Introduction There is still an ongoing discussion whether a prophylactic or a preemptive therapy against cytomegalovirus (CMV) is superior to reduce the incidence of CMV viremia, acute rejections (AR) and cardiac allograft vasculopathy (CAV) in the long-term after heart transplantation (HTx). Thus, in this study we evaluated different CMV treatmnent strategies in this setting. Materials and Methods In this retrospective study we included 56 patients, who got a HTx between 1st of January 2010 and 31st of July 2016 at our center. Excluded were all patients who died within the first 90 days or who had a loss to follow-up in the first year after HTx. Study end points were the CMV-free survival viremia, AR, CAV and death. The patients were followed up for an average of 4.15 years (355 days up to 7.5 years). Patients were classified into 3 groups according to their received CMV-protocol: preemptive therapy (n=19), prophylactic mono drug therapy (either valganciclovir for average of 110 days or early single dose of 100mg/kg/BW of cytomegaly virus immunoglobulin, CMVIG, within the first two weeks post-HTx, n=18) or prophylactic double drug therapy (valganciclovir for 3 months plus early single dose of CMVIG, n=19). For statistical analysis X2, X2-log-rank and T-Tests were used. Results and Discussion Overall seven patients of our study cohort died (unknown cause n=2, AR n=3, and sepsis n=2). The median patient survival post-HTx was not significant different among the study groups: preemptive group 2243 days, prophylactic monotherapy 2417 days, and prophylactic double therapy 2410 days, respectively (p=0.73). However, the median CMV-viremia free survival was different among the groups: 1817 days in the prophylactic double group, 1459 days in the prophylactic mono group and 1482 in the preemptive group (p=0.52). Especially, in a subanalysis patients with a high risk for CMV infection (donor positive and recipient negative CMV status, n=13) the CMV-free survival was significantly higher when patients received double prophylaxis therapy compared to the other two groups (p<0.01). Whether the incidence of AR nor of CAV was not significantly influenced by the choice of CMV treatment regimen (p=0.87 and p=0.215, respectively). Overall in 15 patients the antiviral medication was discontinuated due to side effects such as leukopenia, preemptive group 10.5%, prophylactic monogroup 38.9%, and prophylactic double group 31.6%, respectively. Conclusion Our study results suggest that early therapy with CMVIG as adjunct to antiviral treatment could prolong CMV-free survival in patients with high risk of CMV infection. If a repetitive CMVIG dosing post-HTx will further reduce CMV infection needs to be explored in the future.

BACKGROUND:Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus with significant clinical sequelae that can affect a patient's quality of life. Metabolic and microvascular factors are responsible for nerve damage, causing loss of nerve function, numbness, painful sensory symptoms, and muscle weakness. Therapy is limited to anti-convulsant or anti-depressant drugs for neuropathic pain and paresthesia. However, reduced sensation, balance and gait problems are insufficiently covered by this treatment. Previous data suggests that acupuncture, which has been in use in Traditional Chinese Medicine for many years, may potentially complement the treatment options for peripheral neuropathy. Nevertheless, more objective data on clinical outcome is necessary to generally recommend acupuncture to the public.METHODS:We developed a study design for a prospective, randomized (RCT), placebo-controlled, partially double-blinded trial for investigating the effect of acupuncture on DPN as determined by nerve conduction studies (NCS) with the sural sensory nerve action potential amplitude as the primary outcome. The sural sensory nerve conduction velocity, tibial motor nerve action potential amplitude, tibial motor nerve conduction velocity, the neuropathy deficit score, neuropathy symptom score, and numeric rating scale questionnaires are defined as secondary outcomes. One hundred and eighty patients with type 2 diabetes mellitus will be randomized into three groups (needle acupuncture, verum laser acupuncture, and placebo laser acupuncture). We hypothesize that needle and laser acupuncture have beneficial effects on electrophysiological parameters and clinical and subjective symptoms in relation to DPN in comparison with placebo.DISCUSSION:The ACUDIN trial aims at investigating whether classical needle acupuncture and/or laser acupuncture are efficacious in the treatment of DPN. For the purpose of an objective parameter, NCS were chosen as outcome measures. Acupuncture treatment may potentially improve patients' quality of life and reduce the socio-economic burden caused by DPN.TRIAL REGISTRATION:German Clinical Trial Register (DRKS), No. DRKS00008562 , trial search portal of the WHO ( http://apps.who.int/trialsearch/ ).

