The gender differences in growth hormone-binding protein and leptin persist in 80-year-old men and women and is not caused by sex hormones.

objective Leptin and growth hormone-binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80-year-old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated. design and subjects Ninety-four subjects (55 females and 39 males), all 80 years old, were investigated in a community-based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement. methods Levels of testosterone, oestradiol, SHBG, IGF-I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA). results As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P 0·1). Leptin correlated to kilogram fat mass in both women (r = 0·55, P 0·2). Insulin and leptin were significantly associated with GHBP, both in women (r = 0·48, P < 0·001 and r = 0·43, P = 0·001, respectively) and in men (r = 0·40, P = 0·01 and r = 0·34, P = 0·03, respectively). conclusions Although the 80-year-old men had higher oestradiol levels than the women, the women had higher levels of leptin and GHBP. There were no correlations between sex hormones and leptin and GHBP, which indicates that the gender differences are not caused by sex hormones in old age. In contrast to studies in younger subjects, GHBP did not correlate to fat mass in the investigated 80-year-old men and women. In the older subjects investigated, as in younger subjects, GHBP was significantly correlated with leptin and insulin

Semi-supervised learning with natural language processing for right ventricle classification in echocardiography - a scalable approach

We created a deep learning model, trained on text classified by natural language processing (NLP), to assess right ventricular (RV) size and function from echocardiographic images. We included 12,684 examinations with corresponding written reports for text classification. After manual annotation of 1489 reports, we trained an NLP model to classify the remaining 10,651 reports. A view classifier was developed to select the 4-chamber or RV-focused view from an echocardiographic examination (n\ua0=\ua0539). The final models were two image classification models trained on the predicted labels from the combined manual annotation and NLP models and the corresponding echocardiographic view to assess RV function (training set\ua0n\ua0=\ua011,008) and size (training set\ua0n\ua0=\ua09951. The text classifier identified impaired RV function with 99% sensitivity and 98% specificity and RV enlargement with 98% sensitivity and 98% specificity. The view classification model identified the 4-chamber view with 92% accuracy and the RV-focused view with 73% accuracy. The image classification models identified impaired RV function with 93% sensitivity and 72% specificity and an enlarged RV with 80% sensitivity and 85% specificity; agreement with the written reports was substantial (both κ\ua0=\ua00.65). Our findings show that models for automatic image assessment can be trained to classify RV size and function by using model-annotated data from written echocardiography reports. This pipeline for auto-annotation of the echocardiographic images, using a NLP model with medical reports as input, can be used to train an image-assessment model without manual annotation of images and enables fast and inexpensive expansion of the training dataset when needed

Cerebral palsy in a total population of 4–11 year olds in southern Sweden. Prevalence and distribution according to different CP classification systems

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to investigate the prevalence of cerebral palsy (CP) as well as to characterize the CP population, its participation in a secondary prevention programme (CPUP) and to validate the CPUP database.</p> <p>Methods</p> <p>The study population was born 1990–1997 and resident in Skåne/Blekinge on Jan 1^st2002. Multiple sources were used. Irrespective of earlier diagnoses, neuropaediatrician and other professional medical records were evaluated for all children at the child habilitation units. The CPUP database and diagnosis registers at hospital departments were searched for children with CP or psychomotor retardation, whose records were then evaluated. To enhance early prevention, CP/probable CP was searched for also in children below four years of age born 1998–2001.</p> <p>Results</p> <p>The prevalence of CP was 2.4/1,000 (95% CI 2.1–2.6) in children 4–11 years of age born in Sweden, excluding post-neonatally acquired CP. Children born abroad had a higher prevalence of CP with more severe functional limitations. In the total population, the prevalence of CP was 2.7/1,000 (95% CI 2.4–3.0) and 48% were GMFCS-level I (the mildest limitation of gross motor function).</p> <p>One third of the children with CP, who were born or had moved into the area after a previous study in 1998, were not in the CPUP database. The subtype classification in the CPUP database was adjusted in the case of every fifth child aged 4–7 years not previously reviewed.</p> <p>Conclusion</p> <p>The prevalence of CP and the subtype distribution did not differ from that reported in other studies, although the proportion of mild CP tended to be higher.</p> <p>The availability of a second opinion about the classification of CP/CP subtypes is necessary in order to keep a CP register valid, as well as an active search for undiagnosed CP among children with other impairments.</p

