Early Biomarkers in the Prediction of Later Functional Impairment in Preterm Children With Cerebral Palsy.

BACKGROUND: To identify early biomarkers that could predict later functional capabilities in preterm children with later cerebral palsy (CP). METHODS: Data from 968 preterm children with later CP were extracted from the Canadian Cerebral Palsy Registry. One hundred eighty-two infants were born before 27 weeks of gestation, 461 infants were born between 27 and 33 weeks, and 325 infants were born between 34 and 37 weeks. Univariate and chi-square analyses were conducted to measure the association between early objective biomarkers and later mobility status defined as Gross Motor Function Classification System (GMFCS) levels IV and V as well as tube feeding dependence. RESULTS: Univariate analysis suggested no significant association between GMFCS levels IV and V or impaired feeding status and bilateral white matter injury on magnetic resonance imaging, high-grade intraventricular hemorrhage on head ultrasound, chorioamnionitis, a birth weight of 1000 to 1500 g or <1000 g, as well as an Apgar score of ≤5 at five minutes of life. Similar results were found for gestational age <28 weeks at birth. Only a significant association between GMFCS levels IV and V and a cord or first hour of life pH of ≤7 was reported (mobility status: odds ratio [OR] 1.95, 95% confidence interval [CI] 1.09 to 3.57) and feeding status: OR 2.23, CI 0.97 to 4.65)]. CONCLUSIONS: Prediction of functional outcomes based on specific early biomarkers appears hard to obtain in children with CP born preterm in contrast to those born at term. The complications and causal pathways inherent to prematurity may contribute to making prognostication less determinant.

Physiotherapists' Treatment Strategies and Delineation of Areas of Responsibility for People With Musculoskeletal Conditions and Comorbidities in Private Physiotherapy Practice: A Qualitative Study.

BACKGROUND: Patients with multiple chronic conditions, for example, musculoskeletal conditions and comorbidities, often receive inadequate and sometimes even contradictory care. Physiotherapists are well qualified to manage patients with musculoskeletal conditions and comorbidities due to their education and experience with rehabilitation; however, it is unknown which challenges they face when treating these patients. AIM: To identify challenges, treatment strategies, and delineations of areas of responsibility among physiotherapists working in private physiotherapy practice when treating people with musculoskeletal conditions and comorbidities. METHODS: Qualitative study using focus group discussions and participant observations of 13 physiotherapists working in Danish private physiotherapy clinics. Grounded theory was applied to guide the analysis. RESULTS: Two major themes emerged from the focus groups and the observations (1) The necessity of adapting management to the patients and their treatment trajectory; (2) The dilemma of overall responsibility for coordinating care. The physiotherapists described different elements of adapting their management, including being challenged on time, taking extra care of the patient, and having to adjust to a fluctuating course of treatment. The dilemma in coordinating care concerned whether the responsibility should lie with the physiotherapist, other healthcare professionals, or the patients, and whether to treat only the condition on the referral or to treat all the conditions the patient had. CONCLUSION: Physiotherapists use adapted strategies for diagnosing and treating patients with musculoskeletal conditions and comorbidities and are uncertain about the overall responsibility for coordinating care and whether they should focus on the index condition alone or also the other comorbidities the patient has.

Optimal configurations of an electromagnetic tracking system for 3D ultrasound imaging of pediatric hips - A phantom study.

Tracking the position and orientation of a two-dimensional (2D) ultrasound scanner to reconstruct a 3D volume is common, and its accuracy is important. In this study, a specific miniaturized electromagnetic (EM) tracking system was selected and integrated with a 2D ultrasound scanner, which was aimed to capture hip displacement in children with cerebral palsy. The objective of this study was to determine the optimum configuration, including the distance between the EM source and sensor, to provide maximum accuracy. The scanning volume was aimed to be 320 mm × 320 mm × 76 mm. The accuracy of the EM tracking was evaluated by comparing its tracking with those from a motion capture camera system. A static experiment showed that a warm-up time of 20 min was needed. The EM system provided the highest precision of 0.07 mm and 0.01° when the distance between the EM source and sensor was 0.65 m. Within the testing volume, the maximum position and rotational errors were 2.31 mm and 1.48°, respectively. The maximum error of measuring hip displacement on the 3D hip phantom study was 4 %. Based on the test results, the tested EM system was suitable for 3D ultrasound imaging of pediatric hips to assess hip displacement when optimal configuration was used.

