TACTICS VR Stroke Telehealth Virtual Reality Training for Health Care Professionals Involved in Stroke Management at Telestroke Spoke Hospitals: Module Design and Implementation Study.

BACKGROUND: Stroke management in rural areas is more variable and there is less access to reperfusion therapies, when compared with metropolitan areas. Delays in treatment contribute to worse patient outcomes. To improve stroke management in rural areas, health districts are implementing telestroke networks. The New South Wales Telestroke Service provides neurologist-led telehealth to 23 rural spoke hospitals aiming to improve treatment delivery and patient outcomes. The training of clinical staff was identified as a critical aspect for the successful implementation of this service. Virtual reality (VR) training has not previously been used in this context. OBJECTIVE: We sought to develop an evidence-based VR training module specifically tailored for stroke telehealth. During implementation, we aimed to assess the feasibility of workplace deployment and collected feedback from spoke hospital staff involved in stroke management on training acceptability and usability as well as perceived training impact. METHODS: The TACTICS VR Stroke Telehealth application was developed with subject matter experts. During implementation, both quantitative and qualitative data were documented, including VR use and survey feedback. VR hardware was deployed to 23 rural hospitals, and use data were captured via automated Wi-Fi transfer. At 7 hospitals in a single local health district, staff using TACTICS VR were invited to complete surveys before and after training. RESULTS: TACTICS VR Stroke Telehealth was deployed to rural New South Wales hospitals starting on April 14, 2021. Through August 20, 2023, a total of 177 VR sessions were completed. Survey respondents (n=20) indicated a high level of acceptability, usability, and perceived training impact (eg, accuracy and knowledge transfer; mean scores 3.8-4.4; 5=strongly agree). Furthermore, respondents agreed that TACTICS VR increased confidence (13/18, 72%), improved understanding (16/18, 89%), and improved awareness (17/18, 94%) regarding stroke telehealth. A comparison of matched pre- and posttraining responses revealed that training improved the understanding of telehealth workflow practices (after training: mean 4.2, SD 0.6; before training: mean 3.2, SD 0.9; P<.001), knowledge on accessing stroke telehealth (mean 4.1, SD 0.6 vs mean 3.1, SD 1.0; P=.001), the awareness of stroke telehealth (mean 4.1, SD 0.6 vs mean 3.4, SD 0.9; P=.03), ability to optimally communicate with colleagues (mean 4.2, SD 0.6 vs mean 3.7, SD 0.9; P=.02), and ability to make improvements (mean 4.0, SD 0.6 vs mean 3.5, SD 0.9; P=.03). Remote training and deployment were feasible, and limited issues were identified, although uptake varied widely (0-66 sessions/site). CONCLUSIONS: TACTICS VR Stroke Telehealth is a new VR application specifically tailored for stroke telehealth workflow training at spoke hospitals. Training was considered acceptable, usable, and useful and had positive perceived training impacts in a real-world clinical implementation context. Additional work is required to optimize training uptake and integrate training into existing education pathways.

Evaluation of a mental health service reform program, the Pathways to Community Living Initiative, for people with severe mental illness and complex needs.

OBJECTIVE: The Pathways to Community Living Initiative (PCLI) aims to reform mental health care for people with severe and persistent mental illness (SPMI) and complex needs. This study reports independent evaluation findings on transitions from hospital and practice change in mental health services. METHODS: Data for this mixed-methods evaluation were obtained from administrative collections and semi-structured interviews with PCLI program managers, teams and executive leads; aged care managers; and leaders in inpatient, community and older people's mental health services. RESULTS: Between July 2015 and December 2020, 674 participants (67% of those eligible for the PCLI) were transitioned from hospital to community. Of those transitioned, 21 required subsequent long-stay admissions. The PCLI introduced resources, clearly defined processes, and state-wide networks to guide changes in practice which are becoming embedded in the operations and governance of mental health services across New South Wales. CONCLUSIONS: Severe and persistent mental illness and complex needs can be managed in community settings with highly individualised planning and care, supported by specialised clinical teams in partnership with mental health, aged care and disability services. Evaluation findings highlight the importance of continued investment in rehabilitation psychiatry.

