Algorithmic approach to finding people with multiple sclerosis using routine healthcare data in Wales.

BACKGROUND: Identification of multiple sclerosis (MS) cases in routine healthcare data repositories remains challenging. MS can have a protracted diagnostic process and is rarely identified as a primary reason for admission to the hospital. Difficulties in identification are compounded in systems that do not include insurance or payer information concerning drug treatments or non-notifiable disease. AIM: To develop an algorithm to reliably identify MS cases within a national health data bank. METHOD: Retrospective analysis of the Secure Anonymised Information Linkage (SAIL) databank was used to identify MS cases using a novel algorithm. Sensitivity and specificity were tested using two existing independent MS datasets, one clinically validated and population-based and a second from a self-registered MS national registry. RESULTS: From 4 757 428 records, the algorithm identified 6194 living cases of MS within Wales on 31 December 2020 (prevalence 221.65 (95% CI 216.17 to 227.24) per 100 000). Case-finding sensitivity and specificity were 96.8% and 99.9% for the clinically validated population-based cohort and sensitivity was 96.7% for the self-declared registry population. DISCUSSION: The algorithm successfully identified MS cases within the SAIL databank with high sensitivity and specificity, verified by two independent populations and has important utility in large-scale epidemiological studies of MS.

Efficacy of Single-Dose Primaquine With Artemisinin Combination Therapy on Plasmodium falciparum Gametocytes and Transmission: An Individual Patient Meta-Analysis.

BACKGROUND: Since the World Health Organization recommended single low-dose (0.25 mg/kg) primaquine (PQ) in combination with artemisinin-based combination therapies (ACTs) in areas of low transmission or artemisinin-resistant Plasmodium falciparum, several single-site studies have been conducted to assess efficacy. METHODS: An individual patient meta-analysis to assess gametocytocidal and transmission-blocking efficacy of PQ in combination with different ACTs was conducted. Random effects logistic regression was used to quantify PQ effect on (1) gametocyte carriage in the first 2 weeks post treatment; and (2) the probability of infecting at least 1 mosquito or of a mosquito becoming infected. RESULTS: In 2574 participants from 14 studies, PQ reduced PCR-determined gametocyte carriage on days 7 and 14, most apparently in patients presenting with gametocytemia on day 0 (odds ratio [OR], 0.22; 95% confidence interval [CI], .17-.28 and OR, 0.12; 95% CI, .08-.16, respectively). Rate of decline in gametocyte carriage was faster when PQ was combined with artemether-lumefantrine (AL) compared to dihydroartemisinin-piperaquine (DP) (P = .010 for day 7). Addition of 0.25 mg/kg PQ was associated with near complete prevention of transmission to mosquitoes. CONCLUSIONS: Transmission blocking is achieved with 0.25 mg/kg PQ. Gametocyte persistence and infectivity are lower when PQ is combined with AL compared to DP.

Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data.

