Preventing severe hypoglycemia in adults with type 2 diabetes (PHT2): Design, delivery and evaluation framework for a randomized controlled trial.

BACKGROUND: Severe hypoglycemia is a common and feared complication of medications used to lower blood glucose levels in individuals with diabetes. Psychoeducational interventions can prevent severe hypoglycemia in individuals with type 1 diabetes (T1D). We aim to determine the effectiveness of this approach among adults with type 2 diabetes (T2D) at elevated risk for severe hypoglycemia. METHODS: Preventing Hypoglycemia in Type 2 diabetes (PHT2) is a two-arm, parallel, randomized controlled trial. Participants are eligible if they are adults with T2D receiving care at an integrated group practice in Washington state and have experienced one or more episodes of severe hypoglycemia in the prior 12 months or have impaired awareness of hypoglycemia (Gold score ≥ 4). Participants are randomized to proactive nurse care management with or without my hypo compass, an evidence-based, psychoeducational intervention combining group and individual self-management training. For this study, my hypo compass was adapted to be suitable for adults with T2D and from an in-person to a virtual intervention over videoconference and telephone. The primary outcome is any self-reported severe hypoglycemia in the 12 months following the start of the intervention. Secondary outcomes include biochemical measures of hypoglycemia, self-reported hypoglycemia awareness, fear of hypoglycemia, and emergency department visits and hospitalizations for severe hypoglycemia. The study includes a process evaluation to assess implementation fidelity and clarify the causal pathway. CONCLUSION: The PHT2 trial will compare the effectiveness of two approaches for reducing severe hypoglycemia in adults with T2D. TRIAL REGISTRATION: clinicaltrials.gov, # NCT04863872.

Anatomy of the lumbar interspinous ligament: findings relevant to epidural insertion using loss of resistance.

BACKGROUND AND OBJECTIVES: The 'loss of resistance' technique is used to determine entry into the epidural space, often by a midline needle in the interspinous ligament before the ligamentum flavum. Anatomical explanations for loss of resistance without entry into the epidural space are lacking. This investigation aimed to improve morphometric characterization of the lumbar interspinous ligament by observation and measurement at dissection and from MRI. METHODS: Measurements were made on 14 embalmed donor lumbar spines (T12 to S1) imaged with MRI and then dissected along a tilted axial plane aligned with the lumbar interspace. RESULTS: In 73 interspaces, median (IQR) lumbar interspinous plus supraspinous ligament length was 29.7 mm (25.5-33.4). Posterior width was 9.2 mm (7.7, 11.9), with narrowing in the middle (4.5 mm (3.0, 6.8)) and an anterior width of 7.3 mm (5.7, 9.8).Fat-filled gaps were present within 55 (75%). Of 51 anterior gaps, 49 (67%) were related to the ligamenta flava junction. Median (IQR) gap length and width were 3.5 mm (2.5, 5.1) and 1.1 mm (0.9, 1.7).Detection of gaps with MRI had 100% sensitivity (95% CI 93.5 to 100), 94.4% specificity (72.7, 99.9), 98.2% (90.4, 100) positive predictive value and 100% (80.5, 100) negative predictive value against dissection as the gold standard. CONCLUSIONS: The lumbar interspinous ligament plus supraspinous ligament are biconcave axially. It commonly has fat-filled gaps, particularly anteriorly. These anatomical features may form the anatomical basis for false or equivocal loss of resistance.

Variation in referral rates to emergency departments and inpatient services from a GP out of hours service and the potential impact of alternative staffing models.

INTRODUCTION: Out of hours (OOHs) primary care is a critical component of the acute care system overnight and at weekends. Referrals from OOH services to hospital will add to the burden on hospital assessment in the ED and on-call specialties. METHODS: We studied the variation in referral rates (to the ED and direct specialty admission) of individual clinicians working in the Oxfordshire, UK OOH service covering a population of 600 000 people. We calculated the referral probability for each clinician over a 13-month period of practice (1 December 2014 to 31 December 2015), stratifying by clinician factors and location and timing of assessment. We used Simul8 software to determine the range of hospital referrals potentially due to variation in clinician referral propensity. RESULTS: Among the 119 835 contacts with the service, 5261 (4.4%) were sent directly to the ED and 3474 (3.7%) were admitted directly to specialties. More referrals were made to ED by primary care physicians if they did not work in the local practices (5.5% vs 3.5%, p=0.011). For clinicians with >1000 consultations, percentage of patients referred varied from 1% to 21% of consultations. Simulations where propensity to refer was made less extreme showed a difference in maximum referrals of 50 patients each week. CONCLUSIONS: There is substantial variation in clinician referral rates from OOHs primary care to the acute hospital setting. The number of patients referred could be influenced by this variation in clinician behaviour. Referral propensity should be studied including casemix adjustment to determine if interventions targeting such behaviour are effective.

Paediatric contacts with the UK out-of-hours primary care service and contact outcomes: a regional service evaluation.