Reliability and Accuracy of Ultrasound Measurement of Hip Displacement in Children with Cerebral Palsy.

OBJECTIVE: Hip migration percentage (MP) measured on anteroposterior pelvis radiographs is the gold standard to assess the severity of hip displacement in children with cerebral palsy (CP). Repeated exposure of these children to ionizing radiation under a hip surveillance program is undesirable. Recently, a semi-automatic approach to measure MPUS on ultrasound (US) images was validated in a phantom study. This pilot in vivo study applied the previous phantom method and aimed to determine the reliability and accuracy of the MPUS. METHODS: Thirty-four children (23 boys and 11 girls) aged 8.9 ± 3.1 y old and diagnosed with CP were recruited. A total of 59 hips were scanned once, while 43 of these were scanned twice to evaluate the test-retest reliability. Two raters (R1 and R2) manually measured MPUS; procedures included selecting images of interest, cropping a region of interest and removing soft tissues on hip US images. Custom software was developed to measure MP automatically after the manual pre-image processing. RESULTS: The intra-class correlation coefficients (ICC2,1) for the test-retest (R1), intra-rater (R1) and inter-rater (R1 vs R2) reliabilities were 0.90, 0.94 and 0.82, respectively. The standard error of measurement of MPUS for all three evaluations was ≤3.0%. The mean absolute difference between MPUS and MPX-ray and the percentage of MPUS within clinical acceptance error of 10% for R1 and R2 were (R1: 6.2% ± 4.9%, 84.7%) and (R2: 7.6% ± 6.1%, 73.7%), respectively. CONCLUSION: This study demonstrated that US scans were repeatable and MPUS could be measured reliably and accurately.

Effects of a staff physical activity professional development intervention on preschoolers' mental health and self-regulation: The active learning Norwegian Preschool(er)s (ACTNOW) cluster randomised controlled trial.

BACKGROUND AND AIM: Physical activity may have positive effects on preschoolers' mental health and self-regulation. The preschool setting provides children with opportunities to meet physical activity guidelines and could improve with staff training in delivering physical activity. This study examined the effect of physical activity professional development for preschool staff on preschoolers' proxy-measured mental health and self-regulation. METHODS: In total, 1265 children from 46 preschools were cluster randomised to either the intervention or the control group. The intervention was nested within two levels implemented concurrently: the preschool level, formed as a professional development where preschools conducted development work, and the child level, with whom the staff implemented physical activity with four core components. Data were analysed using an ANCOVA model through structural equation modelling with latent outcome factors of: emotional problems, peer problems, hyperactivity, and prosocial behaviour from the Strength and Difficulties Questionnaire; and cognitive, emotional, and behavioural self-regulation from the Child Self-regulation and Behaviour Questionnaire. RESULTS: No effects of the intervention (standardised effect sizes -0.195-0.145, p-values 0.118-0.893) were observed. Secondary analysis showed that children with initially high prosocial behaviour and behavioural self-regulation positively benefited from the intervention (p = 0.035 and p = 0.047, respectively). CONCLUSION: The ACTNOW intervention had no effects on preschoolers' mental health or self-regulation after 18 months, besides effects for children with initially the highest prosocial behaviour and behavioural self-regulation. Although the professional development was more extensive than previous studies it may have been insufficient to change the preschools physical activity practices. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier NCT04048967.

A new setup for measurements of absolute saturation vapor pressures using a dynamical method: Experimental concept and validation.

We describe a new experimental system for direct measurements of the absolute saturation vapor pressures of liquid or solid samples. The setup allows the isolation of the sample under steady conditions in an ultra-high vacuum chamber, where the measurement of the sample's vapor pressure as a function of its temperature can be performed in a range around room temperature and in a pressure range defined only by the applied absolute pressure sensor. We characterize the setup and illustrate its capability to measure saturation vapor pressures as well as enthalpies of evaporation around room temperature with explicit measurements on four liquid compounds (diethyl phthalate, 1-decanol, 1-heptanol, and 1-hexanol) for which accurate vapor pressures have previously been reported.

