Alfried Krupp von Bohlen und Halbach Foundation

The objective of this systematic review is to analyse the relative risk reduction on medication error and adverse drug events (ADE) by computerized physician order entry systems (CPOE). We included controlled field studies and pretest-posttest studies, evaluating all types of CPOE systems, drugs and clinical settings. We present the results in evidence tables, calculate the risk ratio with 95% confidence interval and perform subgroup analyses for categorical factors, such as the level of care, patient group, type of drug, type of system, functionality of the system, comparison group type, study design, and the method for detecting errors. Of the 25 studies that analysed the effects on the medication error rate, 23 showed a significant relative risk reduction of 13% to 99%. Six of the nine studies that analysed the effects on potential ADEs showed a significant relative risk reduction of 35% to 98%. Four of the seven studies that analysed the effect on ADEs showed a significant relative risk reduction of 30% to 84%. Reporting quality and study quality was often insufficient to exclude major sources of bias. Studies on home-grown systems, studies comparing electronic prescribing to handwriting prescribing, and studies using manual chart review to detect errors seem to show a higher relative risk reduction than other studies. Concluding, it seems that electronic prescribing can reduce the risk for medication errors and ADE. However, studies differ substantially in their setting, design, quality, and results. To further improve the evidence-base of health informatics, more randomized controlled trials (RCTs) are needed, especially to cover a wider range of clinical and geographic settings. In addition, reporting quality of health informatics evaluation studies has to be substantially improved.

Measurement of health care costs is a crucial task in health economic evaluation. Various guidelines with different amount of details have been set up for costing methods in economic evaluation which, however, do not precisely stipulate how to value resource consumption. In this article we present a proposal for the standardisation of the monetary valuation of health care utilisation occurring in the follow up period after the actual intervention to be evaluated. From a societal perspective the primary direct and indirect cost components are considered, such as outpatient medical care, pharmaceuticals, non-physician health services, inpatient care, days of sick leave and early retirement due to sickness. The standard costs are based on administrative charges and rates or on official statistics. They are based on the most current data sources which are mainly from 2002 and 2003. This system of standard costs aims at an average valuation of resource consumption. This makes for the comparability of different health economic studies. Most standard costs are not based on market prices but on administratively specified charges and rates. This implies that institutional changes which are quite common in the health care system, may also affect the valuation rates, for example the introduction of DRGs. This should be taken into account when updating the system of standard costs.

BACKGROUND AND PURPOSE: We describe the clinical, diagnostic, and outcome features of a cohort of white patients with idiopathic moyamoya disease treated in a German institution. METHODS: Our cohort included 21 white patients with moyamoya disease. Clinical and diagnostic features were obtained by retrospective chart review; follow-up information and outcome were obtained prospectively. We used the Kaplan-Meier methods to estimate stroke risk by treatment status. RESULTS: The mean age at onset of symptoms was 31 years. The female predominance was 4.25:1. In our cohort, the initial symptom was a cerebral ischemic event in all patients. There was no patient with a hemorrhage at onset; only one patient experienced subarachnoidal hemorrhage in the further course of disease. The Kaplan-Meier risk for recurrent stroke was very high after the first ischemic event and smaller after angiographic diagnosis. The 5-year-Kaplan-Meier risk of recurrent stroke was 80.95% after the first ischemic event for all patients. Most subsequent ischemic events appeared in the first 2 years after symptom onset. Eleven patients (52.3%) underwent neurosurgical revascularizing procedures. After surgery, the Kaplan-Meier risk of perioperative or subsequent stroke was 27.27% within the first month and was stable thereafter. CONCLUSIONS: Clinical features and course of moyamoya disease of whites analyzed in this German study are comparable to American results. Moyamoya disease in whites differs clearly from Asian moyamoya disease in timing of onset of vasculopathy and lower rate of hemorrhages.