What are the evidence bases for developing models of rehabilitation for older people with mental illness in Australia?

OBJECTIVE: This paper updates clinicians and service leaders on evidence bases relevant to rehabilitation for older Australians with mental illness. METHODS: Narrative review of literature and relevant public domain data supported by reflections on NSW service development. RESULTS: There is a paucity of high-quality evidence regarding mental health rehabilitation in older people. Available evidence supports integrating lessons from physical healthcare with adaptations of 'adult' mental health rehabilitation. Adaptation is required to respond to the specific needs, strengths and service use of older people with mental illness. Challenges for older people include ageism, increased physical and cognitive comorbidities, lower access to mental health services and earlier residential aged care entry. Strengths of older people include an ongoing desire for recovery, ongoing developmental change and often closer connections with carers and GPs. Evidence is consistent with evaluation of relevant NSW service models and initiatives including the Pathways to Community Living Initiative. Integration of recovery-oriented practice and wellness models may provide a framework for future innovative inpatient and community-based models. CONCLUSIONS: There is sufficient evidence to guide development of models of rehabilitation with older people, but innovation and evaluation are essential if older people are to have equal opportunities in their recovery journeys.

Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study.

Historically, the majority of patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS) progress to end-stage kidney disease (ESKD). Single-arm trials of eculizumab with a short follow-up suggested efficacy. We prove, for the first time to our knowledge, in a genotype matched CaHUS cohort that the 5-year cumulative estimate of ESKD-free survival improved from 39.5% in a control cohort to 85.5% in the eculizumab-treated cohort (hazard ratio, 4.95; 95% confidence interval [CI], 2.75-8.90; P = .000; number needed to treat, 2.17 [95% CI, 1.81-2.73]). The outcome of eculizumab treatment is associated with the underlying genotype. Lower serum creatinine, lower platelet count, lower blood pressure, and younger age at presentation as well as shorter time between presentation and the first dose of eculizumab were associated with estimated glomerular filtration rate >60 ml/min at 6 months in multivariate analysis. The rate of meningococcal infection in the treated cohort was 550 times greater than the background rate in the general population. The relapse rate upon eculizumab withdrawal was 1 per 9.5 person years for patients with a pathogenic mutation and 1 per 10.8 person years for those with a variant of uncertain significance. No relapses were recorded in 67.3 person years off eculizumab in those with no rare genetic variants. Eculizumab was restarted in 6 individuals with functioning kidneys in whom it had been stopped, with no individual progressing to ESKD. We demonstrated that biallelic pathogenic mutations in RNA-processing genes, including EXOSC3, encoding an essential part of the RNA exosome, cause eculizumab nonresponsive aHUS. Recessive HSD11B2 mutations causing apparent mineralocorticoid excess may also present with thrombotic microangiopathy.

Alternative pathway activation in pregnancy, a measured amount "complements" a successful pregnancy, too much results in adverse events.

During pregnancy, the maternal host must adapt in order to enable growth of the fetus. These changes affect all organ systems and are designed both to protect the fetus and to minimize risk to the mother. One of the most prominent adaptations involves the immune system. The semi-allogenic fetoplacental unit has non-self components and must be protected against attack from the host. This requires both attenuation of adaptive immunity and protection from innate immune defense mechanisms. One of the key innate immune players is complement, and it is important that the fetoplacental unit is not identified as non-self and subjected to complement attack. Adaptation of the complement response must, however, be managed in such a way that maternal protection against infection is not compromised. As the complement system also plays a significant facilitating role in many of the stages of a normal pregnancy, it is also important that any necessary adaptation to accommodate the semi-allogenic aspects of the fetoplacental unit does not compromise this. In this review, both the physiological role of the alternative pathway of complement in facilitating a normal pregnancy, and its detrimental participation in pregnancy-specific disorders, are discussed.