Usual care for low back pain and barriers to best practice: A cross-sectional study in Danish general practice.

OBJECTIVES: To describe the current content of low back pain (LBP) care in Danish general practice, the patients' self-management activities, and the clinicians' experienced barriers to providing best practice care. METHODS: This cross-sectional observational study included adults with LBP seeking care in Danish general practice from August 2022 to June 2023. Patient-reported information included demographics, pain intensity, medical history, treatments, and self-management strategies. Clinicians provided data specific to each consultation, detailing the content of these consultations, and barriers to best practice in the specific cases. RESULTS: The study involved 71 clinicians from 42 general practice clinics, with patient-reported data from 294 patients, and clinician-reported data from 283 (95%) consultations. The mean age for the included patients was 53 years, 56% were female, and 31% had been on sick leave for LBP during the previous 3 months. Moreover, 44% had seen two or more healthcare professionals in the previous month, 55% had previously undergone diagnostic imaging for LBP, 81% reported using any type of analgesics, and 14% reported using opioids. The majority (91%) reported engaging in self-management activities to alleviate pain. Consultations typically included a physical examination (84%), information about the cause of the pain (74%), and management advice (68%), as reported by clinicians or patients. In general, clinicians reported consultation elements more frequently than patients. Clinicians reported providing best practice care in 84% of cases, with time constraints (23%) and patient expectations (10%) being the most common barriers. CONCLUSIONS: This study provides detailed insights into the management of LBP in Danish general practice. It reveals a complex landscape of patient engagement, varying management strategies, and differing perceptions of care content between patients and clinicians. Patients were often engaged in self-management activities and clinicians reported few barriers to providing best practice care.

Designing strategies to support Implementation of iNtensive Therapy for Early Reach through PLAY (INTERPLAY) for young children with cerebral palsy: a study protocol.

BACKGROUND: Intensive manual therapy is important for improving lifelong upper limb motor outcomes for infants and toddlers with cerebral palsy. This play-based therapy is delivered by caregivers who are coached by occupational therapists. However, access to this therapy is very limited for Canadian children with cerebral palsy younger than two years old. This project aims to first identify barriers and facilitators and then design implementation strategies to support early intensive manual therapy delivery for infants and toddlers with cerebral palsy across Canada. METHODS: A mixed-methods sequential explanatory design will be used with four consecutive phases. The updated Consolidated Framework for Implementation Research will guide the study. Quantitative data will be collected from a survey in Phase One. Participants will be recruited from three groups: (1) Caregivers of children with cerebral palsy six years old and younger who are eligible for manual therapy; (2) occupational therapists who treat children with cerebral palsy; and (3) healthcare administrators or people responsible for managing pediatric occupational therapy programs. In Phase Two, quantitative data from the survey will be used to map to implementation strategies known to be effective at addressing the identified modifiable barriers and facilitators. Phase Three will collect qualitative data from semi-structured interviews for the purpose of explaining Phase One quantitative findings in greater depth, and for understanding the appropriateness of strategies identified in Phase Two. The participant recruitment strategy and interview guide content for Phase Three will be informed by results of Phase One. Phase Four will use a modified nominal group technique to refine and prioritize an implementation strategy toolbox. Results will be widely disseminated to knowledge users to provide them with tailorable strategies to increase delivery of early intensive manual interventions. DISCUSSION: This study will provide a comprehensive understanding of the barriers and facilitators to implementation of early intensive manual therapy for young children with cerebral palsy in Canada. A toolbox of evidence-based and tailorable implementation strategies will be disseminated nationally to support uptake of early intensive manual therapy into clinical practice for young children with cerebral palsy.

Mechanism of complement inhibition by a mosquito protein revealed through cryo-EM.

