Is loneliness associated with cancellation of medical appointments during the COVID-19 pandemic? Evidence from the Hamburg City Health Study (HCHS).

BACKGROUND: The COVID-19 pandemic engendered numerous societal and economic challenges in addition to health-related concerns. Maintenance of healthcare utilization assumed immense significance during this period. However, few studies have examined the association between loneliness and cancelled medical appointments during the COVID-19 pandemic. This study aimed to examine whether medical appointments are less likely to be cancelled with increased loneliness during a pandemic. We analyzed the association between loneliness and both patient- and provider-initiated appointment cancellations. METHODS: Cross-sectional data from the Hamburg City Health Study (HCHS) were collected during April 2020-November 2021. The analytical sample included 1,840 participants with an average age of 55.1 years (standard deviation: 6.5, range 45-76 years). Medical appointments cancelled by individuals-medical appointments in general, and GP, specialist, and dentist appointments-and appointments cancelled by healthcare providers served as outcome measures. Loneliness was quantified using a single item ranging from 0 to 10. Accordingly, we created empirical loneliness tertiles. Covariates were selected based on the Andersen model. Several penalized maximum likelihood logistic regressions were utilized to examine the association between loneliness and cancellation of medical appointments during the COVID-19 pandemic. RESULTS: The penalized maximum likelihood logistic regressions showed that, compared to individuals in the lowest loneliness tertiles, individuals in the other two tertiles reported a higher chance of medical appointments cancellation by individuals, particularly driven by cancelled GP appointments. Except for age and sex, none of the covariates were comparably associated with the outcomes. When appointments cancelled by healthcare providers served as outcomes, only a higher number of chronic conditions was significantly positively associated with it. CONCLUSIONS: Individuals scoring higher in loneliness had a greater chance of cancelling medical (particularly GP) appointments. This may contribute to a potential cascade of loneliness and skipped medical appointments in the future, resulting in adverse health outcomes over the medium-to-long term. Future research should examine whether lonely people are more likely to lack the social motivation to visit the doctor.

Host traits, lifestyle and environment are associated with human skin bacteria.

BACKGROUND: The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts with the broader knowledge about factors influencing gut microbiota. OBJECTIVES: We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations. METHODS: This is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1-V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). RESULTS: We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. CONCLUSIONS: We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.

[Breathing: Ambient Air Pollution and Health - Part III]. / Atmen: Luftschadstoffe und Gesundheit ­ Teil III.

The third part of the DGP statement introduces the current body of knowledge on less studied health outcomes associated with exposure to ambient air pollution: the negative impact on metabolism leading to impaired glucose tolerance and diabetes as well as contribution to the development of neurodegenerative disorders and delayed cognitive function in children. Furthermore, prenatal exposure and adverse effects on mother and child are addressed. Finally, the currently discussed biological mechanisms underlying various health effects associated with exposure to air pollution are described.Differing, but often complementary biological mechanisms create the basis for the diverse health outcomes caused by air pollution. Oxidative stress and a subclinical inflammatory response in the lungs and on a systemic level ("low-grade systemic inflammation") are considered to be key mechanisms. They promote secondary alterations in the body, such as vascular or metabolic processes, and may also result in the currently studied epigenetic phenomena or neuroinflammation. In this context, the health significance of soluble particulate matter and the role of ultrafine particles translocated across biological membranes into blood vessel and transported via the circulation to secondary target organs, such as liver, brain or the fetus, are intensively discussed.Diabetes is one of the leading chronic diseases worldwide, with a prevalence of almost 14 % in Germany. Although lifestyle factors are the main causes, current evidence suggests that long-term exposure to air pollution may additionally increase the risk for type 2 diabetes. Supporting evidence for a causal role of air pollution is provided by studies addressing the regulation of the blood glucose levels in metabolically healthy participants, insulin sensitivity, or pregnancy-related diabetes. Experimental studies provide further support for plausible biological mechanisms. However, prospective studies are needed to gain more evidence, taking multiple lifestyle and environmental factors, such as green space and noise, and an improved individual exposure assessment into account.The aging population has an increased risk of neurodegenerative diseases. First studies point towards a contribution of chronic exposure to air pollution, specifically by particulate matter. Several studies report its association with decreased neurocognitive capacity or an increased prevalence of dementia or Alzheimer's disease in adults. However, the studies are inhomogeneous regarding design, exposure and outcome, leading to inconsistent results. With respect to the influence on neurocognitive development of children, first studies suggest an association between the level of air pollution, e. g. at school, and delayed cognitive development.Even though the evidence for the different biological endpoints during pregnancy is still heterogeneous, the studies generally point towards an adverse impact of air pollution on the maternal and fetal organisms. The strongest evidence exists for low birth weight, with small effect sizes of only some grams, and for a higher incidence of reduced birth weight (< 2500 g). An increased risk for gestational hypertension and preeclampsia underscores the possible impact of exposure to air pollution on the maternal organism. However, the current body of evidence does not yet allow a final conclusion on the influence of intrauterine exposure to air pollution regarding early childhood lung function and development of allergies, particularly in light of the fact that it is hard to distinguish in epidemiological studies between the effects of pre- and postnatal exposure.