BACKGROUND: Programmed cell death 4 (Pdcd4) inhibits malignant transformation, and initial studies of Pdcd4 suggested the regulation of Pdcd4 localization by protein kinase B (Akt). However, supporting patient tissue data are missing, and the diagnostic/prognostic potential of Pdcd4 rarely has been studied. The objectives of the current were 1) to determine Pdcd4 as a diagnostic marker in the adenoma-carcinoma sequence, 2) to support phosphorylated Akt (pAkt)-mediated Pdcd4 regulation in vivo, and 3) to obtain the first prognostic evidence of Pdcd4 in colorectal cancer. METHODS: Tumor samples and normal tissues from 71 patients with colorectal cancer who were followed prospectively (median follow-up, 36 months) and 42 adenomas were analyzed for Pdcd4, Akt, and pAkt in immunohistochemical and Western blot analyses. RESULTS: A significant reduction in Pdcd4 was observed between normal mucosa and adenomas and between adenomas and tumor samples (P < .01 and P < .01, respectively). Normal mucosa demonstrated strong nuclear Pdcd4, which was reduced significantly in adenomas (P < .01) and almost was lost in tumors (P < .01). pAkt was correlated inversely with Pdcd4 and with the transition of Pdcd4 from nucleus to cytoplasm (P < .01). Kaplan-Meier analysis (using the Mantel-Cox log-rank test) indicated a significant correlation between the loss of total and nuclear Pdcd4 in tumors and overall survival (P < .05 and P < .02, respectively) and disease-specific survival (P < .01 and P < .01, respectively). In multivariate analysis, loss of total or nuclear Pdcd4 was an independent predictor of disease-specific or overall survival. CONCLUSIONS: To the authors' knowledge, this is the first study to demonstrate an independent prognostic impact of Pdcd4 and its expression pattern in colorectal cancer. Data from this study support the regulation of Pdcd4 localization by pAkt in vivo. Pdcd4 immunohistochemistry may be useful as a supportive diagnostic tool for the transition between normal, adenoma, and tumor tissues.

This contribution addresses the following questions: Does unilateral sports-specific strain affect the skeletal system of the athlete? Specifically, can any differences be found in longitudinal growth of the bones of the forearm and hand in professional tennis players between the stroke arm and the contralateral arm? An investigation was conducted involving 20 high-ranking professional tennis players (12 male and eight female players) between 13 and 26 years of age as well as 12 controls of the same age range. The radiologic examinations of the bones of the forearm and hand yielded an increase in density of bone substance and bone diameter as well as length in the stroke arm as compared with the contralateral arm. Whereas the first results confirm previous findings, the stimulation of longitudinal growth has never been reported. This change in bone structure and size can be attributed to two factors: mechanical stimulation and hyperemia of the constantly strained extremity. It may thus be regarded as a biopositive adaptation process.

BACKGROUND AND PURPOSE: Cerebral emboli can be identified by the presence of typical microembolic signals (MES) in transcranial Doppler (TCD) spectral curves. The usefulness of this technique was studied by evaluating the prevalence and time course of MES in patients with acute stroke. In addition, we examined the influence of anticoagulation therapy on the occurrence of MES. Another study objective was to identify the value of MES in elucidation of the underlying pathology of cerebral ischemia in patients with acute stroke. METHODS: We used bilateral TCD monitoring of the middle cerebral artery to search for microemboli in 100 patients with acute nonhemorrhagic stroke in the anterior circulation. Monitoring time was for 30 minutes at admission (examination I), after 24 hours (examination II), and again after 48 hours (examination III). RESULTS: Twenty-two of the 100 patients had to be excluded from the study after examination 1 because retrospectively they did not fulfill the inclusion criterion or because they had an insufficient bone window. Forty of the patients (51%) showed MES during at least one of the three TCD examinations. In 9 of the 47 patients without MES during examination I (19%), MES could be recorded subsequently during examinations II and III. A statistically significant decrease in the prevalence of MES occurred between examinations I and III (P = .01). The frequency of MES in a single patient decreased between examinations I and II but increased again in examination III, although it did not reach the initial level. Prevalence of MES was the highest during the period up to 6 hours after the onset of symptoms. However, even at > 72 hours after the onset of symptoms, a substantial number of MES could be recorded. In 18 of the 21 patients with carotid artery stenosis or occlusion who showed MES (86%), these signals occurred ipsilateral to the affected carotid artery. In 5 of the 13 patients with MES and a potential cardiac source of embolism (38%), MES were observed bilaterally. Forty-one patients were without anticoagulation treatment at the time of examination: 19 of these patients (46%) presented with MES. In contrast, of the 37 patients receiving anticoagulation treatment at the time of the first examination, MES could be recorded in only 12 (32%). CONCLUSIONS: Microemboli are a frequent phenomenon in patients with acute stroke arising from a variety of causes, both in the very early stages and several days after the onset of symptoms. The prevalence of MES decreases significantly over time. MES occur more frequently in patients with carotid artery disease than in patients with a potential cardiac source of embolism. Ipsilateral MES are frequent in patients with carotid artery disease, whereas bilateral MES are suggestive of a cardioembolic origin. Anticoagulation treatment appears to decrease the prevalence of MES, but microemboli still occur in patients receiving intravenous therapy with heparin. Because MES occur intermittently, TCD examinations should be repeated several times, even in patients without MES in the first examination, and long-term monitoring equipment is necessary.

