Multiple sclerosis by phenotype in Germany.

BACKGROUND: A diagnosis of multiple sclerosis (MS) can be categorized based on its disease course into the following phenotypes: relapsing-remitting MS (RRMS), primary progressive MS (PPMS), and secondary progressive MS (SPMS). With one exception, studies of MS by phenotype either provide only prevalence data or if describing drug utilization, the emphasis is on patients with RRMS; while drug utilization by phenotype tends to be examined over the course of a year. No recent studies have comprehensively evaluated MS phenotypes by prevalence, drug utilization, and comorbidities over time from a population-based perspective, which is essential for understanding the disease burden and identifying unmet needs in MS. Germany is one of the few countries where specific MS phenotypes are commonly recorded in routine clinical practice. The purpose of this study was to compare MS phenotypes with respect to changes in their population-based prevalence rates and the types of MS treatments prescribed over time, as well as the frequency of clinical conditions associated with MS based on data from a German health insurance database. METHODS: This retrospective, observational, cohort study used data from a German health insurance database for the period 2010 to 2017. Patients aged 18+ years with a specified phenotype of MS based on ICD-10 diagnosis coding were included in the analysis. RESULTS: In 2010, RRMS was reported in 73%, PPMS in 8%, and SPMS in 19% of patients with MS with a known phenotype. The mean ages of patients were 41.4, 53.6, and 52.8 years, respectively, and all phenotypes were associated with a female predominance (69%, 63% and 63%, respectively). The prevalence rate of each phenotype markedly increased during the study period (RRMS +113%, PPMS +40%, SPMS +54%; in 2017 the rates were 183, 14, and 34 per 100,000, respectively). The mean age of patients reporting each phenotype also increased (p<0.01), while the female:male proportion remained stable in RRMS and SPMS, the proportion of females significantly declined over time in the PPMS group. The overall percentage of patients prescribed a disease-modifying drug increased across the phenotypes from 51% to 57%. Prescription of interferon-based therapies declined in each phenotype, with the greatest declines observed in RRMS and PPMS. The PPMS and SPMS groups had significantly more prescriptions for symptom management than the RRMS group. Depression was the most prevalent clinical condition associated with each phenotype. There was a significant difference in the percentage of patients with depression across the phenotypes (p = 0.03), with the highest among SPMS (44%) compared with RRMS (35%) or PPMS (37%). Significant differences (p<0.05) across the phenotypes were also observed for the composite prevalence of cardiovascular conditions (highest in PPMS) and cognitive dysfunction (highest in SPMS). CONCLUSION: The increasing numbers of patients across each MS phenotype, aging population in patients with MS regardless of phenotype, gender differences and variations across the types of treatments prescribed, and clinical conditions associated with each MS phenotype present new insight into the disease burden and treatment strategies of MS. These should be considered when developing healthcare strategies and optimizing care for patients with MS.

Pediatric Acute Ischemic Stroke by Age-Group: A Systematic Review and Meta-Analysis of Published Studies and Hospitalization Records.

BACKGROUND: Although stroke is rare among the pediatric population, it is nevertheless associated with serious or life-threatening consequences. The etiologic factors of acute ischemic stroke (AIS) are likely to vary over the course of childhood development. The incidence rates of AIS, not previously systematically examined by pediatric age subgroup, could guide studies of its etiology. OBJECTIVE: The aim of this study is to evaluate the incidence rate of AIS by age-group in the pediatric population (aged 0-17/18 years) and identify any common trends or sources of variability across different countries. METHODS: Rates of pediatric AIS were collated from a systematic literature review of published studies globally (1983-2020) and hospitalization records from Europe and the USA (2015-2018). Records that were included in the analysis reported the code or description used for AIS diagnosis and age-specific data for children aged 0-17/18 years. AIS incidence rates were summarized by age-group, data source, country, and geographic region. A meta-analysis was conducted to assess the heterogeneity of AIS rates in neonates. RESULTS: The pooled AIS incidence rate was 5.6 per 100,000 children across all records. When only records reporting the AIS incidence rates for children across the full age range (0-17/18 years) were analyzed, the pooled AIS incidence rate was 4.6 per 100,000 children and ranged from 7.0 per 100,000 (Germany) to 1.3 per 100,000 (Denmark). The highest pooled rates were observed in the 0-28-day age-group (24.6 per 100,000 live births), declining to the lowest rates in the 5-9-year age-group, and rising again in the 10-17/18-year age-group. AIS rates were the most heterogeneous in the 0-28-day age-group and across European countries. Significantly higher AIS rates in neonates were observed from hospital databases (35.9 per 100,000) than in the literature (19.4 per 100,000). AIS rates may be underestimated as pediatric AIS events are rare and challenging to diagnose, and limited age-specific data are available. CONCLUSIONS: Incidence rates of pediatric AIS by age-groups followed a consistent overall pattern of a reverse J-shaped curve, with the highest rates in neonates, across predominantly European and North American countries. Further research is warranted to examine if this pattern is observed in other geographic regions and to identify AIS risk factors specific to different phases of childhood development.