Assessing the Impact of Prophylactic Eculizumab on Renal Graft Survival in Atypical Hemolytic Uremic Syndrome.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare cause of end-stage kidney disease and associated with poor outcomes after kidney transplantation from early disease recurrence. Prophylactic eculizumab treatment at the time of transplantation is used in selected patients with aHUS. We report a retrospective case note review describing transplant outcomes in patients with aHUS transplanted between 1978 and 2017, including those patients treated with eculizumab. METHODS: The National Renal Complement Therapeutics Centre database identified 118 kidney transplants in 86 recipients who had a confirmed diagnosis of aHUS. Thirty-eight kidney transplants were performed in 38 recipients who received prophylactic eculizumab. The cohort not treated with eculizumab comprised 80 transplants in 60 recipients and was refined to produce a comparable cohort of 33 transplants in 32 medium and high-risk recipients implanted since 2002. Complement pathway genetic screening was performed. Graft survival was censored for graft function at last follow-up or patient death. Graft survival without eculizumab treatment is described by complement defect status and by Kidney Disease: Improving Global Outcomes risk stratification. RESULTS: Prophylactic eculizumab treatment improved renal allograft survival ( P = 0.006) in medium and high-risk recipients with 1-y survival of 97% versus 64% in untreated patients. Our data supports the risk stratification advised by Kidney Disease: Improving Global Outcomes. CONCLUSIONS: Prophylactic eculizumab treatment dramatically improves graft survival making transplantation a viable therapeutic option in aHUS.

Plasminogen activator-coated nanobubbles targeting cellbound ß2-glycoprotein I as a novel thrombus-specific thrombolytic strategy.

ß2-glycoprotein I (ß2-GPI) is a serum protein widely recognized as the main target of antibodies present in patients with antiphospholipid syndrome (APS). ß2-GPI binds to activated endothelial cells, platelets and leukocytes, key players in thrombus formation. We developed a new targeted thrombolytic agent consisting of nanobubbles (NB) coated with recombinant tissue plasminogen activator (rtPA) and a recombinant antibody specific for cell-bound ß2-GPI. The therapeutic efficacy of targeted NB was evaluated in vitro, using platelet-rich blood clots, and in vivo in three different animal models: i) thrombosis developed in a rat model of APS; ii) ferric chloride-induced mesenteric thrombosis in rats, and iii) thrombotic microangiopathy in a mouse model of atypical hemolytic uremic syndrome (C3-gain-of-function mice). Targeted NB bound preferentially to platelets and leukocytes within thrombi and to endothelial cells through ß2-GPI expressed on activated cells. In vitro, rtPA-targeted NB (rtPA-tNB) induced greater lysis of platelet-rich blood clots than untargeted NB. In a rat model of APS, administration of rtPA-tNB caused rapid dissolution of thrombi and, unlike soluble rtPA that induced transient thrombolysis, prevented new thrombus formation. In a rat model of ferric chloride triggered thrombosis, rtPA-tNB, but not untargeted NB and free rtPA, induced rapid and persistent recanalization of occluded vessels. Finally, treatment of C3-gain-of-function mice with rtPA-tNB, that target ß2-GPI deposited in kidney glomeruli, decreased fibrin deposition, and improved urinalysis data with a greater efficiency than untargeted NB. Our findings suggest that targeting cell-bound ß2-GPI may represent an efficient and thrombus-specific thrombolytic strategy in both APS-related and APS-unrelated thrombotic conditions.

Prevalence and therapeutic management of snakebite cases in the health facilities of the Bouenza department from 2009 to 2021, Republic of Congo.