Background Do the current swallow-specific subquestions of neurological diagnostic tools reflect the objective swallowing function in Parkinson's disease (PD) patients or are clinical factors superior to predict critical aspiration? Methods In a cross-sectional, observational study a total of 119 Parkinson outpatients were examined clinically and by flexible-endoscopic evaluation of swallowing (FEES). Self-reported dysphagia by subquestions of the MDS-UPDRS and NMS questionnaire and history of subjective aspiration signs were collected. Key Results Nearly, all PD patients showed deglutition abnormalities in FEES (113/119) while only 12%-27% of them reported swallowing problems in the swallow-specific subquestions of neurological standard diagnostic tools (MDS-UPDRS and NMS-Quest), and the answers were heterogeneous and poorly reproducible. With a sensitivity of up to a maximum of 50%, self-reported dysphagia is therefore no reliable tool for identifying dysphagia in PD. While most clinical parameters were linked to dysphagia to some extent, logistic regression analysis revealed high age (Odds Ratio (OR) 1.1 in years, 95% CI 1.03-1.18, P < 0.01), gender (OR 0.3 for females, 95% CI 0.08-0.97, P = 0.04), and affirmed subjective aspiration signs (OR 8.6, 95% CI 3.05-26.52, P < 0.001) as the most significant predictors for critical dysphagia. Conclusions and Inferences Self-perception of swallowing is no reliable tool for identifying dysphagia and questionnaires are insufficient for detecting previous aspiration. Consequent and specific asking for previous subjective aspiration signs is the single most important measure for identifying PD patients at risk for critical aspiration.

To assess the prevalence of dysphagia and its typical findings in unselected “real-world” Parkinson patients using an objective gold-standard method. This was a prospective, controlled, cross-sectional study conducted in 119 consecutive Parkinson patients of all stages independent of subjective dysphagia. Patients and 32 controls were clinically and endoscopically examined by flexible endoscopic evaluation of swallowing (FEES) to evaluate the deglutition with regard to three consistencies (water, biscuit, and bread). Typical findings of dysphagia like penetration and aspiration, residues, and leakage were assessed. Dysphagia was common in Parkinson patients and occurred in all, even early, disease stages. Only 5% (6/119) of patients showed a completely unremarkable deglutition. Aspiration was seen in 25% (30/119) of patients and always related to water. Residues occurred in 93% (111/119), most commonly for bread. Leakage was much less frequent and was found in only 3–18%, depending on consistency. In a significant fraction of patients, objective dysphagia was not subjectively perceived. A total of 16% of asymptomatic patients suffered from critical aspiration. Significant swallowing deficiencies already occurred in early disease. Aspiration was found in 4 of 20 (20%) patients with disease duration of less than 2 years. Seven of 57 patients (12%) with Hoehn and Yahr stage 2 suffered from severe aspiration. Given the high frequency of critical aspiration in Parkinson disease, these patients should be evaluated early for dysphagia to avoid complications and recommend an adequate therapy. FEES is a simple, cost efficient, minimally invasive method that is ideally suited for this purpose.

Objective Primary adhesive capsulitis (AC), or frozen shoulder, is an insidious and idiopathic disease. Severe pain is predominant in the first two of the three stages of the condition, which can last up to 21 months. Design, Setting, and Subjects Sixty volunteers with primary AC were randomly assigned to acupuncture with press tack needles compared with press tack placebos in a patient- and observer-blinded placebo-controlled study. The participants were subsequently offered classical needle acupuncture in an open follow-up clinical application. Thirty-four volunteers received conservative therapy, including 10 classical needle acupuncture treatments over 10 weeks, 13 volunteers received conservative therapy without classical needle acupuncture. All subjects agreed to follow-up after one year. Methods Acupuncture treatment was performed using a specific distal needling concept, using reflex areas on distant extremities avoiding local treatment. Results An immediate improvement of 3.3 ± 3.2 points in Constant-Murley Shoulder Score (CMS) pain subscore was seen in the press tack needles group and of 1.6 ± 2.8 points in the press tack placebos group (P <0.02). Conservative therapy including classical needle acupuncture significantly improved the pain subscore within 14.9 ± 15.9 weeks compared with 30.9 ± 15.8 weeks with only conservative therapy (P < 0.001). Conclusion The efficiency of distal needling acupuncture on immediate pain reduction was demonstrated in patients with AC and confirmed the applicability of press tack needles and press tack placebos for double-blind studies in acupuncture. Subsequent clinical application observation proved that results obtained with press tack needles/press tack placebos can be transferred to classical needle acupuncture. Integrating acupuncture with conservative therapy showed superior effectiveness with respect to the time course of the recovery process in AC compared with conservative therapy alone.