BACKGROUND AND PURPOSE: Cerebral emboli can be recognized by typical "high-intensity transient signals" (HITS) in the transcranial Doppler (TCD) spectral curves. Patients with potential cardiac sources of embolism are at higher risk for stroke. METHODS: We examined the frequency of HITS in the left middle cerebral artery (MCA) with TCD over periods of 30 minutes in 100 patients having potential cardiac sources of embolism, as indicated by transthoracic or transesophageal echocardiography. RESULTS: Thirty-six (36%) of the patients presented with HITS. Sex, age, sufficient anticoagulation level, antiplatelet therapy, neurological symptoms, and a history of thrombosis had no influence on the prevalence and number of HITS. The patients with a single echocardiographic diagnosis were separated into eight echocardiographically defined groups: patients with (1) atrial fibrillation, (2) coronary artery disease plus ejection fraction of more than 30% including at least three wall segments of hypokinesia/akinesia, (3) coronary artery disease with less than 30% ejection fraction, (4) dilated cardiomyopathy, (5) infectious endocarditis, (6) aortic stenosis, (7) mitral stenosis, and (8) patent foramen ovale. A significant difference in HITS occurrence could not be found in any of the defined groups. Only patients with infectious endocarditis showed a tendency for a higher HITS prevalence. CONCLUSIONS: HITS are common phenomena in patients with potential cardiac sources of embolism. The clinical relevance of these HITS remains unclear.

OBJECTIVES: To evaluate the time course and extent of the restenosis that occurs after an endoscopic modified Lothrop procedure (EMLP) and to identify factors that contribute to this process. STUDY DESIGN: : Retrospective study of prospectively collected data. METHODS: Seventy-seven consecutive patients undergoing EMLP between November 1998 and June 2005 with frontal ostium measurements documented intraoperatively and at follow-up visits for a minimum of 12 months were included. Data on patient demographics, medical history, comorbidities, and computed tomography scans were collected. RESULTS: Significant restenosis of the frontal sinus neo-ostia was defined as a loss of more than 60% of the original intraoperative area. The mean follow-up in our cohort was 29.2 months. Twenty-two patients were identified with increased stenosis, all of which arose within the first 12 months postsurgery. Nine of these 22 patients required revision EMLP. In all patients, the new frontal ostium narrowed at 1 year by an average of 33% (from 290 to 191 mm2, confidence interval 159-223 mm2). Restenosis and revision surgery are partly predicted by the presence of eosinophilic mucin chronic rhinosinusitis as demonstrated by logistic regression analysis. Linear regression analysis confirmed that the intraoperative frontal ostium size determines the frontal ostium area at 1 year. CONCLUSION: This study provides benchmarking values for the time course of the frontal ostium area after EMLP for normal wound healing and increased stenosis. On the basis of our results, patients with a higher risk for developing restenosis and of having revision surgery can be identified preoperatively and during the early postoperative period to facilitate special postoperative care.