Introduction: few studies exist of snake bites in the Republic of Congo. This study reports epidemiological and management data on snake bites in the Bouenza department of the Republic of Congo. Methods: this is a retrospective and descriptive study based on questionnaire and analysis of files of snakebite victims over a period of 13 years (2009-2021). We collected data on incidence, age, gender, site of the bite, the season of the bite, deaths and treatment. Results: we identified 81 cases of bites recorded in 14 healthcare facilities: 54.32% of cases (44/81) at Nkayi Base Hospital; 11.11% (9/81) at Madingou Base Hospital; 1-5% (1-4/81) at each of the remaining facilities. Eight deaths were recorded in four health facilities. The sex ratio of snakebite victims was 1 (41 males: 40 females). The age most affected was 25-55 years (54.32% or 44/81). The lower limb was the bite site most reported at 13.98% (but in 84% or 68/81 cases the site was not recorded). More bites occurred during the rainy season (80.25%; 65/81). All victims received only symptomatic treatment based on antibiotics, anti-inflammatories and analgesics, as anti-venom serums are unavailable. The recorded incidence of snake bites in Bouenza was 18.62 per 100,000 of population. Conclusion: our study offers a preliminary report from a little-studied region. The incidence of snakebites recorded in Bouenza is lower than expected compared with studies from other African countries, and with earlier (20 years ago) studies from Congo. This may reflect incomplete record-keeping in under-resourced healthcare facilities.

Teaching veterinary surgical skills: Comparison of massed versus spaced instruction.

OBJECTIVE: To determine the effect of massed instruction (MI) versus spaced instruction (SI) of veterinary surgical skills on students' cognitive load and skill retention. STUDY DESIGN: Prospective randomized cohort study STUDY POPULATION: First-year veterinary students from Louisiana State University (LSU; n = 47) and Lincoln Memorial University (LMU; n = 101). METHODS: Students were randomized to MI (two skills in a single session of twice the duration) or SI (one skill per session on two consecutive days). Instructors, instructional ratio, and total educational time was equivalent. Following instruction, students completed a cognitive load questionnaire and underwent a structured assessment immediately after (LMU only), 1 day after, and 3-4 weeks after learning the second skill. Students completed two supervised practice sessions one and 2 weeks after the initial laboratory session(s). RESULTS: Overall cognitive load did not differ between groups (p > .05), although LMUs MI group reported higher physical and time demands, effort, and frustration. At initial assessment, SI students scored higher than MI students for the first skill at both LSU (mean checklist score = 27.7 vs. mean = 24; p = .004) and LMU (mean global rating score = 4.76 vs. mean = 4.55; p = .029). Differences between groups were no longer evident by 3-4 weeks after instruction. CONCLUSION: SI may lead to improved immediate performance; however, supervised practice was sufficient to overcome the initial disparity. CLINICAL SIGNIFICANCE: SI may be beneficial for initial skill performance. However, SI and MI students had similar performance after 3 weeks, suggesting the more convenient curricular design of MI may be sufficient as long as practice sessions are incorporated.

The Potential Impact of a Public Health Approach to Improving the Physical Health of People Living with Mental Illness.

With already wide disparities in physical health and life expectancy, COVID-19 presents people with mental illness with additional threats to their health: decreased access to health services, increased social isolation, and increased socio-economic disadvantage. Each of these factors has exacerbated the risk of poor health and early death for people with mental illness post-COVID-19. Unless effective primary care and preventative health responses are implemented, the physical illness epidemic for this group will increase post the COVID-19 pandemic. This perspective paper briefly reviews the literature on the impact of COVID-19 on service access, social isolation, and social disadvantage and their combined impact on physical health, particularly cancer, respiratory diseases, heart disease, smoking, and infectious diseases. The much-overlooked role of poor physical health on suicidality is also discussed. The potential impact of public health interventions is modelled based on Australian incidence data and current research on the percentage of early deaths of people living with mental illnesses that are preventable. Building on the lessons arising from services' response to COVID-19, such as the importance of ensuring access to preventive, screening, and primary care services, priority recommendations for consideration by public health practitioners and policymakers are presented.

Implementing recovery-oriented practice in older people’s mental health services: the NSW experience.