BACKGROUND: In 2012, the World Health Organization (WHO) recommended single low-dose (SLD, 0.25 mg/kg) primaquine to be added as a Plasmodium (P.) falciparum gametocytocide to artemisinin-based combination therapy (ACT) without glucose-6-phosphate dehydrogenase (G6PD) testing, to accelerate malaria elimination efforts and avoid the spread of artemisinin resistance. Uptake of this recommendation has been relatively slow primarily due to safety concerns. METHODS: A systematic review and individual patient data (IPD) meta-analysis of single-dose (SD) primaquine studies for P. falciparum malaria were performed. Absolute and fractional changes in haemoglobin concentration within a week and adverse effects within 28 days of treatment initiation were characterised and compared between primaquine and no primaquine arms using random intercept models. RESULTS: Data comprised 20 studies that enrolled 6406 participants, of whom 5129 (80.1%) had received a single target dose of primaquine ranging between 0.0625 and 0.75 mg/kg. There was no effect of primaquine in G6PD-normal participants on haemoglobin concentrations. However, among 194 G6PD-deficient African participants, a 0.25 mg/kg primaquine target dose resulted in an additional 0.53 g/dL (95% CI 0.17-0.89) reduction in haemoglobin concentration by day 7, with a 0.27 (95% CI 0.19-0.34) g/dL haemoglobin drop estimated for every 0.1 mg/kg increase in primaquine dose. Baseline haemoglobin, young age, and hyperparasitaemia were the main determinants of becoming anaemic (Hb < 10 g/dL), with the nadir observed on ACT day 2 or 3, regardless of G6PD status and exposure to primaquine. Time to recovery from anaemia took longer in young children and those with baseline anaemia or hyperparasitaemia. Serious adverse haematological events after primaquine were few (9/3, 113, 0.3%) and transitory. One blood transfusion was reported in the primaquine arms, and there were no primaquine-related deaths. In controlled studies, the proportions with either haematological or any serious adverse event were similar between primaquine and no primaquine arms. CONCLUSIONS: Our results support the WHO recommendation to use 0.25 mg/kg of primaquine as a P. falciparum gametocytocide, including in G6PD-deficient individuals. Although primaquine is associated with a transient reduction in haemoglobin levels in G6PD-deficient individuals, haemoglobin levels at clinical presentation are the major determinants of anaemia in these patients. TRIAL REGISTRATION: PROSPERO, CRD42019128185.

A Rapid Electronic Cognitive Assessment Measure for Multiple Sclerosis: Validation of Cognitive Reaction, an Electronic Version of the Symbol Digit Modalities Test.

BACKGROUND: Incorporating cognitive testing into routine clinical practice is a challenge in multiple sclerosis (MS), given the wide spectrum of both cognitive and physical impairments people can have and the time that testing requires. Shortened paper and verbal assessments predominate but still are not used routinely. Computer-based tests are becoming more widespread; however, changes in how a paper test is implemented can impact what exactly is being assessed in an individual. The Symbol Digit Modalities Test (SDMT) is one validated test that forms part of the cognitive batteries used in MS and has some computer-based versions. We developed a tablet-based SDMT variant that has the potential to be ultimately deployed to patients' own devices. OBJECTIVE: This paper aims to develop, validate, and deploy a computer-based SDMT variant, the Cognition Reaction (CoRe) test, that can reliably replicate the characteristics of the paper-based SDMT. METHODS: We carried out analysis using Pearson and intraclass correlations, as well as a Bland-Altman comparison, to examine consistency between the SDMT and CoRe tests and for test-retest reliability. The SDMT and CoRe tests were evaluated for sensitivity to disability levels and age. A novel metric in CoRe was found: question answering velocity could be calculated. This was evaluated in relation to disability levels and age for people with MS and compared with a group of healthy control volunteers. RESULTS: SDMT and CoRe test scores were highly correlated and consistent with 1-month retest values. Lower scores were seen in patients with higher age and some effect was seen with increasing disability. There was no learning effect evident. Question answering velocity demonstrated a small increase in speed over the 90-second duration of the test in people with MS and healthy controls. CONCLUSIONS: This study validates a computer-based alternative to the SDMT that can be used in clinics and beyond. It enables accurate recording of elements of cognition relevant in MS but offers additional metrics that may offer further value to clinicians and people with MS.

Child's Play or Sexual Abuse? Reviewing the Efficacy of the Justice Framework in Dealing with Child on Child Sexual Abuse in the United Kingdom.

This literature review appraises how the justice system of the United Kingdom deals with child on child sexual abuse allegations. It is crucial to consider the impact of minor sexual abuse within the community. Sensationalized reporting of sex crimes demonizes offenders and unintentionally hides some perpetrators by not representing children can cause harm. Cases where children demonstrate sexual agency are confusing and uncomfortable to appropriate blame. A freedom of information request to the Metropolitan Police uncovered 5,500 minor sex abuse allegations in England and Wales between 2011 and 2014, including, 4,000 physical assaults and 600 rape allegations. Officials caution these figures only represent a small proportion of known sexual abuse cases but the full extent of the problem is yet to be seen. Children are being exposed to explicit imagery far beyond their developmental age causing a blurring of the lines between normal sexual curiosity, harmful behavior, sexual deviance, and abuse. Evidence suggests societal failings and technological advances have created vulnerabilities from which new and dangerous sexual norms have evolved. Therefore, this paper reviews the justice, welfare, and restorative justice frameworks to explore the efficacy of the justice system in dealing with child on child sexual abuse in the UK.