[Breathing: Ambient Air Pollution and Health - Part II]. / Atmen: Luftschadstoffe und Gesundheit ­ Teil II.

The second part of the DGP-statement on adverse health effects of ambient air pollution provides an overview of the current ambient air quality in Germany and its development in the past 20 years. Further, effects of air pollution on the cardiovascular system und underlying pathophysiological mechanisms are introduced. Air pollutants form a highly complex and dynamic system of thousands of organic and inorganic components from natural and anthropogenic sources. The pollutants are produced locally or introduced by long-range transport over hundreds of kilometers and are additionally subjected to local meteorological conditions. According to air quality regulations ambient air quality is monitored under uniform standards including immission of particulate matter, up to 2.5 µm (PM2.5) or 10 µm (PM10) in aerodynamic diameter, and of nitrogen dioxide (NO2) or ozone (O3). The clean air measures of recent years led to a continuous decline of air pollution in the past 20 years in Germany. Accordingly, the focus is nowadays directed at population-related health hazards caused by low concentrations of air pollution. Exceeded limits for sulfur dioxide, carbon monoxide, benzene and lead are not detected anymore. Also the number of days with increased ozone concentration declined, although the annual mean concentration is unaltered. Decreasing concentrations of particulate matter and NO2 have been observed, however, about 40 % of the monitoring stations at urban traffic sites still measure values exceeding current limits for NO2. Moreover, the stricter, solely health-based WHO-standards for PM2.5, PM10 and NO2 are still not met so that an optimal protection from air pollution-related health hazards is currently not given for the German population. In recent years, the findings of numerous cross-sectional and longitudinal studies underscored adverse effects of air pollution on the cardiovascular system, especially for particulate matter, although the level of evidence still varies for the different health outcomes. Further, the studies show that cardiovascular health hazards on the population level are of higher relevance than those for the respiratory system. The existing evidence for cardiovascular mortality, hospitalization, ischemic heart diseases, myocardial infarction and stroke can be regarded as strong, while that for heart failure is rather moderate. While the evidence for air pollution-related short-term alteration of the cardiac autonomic balance can be considered as sufficient, long-term effects are still unclear. Likewise, the heterogeneous findings on air pollution-related arrhythmia do currently not allow a distinct conclusion in this regard. A large number of studies support the observation that both, short- and long-term air pollution exposure contribute to increased blood pressure, may impair vascular homeostasis, induce endothelial dysfunction and promote the progression of atherosclerotic lesions. These effects provide reasonable biological explanation for the fatal events associated with exposure to air pollution. Short-term exposure may not pose a significant risk on healthy individuals but may be considered as precursor for fatal events in susceptible populations, while repetitive or long-term exposure may contribute to the development of cardiovascular diseases even in healthy subjects.

EVITA-a double-blind, vehicle-controlled, randomized phase II trial of vitamin K1 cream as prophylaxis for cetuximab-induced skin toxicity.