Personal recovery is central to Australian mental health standards, but promoting recovery-oriented practice remains a wicked problem (ie complex, with definitions and appropriate interventions impacted upon by context and values), with limited evidence regarding effective implementation. This case study re-examines a statewide initiative to enhance recovery-oriented practice in older people's mental health services in New South Wales from the perspective of complex adaptive systems. The initiative consisted of three key strategies: (1) statewide collaborative leadership and practice resources; (2) locally determined and led improvement projects; and (3) evaluating, disseminating and sustaining initiative outcomes. Published outcomes of the initiative, related policy and benchmarking materials and author reflections are used to propose lessons for other services and policy makers. From a systems perspective, a relatively small investment from a state policy unit to enhance a facilitating environment resulted in the emergence of local leaders and voluntary participation of services within 80% of local health districts without funding incentives. Local leaders and activities informed statewide policies and models of care to sustain practice change. Limitations included variability in project scopes and the involvement of people with lived experience, as well as the level of refinement in change management approach. Self-audit and consumer-rated experience suggest resilience of practice and culture change. The outcomes are consistent with conceptualisations of mental health services being complex adaptive systems requiring distributive leadership. Established mechanisms encouraging statewide cooperation between clinicians, service managers and policy makers may have been significant facilitators of engagement in practice change. What is known about this topic? Recovery remains an important concept for older people with mental ill health, with implementation of recovery-oriented practice a wicked problem. What does this paper add? Central policy investment in a collaborative facilitatory environment can stimulate the emergence of local leadership and investment in actions to enhance recovery orientation. As predicted by complex adaptive systems theory, the impact of the leaders developed may be broader than the sum of individual project outcomes. What are the implications for practitioners? A start where you can message can engage and enable leaders in feasible and locally relevant changes consistent with a statewide strategy. This may be a feasible approach to improving recovery orientation in mental health care services for and beyond older people, with potential implications for addressing other wicked problems in health care.

A novel method for real-time analysis of the complement C3b:FH:FI complex reveals dominant negative CFI variants in age-related macular degeneration.

Age-related macular degeneration (AMD) is linked to 2 main disparate genetic pathways: a chromosome 10 risk locus and the alternative pathway (AP) of complement. Rare genetic variants in complement factor H (CFH; FH) and factor I (CFI; FI) are associated with AMD. FH acts as a soluble cofactor to facilitate FI's cleavage and inactivation of the central molecule of the AP, C3b. For personalised treatment, sensitive assays are required to define the functional significance of individual AP genetic variants. Generation of recombinant FI for functional analysis has thus far been constrained by incomplete processing resulting in a preparation of active and inactive protein. Using an internal ribosomal entry site (IRES)-Furin-CFI expression vector, fully processed FI was generated with activity equivalent to serum purified FI. By generating FI with an inactivated serine protease domain (S525A FI), a real-time surface plasmon resonance assay of C3b:FH:FI complex formation for characterising variants in CFH and CFI was developed and correlated well with standard assays. Using these methods, we further demonstrate that patient-associated rare genetic variants lacking enzymatic activity (e.g. CFI I340T) may competitively inhibit the wild-type FI protein. The dominant negative effect identified in inactive factor I variants could impact on the pharmacological replacement of FI currently being investigated for the treatment of dry AMD.

Homodimeric Minimal Factor H: In Vivo Tracking and Extended Dosing Studies in Factor H Deficient Mice.

C3 glomerulopathy (C3G) is associated with dysregulation of the alternative pathway (AP) of complement and treatment options remain inadequate. Factor H (FH) is a potent regulator of the AP. An in-depth analysis of FH-related protein dimerised minimal (mini)-FH constructs has recently been published. This analysis showed that addition of a dimerisation module to mini-FH not only increased serum half-life but also improved complement regulatory function, thus providing a potential treatment option for C3G. Herein, we describe the production of a murine version of homodimeric mini-FH [mHDM-FH (mFH1-5^18-20^R1-2)], developed to reduce the risk of anti-drug antibody formation during long-term experiments in murine models of C3G and other complement-driven pathologies. Our analysis of mHDM-FH indicates that it binds with higher affinity and avidity to WT mC3b when compared to mouse (m)FH (mHDM-FH KD=505 nM; mFH KD=1370 nM) analogous to what we observed with the respective human proteins. The improved binding avidity resulted in enhanced complement regulatory function in haemolytic assays. Extended interval dosing studies in CFH-/- mice (5mg/kg every 72hrs) were partially effective and bio-distribution analysis in CFH-/- mice, through in vivo imaging technologies, demonstrates that mHDM-FH is preferentially deposited and remains fixed in the kidneys (and liver) for up to 4 days. Extended dosing using an AAV- human HDM-FH (hHDM-FH) construct achieved complete normalisation of C3 levels in CFH-/- mice for 3 months and was associated with a significant reduction in glomerular C3 staining. Our data demonstrate the ability of gene therapy delivery of mini-FH constructs to enhance complement regulation in vivo and support the application of this approach as a novel treatment strategy in diseases such as C3G.