BACKGROUND: In this preliminary trial we investigated the effects of dry cupping, an ancient method for treating pain syndromes, on patients with chronic non-specific neck pain. Sensory mechanical thresholds and the participants' self-reported outcome measures of pain and quality of life were evaluated. METHODS: Fifty patients (50.5 ± 11.9 years) were randomised to a treatment group (TG) or a waiting-list control group (WL). Patients in the TG received a series of 5 cupping treatments over a period of 2 weeks; the control group did not. Self-reported outcome measures before and after the cupping series included the following: Pain at rest (PR) and maximal pain related to movement (PM) on a 100-mm visual analogue scale (VAS), pain diary (PD) data on a 0-10 numeric rating scale (NRS), Neck Disability Index (NDI), and health-related quality of life (SF-36). In addition, the mechanical-detection thresholds (MDT), vibration-detection thresholds (VDT), and pressure-pain thresholds (PPT) were determined at pain-related and control areas. RESULTS: Patients of the TG had significantly less pain after cupping therapy than patients of the WL group (PR: Δ-22.5 mm, p = 0.00002; PM: Δ-17.8 mm, p = 0.01). Pain diaries (PD) revealed that neck pain decreased gradually in the TG patients and that pain reported by the two groups differed significantly after the fifth cupping session (Δ-1.1, p = 0.001). There were also significant differences in the SF-36 subscales for bodily pain (Δ13.8, p = 0.006) and vitality (Δ10.2, p = 0.006). Group differences in PPT were significant at pain-related and control areas (all p < 0.05), but were not significant for MDT or VDT. CONCLUSIONS: A series of five dry cupping treatments appeared to be effective in relieving chronic non-specific neck pain. Not only subjective measures improved, but also mechanical pain sensitivity differed significantly between the two groups, suggesting that cupping has an influence on functional pain processing. TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT01289964).

BACKGROUND: The metabolic syndrome (MetSyn) places individuals at increased risk for type 2 diabetes and cardiovascular disease. Prevalence rates of the population of the MetSyn are still scarce. Moreover, the impact of different definitions of the MetSyn on the prevalence is unclear. Aim here is to assess the prevalence of the MetSyn in primary health care and to investigate the impact of four different definitions of the MetSyn on the determined prevalence with regard to age, gender and socio-economic status. METHODS: The German-wide cross-sectional study was conducted during two weeks in October 2005 in 1.511 randomly selected general practices. Blood samples were analyzed, blood pressure and waist circumference assessed, data on lifestyle, medication, chronic disorders, and socio-demographic characteristics collected. MetSyn prevalence was estimated according to the definitions of NCEP ATP III (2001), AHA/NHLBI (2004, 2005), and IDF (2005). Descriptive statistics and prevalence rate ratios using the PROG GENMOD procedure, were calculated. Cohen's kappa was used as measure for interreliability between the different prevalence estimates. RESULTS: Data of 35,869 patients (age range: 18-99, women 61.1%) were included. The prevalence was lowest using the NCEP ATP III- (all: 19.8%, men 22.7%, women: 18.0%), highest according to the IDF-definition (32.7%, 40.3%, 28.0%). The increase in prevalence with recent definitions was more pronounced for men than for women, and was particularly high for men and women aged 60-79 years. The IDF-definition resulted in a higher prevalence especially in those with the highest educational status. Agreement (kappa) between the NCEP ATP III- and IDF-definition was 0.68 (men 0.61, women 0.74), between the updated the AHA/NHLBI- (2005) and IDF-definition 0.85 (men 0.79, women 0.89). CONCLUSION: The prevalence of metabolic syndrome is associated with age, gender, and educational status and increases considerably with each newly published definition. Our data highlight the need for a better evidence regarding thresholds of the components of the metabolic syndrome, especially with regard to the IDF-definition - according to which in some populations a majority of subjects are diagnosed with the metabolic syndrome.

