The combination therapy with alfacalcidol and risedronate improves the mechanical property in lumbar spine by affecting the material properties in an ovariectomized rat model of osteoporosis

Background

The to date evidence for a dose-response relationship between physical workload and the development of lumbar disc diseases is limited. We therefore investigated the possible etiologic relevance of cumulative occupational lumbar load to lumbar disc diseases in a multi-center case-control study.

Methods

In four study regions in Germany (Frankfurt/Main, Freiburg, Halle/Saale, Regensburg), patients seeking medical care for pain associated with clinically and radiologically verified lumbar disc herniation (286 males, 278 females) or symptomatic lumbar disc narrowing (145 males, 206 females) were prospectively recruited. Population control subjects (453 males and 448 females) were drawn from the regional population registers. Cases and control subjects were between 25 and 70 years of age. In a structured personal interview, a complete occupational history was elicited to identify subjects with certain minimum workloads. On the basis of job task-specific supplementary surveys performed by technical experts, the situational lumbar load represented by the compressive force at the lumbosacral disc was determined via biomechanical model calculations for any working situation with object handling and load-intensive postures during the total working life. For this analysis, all manual handling of objects of about 5 kilograms or more and postures with trunk inclination of 20 degrees or more are included in the calculation of cumulative lumbar load. Confounder selection was based on biologic plausibility and on the change-in-estimate criterion. Odds ratios (OR) and 95% confidence intervals (CI) were calculated separately for men and women using unconditional logistic regression analysis, adjusted for age, region, and unemployment as major life event (in males) or psychosocial strain at work (in females), respectively. To further elucidate the contribution of past physical workload to the development of lumbar disc diseases, we performed lag-time analyses.

Results

We found a positive dose-response relationship between cumulative occupational lumbar load and lumbar disc herniation as well as lumbar disc narrowing among men and women. Even past lumbar load seems to contribute to the risk of lumbar disc disease.

Conclusion

According to our study, cumulative physical workload is related to lumbar disc diseases among men and women.     

Use of antipsychotics in elderly patients with dementia: Do atypical and conventional agents have a similar safety profile?

Pharmacological treatment of dementia addresses two main clinical features of the disease: cognitive deterioration with predominantly memory loss and behavioural and psychological symptoms (BPSD). While cholinesterase inhibitors are recommended in an attempt to delay memory loss and disability, what should be considered the most appropriate pharmacological treatment for BPSD has remained questionable. Antipsychotic medications, conventional and atypical agents, have been increasingly utilized in clinical practice but only a small number of clinical studies have investigated their relative cost–benefit ratio. This review focuses on the safety of atypical and conventional antipsychotics when used in patients with BPSD. Overall, atypical and conventional antipsychotics are associated with a similarly increased risk for all-cause mortality and cerebrovascular events. Relative to atypical agents users, patients being treated with conventional antipsychotics have an increased incidence of cardiac arrhythmias and extrapyramidal symptoms. Conversely, users of atypical antipsychotics are exposed to an increased risk of venous thromboembolism and aspiration pneumonia. Also, metabolic effects (i.e. increased risk of diabetes, weight gain) have consistently been documented in clinical studies with atypical antipsychotics, although this effect tends to be attenuated with advancing age and in elderly patients with dementia. Antipsychotics, both conventional and atypical, should be used with caution only when nonpharmacologic approaches have failed to adequately control BPSD. More effective interventions are necessary to improve postmarket drug safety in vulnerable populations.     

Reliability and item content of the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT): Parts 1–3

The success of early intervention programs has in large part spurred increasing emphasis on identifying children with autism and Pervasive Developmental Disorder-Not Otherwise Specified (PDD-NOS) at the earliest possible ages. National and international professional groups have called for early screening and diagnosis, yet the technology to effectively meet these goals are insufficient. The Checklist for Autism in Toddlers (CHAT) and its variants is the only scale with acceptable psychometrics at present, but measures autism only. In this paper we describe a new measure, the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT), which is geared toward identifying young children with autism and PDD-NOS, and which also assesses for comorbid psychopathology and challenging behaviors. This initial study describes item selection and reliability for all three parts of the measure, which were individually administered to the parents of 276 children ages 17–37 months identified as at risk for developmental and/or physical disabilities.     

