Reproductive and developmental toxicity assessment of palbociclib, a CDK4/6 inhibitor, in Sprague-Dawley rats and New Zealand White rabbits.

Palbociclib is a selective inhibitor of the cyclin-dependent kinase (CDK) 4/6, approved for the treatment of breast cancer. We assessed the potential effects of oral administration of palbociclib on reproduction and development. There were no effects on female or male fertility indices; however, in the male there was seminiferous tubule degeneration in the testes and secondary findings in the epididymides, lower testicular and epididymal weights, sperm density and motility. Palbociclib was not teratogenic in rats or rabbits; however, in the presence of maternal toxicity (lower maternal body weight gain and food consumption), low fetal body weights were observed in rats and small forepaw phalanges were noted in rabbits. There were, however, no adverse effects on the F1 generation in a pre- and post-natal developmental toxicity study in the rat.

[Quality Assurance using routine data: Overdiagnosis by radiological imaging for back pain]. / Überdiagnostik mit Bildgebung bei Rückenschmerzen.

UNLABELLED: Background and Problem: Acute nonspecific back pain disorders are typically self-limiting. According to the national guideline low back pain, only in case of clinical suspicion of a serious course radiological imaging should take place immediately. Otherwise, the guideline recommends waiting at least six weeks. PATIENTS AND METHODOLOGY: Using Statutory Health Insurance (SHI) routine data of the Techniker Krankenkasse we analyzed how many of the insured persons suffering from acute back pain for the first time with no indication of a serious outcome received a non-indicated diagnostic imaging. RESULTS: In about 10 % diagnostic imaging is conducted after initial diagnosis. If an imaging is carried out, roughly one third of these cases takes place ahead of time or is completely unnecessary. Methodically this is a very conservative estimation, thus it seems likely that the extent of overdiagnosis in actual medical care situation is even larger. CONCLUSIONS: Every third patient who received radiological diagnostics due to first acute nonspecific back pain underwent the procedure more quickly than recommended (less than six weeks). Overdiagnosis is not only economically problematic but also with respect to patient orientation and patient safety. It may cause substantial damage to patients - either by the use of diagnostics itself or by means of therapies initiated after diagnostics.

[Brachytherapy for Prostate Cancer: Potentials and Limitations of Social Health Insurance Data for Benefit Assessment]. / Brachytherapie beim Prostata-Ca: Möglichkeiten und Limitationen von GKV-Routinedaten für eine Nutzenbewertung.

BACKGROUND: Due to the insufficient data base the Federal Joint Committee (G-BA) had in 2009 after 7 years of deliberation decided to initiate consultation regarding ambulatory brachytherapy for localised prostate cancer for 10 years from social health insurance (SHI) benefits. The aim is to gain more findings by means of comparative studies. PROBLEM: Based on the non-availability of clinical primary data of a methodologically acceptable level, it was analysed to what extent secondary data of the SHI may be used in order to arrive at valid conclusions for benefit aspects. METHODS: As base approx. 8 million insured of TK with their data of cost reimbursement between 2006 and 2011 were considered. In SHI secondary data no clinical information regarding tumour stage and other prognostic factors are available. Therefore, a novel method with therapy-specific multisectoral inclusion and exclusion criteria, respectively, was developed in order to differentiate between localised and advanced tumours of the prostate. Overall survival, relapse-free survival, event-free survival and side-effects associated to prostate cancer were analysed. RESULTS: Out of 87 822 insured persons with the diagnosis prostate cancer, 795 with PBT, 10 936 with RP and 1 925 with EBRT were investigated in detail. The 4-year event-free survival rate was 73% for RP, 77% for PBT and 71% for EBRT. Many prostate cancer-specific side effects appeared already before intervention. Side effects of the intestinal tract (23.8%) and sexual impairments (26.5%) were more frequent for EBRT than for RP (17.1%/14.8%) and PBT (16.4%/13.2%). CONCLUSION: By means of SHI secondary data and adequate operationalisation important findings regarding relevant aspects of prostate cancer in healthcare research can be generated. However, these hold methodological limitations and are not suited to draw valid conclusions for benefit assessment. Based solely on SHI routine data valid statements regarding comparative benefit assessment are limited. Limitations could be reduced by applying a record linkage with clinical data. Such primary data should include information on tumour stages as well as therapy assignment and observation of survival time.

