reorientation of services informed by evidence of effectiveness and cost-effectiveness. Trial registration UK Clinical Trials Registry identifier: ISRCTN 10585019.

Comparative taste-masking evaluation of microencapsulated bitter drugs using Smartseal 30D and ReadyMix for paediatric dosage forms.

The taste of drug substances plays a key role in the development of paediatric formulations with suitable organoleptic properties. The aim of the study was to evaluate the taste masking effectiveness of Smartseal 30D and ReadyMix on a range of bitter drug substances such as diphenhydramine HCl (DPD), ibuprofen lysine (IBU-LS), and phenylephrine HCl (PPH) for the development of paediatric dosage forms. The drugs were microencapsulated in the polymer carriers at 10-20% loadings using spray-drying processing. Spray drying of drug formulations was optimized in terms of percent yield and encapsulation efficiency followed by physicochemical characterization in order to identify the drugs' physical state in the polymer microparticles. The in vivo taste masking efficiency was evaluated using human test panel and showed noticeable reduction of drug's bitterness at all loadings in comparison to the bulk substances.

Biomechanical Evaluation of a Cadaveric Flatfoot Model and Lateral Column Lengthening Technique.

Patients with adult acquired flatfoot have progressive worsening of bony alignment with many being unable to perform a heel rise. Following reconstruction, pathologic skeletal alignment is corrected and the ability to perform a heel rise is often restored. The purpose of this study was to evaluate the relationship between forefoot liftoff forces and skeletal alignment in a cadaveric flatfoot model by assessing the effect of sequential lengthening of the lateral column using an Evans-type calcaneal osteotomy. Bony alignment was measured in 8 cadaveric specimens with the use of a 3-dimensional digitizing system. Transection of the spring ligament, pie-crusting of the plantar fascia, and cyclic axial loading of the foot was performed to create an anatomic and functional flatfoot model. An Evans-type calcaneal osteotomy using 6, 8, 10, and 12 mm wedges was performed. Specimens were mounted to a custom jig that applies tensile loads to the Achilles, peroneus brevis, peroneus longus, and tibialis posterior tendons. Creation of a flatfoot reduced the lateral talo-first metatarsal angle (Meary's angle) by 13° (23.6° ± 2.8° vs 10.6° ± 3.8°, p < .05) and forefoot force by 7% (199.3 N ± 7.3 N vs 185.4 N ± 9 N, p < .05). Sequential lengthening of the lateral column restored skeletal alignment and force transfer to the forefoot (12 mm wedge: Meary's angle 22.7° ± 3.9°, liftoff force 206.8 N ± 7.5 N). The cadaveric flatfoot model demonstrated decreased forefoot forces that were restored with an Evans-type calcaneal osteotomy wedge. This highlights the importance of restoring skeletal alignment when correcting advanced adult acquired flatfoot.

The Effect of Alcohol Consumption on Geriatric Trauma Outcomes.

BACKGROUND: There is little consensus in the literature regarding the effect of ethanol intoxication on trauma outcomes. Data on its effect in the elderly are even sparser. Our aim was to better define the impact of alcohol use in the geriatric trauma population. MATERIALS AND METHODS: We conducted a retrospective review at a level I trauma center looking at admissions from January 2015 through December 2018. Patients were grouped by age: 15-64 y old (YOUNG) versus ≥ 65 y old (OLD). Blood alcohol content (BAC) ≤0.10 g/dL was ETOH (-), and BAC >0.10 g/dL was ETOH (+). These were then propensity matched by injury severity score and mechanism of injury. Fisher's exact test and linear regression were applied as appropriate. Significance was defined as P < 0.05. RESULTS: There were 8754 patients admitted during the study time frame. A total of 6106 patients were YOUNG and 2647 were OLD. A total of 146 (5.5%) OLD patients were ETOH (+), whereas 1488 (24.4%) YOUNG patients were ETOH (+) (P < 0.0001). To assess the impact of alcohol between the two age groups, 285 OLD patients were propensity matched with 285 YOUNG patients. Mortality was significantly higher in the OLD (11.9%) group than that in the YOUNG (3.5%) group (P < 0.001). Morbidity was also higher in OLD versus YOUNG patients overall (P < 0.05). The presence of ethanol did not significantly impact morbidity or mortality in YOUNG or OLD patients. CONCLUSIONS: Higher mortality and morbidity is unsurprising in geriatric trauma patients; however, alcohol does not appear to play a significant role in these outcomes.

Comparison of Urban Off-Road Vehicle and Motorcycle Injuries at a Level 1 Trauma Center.