BACKGROUND: Demand on hospital emergency departments for paediatric problems is increasing. However, the volume and nature of paediatric health demands placed on other parts of the urgent care system have not been explored. This understanding is an important first step in developing and improving out-of-hospital care. We aimed to describe the volume, nature, and outcomes of paediatric contacts with out-of-hours general practice (OOH GP). We performed a retrospective service evaluation using data from 12 months of paediatric patient contacts with the Oxfordshire OOH GP service. METHODS: A database of contacts with the Oxfordshire OOH GP service was created for a 12 month period from December 2014 to November 2015. Descriptive statistics were calculated using SPSS Version 25. RESULTS: 27,455 contacts were made by 18,987 individuals during a 12 month period. The majority of these were for children aged under 5. Over 70% of contacts were at the weekend. The peak contact period was between 18:30 and 21:30. Over 40% of contacts resulted in advice only (no onward referral, requirement for GP follow up, or prescription). 19.7% of contacts resulted in an antibiotic prescription, most commonly those linked with ear, chest, and throat infections. DISCUSSION: Paediatric contacts with the Oxfordshire OOH GP service were predominantly in younger age groups and in the evening, with 19.7% resulting in an antibiotic prescription. Almost half of the contacts had no follow up or prescription, suggesting non-prescribing health care professionals could be involved in providing care in OOH GP. Further research should consider how children and their parents can be best supported to optimise OOH consulting.

Point-of-care blood tests during home visits by out-of-hours primary care clinicians; a mixed methods evaluation of a service improvement.

OBJECTIVES: We aimed to evaluate test usage and patient and clinician experience following the introduction of point-of-care (POC) blood tests into a primary care out-of-hours service. DESIGN: A mixed methods service evaluation comprising quantitative records of the clinical contexts of tests taken and qualitative interviews with clinicians. Research permissions and governance were obtained for patient interviews. SETTING: Out-of-hours primary care. PARTICIPANTS: All patients requiring home visits from the service during the implementation period. INTERVENTIONS: The i-STAT POC blood test platform was introduced to two bases providing home visits for a period of 8 months. Venous blood samples were used and two cartridges were available. The CHEM8 cartridge measures sodium, potassium, chloride, total carbon dioxide (TCO2), anion gap, ionised calcium, glucose, urea, creatinine, haematocrit and haemoglobin. The CG4 cartridge measures lactate, pH, PaO2 and PCO2, TCO2, bicarbonate, base excess and oxygen saturation. PRIMARY AND SECONDARY OUTCOME MEASURES: The proportion of home visits where tests were taken, the clinical contexts of those tests, the extent to which clinicians felt the tests had influenced their decisions, time taken to perform the test and problems encountered. Clinician and patient experiences of using POC tests. RESULTS: i-STAT POC tests were infrequently used, with successful tests taken at just 47 contacts over 8 months of implementation. The patients interviewed felt that testing had been beneficial for their care. Clinician interviews suggested barriers to POC tests, including practical challenges, concerns about time, doubt over whether they would improve clinical decision making and concern about increased medicolegal risk. Suggestions for improving adoption included sharing learning, adopting a whole team approach and developing protocols for usage. CONCLUSIONS: POC tests were not successfully adopted by an out-of-hours home visiting service in Oxfordshire. While some clinicians felt they could not add value, in other cases they resulted in improved patient experience. Adoption could be promoted by improving technical, team and education factors.

Out-of-hours primary care end of life prescribing: a data linkage study.

OBJECTIVES: Out-of-hours (OOH) primary care services are contacted in the last 4 weeks of life by nearly 30% of all patients who die, but OOH palliative prescribing remains poorly understood. Our understanding of prescribing demand has previously been limited by difficulties identifying palliative patients seen OOH. This study examines the volume and type of prescriptions issued by OOH services at the end of life. METHODS: A retrospective cohort study was performed by linking a database of Oxfordshire OOH service contacts over a year with national mortality data, identifying patients who died within 30 days of OOH contact. Demographic, service and prescribing data were analysed. RESULTS: A prescription is issued at 14.2% of contacts in the 30 days prior to death, compared with 29.9% of other contacts. The most common prescriptions were antibiotics (22.2%) and strong opioids (19%). 41.8% of prescriptions are for subcutaneously administered medication. Patients who were prescribed a syringe driver medication made twice as many OOH contacts in the 30 days prior to death compared with those who were not. CONCLUSION: Absolute and relative prescribing rates are low in the 30 days prior to death. Further research is required to understand what occurs at these non-prescribing end of life contacts to inform how OOH provision can best meet the needs of dying patients. Overall, relatively few patients are prescribed strong opioids or syringe drivers. When a syringe driver medication is prescribed this may help identify patients likely to be in need of further support from the service.

What proportion of patients at the end of life contact out-of-hours primary care? A data linkage study in Oxfordshire.