Severe COVID-19 in people with type 1 and type 2 diabetes in Sweden: a nationwide retrospective cohort study

Background: Whether infection with SARS-CoV-2 leads to excess risk of requiring hospitalization or intensive care in persons with diabetes has not been reported, nor have risk factors in diabetes associated with increased risk for these outcomes. Methods: We included 44,639 and 411,976 adult patients with type 1 and type 2 diabetes alive on Jan 1, 2020, and compared them to controls matched for age, sex, and county of residence (n=204,919 and 1,948,900). Age- and sex-standardized rates for COVID-19 related hospitalizations, admissions to intensive care and death, were estimated and hazard ratios were calculated using Cox regression analyses. Findings: There were 10,486 hospitalizations and 1,416 admissions into intensive care. A total of 1,175 patients with diabetes and 1,820 matched controls died from COVID-19, of these 53•2% had been hospitalized and 10•7% had been in intensive care. Patients with type 2 diabetes, compared to controls, displayed an age- and sex-adjusted hazard ratio (HR) of 2•22, 95%CI 2•13-2•32) of being hospitalized for COVID-19, which decreased to HR 1•40, 95%CI 1•34-1•47) after further adjustment for sociodemographic factors, pharmacological treatment and comorbidities, had higher risk for admission to ICU due to COVID-19 (age- and sex-adjusted HR 2•49, 95%CI 2•22-2•79, decreasing to 1•42, 95%CI 1•25-1•62 after adjustment, and increased risk for death due to COVID-19 (age- and sex-adjusted HR 2•19, 95%CI 2•03-2•36, complete adjustment 1•50, 95%CI 1•39-1•63). Age- and sex-adjusted HR for COVID-19 hospitalization for type 1 diabetes was 2•10, 95%CI 1•72-2•57), decreasing to 1•25, 95%CI 0•3097-1•62) after adjustment• Patients with diabetes type 1 were twice as likely to require intensive care for COVID-19, however, not after adjustment (HR 1•49, 95%CI 0•75-2•92), and more likely to die (HR 2•90, 95% CI 1•6554-5•47) from COVID-19, but not independently of other factors (HR 1•38, 95% CI 0•64-2•99). Among patients with diabetes, elevated glycated hemoglobin levels were associated with higher risk for most outcomes. Interpretation: In this nationwide study, type 2 diabetes was independently associated with increased risk of hospitalization, admission to intensive care and death for COVID-19. There were few admissions into intensive care and deaths in type 1 diabetes, and although hazards were significantly raised for all three outcomes, there was no independent risk persisting after adjustment for confounding factors

Simplified routines in prescribing physical activity can increase the amount of prescriptions by doctors, more than economic incentives only: an observational intervention study

<p>Abstract</p> <p>Background</p> <p>Physical inactivity is one well-known risk factor related to disease. Physical activity on prescription (PAP) has been shown in some studies to be a successful intervention for increasing physical activity among patients with a sedentary lifestyle. The method involves motivational counselling that can be time-consuming for the prescribing doctor and might be a reason why physical activity on prescription is not used more frequently. This study might show a way to make the method of prescribing physical activity more user-friendly. The purpose is to determine whether a change in procedures increases the use of physical activity on prescription, and thus the aim of this study is to describe the methodology used.</p> <p>Results</p> <p>The observational intervention study included an intervention group consisting of one Primary Health Care (PHC) clinic and a control group consisting of six PHC clinics serving 149,400 inhabitants in the County of Blekinge, Sweden.</p> <p>An economic incentive was introduced in both groups when prescribing physical activity on prescription. In the intervention group, a change was made to the process of prescribing physical activity, together with information and guidance to the personnel working at the clinics. Physical therapists were used in the process of carrying out the prescription, conducting the motivational interview and counselling the patient. This methodology was used to minimise the workload of the physician. The chi-2 test was used for studying differences between the two groups. PAP prescribed by doctors increased eightfold in the intervention group compared to the control group. The greatest increase of PAP was seen among physicians in the intervention group as compared to all other professionals in the control group. The economic incentive gave a significant but smaller increase of PAP by doctors.</p> <p>Conclusion</p> <p>By simplifying and developing PAP, this study has shown a concrete way to increase the implementation of physical activity on prescription in general practice, as opposed to what can be gained by an economic bonus system alone. This study indicates that a bonus system may not be enough to implement an evidence-based method.</p