Spinal cord or cauda equina compression (SCC) is an increasing challenge in clinical oncology due to a higher prevalence of long-term cancer survivors. Our aim was to determine the clinical relevance of SCC regarding patient outcome depending on different tumor entities and their anatomical localization (extradural/intradural/intramedullary). We retrospectively analyzed 230 patients surgically treated for SCC. Preoperative status for pain and neurological impairment were correlated to the degree of compression, tumor location, and early as well as short-term follow-up outcome parameters. Interestingly, we did not observe any differences between intradural-extramedullary compared to extradural tumors. Unilaterally localized tumors were likely to present with pain (72.9 %, p < 0.01), whereas concentric growth was associated with motor deficits (41.0 %, p < 0.01, as primary symptom, 49.3 % on admission, p < 0.05). In concentric tumors, the pain pattern was diffuse (40.5 % vs. 17.5 in unilateral disease, p < 0.01), whereas unilateral tumors resulted in localized pain (61.4 % local axial or radicular, p < 0.01). Diffuse pain, patients without a sensory or motor deficit, progressive disease, cervical localization, and a higher degree of stenosis were identified as beneficial for an early improvement in pain (p < 0.05). Notably, 29 % of patients with unchanged pain and 30.8 % with unchanged neurologic function at day 7 postoperative improved during follow-up (p < 0.001). Our data demonstrate that the preoperative tumor anatomy in patients with SCC was closely related to their presenting symptoms and early clinical outcome. The detailed analysis elucidates the biology of SCC and might thereby aid in determining which patients will benefit from surgery.

The underlying ethos of dbGaP is that access to these data by secondary data analysts facilitates advancement of science. NIH has required that genome-wide association study data be deposited in the Database of Genotypes and Phenotypes (dbGaP) since 2003. In 2013, a proposed updated policy extended this requirement to next-generation sequencing data. However, recent literature and anecdotal reports suggest lingering logistical and ethical concerns about subject identifiability, informed consent, publication embargo enforcement, and difficulty in accessing dbGaP data. We surveyed the International Genetic Epidemiology Society (IGES) membership about their experiences. One hundred and seventy five (175) individuals completed the survey, a response rate of 27%. Of respondents who received data from dbGaP (43%), only 32% perceived the application process as easy but most (75%) received data within five months. Remaining challenges include difficulty in identifying an institutional signing official and an overlong application process. Only 24% of respondents had contributed data to dbGaP. Of these, 31% reported local IRB restrictions on data release; an additional 15% had to reconsent study participants before depositing data. The majority of respondents (56%) disagreed that the publication embargo period was sufficient. In response, we recommend longer embargo periods and use of varied data-sharing models rather than a one-size-fits-all approach.

SUMMARY PedMerge allows users to accurately and efficiently merge separately ascertained pedigrees that belong to the same extended family. In addition to validation checks of pedigree structure, the software provides files in LINKAGE or PEDSYS format that easily allow to be used by a variety of genetic statistical software packages including LINKAGE, SOLAR, SLINK or can be further manipulated with Mega2. AVAILABILITY http://sites.google.com/site/rosemarieplaetke/home/s/pedmerge

Adiponectin, a protein secreted by adipose tissue, has antiatherogenic, anti-inflammatory, and insulin-sensitizing actions. We examined the relationship between plasma adiponectin and adiposity, insulin resistance, plasma lipids, glucose, leptin, and anthropometric measurements in 316 adult men and 353 adult women Yup'ik Eskimos in Southwest Alaska. Adiponectin concentration was negatively associated with body mass index, percentage of body fat, sum of skin folds, waist circumference, triglycerides, insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR]), fasting insulin, and leptin in both men and women, and also with glucose in women. Adiponectin concentration correlated positively with high-density lipoprotein cholesterol concentration, and also with low-density lipoprotein cholesterol in women. Insulin-sensitive individuals (HOMA-IR <3.52, n = 442) had higher plasma adiponectin concentrations than more insulin-resistant individuals (HOMA-IR ≥3.52, n = 224): 11.02 ± 0.27 μg/mL vs 8.26 ± 0.32 μg/mL, P < .001. Adiponectin concentrations did not differ between groups of participants with low and high level of risk for developing coronary heart disease. No difference in plasma adiponectin levels was found among Yup'ik Eskimos and whites matched for sex, age, and body mass index. In conclusion, circulating adiponectin concentrations were most strongly associated with sum of skin folds in Yup'ik men and with high-density lipoprotein cholesterol levels, sum of skin folds, waist circumference, and insulin and triglycerides concentrations in Yup'ik women.

Objective: This study investigated the prevalence of metabolic syndrome and its defining components among Yup'ik Eskimos.Research Methods and Procedures: A cross-sectional study design that included 7 10 adult Yup'ik Eskimos >= 18 years of age residing in 8 communities in Southwest Alaska. The prevalence of metabolic syndrome was determined using the recently updated Adult Treatment Panel III criteria.Results: The prevalence of metabolic syndrome in this study cohort was 14.7%, and varied by sex with 8.6% of the men and 19.8% of the women having metabolic syndrome. This is lower than the prevalence of 23.9% in the general U.S. adult population. The most common metabolic syndrome components/risk factors were increased waist circumference and elevated blood glucose. High-density lipoprotein (HDL) cholesterol levels in Yup'ik Eskimos were significantly higher, and triglycerides lower than levels re- ported in National Health and Nutritional Examination III.Discussion: Compared with other populations, metabolic syndrome is relatively uncommon in Yup'ik Eskimos. The higher prevalence among Yup'ik women is primarily explained by their large waist circumference, suggesting central body fat accumulation. Further increases in metabolic syndrome risk factors among Yup'ik Eskimos could lead to increases in the prevalence of type 2 diabetes and cardiovascular disease, once rare in this population.