OBJECTIVES: The aim of this study was to implement fasting therapy in an inpatient integrative medicine ward and to evaluate safety, acceptance, and effects on health-related outcomes and lifestyle adherence. DESIGN: This was a prospective observational study with consecutive inpatients over 3 [corrected] years. Inclusion and exclusion criteria for fasting therapy were checked by treating physicians and recommendations given. After receiving full information patients decided whether they would participate in fasting. Outcomes were assessed on admission, at discharge, and 3 and 6 months after discharge. SETTING: The study took place in an integrative medicine department of an academic teaching hospital. SUBJECTS: Subjects were newly admitted inpatients with chronic internal diseases and chronic pain syndromes, with lengths of hospital stay of >3 days. INTERVENTIONS: All patients received intensive integrative treatments including Mind/Body Medicine, acupuncture, nutritional/lifestyle education, and hydrotherapy. Fasting patients participated in a 7-day juice fast (intake <350 kcal/day) with accompanying bowel cleansing, 2 prefasting relief days, and 3 days with stepwise reintroduction of food. OUTCOME MEASURES: Outcomes were assessed based on rate of participation in fasting, severity of main complaint, quality of life (QOL, MOS 36-Item Short-Form Health Survey), safety, lifestyle adherence to recommendations given (relaxation, diet, exercise). RESULTS: Of 2121 patients with complete discharge questionnaires, 952 patients participated in fasting, 873 had a normocaloric vegetarian diet, and 296 patients had other diets and were excluded. Response rates were 71% and 56% at 3- and 6-month follow-up. The main disease-related complaint at discharge was significantly greater improved in fasters versus nonfasters (p < 0.01). Patient QOL increased significantly and comparably from baseline to discharge in both groups. Fasting was well tolerated and no serious fasting-related adverse effects were reported. In all, 743 (78%) of fasting patients reported improvement of their health through fasting. Descriptors of lifestyle adherence showed higher levels of related activities in the 3 and 6 months of follow-up. CONCLUSIONS: Fasting can safely and successfully be implemented in an inpatient integrative medicine concept and is perceived as a health-promoting method by the majority of patients. Potential effects on disease-related complaints and lifestyle adherence should be further evaluated in randomized trials.

AIMS: During the COVID-19 pandemic, hospital admissions for cardiac care have declined. However, effects on mortality are unclear. Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths. Simultaneously we looked at catheterization activities in the same region. METHODS AND RESULTS: Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019. Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected. Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area. Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated. In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2.6% [incidence rate ratio (IRR) 1.03, 95% confidence interval (CI) 0.99-1.06; p = 0.16]. Cardiovascular and cardiac mortality increased significantly by 7.6% (IRR 1.08, 95%-CI 1.01-1.14; p = 0.02) and by 11.8% (IRR 1.12, 95%-CI 1.05-1.19; p < 0.001), respectively. During the same period, our data revealed a drop in cardiac catherization procedures. CONCLUSION: During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced. The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality.

BACKGROUND: Based on the AHA/NHLBI-definition three out of five cardiometabolic traits must be present for the diagnosis of the metabolic syndrome (MetS), resulting in 16 different combination types. The associated cardiovascular risk may however be different and specific combination may be indicative of an increased risk, furthermore little is known to which extent these 16 combinations contribute to the overall prevalence of MetS. Here we assessed the prevalence of all 16 combination types of MetS, analyzed the impact of age and gender on prevalence rates, and estimated the 10-year risk of fatal and non-fatal myocardial infarction (MI) of each MetS combination type. METHODS: We used data of the German Metabolic and Cardiovascular Risk Project (GEMCAS), a cross-sectional study, performed during October 2005, including 35,869 participants (aged 18-99 years, 61% women). Age-standardized prevalence and 10-year PROCAM and ESC risk scores for MI were calculated. RESULTS: In both men and women the combination with elevated waist-circumference, blood pressure and glucose (WC-BP-GL) was the most frequent combination (28%), however a distinct unequal distribution was observed regarding age and sex. Any combination with GL was common in the elderly, whereas any combination with dyslipidemia and without GL was frequent in the younger. Men without MetS had an estimated mean 10-year risk of 4.7% (95%-CI: 4.5%-4.8%) for MI (PROCAM), whereas the mean 10-year risk of men with MetS was clearly higher (age-standardized 7.9%; 7.8-8.0%). In women without MetS the mean 10-year risk for MI was 1.1%, in those with MetS 2.3%. The highest impact on an estimated 10-year risk for MI (PROCAM) was observed with TG-HDL-GL-BP in both sexes (men 14.7%, women 3.9%). However, we could identify combinations with equal risks of non-fatal and fatal MI compared to participants without MetS. CONCLUSIONS: We observed large variations in the prevalence of all 16 combination types and their association to cardiovascular risk. The importance of different combinations of MetS changes with age and between genders putting emphasis on a tailored approach towards very young or very old subjects. This knowledge may guide clinicians to effectively screen individuals and prioritize diagnostic procedures depending on age and gender.