BACKGROUND: Recently, there has been an increase in the usage of dirt bikes and all-terrain vehicles in urban environments. Previously, it has been shown that crashes involving these urban off-road vehicles (UORVs) resulted in different injury patterns from crashes that occurred in rural environments. The aim of this study was to compare injury patterns of patients involved in crashes while riding UORVs versus motorcycles (MCs). METHODS: A retrospective review (2005-2016) of patients who presented to our urban level I trauma center as a result of any MC or UORV crash was performed. Patients who presented after 48 h from the time of accident were excluded. A P < 0.05 was considered significant. RESULTS: We identified 1556 patients who were involved in an MC or UORV crash resulting in injury (MC: n = 1324 [85%]; UORVs: n = 232 [15%]). Patients in UORV crashes were younger (26.2 y versus 39.6 y), less likely to be helmeted (39.6% versus 90.2%), required fewer emergent trauma bay procedures (28.4% versus 36.7%), and needed fewer operative interventions (45.9% versus 54.2%) (all P < 0.05). Both groups had a similar Injury Severity Score (12.2 versus 12.6; P = 0.54) and Glasgow Coma Score (13.8 versus 13.5; P = 0.46). UORV patients had a lower mortality (0.9% versus 4.7%; P < 0.05) compared to MC crash patients despite similar injury patterns. CONCLUSIONS: Our data demonstrate that patients sustaining UORV injuries were younger and less likely to be helmeted but have a lower mortality rate after a crash, despite sustaining similar injuries as motorcyclists. This study provides an overview of how crashes involving UORV usage is a unique phenomenon and not entirely comparable to MC crashes.

Implementing and Evaluating SBIRT for Alcohol Use at a Level 1 Trauma Center: A Behavioral Medicine Approach.

To facilitate the early identification and treatment of alcohol misuse among trauma patients, the American College of Surgeons (ACS) requires ACS-accredited level 1 trauma centers to have an active alcohol screening and brief intervention program. The development, implementation, and evaluation of a screening, brief intervention, and referral to treatment as a new institutional standard of care for alcohol misuse at a level 1 trauma center is described. The Division of Behavioral Medicine, a health psychology-based service, was nominated to manage this initiative as a result of clinical training and expertise in assessment, evidence-based psychological interventions, and case management. Trauma patients with elevated blood alcohol concentrations were screened at the time of admission and several months post-hospitalization. Clinical data suggest that screening for alcohol misuse can help identify patients at risk for, and struggling with, alcohol use disorders, encourage positive changes in alcohol consumption patterns, and increase access to treatment. Recommendations for enhancing the effectiveness of this process, associated challenges and limitations, and considerations for future clinical and research endeavors are discussed.

First evaluation of the population structure, genetic diversity and landscape connectivity of the Endangered Arabian tahr.

The Arabian tahr (Arabitragus jayakari) occurs only in the mountains of northern Oman and the United Arab Emirates. The species is classified as Endangered due to its small declining population. In this study, we combined genetic and landscape ecology techniques in order to inform landscape scale conservation and genetic management of Arabian tahr. Using 540 base pairs of mitochondrial control region in a dataset of 53 samples, we found eight haplotypes, which fell into two haplogroups. Population genetic analysis using a panel of 14 microsatellite loci also showed a weak, but significant division. Analyses of landscape connectivity supported the genetic results showing poor connectivity between populations in the far south of the study area and those in the north. The most likely location of corridors connecting Arabian tahr populations were identified. Many corridors between tahr populations are impeded by multi-lane highways and restoration of these connections is required to maintain population viability of Arabian tahr. Owing to limited genetic samples outside of Wadi Sareen, further sampling is needed to elucidate both mtDNA and the nuclear structure of Arabian tahr more fully. Our study provides a toolkit that may be used for future genetic and connectivity monitoring of the Arabian tahr population.

Twelve-Year Review of Urban Versus Rural Off-road Vehicle Injuries at a Level 1 Trauma Center.