Background: Acne-like skin rash is a frequently occurring adverse event associated with drugs against the epidermal growth factor receptor. This randomized vehicle-controlled study investigated the addition of vitamin K1 cream to doxycycline in patients with metastatic colorectal cancer treated with cetuximab. Patients and methods: Patients receiving first-line cetuximab + FOLFIRI were randomly assigned to prophylactic treatment with doxycylin and vitamin K1 cream or doxycycline and the vehicle. The primary end point of the study was the incidence of grade ≥ 2 skin rash (NCI CTCAE version 4.02) during 8 weeks of skin treatment. Secondary end points comprised skin rash according to a more thorough tripartite skin toxicity score (WoMo), quality of life, efficacy, and compliance. The study had 80% power to show a 20% reduction of the incidence of grade ≥ 2 skin rash. Results: A total of 126 patients were analyzed. The incidence of skin rash grade ≥ 2 was comparable between the arms. Likewise, no difference was seen in the WoMo score with respect to the percentage of skin affected. However, starting in week 5 and increasing over time patients treated with vitamin K1 cream had less severe rash and fewer fissures. Quality of life as well as efficacy and compliance with study medication and anticancer treatment was comparable in both arms. Conclusion: The primary end point of decreasing grade ≥ 2 skin rash was not met. However, using vitamin K1 cream as part of prophylactic treatment decreased the severity of acne-like skin rash according to WoMo, an alternative and more thorough skin toxicity scoring tool.

One in two cancer patients is significantly distressed: Prevalence and indicators of distress.

OBJECTIVE: Psychological distress is common in cancer patients, and awareness of its indicators is essential. We aimed to assess the prevalence of psychological distress and to identify problems indicative of high distress. METHODS: We used the distress thermometer (DT) and its 34-item problem list to measure psychological distress in 3724 cancer patients (mean age 58 years; 57% women) across major tumor entities, enrolled in an epidemiological multicenter study. To identify distress-related problems, we conducted monothetic analyses. RESULTS: We found high levels of psychological distress (DT ≥ 5) in 52% of patients. The most prevalent problems were fatigue (56%), sleep problems (51%), and problems getting around (47%). Sadness, fatigue, and sleep problems were most strongly associated with the presence of other problems. High distress was present in 81.4% of patients reporting all 3 of these problems (DT M = 6.4). When analyzing only the subset of physical problems, fatigue, problems getting around, and indigestion showed the strongest association with the remaining problems and 76.3% of patients with all 3 problems were highly distressed (DT M = 6.1). CONCLUSIONS: Our results show a high prevalence of psychological distress in cancer patients, as well as a set of problems that indicate the likely presence of other problems and high distress and can help clinicians identify distressed patients even if no routine distress screening is available.

Physical activity, muscular strength, and polypharmacy among older multimorbid persons: Results from the KORA-Age study.

The purpose of this study was to examine whether physical activity (PA) and muscular strength (MS) are related to polypharmacy. Our cross-sectional analysis was based on 711 patients with multimorbidity (MMB), aged 65-94 years, who participated in the KORA-Age study. Participants underwent a face-to-face interview and extensive physical examinations including anthropometric measurements, registration of chronic diseases, determination of health-related behaviors (smoking, alcohol intake, physical activity, etc.), collection of blood samples and measurement of hand-grip strength. PPha was defined as the use of >4 drugs and MMB as having ≥2 of 13 chronic diseases. Prevalence of PPha was 44.6% (n=317), and a significant difference was found in the number of drugs used between participants with and without PPha (7.2±2.1 vs 2.5±1.2, P<.001). Patients in the lower compared to the upper tertile of physical activity had a significantly increased odds to be on PPha (OR: 1.64, 95% CI: 1.05-2.56, P=.031) after controlling for age, gender, BMI, family status, education, alcohol intake, smoking habits, number of diseases, hs-CRP, and telomere length. On the contrary, no significant association between muscular strength and PPha was found (OR: 1.04, 95% CI: 0.66-1.63, P=.873) after multivariable adjustment. Among older persons with MMB, lower levels of physical activity, but not low muscular strength, are associated with higher odds of PPha. Increasing the levels of physical activity appears to be highly recommended in order to potentially reduce the risk of PPha among multimorbid persons aged 65 and older.

[Liquid biopsy in human non-small-cell lung cancer : Blood-based analysis of ctDNA methylation]. / Liquid Biopsy im nicht-kleinzelligen Lungenkarzinom : Die blutbasierte Analyse der ctDNA-Methylierung.