Serous Tubal Intraepithelial Carcinoma (STIC)-like Lesions Arising in Ovarian Serous Cystadenofibroma: Report of 2 Cases.

Recent studies have demonstrated that most so-called ovarian high-grade serous carcinomas are likely to arise from the epithelium of the distal fimbrial portion of the fallopian tube from a precursor lesion known as serous tubal intraepithelial carcinoma (STIC). We report 2 cases in patients aged 56 and 71 of lesions morphologically identical to STIC (referred to as STIC-like lesions) arising from the benign ciliated epithelium of ovarian serous cystadenofibromas. In 1 case, 2 glands within the serous cystadenofibroma exhibited high-grade nuclear atypia and mitotic activity and in the other similar changes were multifocal. No invasion of the stroma was seen. In both cases, the STIC-like lesion exhibited aberrant "mutation-type" staining with p53 (1 diffuse intense positivity, 1 null pattern). As far as we are aware, a STIC-like lesion involving the epithelium of a benign ovarian serous neoplasm has not been reported previously. Both patients were followed up without adjuvant treatment. One case is recent, and follow-up in the other patient is uneventful at 12 mo.

The malignant transformation of endometriosis: Is there a left lateral predisposition of ovarian clear cell and endometrioid carcinomas?

INTRODUCTION: Endometriosis affects 10% of women of reproductive age. There is evidence for a left lateral predisposition of endometriotic lesions and a 1.9-fold greater risk of ovarian cancer in endometriosis. The aim of this study is to determine whether a left lateral predisposition of ovarian clear-cell carcinoma (CCC) and endometrioid carcinoma (EC) exists. MATERIALS AND METHODS: A retrospective cohort study of all EC and CCC patients in Northern Ireland between March-2011 and June-2018. ANOVA was used to analyse preoperative prediction of stage, chi-squared (χ2) was used to compare left- and right-sided masses. Survival was estimated using Kaplan-Meier and log-rank test. A p-value <0.05 was considered significant. RESULTS: 158 patients were identified (95 EC, 55 CCC, 8 mixed). Mean age was 57.65 years with 69% presenting at stage 1. The mean CA125 was 559 U/mL (p = 0.850) and mean abdominal mass size was 14.12 cm (p = 0.732). The most common presenting symptom was an abdominal mass (37%). Despite 67% of patients having endometriosis on final pathology, only 8.9% had a known history pre-operatively. 51% of tumours were located on the left (p = 0.036). For unilateral tumours this was significant for EC (P = 0.002) but not for CCC (P = 0.555). The 1-, 3- and 5-year overall survival for all types/stages was 85%, 78% and 71% respectively. CONCLUSION: While CCC and EC are associated with endometriosis, only EC exhibits a left lateral predisposition. There is no association between preoperative CA125 or abdominal mass size and stage of disease.

Disease-modifying therapy initiation patterns in multiple sclerosis in three large MS populations.