There is increasing clinical evidence that reflex therapies such as massage, Gua Sha, cupping, wet packs, acupuncture etc. are helpful in reducing symptoms of chronic pain. However, the neurobiological basis of these effects has rarely been investigated even though the increasing knowledge of the pathophysiology of chronic pain syndromes allows for specific hypotheses. Reflex therapies are likely able to influence chronic pain at the level of the nociceptor and the spinal cord. Moreover, it can be speculated that these therapies have a strong impact on relaxation and maybe understood as a social, comforting interaction. Since it is well accepted that the positive effect of grooming has a neurobiological basis in non-human primates, its biosocial impact on wellbeing and pain processing in humans may be underestimated. A synopsis of the neurobiological foundations of pain perception, from the nociceptor up the spinal cord to brain mechanisms provides the basis for the investigation of the 'way of action' of reflex therapies. Specific hypotheses on their neurobiological bases and methods suitable for their investigation are outlined. Further clarification of the mechanisms of action of reflex therapies will support their clinical evidence and add to our understanding of the neurobiology of complementary medicine.

OBJECTIVES: Our objectives were to determine if: (1) patients with migraine have B wave abnormalities in comparison to normal controls and patients with chronic tension headache and (2) patients with chronic tension headache have an imbalance in autonomic activity that is reflected in differences in Mayer wave activity in comparison to normal controls. BACKGROUND: B waves and Mayer waves are spontaneous oscillations in cerebral blood flow velocity with a frequency of 0.5 to 3 or 4 to 7 cycles per minute, respectively, and can be measured by transcranial Doppler sonography. There is experimental evidence that B waves are generated by certain brain stem nuclei which modulate the lumen of the small intracerebral vessels via monoaminergic nerve endings. In contrast, Mayer waves in cerebral blood flow velocity have no central generator but mirror the Mayer waves in arterial blood pressure which represent peripheral autonomic activity. Migraine may be attributed to a neurotransmitter imbalance in brain stem nuclei. Dysfunctions of the peripheral autonomic nervous system are known in patients with chronic tension headache. METHODS: Using bilateral transcranial Doppler monitoring of the middle cerebral artery B waves and Mayer waves were studied in 30 patients with migraine without aura, 28 subjects with tension-type headache, and 30 normal controls. Coefficient of variation as a quantitative parameter for amplitude of waves and the mean frequency were calculated from the envelope curves of the Doppler spectra. RESULTS: The coefficient of variation of B waves was higher in migrainous patients compared with patients with tension-type headache and normal controls (P<.05), indicating an increase in activity of brain stem nuclei in migraine only. Patients with chronic tension headaches had lower values for Mayer wave activity in comparison with normal controls (P<.05), a sign of an impairment of sympathetic activity. CONCLUSIONS: Our data support the dysfunction of the brain stem monoaminergic/serotonergic system in migraine. In contrast, patients with chronic tension headache have an autonomic dysfunction of peripheral origin presenting as a decrease of sympathetic activity.

Background: Human immunodeficiency virus (HIV) infection is an independent risk factor for coronary heart disease (CHD) and is associated with perturbation of the gut microbiota. Methods: We analyzed gut microbiota in 30 HIV-infected individuals with CHD (CHD+) and 30 without CHD (CHD-) of the HIV-HEART study group. Results: Gut microbiota linked to CHD was associated with lower α-diversity. Despite insignificant differences in β-diversity, co-occurrence networks of bacterial genera clearly diverged between CHD+ and CHD- individuals. Multidimensional scaling separated HIV-infected individuals into 2 microbiome clusters, dominated by the genus Prevotella or Bacteroides. The relative abundance of 49 other genera was significantly different between both clusters. The Prevotella-rich cluster was largely composed of men who have sex with men (MSM) (97%), whereas the Bacteroides-rich cluster comprised both MSM (45%) and heterosexual individuals (55%). MSM of the Bacteroides-rich cluster were characterized by reduced α-diversity, advanced immunological HIV stage, longer antiretroviral therapy with more ART regimens, and longer use of protease inhibitors, compared with Prevotella-rich MSM. Conclusions: Community structures of gut microbiota rather than individual species might facilitate risk assessment of CHD in HIV-infected individuals. Sexual behavior appears to be an important factor affecting gut microbiota β-diversity and should be considered in future studies.