An Emergency Preparedness Response to Opioid-Prescribing Enforcement Actions in Maryland, 2018-2019.

Federal and state enforcement authorities have increasingly intervened on the criminal overprescribing of opioids. However, little is known about the health effects these enforcement actions have on patients experiencing disrupted access to prescription opioids or medication-assisted treatment/medication for opioid use disorder. Simultaneously, opioid death rates have increased. In response, the Maryland Department of Health (MDH) has worked to coordinate mitigation strategies with enforcement partners (defined as any federal, state, or local enforcement authority or other governmental investigative authority). One strategy is a standardized protocol to implement emergency response functions, including rapidly identifying health hazards with real-time data access, deploying resources locally, and providing credible messages to partners and the public. From January 2018 through October 2019, MDH used the protocol in response to 12 enforcement actions targeting 34 medical professionals. A total of 9624 patients received Schedule II-V controlled substance prescriptions from affected prescribers under investigation in the 6 months before the respective enforcement action; 9270 (96%) patients were residents of Maryland. Preliminary data indicate fatal overdose events and potential loss of follow-up care among the patient population experiencing disrupted health care as a result of an enforcement action. The success of the strategy hinged on endorsement by leadership; the establishment of federal, state, and local roles and responsibilities; and data sharing. MDH's approach, data sources, and lessons learned may support health departments across the country that are interested in conducting similar activities on the front lines of the opioid crisis.

Epidemiology of race day injury in young professional jockeys in Great Britain from 2007 to 2018: a retrospective cohort study.

INTRODUCTION: There are limited injury data in professional horse racing, particularly by sex. OBJECTIVES: To describe injury incidence, characteristics and falls in male and female, flat and jump jockeys in Great Britain. DESIGN AND SETTING: Retrospective cohort study of professional jockeys in Britain. PARTICIPANTS: 245 jockeys licensed between 2007 and 2017. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was injury on a race day. Injury incidence (per 1000 rides; per 1000 falls) was derived. Incidence-rate ratios (IRR) were calculated to compare incidence between flat and jump racing, male and female jockeys, and male flat and male jump jockeys for: (i) injury incidence, (ii) fall incidence and (iii) injuries per fall. RESULTS: 234 British professional jockeys were included. Jockeys were on average 19.5±2.0 years old at licence date, 79.9% male and 58.1% flat. The time of follow-up (racing in the study) was 3.7 (SD=2.3) years. There were 278 injuries, occurring in-race (81.7%), in the stalls (10.8%) or parade ring (6.1%). After one injury was removed to preserve anonymity, 57.2% were soft tissue injuries, 25.3% fractures and 10.5% concussion. There were 1634 falls, with 92% in male jump racing. The injury incidence was higher in jump racing (5.1 vs 1.0/1000 jockey rides). The falls incidence was 1.8/1000 rides in flat and 46.2/1000 rides in jump racing (IRR 0.04, 95% CI 0.03 to 0.04). There were over five times higher injuries/1000 falls in flat than jump racing (IRR 5.56, 95% CI 4.05 to 7.53). Male flat jockeys fell less than female flat (IRR 0.57, 95% CI 0.35 to 0.97). CONCLUSION: Most injuries occurred in-race and were soft tissue injuries. Jump jockeys fell more often than flat, and female flat jockeys fell more often than male flat. Flat jockeys injured more frequently when falling. No sex differences were seen for injuries per fall.

Performance of a Predictive Model versus Prescription-Based Thresholds in Identifying Patients at Risk of Fatal Opioid Overdose.