BACKGROUND: Use of liquid biopsy for minimal invasive follow-up diagnostics of non-small-cell lung carcinomas (NSCLCs). OBJECTIVES: Systematic search for new putative blood-based hypermethylation biomarkers to discriminate NSCLC patients from patients without a malign disease. METHODS: Quantitative analysis of gene promoter DNA methylation of potential biomarkers from cfDNA (plasma) with pyrosequencing. RESULTS: cfDNA hypermethylation in plasma confirmed significant higher methylation frequencies of the candidate gene CFTR of the NSCLC patients compared to the combined control groups and to NSCLC patients after curative therapy of primary NSCLC (post-NSCLC). ROC-analysis of the best discriminatory CpGs of the CFTR promotor (CpG1-2-4) revealed a sensitivity of 52% in NSCLC patients and a specificity of 90% in the post-NSCLC group (AUC: 0.69; p < 0.05). CONCLUSIONS: Promotor hypermethylation of the potential biomarker CFTR shows a discriminatory potential for differentiation of NSCLC patients to patients without a malign disease and should further be investigated.

Achalasia-an unnecessary long way to diagnosis.

Although achalasia presents with typical symptoms such as dysphagia, regurgitation, weight loss, and atypical chest pain, the time until first diagnosis often takes years and is frustrating for patients and nevertheless associated with high costs for the healthcare system. A total of 563 patients were interviewed with confirmed diagnosis of achalasia regarding their symptoms leading to diagnosis along with past clinical examinations and treatments. Included were patients who had undergone their medical investigations in Germany. Overall, 527 study subjects were included (male 46%, female 54%, mean age at time of interview 51 ± 14.8 years). Dysphagia was present in 86.7%, regurgitation in 82.9%, atypical chest pain in 79%, and weight loss in 58% of patients before diagnosis. On average, it took 25 months (Interquartile Range (IQR) 9-65) until confirmation of correct diagnosis of achalasia. Though, diagnosis was confirmed significantly quicker (35 months IQR 9-89 vs. 20 months IQR 8-53; p < 0.01) in the past 15 years. The majority (72.1%) was transferred to three or more specialists. Almost each patient underwent at least one esophagogastroduodenoscopy (94.2%) and one radiological assessment (89.3%). However, esophageal manometry was performed in 70.4% of patients only. The severity of symptoms was independent with regard to duration until first diagnosis (Eckardt score 7.14 ± 2.64 within 12 months vs. 7.29 ± 2.61 longer than 12 months; P = 0.544). Fifty-five percent of the patients primarily underwent endoscopic dilatation and 37% a surgical myotomy. Endoscopic dilatation was realized significantly faster compared to esophageal myotomy (1 month IQR 0-4 vs. 3 months IQR 1-11; p < 0.001). Although diagnosis of achalasia was significantly faster in the past 15 years, it still takes almost 2 years until the correct diagnosis of achalasia is confirmed. Alarming is the fact that although esophageal manometry is known as the gold standard to differentiate primary motility disorders, only three out of four patients had undergone this diagnostic pathway during their diagnostic work-up. Better education of medical professionals and broader utilization of highly sensitive diagnostic tools, such as high-resolution manometry, are strictly necessary in order to correctly diagnose affected patients and to offer therapy faster.

Allergic manifestation 15 years after early intervention with hydrolyzed formulas--the GINI Study.