Economic burden of neural tube defects in Germany.

OBJECTIVE: Failure of closure of the neural tube often leads to serious malformations, including spina bifida, anencephaly and encephalocoele. Despite improvements in medical and surgical treatment, the burden associated with spina bifida is substantial but country-specific data are lacking outside North America. This study aims to improve understanding of the economic implications and burden associated with the morbidity of children and adults with neural tube defects (NTDs) in Germany. STUDY DESIGN: Retrospective data analysis. METHODS: 2006-2009 German health insurance data of persons with NTDs (spina bifida and encephalocoele) were analysed to determine the economic burden of illness associated with NTDs in Germany. Cases were identified using ICD-10 codes; data included outpatient and inpatient care, rehabilitation, remedies and medical aids, pharmacotherapy use, long-term care and information on sick leave. The analysis was stratified by age group to provide a burden estimate specific to a person's age. To obtain an indicator of incremental burden to the Statutory Health Insurance (SHI), results were compared to the standardized healthcare expenditures according to the German Risk Compensation Scheme (RSA). RESULTS: Overall, 4141 persons with an ICD code related to NTDs were identified (out of a population of 7.28 million persons screened). The administrative prevalence ranged from 0.54 to 0.58 per 1000 enrollees. Of those, 3952 (95.4%) were diagnosed with spina bifida. The average annual mean healthcare expenditure of persons with spina bifida was €4532 (95% CI = 4375-4689, SD = 9590, Median = 1000), with inpatient care contributing €1358 (30.0%), outpatient care €644 (14.2%), rehabilitation €29 (0.6%), pharmacotherapy €562 (12.4%), and remedies and medical aids €1939 (42.8%). The incremental cost due to spina bifida was substantially higher than the standardized SHI expenditures for all age groups. The difference was highest for persons ≤ 10 years old (€10,971 vs €2360 for the age group ≤ 1, €8599 vs €833 for the age group 2-5 years and €10,601 vs €863 for the age group 6-10 years). The difference was smallest for the age group 41-50 years (€2524 vs €1101) and for 71 years and over (€5278 vs €4389). CONCLUSION: Expenditures of persons with spina bifida exceeded the standardized SHI expenditures, indicating a considerable economic burden. The economic burden is continuous throughout the person's life, with high monetary impact and exposure to the healthcare system (especially in early years of life). Efforts should be devoted to improve the prevention of NTDs and provide appropriate support for persons with NTDs, parents, and caregivers--especially in early years.

[Calculation of disease-related costs in claims data analyses with the example of attention-deficit hyperactivity disorder. Comparison of methods]. / Die Berechnung indikationsspezifischer Kosten bei GKV-Routinedatenanalysen am Beispiel von ADHS. Ein Methodenvergleich.

Claims data have proven useful for carrying out cost-of-illness studies. To avoid overestimating disease-related costs, only those costs that are related to a specific disease should be considered. The present study demonstrates two basic approaches for identifying disease-related costs. Using the example of attention-deficit hyperactivity disorder (ADHD), the advantages and drawbacks of expert-based approaches and those based on control groups are compared. Anonymized data from the "Techniker Krankenkasse" for 2008 were available for the study. The study population encompassed all ADHD patients and a control group that was five times bigger. Additionally, a systematic literature review was carried out on 65 relevant studies. Compared with the control group, disease-related costs were EUR 2,902 per ADHD patient on average. However, using the expert-based approach, costs were established to be EUR 923 lower. This is mainly because a comparison with an appropriate control group incorporates all costs for possible comorbidities and concomitant diseases. Both approaches have specific advantages and drawbacks, and when planning studies the respective limitations need to be considered.

Laparoscopic fenestration of non-parasitic liver cysts and health-related quality of life assessment.