OBJECTIVE: Traditionally, all-terrain vehicles (ATVs) and dirt bikes (DBs) have been used in rural locations for recreation and work. Recently, there has been an increase in the use of these vehicles in an urban environment. The aim of this study is to compare the injury patterns of patients involved in crashes while riding off-road vehicles in both urban (UORV) and rural (RORV) environment. METHODS: A retrospective review (2005-2016) of patients who presented to an urban level 1 trauma center as a result of any ATV or DB crash was performed. UORV was defined as any ATV or DB accident that occurred on paved inner city, suburban, or major roadways. RORV was defined as those accidents that occurred on secondary roadways or off-road. Patients who presented more than 48 h from time of accident were excluded. A P < 0.05 was considered significant. RESULTS: Five hundred and twenty-eight patients were identified to have an ATV or DB injury (RORV n = 296 [56%]; UORV n = 232 [44%]). UORV accidents had a higher Injury Severity Score (12.2 versus 9.7; P < 0.05), lower presenting Glasgow Coma Scale (13.8 versus 14.3; P < 0.05), more likely to need emergent trauma bay procedures (28.5% versus 17.9%; P < 0.05), were less likely to have been helmeted (39.6% versus 71.2%; P < 0.05) with a higher unhelmeted Abbreviated Injury Scale head of ≥3 (13.5% versus 5%; <0.05), and more likely to have extremity injuries (53.5% versus 41.2%; P < 0.05). There were no significant differences in additional injury patterns or hospital outcomes including mortality for the two groups. CONCLUSIONS: Our data suggest that UORV use was associated with decreased helmet use, higher mean Injury Severity Score, lower presenting Glasgow Coma Scale, an increased need for emergent trauma bay procedures, higher unhelmeted Abbreviated Injury Scale head scores, and higher rates of extremity injuries.

Financial Impact of Minor Injury Transfers on a Level 1 Trauma Center.

BACKGROUND: Trauma centers frequently accept patients from other institutions who are being sent due to the need for a higher level of care. We hypothesized that patients with minor traumatic injuries who are transferred from outside institutions would impart a negative financial impact on the receiving trauma center. METHODS: We performed a retrospective review of all trauma patients admitted to our urban level I trauma center from October 1, 2011, through September 30, 2013. Patients were categorized as minor trauma if they did not require operation within 24 h of arrival, did not require ICU admission, did not die, and had a hospital length of stay <24 h. Transferred patients and nontransfers (those received directly from the field) were compared with respect to injury severity, insurance status, and hospital net margin. Student's t-test and z-test for proportions were performed for data analysis. RESULTS: A total of 6951 trauma patients were identified (transfer n = 2228, nontransfer n = 4724). Minor injury transfers (n = 440) were compared to nontransfers (n = 689). Hospital net margin of transferred patients and nontransferred patients were $2227 and $2569, respectively (P = 0.22). Percentages of uninsured/underinsured for transfers and nontransfers were 27.3% and 36.1%, respectively (P = 0.002). CONCLUSIONS: During our study period, 19.7% of transfers and 14.6% of nontransfers can be categorized as having minor trauma. Minor trauma transfer patients are associated with a positive hospital net margin for the trauma center that is similar to that of the nontransfer group. The data also demonstrate a lower percentage of uninsured/underinsured in the transferred group.

Use of Cardiac Troponin Testing in the Outpatient Setting.

OBJECTIVES: Cardiac troponin (cTn) measurement is useful for diagnosing myocardial infarction (MI), particularly in the inpatient setting. A growing body of literature suggests that cTn may be useful for evaluating chronic conditions in the outpatient environment; however, little is known regarding cTn ordering patterns in this setting. We sought to investigate patterns of care and outcomes for patients evaluated with cTn in the outpatient setting. We hypothesized that a majority of outpatient cTn orders would be for the purpose of diagnosing possible MI. METHODS: We analyzed 228 patients who had outpatient orders for standard-sensitivity troponin T assays placed at our institution between January 1, 2013 and December 18, 2015. Data were divided into two cohorts based on the intended utility of cTn measurement: orders placed to evaluate for possible MI versus orders placed for some other purpose. RESULTS: Of the 228 patients, 161 were evaluated for possible MI and 67 for other reasons. Risk factors (hypertension P = 0.32, diabetes mellitus P = 0.41, coronary disease P = 0.38, heart failure P = 0.098, and chronic kidney disease P = 0.70) were similar between the cohorts. In the suspected MI cohort, an electrocardiogram was obtained in only 77% of patients, and only 13.1% were sent to the emergency department (ED) for further evaluation. Within the suspected MI cohort, 10.5% (n = 17) had elevated cTn and the majority of these patients (n = 10) were not sent to the ED. CONCLUSIONS: The majority of outpatient cTn orders were intended to evaluate for MI, although electrocardiograms were frequently not ordered and few patients were sent for further ED evaluation. Providers should be encouraged to use cTn testing in a manner that minimizes the potential risk to patients with possible MI.

3D Printed "Starmix" Drug Loaded Dosage Forms for Paediatric Applications.