Background: Treatment guidelines recommend early disease-modifying therapy (DMT) initiation after diagnosis of multiple sclerosis (MS). Multinational comparative studies that assess time to DMT initiation in MS may allow detection of barriers inherent to healthcare systems to explain potential adverse systematic delays in commencing DMTs. Objectives: To investigate and compare the time to first DMT and its association with sociodemographic and clinical variables after MS diagnosis in three large MS registries. Design: This observational study was conducted using data from the German MS Registry (GMSR), the North American Research Committee on MS Registry (NARCOMS, US data only), and the United Kingdom MS Registry (UKMSR, both self- and clinician-reported). Methods: Data from relapsing people with MS (PwMS), with a diagnosis of MS between 2014 and 2019, and available DMT and disability status were pooled using a meta-analytic approach. Results: A total of 5395 PwMS were included in the analysis (GMSR: n = 2658; NARCOMS: n = 447; UKMSR: n = 2290). Kaplan-Meier estimates for the time to first DMT [median months (95% CI)] were 2.0 (1.9-2.0), 3.0 (2-4), and 9.0 (7.7-10.6) for GMSR, NARCOMS, and UKMSR, respectively. Pooled multivariable Cox regression demonstrated shorter time to first DMT for PwMS diagnosed after 2017 [1.65 (1.42-1.92), p < 0.01], and longer time to DMT when a higher-efficacy DMT was selected (0.69 (0.54-0.90), p < 0.0001]. Conclusion: Time to DMT initiation differs across the populations studied, indicating that barriers may exist in early access to DMT, particularly in the United Kingdom. However, a consistent decrease in time to DMT initiation was noted since 2017 across all registries. Further studies are warranted comparing the effects of time to DMT and time to higher-efficacy DMT on long-term outcome.

Models, frameworks and theories in the implementation of programs targeted to reduce formal coercion in mental health settings: a systematic review.

Introduction: Implementation models, frameworks and theories (hereafter tools) provide researchers and clinicians with an approach to understand the processes and mechanisms for the successful implementation of healthcare innovations. Previous research in mental health settings has revealed, that the implementation of coercion reduction programs presents a number of challenges. However, there is a lack of systematized knowledge of whether the advantages of implementation science have been utilized in this field of research. This systematic review aims to gain a better understanding of which tools have been used by studies when implementing programs aiming to reduce formal coercion in mental health settings, and what implementation outcomes they have reported. Methods: A systematic search was conducted using PubMed, CINAHL, PsycINFO, Cochrane, Scopus, and Web of Science. A manual search was used to supplement database searches. Quality appraisal of included studies was undertaken using MMAT-Mixed Methods Appraisal Tool. A descriptive and narrative synthesis was formed based on extracted data. Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were followed in this review. Results: We identified 5,295 references after duplicates were removed. Four additional references were found with a manual search. In total eight studies reported in nine papers were included in the review. Coercion reduction programs that were implemented included those that were holistic, and/or used professional judgement, staff training and sensory modulation interventions. Eight different implementation tools were identified from the included studies. None of them reported all eight implementation outcomes sought from the papers. The most frequently reported outcomes were acceptability (4/8 studies) and adaptation (3/8). With regards to implementation costs, no data were provided by any of the studies. The quality of the studies was assessed to be overall quite low. Discussion: Systematic implementation tools are seldom used when efforts are being made to embed interventions to reduce coercive measures in routine mental health care. More high-quality studies are needed in the research area that also involves perspectives of service users and carers. In addition, based on our review, it is unclear what the costs and resources are needed to implement complex interventions with the guidance of an implementation tool. Systematic review registration: [Prospero], identifier [CRD42021284959].

Approaches used to prevent and reduce the use of restrictive practices on adults with learning disabilities: Protocol for a realist review.

INTRODUCTION: The use of restrictive practices has significant adverse effects on the individual, care providers and organisations. This review will describe how, why, for whom, and in what circumstances approaches used by healthcare organisations work to prevent and reduce the use of restrictive practices on adults with learning disabilities. METHODS AND ANALYSIS: Evidence from the literature will be synthesised using a realist review approach - an interpretative, theory-driven approach to understand how complex healthcare approaches work in reducing the use of restrictive practices in these settings. In step 1, existing theories will be located to explore what approaches work by consulting with key topic experts, holding consultation workshops with healthcare professionals, academics, and experts by experience, and performing an informal search to help develop an initial programme theory. A systematic search will be performed in the second step in electronic databases. Further searches will be performed iteratively to test particular subcomponents of the initial programme theory, which will also include the use of the CLUSTER approach. Evidence judged as relevant and rigorous will be used to test the initial programme theory. In step three, data will be extracted and coded inductively and deductively. The final step will involve using a realist logic of analysis to refine the initial programme theory in light of evidence. This will then provide a basis to describe and explain what key approaches work, why, how and in what circumstances in preventing and reducing the use of restrictive practices in adults with learning disabilities in healthcare settings. RESULTS: Findings will be used to provide recommendations for practice and policymaking. REGISTRATION: In accordance with the guidelines, this realist review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 4th December 2019 (CRD42019158432).