OBJECTIVES: Out-of-hours (OOH) primary care services are a key element of community care at the end of life, yet there have been no previous attempts to describe the scope of this activity. We aimed to establish the proportion of Oxfordshire patients who were seen by the OOH service within the last 30 days of life, whether they were documented in a palliative phase of care and the demographic and clinical features of these groups. DESIGN: Population-based study linking a database of patient contacts with OOH primary care with the register of all deaths within Oxfordshire (600 000 population) during 13 months. SETTING: Oxfordshire. PARTICIPANTS: Between 1 December 2014 and 30 November 2015 there were 102 877 OOH contacts made by 67 943 patients with the OOH service. MAIN OUTCOME MEASURES: Proportion of patients dying in the Oxfordshire population who were seen by the OOH service within the last 30 days of life. Demographic and clinical features of these contacts. RESULTS: 29.5% of all population deaths were seen by the OOH service in the last 30 days of life. Among the 1530 patients seen, patients whose palliative phase was documented (n=577, 36.4%) were slightly younger (median age=83.5 vs 85.2 years, P<0.001) and were seen closer to death (median days to death=2 vs 8, P<0.001). More were assessed at home (59.8% vs 51.9%, P<0.001) and less were admitted to hospital (2.7% vs 18.0%, P<0.001). CONCLUSIONS: OOH services see around one-third of all patients who die in a population. Most patients at the end of life are not documented as palliative by OOH services and are less likely to receive ongoing care at home.

A longitudinal investigation into cognition and disease progression in spinocerebellar ataxia types 1, 2, 3, 6, and 7.

BACKGROUND: The natural history of clinical symptoms in the spinocerebellar ataxias (SCA)s has been well characterised. However there is little longitudinal data comparing cognitive changes in the most common SCA subtypes over time. The present study provides a preliminary longitudinal characterisation of the clinical and cognitive profiles in patients with SCA1, SCA2, SCA3, SCA6 and SCA7, with the aim of elucidating the role of the cerebellum in cognition. METHODS: 13 patients with different SCAs all caused by CAG repeat expansion (SCA1, n = 2; SCA2, n = 2; SCA3, n = 2; SCA6, n = 4; and SCA7, n = 3) completed a comprehensive battery of cognitive and mood assessments at two time points, a mean of 7.35 years apart. All patients were evaluated clinically using the Scale for the Rating and Assessment of Ataxia (SARA) and the Inventory of Non-Ataxia Signs (INAS). Patients underwent structural MRI imaging at follow-up. RESULTS: Clinical scale scores increased in all patients over time, most prominently in the SCA1 (SARA) and SCA3 (INAS) groups. New impairments on neuropsychological tests were most commonly observed with executive functions, speed, attention, visual memory and Theory of Mind. Results suggest possible differences in cognitive decline in SCA subtypes, with the most rapid cognitive decline observed in the SCA1 patients, and the least in the SCA6 patients, congruent with observed patterns of motor deterioration. Minimal changes in mood were observed, and MRI measures of atrophy did not correlate with cognitive decline. CONCLUSION: As well as increasing physical impairment, cognitive decline over time appears to be a distinct aspect of the SCA phenotype, in keeping with the cerebellar cognitive-affective syndrome. Our data suggest a trend of cognitive decline that is different for each SCA subtype, and for the majority is related to the severity of cerebellar motor impairment.

Genetic diversity loss in a biodiversity hotspot: ancient DNA quantifies genetic decline and former connectivity in a critically endangered marsupial.

The extent of genetic diversity loss and former connectivity between fragmented populations are often unknown factors when studying endangered species. While genetic techniques are commonly applied in extant populations to assess temporal and spatial demographic changes, it is no substitute for directly measuring past diversity using ancient DNA (aDNA). We analysed both mitochondrial DNA (mtDNA) and nuclear microsatellite loci from 64 historical fossil and skin samples of the critically endangered Western Australian woylie (Bettongia penicillata ogilbyi), and compared them with 231 (n = 152 for mtDNA) modern samples. In modern woylie populations 15 mitochondrial control region (CR) haplotypes were identified. Interestingly, mtDNA CR data from only 29 historical samples demonstrated 15 previously unknown haplotypes and detected an extinct divergent clade. Through modelling, we estimated the loss of CR mtDNA diversity to be between 46% and 91% and estimated this to have occurred in the past 2000-4000 years in association with a dramatic population decline. In addition, we obtained near-complete 11-loci microsatellite profiles from 21 historical samples. In agreement with the mtDNA data, a number of 'new' microsatellite alleles was only detected in the historical populations despite extensive modern sampling, indicating a nuclear genetic diversity loss >20%. Calculations of genetic diversity (heterozygosity and allelic rarefaction) showed that these were significantly higher in the past and that there was a high degree of gene flow across the woylie's historical range. These findings have an immediate impact on how the extant populations are managed and we recommend the implementation of an assisted migration programme to prevent further loss of genetic diversity. Our study demonstrates the value of integrating aDNA data into current-day conservation strategies.