Afamelanotide Is Associated with Dose-Dependent Protective Effect from Liver Damage Related to Erythropoietic Protoporphyria.

In animal models, melanocyte-stimulating hormones (MSHs) protect the liver from various injuries. Erythropoietic protoporphyria (EPP), a metabolic disorder, leads to the accumulation of protoporphyrin (PPIX). In addition to the most prominent symptom of incapacitating phototoxic skin reactions, 20% of EPP patients exhibit disturbed liver functioning and 4% experience terminal liver failure caused by the hepatobiliary elimination of excess PPIX. Skin symptoms are mitigated through the application of the controlled-release implant afamelanotide, an α-MSH analog, every sixty days. Recently, we showed that liver function tests (LFTs) improved during afamelanotide treatment when compared to before treatment. The present study investigated whether this effect is dose-dependent, as the evidence of dose dependency would support a beneficial influence of afamelanotide. METHODS: In this retrospective observational study, we included 2933 liver-function tests, 1186 PPIX concentrations and 1659 afamelanotide implant applications in 70 EPP patients. We investigated whether the number of days since the preceding afamelanotide dose or the number of doses during the preceding 365 days had an effect on LFTs and PPIX levels. In addition, we assessed the effect of global radiation. RESULTS: Inter-patient differences exerted the most prominent effect on PPIX and LFTs. In addition, PPIX increased significantly with an increase in the number of days since the last afamelanotide implant (p < 0.0001). ALAT and bilirubin decreased significantly with an increasing number of afamelanotide doses in the preceding 365 days (p = 0.012, p = 0.0299, respectively). Global radiation only influenced PPIX (p = 0.0113). CONCLUSIONS: These findings suggest that afamelanotide ameliorates both PPIX concentrations and LFTs in EPP in a dose-dependent manner.

Motivation and personality factors of Generation Z high school students aspiring to study human medicine.

BACKGROUND: A new generation of medical students, Generation Z (Gen Z), is becoming the predominant population in medical schools and will join the workforce in a few years' time. Medicine has undergone serious changes in high-income countries recently. Therefore, it is unclear how attractive the medical profession still is for high school students of Gen Z. The aim of this study was to investigate what motivation leads Gen Z students in their choice to study human medicine, and how they see their professional future. Our study was guided by motivation theory and the influence of personality traits and other personal factors on students' choice of university major. METHODS: In a cross-sectional online survey, we included third- and fourth-year high school students in Northern Switzerland. We examined the importance of criteria when choosing a university major: personality traits, career motivation, life goals, and other considerations influencing the choice of human medicine versus other fields of study. Results Of 1790 high school students, 456 (25.5%) participated in the survey (72.6% women, mean age 18.4 years); 32.7% of the respondents aspired to major in medicine at university. For all respondents, the foremost criterion for selecting a field of study was 'interest in the field,' followed by 'income' and 'job security.' High school students aiming to study human medicine attached high importance to 'meaningful work' as a criterion; supported by 36.2% of those students answering that helping and healing people was a core motivation to them. They also scored high on altruism (p < 0.001 against all groups compared) and intrinsic motivation (p < 0.001) and were highly performance- (p < 0.001) and career-minded (p < 0.001). In contrast, all the other groups except the law/economics group had higher scores on extraprofessional concerns. CONCLUSIONS: Swiss Gen Z students aspiring to study human medicine show high intrinsic motivation, altruism, and willingness to perform, sharing many values with previous generations. Adequate work-life balance and job security are important issues for Gen Z. Regarding the current working conditions, the ongoing shortage of physicians, and recent findings on physicians' well-being, the potential for improvement and optimization is high.

Beyond pigmentation: signs of liver protection during afamelanotide treatment in Swiss patients with erythropoietic protoporphyria, an observational study.