PURPOSE: Three- dimensional (3D) printing has received significant attention as a manufacturing process for pharmaceutical dosage forms. In this study, we used Fusion Deposition Modelling (FDM) in order to print "candy - like" formulations by imitating Starmix® sweets to prepare paediatric medicines with enhanced palatability. METHODS: Hot melt extrusion processing (HME) was coupled with FDM to prepare extruded filaments of indomethacin (IND), hypromellose acetate succinate (HPMCAS) and polyethylene glycol (PEG) formulations and subsequently feed them in the 3D printer. The shapes of the Starmix® objects were printed in the form of a heart, ring, bottle, ring, bear and lion. Differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Fourier Transform Infra-red Spectroscopy (FT-IR) and confocal Raman analysis were used to assess the drug - excipient interactions and the content uniformity. RESULTS: Physicochemical analysis showed the presence of molecularly dispersed IND in the printed tablets. In vivo taste masking evaluation demonstrated excellent masking of the drug bitterness. The printed forms were evaluated for drug dissolution and showed immediate IND release independently of the printed shape, within 60 min. CONCLUSIONS: 3D printing was used successfully to process drug loaded filaments for the development of paediatric printed tablets in the form of Starmix® designs.

Cardiovascular Safety and Bleeding Risk Associated with Nonsteroidal Anti-Inflammatory Medications in Patients with Cardiovascular Disease.

PURPOSE OF REVIEW: Nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications worldwide. There has been growing concern regarding the cardiovascular risks associated with NSAID use (both selective cyclooxygenase [COX]-2 inhibitors and nonselective NSAIDs). This review will examine the evidence pertaining to cardiovascular safety and bleeding risk related to nonaspirin NSAIDs. RECENT FINDINGS: Earlier studies exposed the cardiovascular risks associated with use of selective COX-2 inhibitors; however, further studies have shown that even nonselective COX inhibition may lead to an increased risk of cardiovascular events. Data have also suggested that nonaspirin NSAIDs carry a higher bleeding risk in patients on antithrombotic therapy. Nonaspirin NSAIDs may confer an increased risk of both adverse cardiovascular outcomes and bleeding complications, regardless of COX selectivity and duration of use. Thus, it remains important to limit their use whenever possible, especially in patients with established cardiovascular disease.

Increased dissolution rates of tranilast solid dispersions extruded with inorganic excipients.

The purpose of this study was to evaluate the performance of Neusilin® (NEU) a synthetic magnesium aluminometasilicate as an inorganic drug carrier co-processed with the hydrophilic surfactants Labrasol and Labrafil to develop Tranilast (TLT)-based solid dispersions using continuous melt extrusion (HME) processing. Twin-screw extrusion was optimized to develop various TLT/excipient/surfactant formulations followed by continuous capsule filling in the absence of any downstream equipment. Physicochemical characterization showed the existence of TLT in partially crystalline state in the porous network of inorganic NEU for all extruded formulations. Furthermore, in-line NIR studies revealed a possible intermolecular H-bonding formation between the drug and the carrier resulting in the increase of TLT dissolution rates. The capsules containing TLT-extruded solid dispersions showed enhanced dissolution rates and compared with the marketed Rizaben® product.

Current Trends on Medical and Pharmaceutical Applications of Inkjet Printing Technology.

Inkjet printing is an attractive material deposition and patterning technology that has received significant attention in the recent years. It has been exploited for novel applications including high throughput screening, pharmaceutical formulations, medical devices and implants. Moreover, inkjet printing has been implemented in cutting-edge 3D-printing healthcare areas such as tissue engineering and regenerative medicine. Recent inkjet advances enabled 3D printing of artificial cartilage and skin, or cell constructs for transplantation therapies. In the coming years inkjet printing is anticipated to revolutionize personalized medicine and push the innovation portfolio by offering new paths in patient - specific treatments.

Brain injury as a risk factor for fever upon admission to the intensive care unit and association with in-hospital case fatality: a matched cohort study.