Although laparoscopic fenestration has become an established treatment in symptomatic liver cyst patients in the recent years, the success of surgical treatment cannot only be evaluated by post-operative morbidity and mortality. Therefore, the aim of this study was to analyze the safety of laparoscopic fenestration of non-parasitic liver cysts and to assess the impact of this therapy on patients' quality of life. A total of 43 patients who underwent laparoscopic fenestration of non-parasitic liver cysts at our center were included in this study. Post-operative course was assessed and patients' quality of life was evaluated before surgery and at present time using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ C-30). The results were that, post-operative morbidity and mortality rates were 0%. After a median follow-up of 49 months (19-97 months) the recurrence rate was 11.1% for simple liver cysts (SLC) and 42.9% for polycystic liver disease (PCLD). Thirty-one out of 43 patients (72.1%) completed the EORTC C-30 questionnaire. There was highly significant post-operative improvement in global health status (p < 0.001) as well as in physical (p = 0.002), role (p = 0.004), emotional (p = 0.003) and social (p = 0.001) functioning. Furthermore, a significant reduction of symptoms could be shown for pain (p < 0.001), nausea and vomiting (p = 0.001), appetite loss (p = 0.006), insomnia (p = 0.04) and fatigue (p = 0.025). To conclude, laparoscopic fenestration of symptomatic non-parasitic liver cysts is a safe procedure with good long-term results and the patients' benefit of this intervention is excellent as shown by highly significant improvement in patients' quality of life.

How should DSM-V classify eating disorder not otherwise specified (EDNOS) presentations in women with lifetime anorexia or bulimia nervosa?

OBJECTIVE: Anorexia nervosa (AN) and bulimia nervosa (BN) are marked by longitudinal symptom fluctuations. DSM-IV-TR does not address how to classify eating disorder (ED) presentations in individuals who no longer meet full criteria for these disorders. To consider this issue, we examined subthreshold presentations in women with initial diagnoses of AN and BN. METHOD: A total of 246 women with AN or BN were followed for a median of 9 years; weekly symptom data were collected at frequent intervals using the Longitudinal Interval Follow-up Evaluation of Eating Disorders (LIFE-EAT-II). Outcomes were ED presentations that were subthreshold for 3 months, including those narrowly missing full criteria for AN or BN, along with binge eating disorder (BED) and purging disorder. RESULTS: During follow-up, most women (77.6%) experienced a subthreshold presentation. Subthreshold presentation was related to intake diagnosis (Wald chi2=8.065, df=2, p=0.018). Individuals with AN most often developed subthreshold presentations resembling AN; those with BN were more likely to develop subthreshold BN. Purging disorder was experienced by half of those with BN and one-quarter of those with AN binge/purge type (ANBP); BED occurred in 20% with BN. Transition from AN or BN to most subthreshold types was associated with improved psychosocial functioning (p<0.001). CONCLUSIONS: Subthreshold presentations in women with lifetime AN and BN were common, resembled the initial diagnosis, and were associated with modest improvements in psychosocial functioning. For most with lifetime AN and BN, subthreshold presentations seem to represent part of the course of illness and to fit within the original AN or BN diagnosis.

[A set of questionnaires for the assessment (screening) of psychological disorders and social problems in cardiac rehabilitation patients]. / Ein Fragebogenset zur Erfassung (Screening) psychischer Störungen und sozialer Probleme von Patienten in der kardiologischen Rehabilitation.

A set of questionnaires for the assessment (screening) of psychological and social problems in cardiac rehabilitation patients is analyzed for its psychometric properties. The test battery had before been consented by a task force of the German Association for the Prevention and Rehabilitation of Cardiovascular Disease, DGPR. It integrates generally approved and well-tried assessments for depression/anxiety, social isolation (vocational) stress, and subjective vocational disability. The questionnaire was administered to a convenience sample of 426 patients undergoing inpatient cardiac rehabilitation. Results on the psychometric properties, a comparison of the cardiac sample to the general population, as well as distributions of quartile ranges are reported. Also, a preliminary appraisal of the need for further assessment or treatment is made. The results confirm that the short test battery is suited for assessing psychological and social problems in cardiac rehabilitation patients.

Energy expenditure during gait using the walkabout and isocentric reciprocal gait orthoses in persons with paraplegia.