Background: Prescription Drug Monitoring Programs (PDMPs) collect controlled substance prescriptions dispensed within a state. Many PDMP programs perform targeted outreach (i.e., "unsolicited reporting") for patients who exceed numerical thresholds, however, the degree to which patients at highest risk of fatal opioid overdose are identified has not been compared with one another or with a predictive model. Methods: A retrospective analysis was performed using statewide PDMP data for Maryland residents aged 18 to 80 years with an opioid fill between April to June 2015. The outcome was opioid-related overdose death in 2015 or 2016. A multivariable logistic regression model and three PDMP thresholds were evaluated: (1) multiple provider episodes; (2) high daily average morphine milligram equivalents (MME); and (3) overlapping opioid and benzodiazepine prescriptions. Results: The validation cohort consisted of 170,433 individuals and 244 deaths. The predictive model captured more individuals who died (46.3% of total deaths) and had a higher death rate (7.12 per 1000) when the risk score cutoff (0.0030) was selected for a comparable size of high-risk individuals (n = 15,881) than those meeting the overlapping opioid/benzodiazepine prescriptions (n = 17,440; 33.2% of total deaths; 4.64 deaths per 1000) and high MME (n = 14,675; 24.6% of total deaths; 4.09 deaths per 1000) thresholds. Conclusions: The predictive model identified more individuals at risk of fatal opioid overdose as compared with PDMP thresholds commonly used for unsolicited reporting. PDMP programs could improve their targeting of unsolicited reports to reach more individuals at risk of overdose by using predictive models instead of simple threshold-based approaches.

The Impact of Various Risk Assessment Time Frames on the Performance of Opioid Overdose Forecasting Models.

BACKGROUND: An individual's risk for future opioid overdoses is usually assessed using a 12-month "lookback" period. Given the potential urgency of acting rapidly, we compared the performance of alternative predictive models with risk information from the past 3, 6, 9, and 12 months. METHODS: We included 1,014,033 Maryland residents aged 18-80 with at least 1 opioid prescription and no recorded death in 2015. We used 2015 Maryland prescription drug monitoring data to identify risk factors for nonfatal opioid overdoses from hospital discharge records and investigated fatal opioid overdose from medical examiner data in 2016. Prescription drug monitoring program-derived predictors included demographics, payment sources for opioid prescriptions, count of unique opioid prescribers and pharmacies, and quantity and types of opioids and benzodiazepines filled. We estimated a series of logistic regression models that included 3, 6, 9, and 12 months of prescription drug monitoring program data and compared model performance, using bootstrapped C-statistics and associated 95% confidence intervals. RESULTS: For hospital-treated nonfatal overdose, the C-statistic increased from 0.73 for a model including only the fourth quarter to 0.77 for a model with 4 quarters of data. For fatal overdose, the area under the curve increased from 0.80 to 0.83 over the same models. The strongest predictors of overdose were prescription fills for buprenorphine and Medicaid and Medicare as sources of payment. CONCLUSIONS: Models predicting opioid overdose using 1 quarter of data were nearly as accurate as models using all 4 quarters. Models with a single quarter may be more timely and easier to identify persons at risk of an opioid overdose.

Prevalence and intensity of persistent post-surgical pain following breast cancer surgery: a systematic review and meta-analysis of observational studies.