BACKGROUND: The documentation of acute and chronic treatment sequelae is a decisive precondition for the appropriate evaluation of the treatment quality of any cancer therapy. METHODS AND RESULTS: Interdisciplinary (inter)national efforts have resulted in a new consensus for recording of treatment sequelae in oncology. While the acute treatment side effects (day 1 to 90 after treatment) are recommended to be documented and evaluated using the Common Toxicity Criteria (CTC), for the chronic treatment side effects (day 91 and thereafter) the Late Effect Normal Tissue (LENT) criteria are to be implemented. The latter classification system allows to differentiate between the Subjective, Objective, Management and Analytic (SOMA) toxicity aspects. Both classification systems can be implemented not only for clinical applications using radiotherapy or chemotherapy alone but also for combinations with each other or with other treatment modalities. This allows for an effective interdisciplinary comparison between different treatment concepts not only within each institution but also in multicenter trials. CONCLUSIONS: Prospective documentation and evaluation of treatment toxicity in oncology should be intensified and systematically included in future mono- and multi-institutional clinical trials.

espite the decrease in overall mortality from coronary artery disease, the number of out-ofhospital deaths from myocardial infarction is in the range of 60% of all infarct related case fatalities. In the general population, it is only 0.5% per year. 2 However, the absolute number in this group is 10 times higher than in the patient population with known SCD risk, reaching more than 300 000 case fatalities per year in the USA. 2 Even renowned cardiologists such as Ronald W Campbell w1 and Jeffry M Isner w2 , who were experts on the topic of arrhythmias and myocardial infarction, suffered SCD. The MONICA (Monitoring trends and determinants in Cardiovascular disease) study reported that of all coronary heart disease (CHD) patients who die within 28 days after onset of chest pain, two thirds die before reaching the hospital. w3 Accordingly, the main task has been to strengthen primary and secondary prevention. w3 This strategy brings about a major challenge: how can we define who is at risk?

Background and Purpose Moyamoya angiopathy (MMA) is a rare cerebral vasculopathy outside of Asia. In Japanese patients, a vast majority of patients carry the founder p.R4810K variant in the RNF213 gene, and familial cases are around 10%. In European patients, data about familial occurrence are limited. The aim of this study was to characterize the clinical and molecular features of several European families with a parent-to-child transmission of MMA. Methods Out of 126 MMA probands referred, we identified 113 sporadic probands and 13 familial probands. Segregation analysis showed a vertical parent-to-child pattern of inheritance in the families of 5 of these probands. All 5 families were of German or Dutch ancestry. We investigated the clinical features of affected members and used whole-exome sequencing to screen RNF213 and 13 genes involved in Mendelian MMA and to identify genes recurrently mutated in these families. Results Twelve affected MMA patients were identified, including 9 females and 3 males. Age at clinical onset ranged from 11 to 65 years. In 3 of 5 families, associated livedo racemosa was found. We did not detect any deleterious variants in the 13 known MMA genes. RNF213 rare missense variants predicted to be pathogenic were detected in all affected members of 2 of these families, as well as 2 candidate variants of the PALD1 gene. Conclusions Nonsyndromic MMA was identified in 5 European families, including 2 to 3 clinically affected cases segregating with a parent-to-child pattern of inheritance in each family. Molecular screening detected rare deleterious variants within RNF213 and PALD1 in all affected members of 2 of these 5 families, as well as in some clinically unaffected members. Altogether these data raise the difficult and, to date unanswered, question of the medical indication of presymptomatic screening.

BACKGROUND: In conditions such as phantom limb pain and low back pain body image is distorted. This qualitative study investigates body image in patients with chronic non-specific neck pain (CNP), its influence on their everyday life and any changes linked to traditional cupping therapy. METHODS: The study was conducted with a convenience sample of 6 patients with CNP from a larger randomised controlled trial (RCT) on cupping. The data came from body image drawings and semi-structured interviews. The latter were analysed using Mayring's content analysis techniques. RESULTS: The patients' drawings showed apparent body image distortions with elements that were missing or deformed. The interviews showed that pain was the predominant perception, influencing patients' body perception. Patients saw their pain as beyond their control, using mostly passive strategies to cope. After cupping, patients reported less pain and improved pain perception. These changes were reflected in their drawings. CONCLUSION: Patients with CNP experienced apparent body image distortions, which traditional cupping therapy appeared to improve. Additional research is needed to further explore this link.