OBJECTIVE: To compare the energy expenditure during walking using the Walkabout Orthosis (WO) and the Isocentric Reciprocal Gait Orthosis (IRGO) in persons with paraplegia. DESIGN: A randomized cross-over design. PATIENTS: Ten individuals with complete T9-12 paraplegia. INTERVENTIONS: Subjects were trained to walk using the WO and the IRGO with elbow crutches. MAIN OUTCOME MEASURES: Subjects' energy expenditures during walking using each orthosis over three different terrains--flat tile, flat carpet, and 4 degrees uphill ramp--were compared. Data collected included expired ventilation (L/min), heart rate (beats/ min), speed of walking (m/min), oxygen uptake (VO2; L/min and mL/kg/min), oxygen cost (O2 cost; mL/kg/m), and Physical Cost Index (PCI; beats/m). Subjects walked at a self-selected pace. RESULTS: Subjects walked significantly slower with the WO than with the IRGO, regardless of the surface (p < .05). The average speed of walking ranged from 5.2+/-1.3 for the WO on the tiled surface to 11.5+/-2.3m/min for the IRGO on the carpeted surface. Despite marked differences in self-selected walking speeds between the two orthoses, there were no differences in either heart rate or VO2 among orthoses or surfaces. However, the O2 cost of gait was significantly greater for the WO (range, 3.95 to 4.91mL/kg/m) compared with the IRGO (range, 1.6 to 1.8mL/kg/m). Likewise, the PCI was significantly greater using the WO (range, 8.4 to 10.3beats/m) than the IRGO (range, 4.3 to 7.0beats/m). CONCLUSIONS: This study shows that the metabolic demands of walking with the WO are greater than walking with the IRGO in individuals with T9-12 paraplegia.

Diabetes care needs of Hispanic patients treated at inner-city neighborhood clinics in New York City.

The charts of 254 Hispanic patients were selected from a sample of 321 patients with diabetes in four urban clinics that received federal funding to provide medical care in underserved communities. A standardized chart-audit protocol was used to assess the process of healthcare delivery and the presence of diabetes-associated comorbidities and complications in patients. Inconsistent recognition of obesity (11% identified vs 59% present), hyperlipidemia (17% identified vs 69% present), and renal dysfunction (3.5% identified vs 16% present) was evident on chart review. We also found inadequate compliance with current recommendations for diabetes care with respect to routine health screenings for diabetes-related complications, recognition of comorbid diagnoses, and referral of patients for recommended specialty consultations. Issues specific to the varied Hispanic populations may need to be considered to improve the delivery of diabetes care for the growing Hispanic population with diabetes.

Assessment of documented foot examinations for patients with diabetes in inner-city primary care clinics.

BACKGROUND: The established guidelines for a diabetes foot examination include assessing circulatory, skin, and neurological status to detect problems early and reduce the likelihood of amputation. OBJECTIVE: To determine documented adherence with guidelines for foot examinations. SETTING: Four clinics in underserved areas. METHODS: Charts of 350 diabetic patients, identified by billing code, were reviewed for foot examination documentation. A documented foot examination was defined as assessing at least two of the three components of a foot examination. The review determined the periodicity and prevalence of foot examinations, referrals to a podiatrist or vascular surgeon during a 2-year period, and risk factors for foot complications. Stepwise logistic regression was used to determine whether risk factors for foot complications predicted foot examination status. RESULTS: The patients had a mean age and duration of diabetes of 57.7 and 8.8 years, respectively; 86% were black or Hispanic. There was no indication of foot examination or referral for 55.7% of the patients during the 2-year period. Patients with foot care referrals were more likely to have foot examinations by their primary care providers (P = .0001). There was almost a fourfold increase in the odds that patients with diagnosed peripheral vascular disease had foot examinations, with twofold greater odds for each 25-year increase in age. CONCLUSIONS: Populations at risk of diabetic complications are unlikely to have foot examinations in their primary medical care, but having peripheral vascular disease increases the likelihood. Efforts are needed to improve adherence to foot examination guidelines for patients with diabetes from underserved populations.

Community activism relating to a cluster of breast cancer.

In 1985, residents of a suburban community in South Florida became concerned when several young women were diagnosed with breast cancer. First as individuals, then through a community-based effort, they attempted to gain attention and action on what they believed to be a cluster of breast cancer. Through their efforts to find out whether some agent or toxic exposure existed in the community that might have caused breast cancer, the women formed a community-based organization. This paper describes the activism of the women to resolve the issue through an epidemiologic study of the breast cancer occurrence in their community. Furthermore, it substantiates the need and role of rational community response in resolving community threats and concerns.