BACKGROUND: The prevalence and intensity of persistent post-surgical pain (PPSP) after breast cancer surgery are uncertain. We conducted a systematic review and meta-analysis to further elucidate this issue. METHODS: We searched MEDLINE, Embase, CINAHL, and PsycINFO, from inception to November 2018, for observational studies reporting persistent pain (≥3 months) after breast cancer surgery. We used random-effects meta-analysis and the Grading of Recommendations, Assessment, Development and Evaluations approach to rate quality of evidence. RESULTS: We included 187 observational studies with 297 612 breast cancer patients. The prevalence of PPSP ranged from 2% to 78%, median 37% (inter-quartile range: 22-48%); the pooled prevalence was 35% (95% confidence interval [CI]: 32-39%). The pooled pain intensity was 3.9 cm on a 10 cm visual analogue scale (95% CI: 3.6-4.2 cm). Moderate-quality evidence supported the subgroup effects of PPSP prevalence for localized pain vs any pain (29% vs 44%), moderate or greater vs any pain (26% vs 44%), clinician-assessed vs patient-reported pain (23% vs 36%), and whether patients underwent sentinel lymph node biopsy vs axillary lymph node dissection (26% vs 43%). The adjusted analysis found that the prevalence of patient-reported PPSP (any severity/location) was 46% (95% CI: 36-56%), and the prevalence of patient-reported moderate-to-severe PPSP at any location was 27% (95% CI: 10-43%). CONCLUSIONS: Moderate-quality evidence suggests that almost half of all women undergoing breast cancer surgery develop persistent post-surgical pain, and about one in four develop moderate-to-severe persistent post-surgical pain; the higher prevalence was associated with axillary lymph node dissection. Future studies should explore whether nerve sparing for axillary procedures reduces persistent post-surgical pain after breast cancer surgery.

Opioid overdose death following criminal justice involvement: Linking statewide corrections and hospital databases to detect individuals at highest risk.

BACKGROUND: Persons who interact with criminal justice and hospital systems are particularly vulnerable to negative health outcomes, including overdose. However, the relationship between justice involvement, healthcare utilization and overdose risk is not well-understood. This data linkage study seeks to improve our understanding of the link between different types of justice involvement as well as hospital interaction and risk of fatal opioid overdose among persons with incarcerations, arrests and parole/probation records for drug and property crimes in Maryland. METHODS: Maryland statewide criminal justice records were obtained for 2013-2016. Data were linked at the person-level to an all-payer hospitalization database and overdose death records for the same years. Logistic regression was performed to determine which criminal justice and hospital characteristics were associated with greatest risk of overdose death. RESULTS: 89,591 adults had criminal-justice records and were included in the study. During the 2013-2016 study period, 4108 (4.59 %) were hospitalized for a non-fatal opioid overdose, and 519 (0.58 %) died of opioid overdose. Strongest risk factors for death included being older, being white, having had an inpatient or emergency hospitalization, having had more arrests, having been arrested for a drug charge (vs. property charge), having a misdemeanor drug charge (vs. a felony charge), and having been released from incarceration during the study period. CONCLUSION: Linking corrections and healthcare information can help advance understanding of risk and target overdose prevention interventions directed at justice-involved individuals with greatest need.

Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy.

Recessive mutations in diacylglycerol kinase epsilon (DGKE) display genetic pleiotropy, with pathological features reported as either thrombotic microangiopathy or membranoproliferative glomerulonephritis (MPGN), and clinical features of atypical hemolytic uremic syndrome (aHUS), nephrotic syndrome or both. Pathophysiological mechanisms and optimal management strategies have not yet been defined. In prospective and retrospective studies of aHUS referred to the United Kingdom National aHUS service and prospective studies of MPGN referred to the National Registry of Rare Kidney Diseases for MPGN we defined the incidence of DGKE aHUS as 0.009/million/year and so-called DGKE MPGN as 0.006/million/year, giving a combined incidence of 0.015/million/year. Here, we describe a cohort of sixteen individuals with DGKE nephropathy. One presented with isolated nephrotic syndrome. Analysis of pathological features reveals that DGKE mutations give an MPGN-like appearance to different extents, with but more often without changes in arterioles or arteries. In 15 patients presenting with aHUS, ten had concurrent substantial proteinuria. Identified triggering events were rare but coexistent developmental disorders were seen in six. Nine with aHUS experienced at least one relapse, although in only one did a relapse of aHUS occur after age five years. Persistent proteinuria was seen in the majority of cases. Only two individuals have reached end stage renal disease, 20 years after the initial presentation, and in one, renal transplantation was successfully undertaken without relapse. Six individuals received eculizumab. Relapses on treatment occurred in one individual. In four individuals eculizumab was withdrawn, with one spontaneously resolving aHUS relapse occurring. Thus we suggest that DGKE-mediated aHUS is eculizumab non-responsive and that in individuals who currently receive eculizumab therapy it can be safely withdrawn. This has important patient safety and economic implications.