BACKGROUND: Data on the long-term impact of hydrolyzed formulas on allergies are scarce. OBJECTIVE: To assess the association between early intervention with hydrolyzed formulas in high-risk children and allergic outcomes in adolescence. METHODS: GINI trial participants (n = 2252) received one of four formulas in the first four months of life as breastmilk substitute if necessary: partial or extensive whey hydrolyzate (pHF-W, eHF-W), extensive casein hydrolyzate (eHF-C) or standard cow's milk formula (CMF) as reference. Associations between these formulas and the cumulative incidence and prevalence of parent-reported physician-diagnosed asthma, allergic rhinitis (AR) and eczema, as well as spirometric indices and sensitization, were examined using generalized linear models. RESULTS: Between 11 and 15 years, the prevalence of asthma was reduced in the eHF-C group compared to CMF (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.26-0.89), which is consistent with the spirometric results. The cumulative incidence of AR was lower in eHF-C (risk ratio (RR) 0.77, 95% CI 0.59-0.99]) and the AR prevalence in pHF-W (OR 0.67, 95% CI 0.47-0.95) and eHF-C (OR 0.59, 95% CI 0.41-0.84). The cumulative incidence of eczema was reduced in pHF-W (RR 0.75, 95% CI 0.59-0.96) and eHF-C (RR 0.60, 95% CI 0.46-0.77), as was the eczema prevalence between 11 and 15 years in eHF-C (OR 0.42, 95% CI 0.23-0.79). No significant effects were found in the eHF-W group on any manifestation,nor was there an effect on sensitization with any formula. CONCLUSION: In high-risk children, early intervention using different hydrolyzed formulas has variable preventative effects on asthma, allergic rhinitis and eczema up to adolescence.

[A Screening-Tool for Three Dimensions of Work-Related Behavior and Experience Patterns in the Psychosomatic Rehabilitation - A Proposal for a Short-Form of the Occupational Stress and Coping Inventory (AVEM-3D)]. / Ein Verfahren zum Screening dreier Dimensionen arbeitsbezogener Verhaltens- und Erlebensmuster in der psychosomatischen Rehabilitation ­ Vorschlag für eine Kurzform AVEM-3D.

Objectives: The assessment of work pressures is of particular importance in psychosomatic rehabilitation. An established questionnaire is the Occupational Stress and Coping Inventory (German abbr. AVEM), but it is quite long and with regard to scoring time-consuming in routine clinical care. It should therefore be tested, whether a shortened version of the AVEM can be developed, which is able to assess the formerly described three second-order factors of the AVEM, namely Working Commitment, Resilience, and Emotions, sufficiently reliable and valid, and which also may be used for screening of patients with prominent work-related behavior and experience patterns. Methods: Data were collected at admission from consecutive samples of three hospitals of psychosomatic rehabilitation (N = 10,635 patients). The sample was randomly divided in two subsamples (design and validation sample). Using exploratory principal component analyses in the design sample, items with the highest factor loadings for the three new scales were selected and evaluated psychometrically using the validation sample. Possible Cut-off values ought to be derived from distribution patterns of scores in the scales. Relationships with sociodemographic, occupational and diagnosis-related characteristics, as well as with patterns of work-related experiences and behaviors are examined. Results: The three performed principal component analyses explained in the design sample on the respective first factor between 31 % and 34 % of the variance. The selected 20 items were assigned to the 3-factor structure in the validation sample as expected. The three new scales are sufficiently reliable with values of Cronbach's α between 0,84 and 0,88. The naming of the three new scales is based on the names of the secondary factors. Cut-off values for the identification of distinctive patient-reported data are proposed. Conclusion: Main advantages of the proposed shortened version AVEM-3D are that with a considerable smaller number of items the three main dimensions of relevant work-related behavior and experience patterns can be reliably measured. The proposed measure is simple and economic to use and interpret. Based on the present sample we provide means and standard deviations as reference at admission of psychosomatic rehabilitation. As a limitation it should be mentioned that further evaluation of reliability, validity and sensitivity to change restricted to the items of the shortened version is necessary. The practicability and validity of the proposed cut-off values cannot yet be conclusively assessed. Finally, the validity of the AVEM-3D in groups of indications other than psychosomatic patients and in healthy persons remains to be examined.

[Replication of the psychometric properties of the ICF-MentalA&P]. / Replikation der psychometrischen Gütekriterien des ICF-PsychA&P.

OBJECTIVE: The ICF provides a useful basis for the description of the mulitfacetted psychosocial impairments for patients with mental disorders. The objectives of this study were the development and psychometric testing of a self-rating instrument that quantifies activity and participation for patients with mental disorders (ICF-MentalA&P). METHODS: The psychometric testing of the 31-item version of the ICF-MentalA&P including a sample of n=1270 patients in psychosomatic rehabilitation treatment are described. RESULTS: The ICF-MentalA&P contains 31 items comprising the subscales functioning, communication, mobility, relationships, leisure and interaction. These were validated by confirmatory factor analysis and showed good internal consistencies. CONCLUSION: The ICF-MentalA&P is a reliable and valid instrument that measures activities and participation of patients with mental disorders using self-ratings on the basis of the ICF.