Salivary complement inhibitors occur in many of the blood feeding arthropod species responsible for transmission of pathogens. During feeding, these inhibitors prevent the production of proinflammatory anaphylatoxins, which may interfere with feeding, and limit formation of the membrane attack complex which could damage arthropod gut tissues. Salivary inhibitors are, in many cases, novel proteins which may be pharmaceutically useful or display unusual mechanisms that could be exploited pharmaceutically. Albicin is a potent inhibitor of the alternative pathway of complement from the saliva of the malaria transmitting mosquito, Anopheles albimanus. Here we describe the cryo-EM structure of albicin bound to C3bBb, the alternative C3 convertase, a proteolytic complex that is responsible for cleavage of C3 and amplification of the complement response. Albicin is shown to induce dimerization of C3bBb, in a manner similar to the bacterial inhibitor SCIN, to form an inactive complex unable to bind the substrate C3. Size exclusion chromatography and structures determined after 30 minutes of incubation of C3b, factor B (FB), factor D (FD) and albicin indicate that FBb dissociates from the inhibited dimeric complex leaving a C3b-albicin dimeric complex which apparently decays more slowly.

Comprehensive Proteomics Analysis of the Hemolymph Composition of Sugar-Fed Aedes aegypti Female and Male Mosquitoes.

In arthropods, hemolymph carries immune cells and solubilizes and transports nutrients, hormones, and other molecules that are involved in diverse physiological processes including immunity, metabolism, and reproduction. However, despite such physiological importance, little is known about its composition. We applied mass spectrometry-based label-free quantification approaches to study the proteome of hemolymph perfused from sugar-fed female and male Aedes aegypti mosquitoes. A total of 1403 proteins were identified, out of which 447 of them were predicted to be extracellular. In both sexes, almost half of these extracellular proteins were predicted to be involved in defense/immune response, and their relative abundances (based on their intensity-based absolute quantification, iBAQ) were 37.9 and 33.2%, respectively. Interestingly, among them, 102 serine proteases/serine protease-homologues were identified, with almost half of them containing CLIP regulatory domains. Moreover, proteins belonging to families classically described as chemoreceptors, such as odorant-binding proteins (OBPs) and chemosensory proteins (CSPs), were also highly abundant in the hemolymph of both sexes. Our data provide a comprehensive catalogue of A. aegypti hemolymph basal protein content, revealing numerous unexplored targets for future research on mosquito physiology and disease transmission. It also provides a reference for future studies on the effect of blood meal and infection on hemolymph composition.

Predictors for surgical treatment in male patients with non-neurogenic lower urinary tract symptoms (LUTS).

OBJECTIVE: This study aimed to identify clinical and biochemical predictors for future surgical intervention in male LUTS patients. MATERIALS AND METHODS: In a prospective cohort study, parameters as International Prostate Symptom Score (IPSS) and IPSS "bother question" (IPSS-BQ), prostate volume (PV), maximal urine flow (Qmax), Prostate specific antigen (PSA), post-voidal residual urine (PVR) were assessed alongside comorbidities quantified using Charlson Comorbidity Index without age adjustment and American Society of Anesthesiology (ASA) score. For the statistical analysis, patients were categorized based on subsequent treatment approaches: Group 1: underwent surgery during follow-up; Group 2: received medical or no treatment. T-test was used to test differences between the groups. Logistic regression models were used to identify independent predictors of the need for future surgery. Following this analysis, we calculated the probability of requiring surgical intervention, with this likelihood being determined based on the accumulation of identified predictive factors. RESULTS: Of 63 patients, 22 underwent surgery over a median follow-up of 42 months. Significant baseline differences were observed in IPSS (p = 0.003), International Prostatic Symptom Score-Voiding subscore (IPSS-VS) (p = 0.002), IPSS-BQ (p = 0.001), Qmax (p = 0.007), and PVR (p = 0.02) between the groups. Higher IPSS-BQ, IPSS-VS, and lower Qmax are emerging as independent surgical treatment predictors in logistic regression analyses. CONCLUSION: The study identified IPSS-VS, IPSS-BQ, and Qmax as baseline predictors of future surgical intervention. A clear pattern of a gradual increase in the likelihood of requiring surgery was directly proportional to the cumulative number of these identified predictive factors.

Surprising features of the energy-mismatched nonlinear dimer.