Occupational exposure to polycyclic aromatic hydrocarbons and DNA damage by industry: a nationwide study in Germany

Exposure to polycyclic aromatic hydrocarbons (PAH) and DNA damage were analyzed in coke oven (n = 37), refractory (n = 96), graphite electrode (n = 26), and converter workers (n = 12), whereas construction workers (n = 48) served as referents. PAH exposure was assessed by personal air sampling during shift and biological monitoring in urine post shift (1-hydroxypyrene, 1-OHP and 1-, 2 + 9-, 3-, 4-hydroxyphenanthrenes, ΣOHPHE). DNA damage was measured by 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and DNA strand breaks in blood post shift. Median 1-OHP and ΣOHPHE were highest in converter workers (13.5 and 37.2 μg/g crea). The industrial setting contributed to the metabolite concentrations rather than the air-borne concentration alone. Other routes of uptake, probably dermal, influenced associations between air-borne concentrations and levels of PAH metabolites in urine making biomonitoring results preferred parameters to assess exposure to PAH. DNA damage in terms of 8-oxo-dGuo and DNA strand breaks was higher in exposed workers compared to referents ranking highest for graphite-electrode production. The type of industry contributed to genotoxic DNA damage and DNA damage was not unequivocally associated to PAH on the individual level most likely due to potential contributions of co-exposures.     

Association between childhood adversity and a diagnosis of personality disorder in young adulthood: a cohort study of 107,287 individuals in Stockholm County

Childhood adversity (CA) may increase the risk for later developing of personality disorder (PD). However, less is known about the association between cumulative CA and PD, and the role of childhood psychopathology and school performance. The current study examined the relationship between a range of CAs and a diagnosis of PD in young adulthood, and the roles of childhood psychopathology and school performance in this relationship. All individuals born in Stockholm County 1987–1991 (n = 107,287) constituted our cohort. Seven CAs were measured between birth and age 14: familial death, parental criminality, parental substance abuse and psychiatric morbidity, parental separation and/or single-parent household, household public assistance and residential instability. Individuals were followed from their 18th birthday until they were diagnosed with PD or until end of follow-up (December 31st 2011). Adjusted estimates of risk of PD were calculated as hazard ratios (HR) with 95% confidence intervals (CI). Associations were observed between cumulative CA and PD. During the follow-up 770 individuals (0.7%) were diagnosed with PD. Individuals exposed to 3+ CAs had the highest risks of being diagnosed with PD (HR 3.0, 95% CI 2.4–3.7). Childhood psychopathology and low school grades further increased the risk of PD among individuals exposed to CA. Cumulative CA is strongly associated with a diagnosis of PD in young adulthood. Our findings indicate that special attention should be given in schools and health services to children exposed to adversities to prevent decline in school performance, and to detect vulnerable individuals that may be on negative life-course trajectories.     

Diffuse (anergic) cutaneous leishmaniasis responding to amphotericin B

American cutaneous leishmaniasis is an important endemic zoonotic disease in the New World that comprises a spectrum of clinical manifestations. Diffuse cutaneous leishmaniasis (DCL) is a rare form of the disease characterized by antigen‐specific immunodeficiency that often presents with multiple disfiguring non‐ulcerated confluent nodules or plaques that involve large areas of the skin, resembling lepromatous leprosy. Relapse is invariable in advanced stages, despite aggressive chemotherapy, and a plethora of drugs has been tested with unchanging results. We report on a severe an exceptional case that resolved after treatment with amphotericin B, a drug considered only mildly effective, and discuss the therapeutic approach to this disease.     

Natural course of treated and untreated chronic HCV infection: results of the nationwide Hepnet.Greece cohort study

Background  Interferon (IFN-α)-based regimens have been used with varying success in the treatment of chronic hepatitis C (CHC) for over two decades. The effect of such treatments on the natural course of CHC has been evaluated in small clinical trials with conflicting results.
Aim  To investigate the natural course of IFNα-based -treated and untreated patients with CHC by analysing data from the HEPNET.GREECE study.
Methods  We retrospectively analysed 1738 patients from 25 Greek Centres (median age 40.1; males 57.6%; cirrhosis 9.2%), 734 untreated and 993 treated with IFNα-based regimens [44.7% sustained viral response (SVR)], followed-up for median 25.2 and 46.8 months, respectively.
Results During follow-up, 48 patients developed liver decompensation and 24 HCC. Older age was significantly related to disease progression (HR = 2.6 per 10 years of increasing age). Stratified by baseline cirrhosis, Cox analysis showed that patients with SVR, but not without SVR, had significantly lower hazard for events compared with nontreated patients (HR = 0.16; P  < 0.001), whereas the detrimental effect of older age remained highly significant. Separate group analysis demonstrated that in cirrhosis, the beneficial effect of treatment was evident even without SVR. Treatment effect interacted significantly with age, indicating that older patients, mainly noncirrhotic, gained the most benefit.
Conclusions IFNα-based treatment does alter the natural course of CHC. A protective effect is mostly present in patients with SVR, but older patients, at higher risk of events, gain the greatest benefit. In established cirrhosis, treatment carries a protective effect even among those without SVR.