PURPOSE: To test the hypothesis that fever was more frequent in critically ill patients with brain injury when compared to nonneurological patients and to study its effect on in-hospital case fatality. METHODS: Retrospective matched cohort study utilizing a single-center prospectively compiled registry. Critically ill neurological patients ≥18 years and consecutively admitted to the intensive care unit (ICU) with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and traumatic brain injury (TBI) were selected. Patients were matched by sex, age, and Acute Physiology and Chronic Health Evaluation II (APACHE-II) to a cohort of nonneurological patients. Fever was defined as any temperature ≥37.5°C within the first 24 hours upon admission to the ICU. The primary outcome measure was in-hospital case fatality. RESULTS: Mean age among neurological patients was 65.6 ± 15 years, 46% were men, and median APACHE-II was 15 (interquartile range 11-20). There were 18% AIS, 27% ICH, and 6% TBI. More neurological patients experienced fever than nonneurological patients (59% vs 47%, P = .007). The mean hospital length of stay was higher for nonneurological patients (18 ± 20 vs 14 ± 15 days, P = .007), and more neurological patients were dead at hospital discharge (29% vs 20%, P < .0001). After risk factor adjustment, diagnosis (neurological vs nonneurological), and the probability of being exposed to fever (propensity score), the following variables were associated with higher in-hospital case fatality: APACHE-II, neurological diagnosis, mean arterial pressure, cardiovascular and respiratory dysfunction in ICU, and fever (odds ratio 1.9, 95% confidence interval 1.04-3.6, P = .04). CONCLUSION: These data suggest that fever is a frequent occurrence after brain injury, and that it is independently associated with in-hospital case fatality.

Motives for meaningful involvement in rural AIDS service organizations.

The research described herein was a three-year exploratory descriptive study to examine how meaningful involvement (MIPA) is conceptualized and experienced in rural regions of the Maritime provinces of Canada. The focus of this paper is one aspect of the research; i.e., what motivates the clients of AIDS Service Organizations (ASOs) in rural Canada to become meaningfully involved? We interviewed 34 people who were past or current clients of ASOs in Maritime Canada and who self-reported as engaging in at-risk behaviors for HIV or living with HIV. The interviews explored participants' perspectives about their motives for becoming meaningfully involved in an ASO. Three themes regarding motives for MIPA were revealed: (1) meeting personal needs; (2) making a difference to others; and (3) recognizing a fit between their skills, goals, needs and the opportunities and experiences within the ASO and with other ASO clients. Participants generally cited more than one motive. This research study contributed to the field of knowledge about the motives for MIPA in which it reveals (1) that MIPA was conceptualized by the rural ASO clients as whatever participation provided them personal meaning (i.e., by fulfilling a personal need, by making a difference, and by recognizing a fit) and (2) the important role that ASO staff and volunteers have in fostering and sustaining MIPA. The study also highlighted a trajectory of involvements that support the need for ASOs to entertain a wide range of roles that are assumed as MIPA.

Do patients with income-based insurance have access to total joint arthroplasty?

The Patient Protection and Affordable Care Act (PPACA) is expected to increase health care availability through Medicaid expansion. The objective of this study was to evaluate potential effects of the PPACA by examining access to total hip arthroplasty in Southern California. 39 orthopaedic surgeons were called to schedule a hip arthroplasty. Insurances used included a Preferred Provider Organization (PPO), Medicare, and three income-based insurances. There was a significant difference in acceptance rate when comparing PPO and Medicare patients with income-based insurances (P < 0.001). This study showed that in Southern California, patients with income-based insurances are limited in the number of surgeons from whom they can receive care. Thus, although the PPACA will increase the number of insured patients, it may not similarly increase access to providers.

Screening, Synthesis, and Characterization of a More Rapidly Dissolving Celecoxib Crystal Form.

The prevalence of poor solubility in active pharmaceutical ingredients (APIs) such as celecoxib (CEL) is a major bottleneck in the pharmaceutical industry, leading to a low concentration gradient, poor passive diffusion, and in vivo failure. This study presents the synthesis and characterization of a new cocrystal of the API CEL. CEL is a nonsteroidal anti-inflammatory drug used for the treatment of osteoarthritis and rheumatoid arthritis. Computational screening was completed for CEL against a large library of generally recognized as safe (GRAS) coformers, based on molecular complementarity and hydrogen bond propensity (HBP). The generated list of 17 coformers with a likelihood for cocrystallization with CEL were experimentally screened using four techniques: liquid-assisted grinding (LAG), solvent evaporation (SE), gas antisolvent crystallization (GAS), and supercritical enhanced atomization (SEA). One new crystalline form was isolated, employing the liquid coformer N-ethylacetamide (NEA). This novel form, celecoxib-di-N-ethylacetamide (CEL·2NEA), was characterized by a variety of different techniques. The crystal structure was determined through single-crystal X-ray diffraction. Both NEA molecules are evolved from the crystal structure at a desolvation temperature of approximately 65 °C. The CEL·2NEA cocrystal exhibited a dissolution rate, with more than a twofold improvement in comparison to as-received CEL after only 15 min.