The quantum mechanical energy-mismatched two-state system with cubic nonlinearity in its governing equation is surprisingly rich in its dynamics and has relevance to a number of subdisciplines of physics ranging from polaron phenomena to Bose-Einstein condensation. We review some of them that have been discussed recently and describe some new results that have not, pointing out their relevance in possible experiments.

The lived experiences of play and the perspectives of disabled children and their parents surrounding brain-computer interfaces.

Brain-computer interfaces (BCI) offer promise to the play of children with significant physical impairments, as BCI technology can enable disabled children to control computer devices, toys, and robots using only their brain signals. However, there is little research on the unique needs of disabled children when it comes to BCI-enabled play. Thus, this paper explored the lived experiences of play for children with significant physical impairments and examined how BCI could potentially be implemented into disabled children's play experiences by applying a social model of childhood disability. Descriptive qualitative methodology was employed by conducting four semi-structured interviews with two children with significant physical impairments and their parents. We found that disabled children's play can be interpreted as passive or active depending on one's definition and perceptions surrounding play. Moreover, disabled children continue to face physical, economic, and technological barriers in their play, as well as play restrictions from physical impairments. We urge that future research should strive to directly hear from disabled children themselves, as their perspectives may differ from their parents' views. Also, future BCI development should strive to incorporate video games, recreational and entertainment applications/platforms, toys and switch-adapted toys, and power wheelchairs to better support the play of children with significant physical impairments.Implications for RehabilitationAssistive technology research should strive to examine the social, infrastructural, and environmental barriers that continue to disable and restrict participation for disabled children and their families through applying a social model of childhood disability and other holistic frameworks that look beyond individual factorsFuture research that examines the needs and lives of disabled children should strive to directly seek the opinions and perspectives of disabled children themselvesBrain-computer interface development should strive to incorporate video games, recreational and entertainment applications/platforms, toys and switch-adapted toys, and power wheelchairs to better support the play of children with significant physical impairments.

The Alberta Infant Motor Scale as an Outcomes Measure of Gross Motor Abilities after Early Complex Cardiac Surgery.

To address the research hypothesis that the Alberta Infant Motor Scale (AIMS) completed following complex cardiac surgery (CCS) is a useful outcomes measure this study determined: (1) AIMS scores at age 8 months after CCS; (2) predictive validity of AIMS at 8 months for Bayley Scales of Infant and Toddler Development-III Gross Motor-scaled scores (GMSS) and diagnosis of cerebral palsy (CP) at 21 months; and (3) predictive demographic and surgical variables of AIMS scores. A prospective cohort study of 250/271 (92.3%) surviving children from Northern Alberta (born 2009-2020) who had CCS at age < 6 months determined AIMS scores at age mean (SD) 8.6 (2.4) and the GMSS at 21.9 (3.8) months. Gross motor delay was defined as AIMS < 5th percentile and GMSS as < 4 (-2SD). Predictions using multiple logistic regressions were expressed as Odds Ratios (OR) and 95% Confidence Interval (CI). Of children, 100/250 (40%) had AIMS < 5th predicting GMSS < 4 (n = 43); sensitivity, specificity, positive, and negative predictive values were 88%, 71%, 40%, and 97%. Hospitalization days were independently associated with AIMS < 5th, OR 1.02 (95% CI 1.007, 1.032; p = 0.005). Excluding hospital days, ventilation days independently predicted AIMS < 5th, OR 1.08 (95% CI 1.038, 1.125, p < 0.001. Gross motor delay determine by AIMS scores of < 5th percentile occurred in 40% of survivors with good prediction of continued delay. Delay determined by AIMS was predicted by longer hospitalization and ventilation; further investigations about the causes are required. AIMS results provide opportunity for early motor intervention.

Bariatric surgery patients in AUD treatment in Norway-an exploratory cross-sectional study.