Taser use on individuals experiencing mental distress: An integrative literature review.

WHAT IS KNOWN ABOUT THE SUBJECT?: People experiencing mental distress have a high rate of contact with police in community crisis events. Police use a continuum of responses when managing situations involving agitation, aggression and behavioural problems. People experiencing mental distress have been subjected to Tasers as part of the police response. Following a number of deaths and numerous reports of injuries, concerns have been raised about the safety of Tasers. WHAT THIS PAPER ADDS?: Police use of Tasers in mental health crises is relatively common. Tasers are used in a range of settings including public places, private residences and healthcare facilities. People experiencing mental distress may be subjected to more use of Tasers than the general population. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Mental health professionals need to work with police towards greater understanding of the needs of people experiencing mental distress and to promote the use of non-coercive interventions in mental health crisis events. Mental health researchers need to explore the qualitative experiences of people who are Tasered, to provide an evidence base for Taser use with people experiencing mental distress. ABSTRACT: Introduction Conducted electrical weapons, or "Tasers," are currently used by over 15,000 law enforcement and military agencies worldwide. There are concerns regarding the effectiveness, potential for harm and overuse with people experiencing mental distress. Aim To explore the literature about police use of Tasers with people experiencing mental distress. Method An integrative review was undertaken, and qualitative and quantitative analytical approaches were used. Results Thirty-one studies were included. Of all recorded usage, overall prevalence of Taser use on people experiencing mental distress was 28%. This population appears to experience higher Taser usage than the general population. Discussion There are substantial gaps in the research literature particularly with respect to the decision-making processes involved in deploying Tasers on this population and the physical and psychological consequences of Taser use in this context. Implications for practice Police use of Tasers in mental health crises is relatively common and occurs in a variety of environments including mental health settings. Mental health professionals need to work with police towards greater understanding of the needs of people with mental illness and to promote the use of non-coercive interventions in mental health crisis events.

Impact of surgical site infection (SSI) following gynaecological cancer surgery in the UK: a trainee-led multicentre audit and service evaluation.

OBJECTIVES: Surgical site infection (SSI) complicates 5% of all surgical procedures in the UK and is a major cause of postoperative morbidity and a substantial drain on healthcare resources. Little is known about the incidence of SSI and its consequences in women undergoing surgery for gynaecological cancer. Our aim was to perform the first national audit of SSI following gynaecological cancer surgery through the establishment of a UK-wide trainee-led research network. DESIGN AND SETTING: In a prospective audit, we collected data from all women undergoing laparotomy for suspected gynaecological cancer at 12 specialist oncology centres in the UK during an 8-week period in 2015. Clinicopathological data were collected, and wound complications and their sequelae were recorded during the 30 days following surgery. RESULTS: In total, 339 women underwent laparotomy for suspected gynaecological cancer during the study period. A clinical diagnosis of SSI was made in 54 (16%) women. 33% (18/54) of women with SSI had prolonged hospital stays, and 11/37 (29%) had their adjuvant treatment delayed or cancelled. Multivariate analysis found body mass index (BMI) was the strongest risk factor for SSI (OR 1.08[95% CI 1.03 to 1.14] per 1 kg/m2 increase in BMI [p=0.001]). Wound drains (OR 2.92[95% CI 1.41 to 6.04], p=0.004) and staple closure (OR 3.13[95% CI 1.50 to 6.56], p=0.002) were also associated with increased risk of SSI. CONCLUSIONS: SSI is common in women undergoing surgery for gynaecological cancer leading to delays in discharge and adjuvant treatment. Resultant delays in adjuvant treatment may impact cancer-specific survival rates. Modifiable factors, such as choice of wound closure material, offer opportunities for reducing SSI and reducing morbidity in these women. There is a clear need for new trials in SSI prevention in this patient group; our trainee-led initiative provides a platform for their successful completion.