The PanCareSurFup consortium:research and guidelines to improve lives for survivors of childhood cancer

Background: Second malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. Methods: The PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. Results: We identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case–control studies of subsequent malignancies and cardiac disease in 5-year survivors. Conclusions: PCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health

Growth in Children with Cerebral Palsy during five years after Selective Dorsal Rhizotomy: a practice-based study

Background: Overweight is reported as a side effect of SDR. The aims were to study the development of weight, height and body mass index (BMI) during five years after SDR. Methods: This prospective, longitudinal and practice-based study included all 56 children with CP spastic diplegia undergoing SDR from the start in March 1993 to April 2003 in our hospital. The preoperative Gross Motor Function Classification System (GMFCS) levels were I-II in 17, III in 15, IV-V in 24 children. Median age at SDR was 4.3 years (range 2.4-7.4 years). Weight and height/recumbent length were measured. Swedish growth charts for typically developing children generated weight, height and BMI z-scores for age and gender. Results: The preoperative median z-scores were for height-1.92 and for body mass index (BMI)-0.22. Five years later, the median BMI z-score was increased by + 0.57 (p + 2 SD) increased (p < 0.05). Baseline BMI and age at the start of follow-up influenced the BMI change during the five years (p < 0.001 and p < 0.05 respectively). The individual growth was highly variable, but a tendency towards increasing stunting with age was seen in severe gross motor dysfunction (GMFCS levels IV-V) and the opposite, a slight catch-up of height in children with walking ability (GMFCS levels I-III). Conclusions: These are the first available subtype-and GMFCS-specific longitudinal growth data for children with CP spastic diplegia. Their growth potential according to these data should be regarded as a minimum, as some children were undernourished. It is unknown whether the spasticity reduction through SDR increased the weight gain velocity, or if the relative weight increase was part of the general "obesity epidemic". For some children the weight increase was highly desirable. In others, it resulted in overweight and obesity with risk of negative health effects. Weight and height should be monitored to enable early prevention of weight aberrations also causing problems with mobility, activity and participation

Analyzing musculoskeletal neck pain, measured as present pain and periods of pain, with three different regression models: a cohort study

<p>Abstract</p> <p>Background</p> <p>In the literature there are discussions on the choice of outcome and the need for more longitudinal studies of musculoskeletal disorders. The general aim of this longitudinal study was to analyze musculoskeletal neck pain, in a group of young adults. Specific aims were to determine whether psychosocial factors, computer use, high work/study demands, and lifestyle are long-term or short-term factors for musculoskeletal neck pain, and whether these factors are important for developing or ongoing musculoskeletal neck pain.</p> <p>Methods</p> <p>Three regression models were used to analyze the different outcomes. Pain at present was analyzed with a marginal logistic model, for number of years with pain a Poisson regression model was used and for developing and ongoing pain a logistic model was used. Presented results are odds ratios and proportion ratios (logistic models) and rate ratios (Poisson model). The material consisted of web-based questionnaires answered by 1204 Swedish university students from a prospective cohort recruited in 2002.</p> <p>Results</p> <p>Perceived stress was a risk factor for pain at present (PR = 1.6), for developing pain (PR = 1.7) and for number of years with pain (RR = 1.3). High work/study demands was associated with pain at present (PR = 1.6); and with number of years with pain when the demands negatively affect home life (RR = 1.3). Computer use pattern (number of times/week with a computer session ≥ 4 h, without break) was a risk factor for developing pain (PR = 1.7), but also associated with pain at present (PR = 1.4) and number of years with pain (RR = 1.2). Among life style factors smoking (PR = 1.8) was found to be associated to pain at present. The difference between men and women in prevalence of musculoskeletal pain was confirmed in this study. It was smallest for the outcome ongoing pain (PR = 1.4) compared to pain at present (PR = 2.4) and developing pain (PR = 2.5).</p> <p>Conclusion</p> <p>By using different regression models different aspects of neck pain pattern could be addressed and the risk factors impact on pain pattern was identified. Short-term risk factors were perceived stress, high work/study demands and computer use pattern (break pattern). Those were also long-term risk factors. For developing pain perceived stress and computer use pattern were risk factors.</p