Epidemiology of skin event rates among users of pumps for the subcutaneous administration of drugs for chronic conditions.

OBJECTIVE: To provide the epidemiology of skin events occurring during long-term administration of medications delivered by continuous subcutaneous infusion pump (CSIP) systems as background rates for the development of novel CSIP treatments to use in community-based settings. METHODS: Using a United Kingdom general practice database, we conducted a study to assess the rates of skin events among new users of apomorphine and insulin delivered by CSIP in patients with Parkinson's disease or diabetes, respectively. Skin events included skin infections, skin nodules/localized swelling, dermatitis/eczema, urticaria/erythema, and rash/other non-specific skin eruptions. RESULTS: Five hundred and fifty-seven adults (age 30+) were included in this descriptive cohort. The median duration of CSIP use was 17 months among 255 apomorphine users and 41 months among 302 insulin users. By 60 months, ∼40% of both cohorts experienced skin events. Repeated skin events occurred in 11% of the apomorphine cohort and 14% of the insulin cohort at any time during follow-up. The overall skin event rate in the apomorphine cohort was 17 per 1000 person-months (PM) and 13 per 1000 PM in the insulin cohort. The most common skin events in both cohorts were infection and rash/unspecified skin eruptions. The highest rates of skin events occurred soon after apomorphine CSIP initiation (36 per 1000 PM in weeks 1-2 and 50 per 1000 PM in weeks 3-4), with lower rates after 4 weeks. Insulin CSIP users' skin event rates were consistent over the treatment duration. CONCLUSIONS: Clinically important skin events are common during long-term administration of medications by CSIP.

Clinical Features Observed in General Practice Associated With the Subsequent Diagnosis of Progressive Supranuclear Palsy.

Background: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disorder that is difficult for primary care physicians to recognize due to its progressive nature and similarities to other neurologic disorders. This case-control study aimed to identify clinical features observed in general practice associated with a subsequent diagnosis of PSP. Methods: We analyzed a de-identified dataset of 152 PSP cases and 3,122 matched controls from electronic medical records of general practices in Germany. We used a random forests algorithm based on machine learning techniques to identify clinical features (medical conditions and treatments received) associated with pre-diagnostic PSP without using an a priori hypothesis. We then assessed the relative effects of the features with the highest importance scores and generated multivariate models using clustered logistic regression analyses to identify a subset of clinical features associated with subsequent PSP diagnosis. Results: Using the random forests approach, we identified 21 clinical features associated with pre-diagnostic PSP (odds ratio ≥2.0 in univariate analyses). From these, we constructed a multivariate model comprising 9 clinical features with ~90% likelihood of identifying a subsequent PSP diagnosis. These features included known PSP symptoms, common misdiagnoses, and 2 novel associations, diabetes mellitus and cerebrovascular disease, which are possible modifiable risk factors for PSP. Conclusion: In this case-control study using data from electronic medical records, we identified 9 clinical features, including 2 previously unknown factors, associated with the pre-diagnostic stage of PSP. These may be used to facilitate recognition of PSP and reduce time to referral by primary care physicians.

Epidemiology of Pediatric-Onset Multiple Sclerosis: A Systematic Review of the Literature.

Multiple sclerosis onset in youth is increasingly recognized. A systematic review was conducted to assess incidence and prevalence of pediatric-onset multiple sclerosis, focusing on occurrence by age subgroups and disease course. A literature search for the period 1965-2018 was carried out, selecting population-based studies of multiple sclerosis in individuals aged 19 years and younger. Nineteen studies met inclusion criteria. One pediatric neurologist extracted the data. Overall incidence ranged from 0.05 (95% confidence interval 0.03-0.08) to 2.85 (95% confidence interval 2.83-2.86) per 100 000 children and overall prevalence from 0.69 (95% confidence interval 0.58-0.80) to 26.92 (95% confidence interval 26.61-27.23) per 100 000 children. Incidence increased with age. The female-male ratio increased from 1.2:1 in children <12 years old to 2.8:1 in children ≥12 years old. Ten studies (n=521 children) reported disease course. Seven studies found only relapsing-remitting disease and 3 studies found primary-progressive disease in 3.0% to 6.7%. Two secondary-progressive disease cases were identified. Epidemiologic data aid in understanding the magnitude of multiple sclerosis and its clinical phenotypes, for planning for new disease-modifying therapies in the pediatric population.