[Benefit assessment in health services research and epidemiology]. / Nutzenbewertung aus Sicht der Versorgungsforschung und der Epidemiologie.

The legal terms "benefit" and "added benefit" and the procedures related to their assessment, given the application of a new medical intervention for approval, should help to restrict the market to those products for which there is much evidence of their benefit or added benefit. The term implies the fiction of an overall benefit for all patients with the same disease. However, from the perspective of health services research and that of epidemiology the term inevitably has to be extended to cover the benefit to a variety of groups of patients or users of a broad spectrum of medical interventions in the real world, ranging from inpatient treatment to vaccination or screening programs. Thus, the assessment of benefit requires a comparison of the new product with all the alternatives currently available for routine care, explicitly taking into account user preferences. Hence, the assessment of benefit in health services research is not one-dimensional and requires new types of studies that go beyond the traditional phase III trials (efficacy trials). New approaches are mainly developed by comparative effectiveness research (CER). CER studies also use randomized designs, because they are currently the best available method for causal inferences. However, randomization in CER is extended to a much broader framework, including health-related databases, registers, epidemiological studies, feasibility studies, and post hoc analyses. CER has developed the necessary and appropriate designs and statistical methods. In addition, some of these methods allow an adaptive assessment of benefit, which can be used to monitor the implementation of new health care interventions or programs.

Reliability of the calculated maximal lactate steady state in amateur cyclists.

Complex performance diagnostics in sports medicine should contain maximal aerobic and maximal anaerobic performance. The requirements on appropriate stress protocols are high. To validate a test protocol quality criteria like objectivity and reliability are necessary. Therefore, the present study was performed in intention to analyze the reliability of maximal lactate production rate ([Formula: see text]Lamax) by using a sprint test, maximum oxygen consumption ([Formula: see text]O2max) by using a ramp test and, based on these data, resulting power in calculated maximum lactate-steady-state (PMLSS) especially for amateur cyclists. All subjects (n = 23, age 26 ± 4 years) were leisure cyclists. At three different days they completed first a sprint test to approximate [Formula: see text]Lamax. After 60 min of recreation time a ramp test to assess [Formula: see text]O2max was performed. The results of [Formula: see text]Lamax-test and [Formula: see text]O2max-test and the body weight were used to calculate PMLSS for all subjects. The intra class correlation (ICC) for [Formula: see text]Lamax and [Formula: see text]O2max was 0.904 and 0.987, respectively, coefficient of variation (CV) was 6.3% and 2.1%, respectively. Between the measurements the reliable change index of 0.11 mmol·l (-1)s (-1) for [Formula: see text]Lamax and 3.3 mlkg (-1)min (-1) for [Formula: see text]O2max achieved significance. The mean of the calculated PMLSS was 237 ± 72 W with an RCI of 9 W and reached with ICC = 0.985 a very high reliability. Both metabolic performance tests and the calculated PMLSS are reliable for leisure cyclists.

Good clinical outcome after accidental intra-arterial injection of flunitrazepam tablets in 16 drug abusers with critical limb ischaemia.

OBJECTIVES: Inadvertent intra-arterial injection of flunitrazepam tablets intended for intravenous use by drug abusers has devastating effects. We report here on the clinical outcome of 16 drug abusers developing critical limb ischaemia after flunitrazepam injection. METHODS: Treatment combined immediate analgesia and anticoagulation, long-lasting local thrombolysis and vasodilatation, antibiotic prophylaxis, and physical mobilization. The immediate bolus injection of 5,000 IU heparin was followed by a continuous heparin infusion up to the target partial thromboplastin time. Under arteriographic control local intra-arterial infusion with alternating 4-h cycles of 5 mg recombinant tissue plasminogen activator followed by 5 µg prostaglandinE1 (PGE1) was performed for 24-48 hours. Subsequently, 60 µg PGE1 was applied once daily. RESULTS: Drug abusers, having been injected with 4-30 mg flunitrazepam, were treated 3-72 hours after the accident, with six of them not being treated until after 24 hours. All showed a high tissue ischaemia score. At the time of being discharged from hospital 13 patients had a normal extremity. In one patient, first receiving treatment 72 hours after injection, minor amputation of fingers was necessary. The life of the patient who injected 30 mg flunitrazepam in the leg was saved after hip disarticulation. One patient developed neurological dysfunction in the affected toes. CONCLUSIONS: Intensive treatment after inadvertent intra-arterial drug injection normalized the affected extremity in most drug abusers, even after the late onset of therapy.