AIMS: Patients who have undergone some forms of bariatric surgery have increased risk of developing alcohol use disorder (AUD). In the present observational study, we compared patients with AUD who themselves reported to having undergone bariatric surgery with other patients in treatment for AUD. MATERIALS: One-hundred-and-six consecutively enrolled patients in residential treatment for AUD were asked if they had undergone bariatric surgery. Sociodemographics, mental health-related, and alcohol use-related parameters were compared between those who had and those who had not undergone bariatric surgery. RESULTS: Of the 106 patients with AUD, seven (6.6%; 95% confidence interval, 2.7%-13.1%) had undergone bariatric surgery. Six of seven patients had undergone such surgery were women (P < .001). The patients with AUD who had undergone bariatric surgery were similar to other patients with AUD on most other parameters, the exception being a larger number of alcohol units ingested to feel an effect of alcohol (adjusted odds ratio 7.1; 95% confidence interval 2.0-12.2; P = .007). CONCLUSION: The high number of patients with AUD that reported having undergone bariatric surgery emphasizes the risks following such a procedure. The overrepresentation of women may reflect than more women undergo such procedures. The unexpected finding that patients with AUD having undergone bariatric surgery seemed to need more alcohol to feel intoxicated warrants further research.

Surgical Aspects of Sleeve Gastrectomy Are Related to Weight Loss and Gastro-esophageal Reflux Symptoms.

INTRODUCTION: A large variation in outcome has been reported after sleeve gastrectomy (SG) across countries and institutions. We aimed to evaluate the effect of surgical technique on total weight loss (TWL) and gastro-esophageal reflux disease (GERD). METHODS: Observational cohort study based on data from the national registries for bariatric surgery in the Netherlands, Norway, and Sweden. A retrospective analysis of prospectively obtained data from surgeries during 2015-2017 was performed based on 2-year follow-up. GERD was defined as continuous use of acid-reducing medication. The relationship between TWL, de novo GERD and operation technical variables were analyzed with regression methods. RESULTS: A total of 5927 patients were included. The average TWL was 25.6% in Sweden, 28.6% in the Netherlands, and 30.6% in Norway (p < 0.001 pairwise). Bougie size, distance from the resection line to the pylorus and the angle of His differed between hospitals. A minimized sleeve increased the expected total weight loss by 5-10 percentage points. Reducing the distance to the angle of His from 3 to just above 0 cm increased the risk of de novo GERD five-fold (from 3.5 to 17.8%). CONCLUSION: Smaller bougie size, a shorter distance to pylorus and to the angle of His were all associated with greater weight loss, whereas a shorter distance to angle of His was associated with more de novo reflux.

Effectiveness of an adaptive, multifaceted intervention to enhance care for patients with complex multimorbidity in general practice: protocol for a pragmatic cluster randomised controlled trial (the MM600 trial).

INTRODUCTION: Patients with complex multimorbidity face a high treatment burden and frequently have low quality of life. General practice is the key organisational setting in terms of offering people with complex multimorbidity integrated, longitudinal, patient-centred care. This protocol describes a pragmatic cluster randomised controlled trial to evaluate the effectiveness of an adaptive, multifaceted intervention in general practice for patients with complex multimorbidity. METHODS AND ANALYSIS: In this study, 250 recruited general practices will be randomly assigned 1:1 to either the intervention or control group. The eligible population are adult patients with two or more chronic conditions, at least one contact with secondary care within the last year, taking at least five repeat prescription drugs, living independently, who experience significant problems with their life and health due to their multimorbidity. During 2023 and 2024, intervention practices are financially incentivised to provide an extended consultation based on a patient-centred framework to eligible patients. Control practices continue care as usual. The primary outcome is need-based quality of life. Outcomes will be evaluated using linear and logistic regression models, with clustering considered. The analysis will be performed as intention to treat. In addition, a process evaluation will be carried out and reported elsewhere. ETHICS AND DISSEMINATION: The trial will be conducted in compliance with the protocol, the Helsinki Declaration in its most recent form and good clinical practice recommendations, as well as the regulation for informed consent. The study was submitted to the Danish Capital Region Ethical Committee (ref: H-22041229). As defined by Section 2 of the Danish Act on Research Ethics in Research Projects, this project does not constitute a health research project but is considered a quality improvement project that does not require formal ethical approval. All results from the study (whether positive, negative or inconclusive) will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05676541.

Inhibition of vertebrate complement system by hematophagous arthropods: inhibitory molecules, mechanisms, physiological roles, and applications.