Electronic health databases for epidemiological research on joint replacements: considerations when making cross-national comparisons.

PURPOSE: The purpose of this study was to examine the rate of primary knee, hip, or shoulder replacement among persons with osteoarthritis (OA) of the knee by gender and age comparing two nations in similar periods using electronic health records, but with different health-care systems. METHODS: Two electronic health care databases of anonymized information were used to construct cohorts of adults with OA of the knee from the United Kingdom (UK) and the United States. Patients were required to have activity in the database at least 6 months before the first diagnosis of knee OA ("index diagnosis") in the study period to ensure that the patient samples were eligible for medical evaluation. The outcomes (numerator) measured were primary knee, hip, or shoulder replacement or the composite of primary knee, hip, or shoulder replacement. The denominator was the person-time at risk computed from time from the date of the index diagnosis to the date of each outcome separately or to the end of the database period if no outcome was documented. RESULTS: There were 93,146 subjects in the UK and 1,468,217 in the United States who were aged 18+ years and met the study eligibility criteria. The composite joint replacement rate (hip, knee, or shoulder) ranged from 11.89 per 100 person-years (PY) in the Unites States to 4.13 per 100 PY in the UK Primary knee replacements rates ranged from 10.38 per 100 PY in the Unites States to 3.40 per 100 PY in the UK and occurred at a somewhat higher rate in males than females in both countries. Both primary hip and shoulder replacement rates were higher in the Unites States than in the UK (hip: 1.19 per 100 PY and 0.76 per 100 PY; shoulder: 0.19 per 100 PY and 0.03 per 100 PY, respectively). The median time to a primary hip or knee replacement in the UK was approximately twice as long as in the Unites States. CONCLUSIONS: Knee replacements are not an uncommon event in persons with knee OA occurring throughout the adult life span, with the rate steeply rising in both sexes until aged 75 years. Although the pattern of the age-specific joint replacement rates was similar between sexes, the magnitude of the rates was markedly lower in the UK.

Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

BACKGROUND: Obesity is a serious and rapidly growing health problem worldwide. Few therapies are available beyond diet, exercise and bariatric surgery. A previously approved medication, sibutramine, has been withdrawn from the market due to concerns over the potential of increased risk of cardiovascular (CV) events, based on a phase IV clinical trial that included only individuals at high risk for CV events. OBJECTIVE: The aim of the study was to compare sibutramine users and matched non-users on rates of CV events, both overall and stratified by whether the patient qualified for on-label sibutramine use, using data from real-life clinical practice. METHODS: A retrospective cohort was constructed from electronic medical record data from physician office practices (mostly primary care) in the UK and Germany, using the LifeLink™ database from IMS Health Incorporated. For patients with at least one physician visit in which sibutramine was prescribed between 1 April 1999 and 31 October 2008, the date of their first such prescription was their index date. Users and non-users were matched 1 : 1 on index date (within 30 days), sex, age group (six categories), Charlson Comorbidity Index and evidence of obesity (high body mass index [BMI] or, if BMI was missing, diagnosis of obesity or very high weight relative to height). The resultant total samples analysed were 6186 in Germany and 7264 in the UK. User and non-user cohorts in the samples were compared according to the ratio of their crude incidence rates of acute myocardial infarction (AMI), stroke and either AMI or stroke per 1000 patient-years of follow-up. Cox regression analysis was used to compare the risk of CV events as a hazard ratio (HR) with 95% confidence intervals (CIs) between sibutramine user and non-user cohorts, controlling for label status and/or history of prior CV disease at baseline. RESULTS: The risk of AMI, stroke and either AMI or stroke was not higher among sibutramine users than comparable non-users of sibutramine in both Germany and the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. CONCLUSION: This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.

Are back supports plus education more effective than education alone in promoting recovery from low back pain?: Results from a randomized clinical trial.