Comparison of selected lactate threshold parameters with maximal lactate steady state in cycling.

The aim of the present investigation was to compare power at "onset of blood lactate accumulation" (OBLA), "individual anaerobic threshold" (IAT) and "+1.5 mmol ∙ l(-1) lactate model" with power in maximal lactate steady state (MLSS) in cycling. However, there is a lack of studies concerning the absolute individual differences between different lactate parameters and MLSS.A total of 57 male participants performed several 30-min constant-load tests to determine MLSS by measuring blood lactate concentration (BLC). Depending on BLC, power was increased or decreased by 10 W in the following 30-min test. For detecting power at different threshold parameters, an incremental test was performed that began at 40 W and increased by 40 W every 4 min.Highly significant correlations were found between OBLA and MLSS: r=0.89 (mean difference -7.4 W); IAT and MLSS: r=0.83 (mean difference 12.4W), "+1.5 mmol ∙ l(-1) lactate model" and MLSS: r=0.88 (mean difference -37.4W). On average, the parameters of OBLA and IAT approximate MLSS with no significant differences. The "+1.5 mmol ∙ l(-1) lactate model" underestimates MLSS significantly.Based on Bland-and-Altman, the comparison of power of all threshold parameters with power in MLSS shows great individual differences despite the high regression coefficients and low mean differences between these methods.

[Data analysis based on the Classification of Therapeutic Procedures (CTL) of inpatient rehabilitation of depressive disorders]. / Analyse von Daten der Klassifikation Therapeutischer Leistungen (KTL) der stationären Rehabilitation bei depressiven Störungen.

OBJECTIVE: As an initiative of the German Pension Insurance Association (DRV), evidence-based therapeutic modules (ETM) for the rehabilitation of patients with depression were developed. The objective of the subsequent analysis was to analyse the therapeutic procedures in inpatient rehabilitation on the basis of the ETM to evaluate the principal needs for therapeutic standards. METHODS: Data based on the German Classification of Therapeutic Procedures (KTL) for 21 529 patients treated in rehabilitation clinics for people with mental illnesses was analysed with respect to differences between diagnostic groups/clinics regarding type, quantity and duration of measures coded. RESULTS: The mean quantity and duration of the interventions for patients with depressive disorders encoded varied greatly between the ETM. No or only minor differences were found between patients with depression and those with other diagnoses regarding the type, quantity and duration of measures coded. However, there were great variances between clinics. CONCLUSIONS: Therapeutic standards for rehabilitative practice appear necessary in order to reduce treatment heterogeneity between rehabilitation facilities, which could improve the quality of healthcare.

[Significance of regional variations in the prevalence and treatment of depressive disorders and implications for health-care research]. / Stellenwert regionaler Variationen in der Prävalenz und Behandlung depressiver Erkrankungen und Implikationen für die Versorgungsforschung.

Providing mental health care to patients with depressive disorders is accompanied by deficits in the diagnostics and in the access and adequacy of treatment. Analyzing regional variations in mental health care is of increasing importance in order to detect and explain these supply shortfalls. This paper discusses different explanatory approaches to the regional variations in diagnosed depressive disorders and their treatment. Differences in demographic structures and in patients' attitudes toward mental disorders as well as in their preferences in the choice of treatment may explain regional variation. Furthermore, the number and distribution of care providers between regions may have an effect on variation. In addition to the density and availability of care givers, the quality of care may differ because of factors such as sensitivity to the detection of depressive disorders, coding quality of diagnosis and treatment, guideline-oriented treatment, as well as treatment outcome. Small-area analyses should consider all perspectives in order to understand the complexity of regional variation in the provision of health-care services and to derive recommendations for health-care services that meet people's needs.