In arthropods, hematophagy has arisen several times throughout evolution. This specialized feeding behavior offered a highly nutritious diet obtained during blood feeds. On the other hand, blood-sucking arthropods must overcome problems brought on by blood intake and digestion. Host blood complement acts on the bite site and is still active after ingestion, so complement activation is a potential threat to the host's skin feeding environment and to the arthropod gut enterocytes. During evolution, blood-sucking arthropods have selected, either in their saliva or gut, anticomplement molecules that inactivate host blood complement. This review presents an overview of the complement system and discusses the arthropod's salivary and gut anticomplement molecules studied to date, exploring their mechanism of action and other aspects related to the arthropod-host-pathogen interface. The possible therapeutic applications of arthropod's anticomplement molecules are also discussed.

The development of type 2 diabetes management in people with severe mental illness in the Capital Region of Denmark from 2001 to 2015.

BACKGROUND: Type 2 diabetes (T2D) treatment has changed markedly within the last decades. We aimed to explore whether people with severe mental illness (SMI) have followed the same changes in T2D treatment as those without SMI, as multiple studies suggest that people with SMI receive suboptimal care for somatic disorders. METHODS: In this registry-based annual cohort study, we explored the T2D treatment from 2001 to 2015 provided in general practices of the Greater Copenhagen area. We stratified the T2D cohorts by their pre-existing SMI status. T2D was defined based on elevated glycated hemoglobin (≥48 mmol/mol) or glucose (≥11 mmol/L) using data from the Copenhagen Primary Care Laboratory Database. Individuals with schizophrenia spectrum disorders (ICD-10 F20-29) or affective disorders (bipolar disorder or unipolar depression, ICD-10 F30-33) were identified based on hospital-acquired diagnoses made within 5 years before January 1 each year for people with prevalent T2D or 5 years before meeting our T2D definition for incident patients. For comparison, we defined a non-SMI group, including people who did not have a hospital-acquired diagnosis of schizophrenia spectrum disorders, affective disorders, or personality disorders. For each calendar year, we assembled cohorts of people with T2D with or without SMI. We used Poisson regression to calculate the rates per 100 person-years of having at least one biochemical test (glycated hemoglobin, low-density lipoprotein cholesterol, estimated glomerular filtration rate, and urine albumin-creatinine ratio), having poor control of these biochemical results, taking glucose-lowering or cardiovascular medications, or experiencing a clinical outcome, including all-cause mortality and cardiovascular mortality. Three outcomes (cardiovascular events, cardiovascular mortality, and all-cause mortality) were additionally examined and adjusted for age and sex in a post hoc analysis. RESULTS: From 2001 to 2015, 66,914 individuals were identified as having T2D. In 2015, 1.5% of the study population had schizophrenia spectrum disorder and 1.4% had an affective disorder. The number of people who used biochemical tests or had poor biochemical risk factor control was essentially unrelated to SMI status. One exception was that fewer LDL cholesterol tests were done on people with affective disorders and schizophrenia spectrum disorders at the beginning of the study period compared to people in the non-SMI group. This difference gradually diminished and was almost nonexistent by 2011. There was also a slightly slower rise in UACR test rates in the SMI groups compared to other people with T2D during the period. Throughout the study period, all groups changed their use of medications in similar ways: more metformin, less sulfonylurea, more lipid-lowering drugs, and more ACEi/ARBs. However, people with schizophrenia disorder consistently used fewer cardiovascular medications. Cardiovascular events were more common in the affective disorder group compared to the non-SMI group from 2009 to 2015 (rate ratio 2015 : 1.36 [95% CI 1.18-1.57]). After adjustment for age and sex, all-cause mortality was significantly higher among people with a schizophrenia spectrum disorder each year from 2003 to 2015 compared to the non-SMI group (rate ratio 2015 : 1.99 [95% CI 1.26-3.12]). CONCLUSION: Persons with schizophrenia or affective disorders demonstrated the same treatment changes for T2D as those without SMI in general practice. The lower use of most types of cardiovascular medications among people with schizophrenia disorders indicates potential undertreatment of hypertension and dyslipidemia and remains throughout the study period. Cardiovascular events were most common among people with affective disorders, but this was not reflected in a higher proportion using cardiovascular preventive medications. This knowledge should be considered in the management of this vulnerable patient group.