STUDY DESIGN: Randomized clinical trial. OBJECTIVES: To evaluate the effectiveness of a back support plus education versus education alone in promoting recovery from a work-related low back disorder (WR-LBD) while simultaneously considering personal, health, and occupational factors and the impact of occupational factors on recovery. SUMMARY OF BACKGROUND DATA: No randomized studies of active industrial workers with low back disorders exist regarding the effectiveness of back supports plus education. METHODS: A total of 433 actively employed hourly union workers who had a recent diagnosis of a WR-LBD: 1) those who wore a specially designed back support plus received education on back health; and 2) those who received education on back health only. Demographic, health, medical, and occupational factors were obtained through interview or abstraction of computer files; individual ergonomic exposures were measured with a lumbar motion monitor. Outcomes evaluated over a 12-month period included: self-reported measures of back pain, back pain disability level, physical health, mental health, and administrative measures of recurrence, lost work time, and medical care utilization. RESULTS: There was no difference between the study groups with respect to mental or physical health, low back pain, back pain disability, neurogenic symptoms, lost work time, likelihood of recurrence of an episode of a back disorder, or other administrative measures of healthcare utilization or lost work time. However, significant decreases in low back pain, low back pain disability, neurogenic symptoms, and an increase in physical health were observed over the 12 months of observation in both study groups. The only occupational variable found to influence was plant group whereby service parts operations workers in the back support plus education group experienced a lower likelihood of WR-LBD recurrence. CONCLUSION: Although there was no overall effect on self-reported recovery or administrative measures or lost work time between the study groups, a back support plus health education may have some value in preventing recurrent WR-LBD in industrial workers who work in psychosocial environments and perform manual material handling tasks similar to those found in parts distribution centers.

Are tri-ethnic low-income women with breast cancer effective teachers of the importance of breast cancer screening to their first-degree relatives? Results from a randomized clinical trial.

The purpose of this study was to determine the efficacy of women with breast cancer as teachers of the importance of breast cancer screening to their first-degree female relatives. The sample was restricted to low-income working age women recruited from four hospitals. The study design was a randomized clinical trial. At each hospital, breast cancer patients (probands) were randomized into one of two study groups: (i) intensive, individual educational training on breast cancer screening or (ii) standard clinic education on breast cancer screening. The probands were instructed to teach at least one of their first-degree female relatives (21+ years of age) about breast cancer screening techniques. Three to six months after the enrollment of the probands, their relatives were contacted by telephone to determine breast cancer screening practices. A total of 79 probands and 96 relatives participated in the study. Relatives in the education group when compared with the control group were: 1.25 times more likely to have clinical breast examination (p = 0.005), 2.83 times more likely to have scheduled a clinical breast examination (p = 0.046), and, 1.36 times more likely to have been told about performing breast self-examination (p = 0.05). Additionally, relatives in the education group were more likely to have received a pamphlet on breast cancer screening (RR = 1.58, p = 0.009) and have discussed the importance of breast cancer screening (RR = 1.33, p = 0.020) from the proband. Special education training did not impact mammography utilization of the relatives. From these findings, a tri-ethnic group of low-income women with breast cancer can be effective teachers of breast cancer screening practices, at least for promoting clinical breast examination and transmitting messaging for performance of breast self-examination if given the adequate training.

Participation in occupational health longitudinal studies: predictors of missed visits and dropouts.

PURPOSE: The purpose of this study is to determine whether demographics, health, and job factors influence continued participation of employed persons in a longitudinal intervention study of tertiary prevention for work-related low-back disorders (WR-LBDs). METHODS: Four hundred fifty-four actively employed persons had enrolled in an intervention study of back supports and education to promote recovery from a WR-LBD. Baseline values were examined according to whether individuals continued in the study, missed a visit, or dropped out; frequency of missed visits; and early or late dropouts at follow-up intervals of 1, 2, 6, and 12 months. RESULTS: Workers who did not complete all study visits were significantly more likely to be younger and have poorer self-reported health. Individuals with a greater percentage of body fat dropped out early. Significantly more missed visits were observed among those who had arthritis and longer duration of low-back pain symptoms. Job factors did not influence study participation. CONCLUSIONS: Continued participation in a longitudinal study of working adults was influenced by age, health status, and factors related to the primary condition targeted by the intervention study. Strategies aimed at those who report lower levels of health and symptoms related to the condition under study may promote follow-up participation in longitudinal studies. Thus, even among actively employed persons, one should not assume that all workers are "healthy."

Risk factors for recurrent episodes of work-related low back disorders in an industrial population.