Long-term outcomes five years after selective dorsal rhizotomy

<p>Abstract</p> <p>Background</p> <p>Selective dorsal rhizotomy (SDR) is a well accepted neurosurgical procedure performed for the relief of spasticity interfering with motor function in children with spastic cerebral palsy (CP). The goal is to improve function, but long-term outcome studies are rare. The aims of this study were to evaluate long-term functional outcomes, safety and side effects during five postoperative years in all children with diplegia undergoing SDR combined with physiotherapy.</p> <p>Methods</p> <p>This study group consisted of 35 children, consecutively operated, with spastic diplegia, of which 26 were Gross Motor Function Classification System (GMFCS) levels III–V. Mean age was 4.5 years (range 2.5–6.6). They were all assessed by the same multidisciplinary team at pre- and at 6, 12, 18 months, 3 and 5 years postoperatively. Clinical and demographic data, complications and number of rootlets cut were prospectively registered. Deep tendon reflexes and muscle tone were examined, the latter graded with the modified Ashworth scale. Passive range of motion (PROM) was measured with a goniometer. Motor function was classified according to the GMFCS and measured with the Gross Motor Function Measure (GMFM-88) and derived into GMFM-66. Parent's opinions about the children's performance of skills and activities and the amount of caregiver assistance were measured with Pediatric Evaluation Disability Inventory (PEDI).</p> <p>Results</p> <p>The mean proportion of rootlets cut in S2-L2 was 40%. Muscle tone was immediately reduced in adductors, hamstrings and dorsiflexors (p < 0.001) with no recurrence of spasticity over the 5 years. For GMFCS-subgroups I–II, III and IV–V significant improvements during the five years were seen in PROM for hip abduction, popliteal angle and ankle dorsiflexion (p = 0.001), capacity of gross motor function (GMFM) (p = 0.001), performance of functional skills and independence in self-care and mobility (PEDI) (p = 0.001).</p> <p>Conclusion</p> <p>SDR is a safe and effective method for reducing spasticity permanently without major negative side effects. In combination with physiotherapy, in a group of carefully selected and systematically followed young children with spastic diplegia, it provides lasting functional benefits over a period of at least five years postoperatively.</p

Ex Vivo Treatment with a Novel Synthetic Aminoglycoside NB54 in Primary Fibroblasts from Rett Syndrome Patients Suppresses MECP2 Nonsense Mutations

BACKGROUND: Nonsense mutations in the X-linked methyl CpG-binding protein 2 (MECP2) comprise a significant proportion of causative MECP2 mutations in Rett syndrome (RTT). Naturally occurring aminoglycosides, such as gentamicin, have been shown to enable partial suppression of nonsense mutations related to several human genetic disorders, however, their clinical applicability has been compromised by parallel findings of severe toxic effects. Recently developed synthetic NB aminoglycosides have demonstrated significantly improved effects compared to gentamicin evident in substantially higher suppression and reduced acute toxicity in vitro. RESULTS: We performed comparative study of suppression effects of the novel NB54 and gentamicin on three MECP2 nonsense mutations (R294X, R270X and R168X) common in RTT, using ex vivo treatment of primary fibroblasts from RTT patients harboring these mutations and testing for the C-terminal containing full-length MeCP2. We observed that NB54 induces dose-dependent suppression of MECP2 nonsense mutations more efficiently than gentamicin, which was evident at concentrations as low as 50 µg/ml. NB54 read-through activity was mutation specific, with maximal full-length MeCP2 recovery in R168X (38%), R270X (27%) and R294X (18%). In addition, the recovered MeCP2 was translocated to the cell nucleus and moreover led to parallel increase in one of the most important MeCP2 downstream effectors, the brain derived neurotrophic factor (BDNF). CONCLUSION: Our findings suggest that NB54 may induce restoration of the potentially functional MeCP2 in primary RTT fibroblasts and encourage further studies of NB54 and other rationally designed aminoglycoside derivatives as potential therapeutic agents for nonsense MECP2 mutations in RTT