Objectives. To describe the background, approach and general results of the Center for Alaska Native Health Research (CANHR) study.Study Design. This was a cross-sectional Community-Based Participatory Research (CBPR) study with one tribal group to assess risk and protection for obesity and the risk factors related to chronic disease, diabetes and cardiovascular disease.Methods. A combination of biological, genetic, nutritional and psychosocial measurements were taken on 922 Alaska Native participants in ten communities in Southwestern Alaska. The paper reports on data from 753 adult participants.Results. The prevalence of type 2 diabetes is 3.3% in the sample population. Metabolic syndrome is significantly lower among the males and equal for females when compared with Caucasians in the NHANES III sample. Obesity among adults is now at the national average. Risk factors for chronic disease include a shift to a Westernized diet, stress, obesity and impaired fasting glucose and protective factors include high levels of polyunsaturated fatty acid dietary intake. Articles in this issue present specific results in these areas.Conclusions. The data strongly indicate that, in general, Yup`ik people in our study are metabolically healthy and that diet and life style provide a delicate combination of protective and risk factors. The results strongly indicate that solution focused research utilizing primary and secondary prevention strategies may provide evidence for how to intervene to prevent further increases of chronic diseases. Research that focuses on relating the intrinsic strengths of indigenous worldviews and practices with basic research may contribute to positive transformations in community health. The Center for Alaska Native Health Research Study: a community-based participatory research study of obesity and chronic disease-related protective and risk factors. Mohatt GV, Plaetke R, Klejka J, Luick B, Lardon C, Bersamin A, Hopkins S, Dondanville M, Herron J, Boyer B ABSTRACT [full text] back to issue 66(1)] OBJECTIVES: To describe the background, approach and general results of the Center for Alaska Native Health Research (CANHR) study.Study Design. This was a cross-sectional Community-Based Participatory Research (CBPR) study with one tribal group to assess risk and protection for obesity and the risk factors related to chronic disease, diabetes and cardiovascular disease.Methods. A combination of biological, genetic, nutritional and psychosocial measurements were taken on 922 Alaska Native participants in ten communities in Southwestern Alaska. The paper reports on data from 753 adult participants.Results. The prevalence of type 2 diabetes is 3.3% in the sample population. Metabolic syndrome is significantly lower among the males and equal for females when compared with Caucasians in the NHANES III sample. Obesity among adults is now at the national average. Risk factors for chronic disease include a shift to a Westernized diet, stress, obesity and impaired fasting glucose and protective factors include high levels of polyunsaturated fatty acid dietary intake. Articles in this issue present specific results in these areas.Conclusions. The data strongly indicate that, in general, Yup`ik people in our study are metabolically healthy and that diet and life style provide a delicate combination of protective and risk factors. The results strongly indicate that solution focused research utilizing primary and secondary prevention strategies may provide evidence for how to intervene to prevent further increases of chronic diseases. Research that focuses on relating the intrinsic strengths of indigenous worldviews and practices with basic research may contribute to positive transformations in community health.

The Center for Alaska Native Health Research (CANHR) is a community-based participatory research project aimed at understanding current risk factors for obesity, diabetes, and cardiovascular disease in Alaska Natives living in Southwest Alaska. We utilize a multidisciplinary approach that includes assessment of genetic, nutritional and behavioral risk factors and their interrelationships with one another in the overall development of disease. The design of the CANHR project involved community participation in the development, implementation and interpretation of research results. We have developed a participatory research program that is designed to be culturally appropriate, relevant to community needs and interests, and respectful to our participants. This manuscript describes the organizational development of our CANHR study and the procedures employed in its progression to date.

This study tested the effectiveness of 2 dissemination methods for the Positively Aging (R) teaching materials. In San Antonio, Texas, 4 middle schools participated in a 3-year controlled trial of dissemination via distance electronic support alone (control) compared to distance electronic support plus in-school support from study staff (intervention). Web site and classroom utilization of lessons were tracked. The results demonstrated that in-school staff support was necessary to disseminate these materials. Potential dissemination barriers included competition for instructional time with other curricula, teacher variability in teacher computer use, teacher and student turnover, and the effects of mandatory testing on the educational process.