STUDY DESIGN: An observational longitudinal design. OBJECTIVES: To characterize the rate of and risk factors for recurrent episodes of work-related low back disorder in industrial workers. SUMMARY OF BACKGROUND DATA: Little data exist on risk factors for recurrent episodes of work-related low back disorders in employed persons. METHODS: A total of 352 active hourly union employees who were diagnosed with a recent work-related low back disorder and who had at least one follow-up visit within 12 months enrolled for participation in a rehabilitation intervention study at the workplace. Information on clinical and job factors was obtained at each study visit. Job risk for low back disorder was quantified using the Lumbar Motion Monitor. The main outcome measure, recurrence of work-related low back pain, was derived from a computerized file of administrative records of visits to the plant's medical department. RESULTS: The rate of repeated episodes was 24.4%; an additional episode occurred in 2.3%. Adjusting for age, gender, health status and job exposures, lower levels of physical health, increasing back pain disability, spinal deformity, high stress, and increasing number of different jobs worked at the same plant were risk factors for a recurrent episodes of low back pain. CONCLUSIONS: Early identification of risk factors for a work-related low back disorder may signal the need for early and intense rehabilitation to prevent recurrent episodes. Because these findings were based on jobs with medium risk of low back disorders, other factors may be significant in higher risk jobs.

Determination of factors associated with hospitalization in breast cancer survivors.

PURPOSE/OBJECTIVES: To identify factors associated with hospitalization after diagnosis of breast cancer in working-age women. DESIGN: Descriptive, retrospective survey. SETTING: Caseload of a single medical oncologist affiliated with an urban, not-for-profit, academic medical center. SAMPLE: 123 consecutively evaluated women aged 21-65 years with breast cancer associated with projected survival greater than three years. METHODS: Data were collected from an electronic clinical file with demographic, diagnostic, and hormone replacement therapy (HRT) information. Four survey forms were mailed to subjects: (a) a form ascertaining personal demographics, health status, and healthcare utilization, (b) menopausal Symptom Rating Scale, (c) a hot flash diary, and (d) the Center for Epidemiologic Studies Depression Scale. MAIN RESEARCH VARIABLES: Menopausal symptoms, depression symptoms, age, time since diagnosis, and overnight hospitalization. FINDINGS: An increasing depression score and increasing menopausal symptoms score were found to be independent predictors of hospitalization controlling for age at diagnosis, disease stage, and time since diagnosis. Demographic variables, HRT use at or prior to diagnosis (a proxy measure of health status), current self-reported health status, and hot flashes were not associated with hospitalization. CONCLUSIONS: Psychological factors can be important significant predictors of hospitalization in survivors of breast cancer independent of disease stage. Further study should be undertaken to determine whether support services directed at identifying and treating those at risk for depression or menopausal symptoms may reduce the likelihood of potentially avoidable hospitalization. IMPLICATIONS FOR NURSING: The identification of those at high risk for hospitalization because of high levels of depressive or menopausal symptoms and prompt intervention offer the opportunity to improve the quality of life of breast cancer survivors and reduce the cost of health care for themselves, their families, and the healthcare system.

Factors affecting recovery from work-related, low back disorders in autoworkers.

OBJECTIVE: To simultaneously evaluate personal, medical, and job factors that could affect recovery from work-related, low back disorders, specifically focusing on an active working sample. DESIGN: Observational, longitudinal study. SETTING: Two US automotive plants. PARTICIPANTS: Employees (N=352; 289 men, 63 women; mean age +/- standard deviation, 45.1+/-7.5 y) who were active hourly autoworkers, diagnosed with work-related, low back disorder by the plant's medical department. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Oswestry Disability Questionnaire for back pain was used to evaluate recovery. RESULTS: Factors associated with better recovery were lower stress levels (P<.001) and exercise or physical activity outside work (P<.001); factors associated with higher disability levels over time were current cigarette smoking (P<.01) and bedrest (P<.001). CONCLUSIONS: Personal modifiable factors are major influences in the recovery from work-related, low back disorders, even in active working populations. Interventions aimed at increasing exercise and decreasing stress should also be considered as a part of rehabilitation in employed persons with low levels of disability.

Medical information and the Internet: do you know what you are getting?

Due to the Internet technology, hundreds of Web sites are accessible for medical information, and the retrieval of such information is quite rapid. Once you as a consumer obtain all of this information, how do you determine whether the information you are looking at is valid and current and even relevant to your needs? This article presents various criteria necessary to evaluate the information on a medical Web site; no standards currently are in place to mandate the validity of information published on the Internet.