Erythropoietic protoporphyria (EPP) is an ultra-rare inherited disorder with overproduction of protoporphyrin in maturating erythroblasts. This excess protoporphyrin leads to incapacitating phototoxic burns in sunlight exposed skin. Its biliary elimination causes cholestatic liver injury in 20% and terminal liver failure in 4% of EPP patients. Thereby, the risk of liver injury increases with increasing erythrocyte protoporphyrin concentrations. Afamelanotide, an α-melanocyte-stimulating hormone (MSH) analog inducing skin pigmentation, was shown to improve sunlight tolerance in EPP. Beyond this well-known effect on pigmentation, the MSHs have liver-protective effects and improve survival of maturating erythroblasts, effects described in animal or in vitro models to date only. We investigated whether afamelanotide treatment in EPP has effects on erythropoiesis, protoporphyrin concentrations, and liver injury by analyzing retrospectively our long-term safety data. Methods: From the 47 Swiss EPP-patients treated at our center since 2006, we included those 38 patients in the current analysis who received at least one afamelanotide dose between 2016 and 2018 and underwent regular laboratory testing before and during the treatment. We compared the means of pretreatment measurements with those during the treatment. Results: Protoporphyrin concentrations dropped from 21.39 ± 11.12 (mean ± SD) before afamelanotide to 16.83 ± 8.24 µmol/L (p < .0001) during treatment. Aspartate aminotransferase decreased from 26.67 ± 13.16 to 22.9 ± 7.76 IU/L (p = .0146). For both entities, patients with higher values showed a more progressive decrease, indicating a risk reduction of EPP-related liver disease. The pre-existing hypochromia and broad mean red-cell distribution width were further augmented under afamelanotide. This was more likely due to an influence of afamelanotide on maturating erythroblasts than due to an exacerbated iron deficiency, as mean zinc-protoporphyrin decreased significantly and ferritin remained unchanged. No serious afamelanotide-related adverse events were observed for a total of 240 treatment years. Conclusion: Our findings point to a protective effect of afamelanotide on erythroblast maturation and protoporphyrin-induced liver injury. Plain Language summary: Afamelanotide, a skin tanning hormone, may protect patients with erythropoietic protoporphyria not only from skin burns, but also from liver injury associated with the disease. Patients with erythropoietic protoporphyria (EPP), an inherited metabolic disease, suffer from light-induced skin burns and liver injury elicited by the accumulated light sensitizer protoporphyrin. The excess protoporphyrin is produced in red cell precursors in the bone marrow, and it is eliminated from the body via the liver and bile. A high protoporphyrin excretion burden damages the liver cells, the risk for this increases with higher protoporphyrin concentrations. About 20% of EPP patients show some sign of liver injury and 4% develop life-threatening liver dysfunction.Afamelanotide, closely related to natural α-melanocyte stimulating hormone (MSH), induces skin tanning. This effect protects EPP patients from light-induced skin burns as shown in previous studies. We have treated Swiss EPP patients with afamelanotide since 2006, and we regularly perform safety tests of this treatment.Recent in vitro and animal studies demonstrated α-MSH effects other than skin tanning, including an improved synthesis of red blood cell precursors in the bone-marrow and protection of the liver from experimentally induced damage. Until now, it is unknown whether afamelanotide has similar effects in the human organism.To study this question, we analyzed retrospectively the safety laboratory data of 38 Swiss patients, who received at least one dose of afamelanotide from 2016 to 2019. We found that both, the average protoporphyrin concentrations and aspartate aminotransferase, a test for liver function, improved during afamelanotide treatment as compared to before.We concluded that afamelanotide applied to EPP patients to protect them from light-induced skin burns also may reduce their risk of liver injury.

The inter-relationship between depressed mood, functional decline and disability over a 10-year observational period within the Longitudinal Urban Cohort Ageing Study (LUCAS).

BACKGROUND: The WHO defines 'healthy ageing' as 'the process of developing and maintaining the functional ability'. Late-life depression and frailty compromise well-being and independence of older people. To date, there exists little research on the interaction of the dynamic processes of frailty and depression and only a few studies were longitudinal. Conclusions about the direction of effects remained uncertain. METHODS: Data were obtained from each of the last six biyearly waves (2007-2017) of the Longitudinal Urban Cohort Ageing Study (LUCAS) in Hamburg, Germany, a prospective observational cohort study of manifold aspects of ageing. Screening of predictor and event variables: depressed mood: one question from the 5-item Mental Health Inventory Screening Test; frailty: LUCAS Functional Ability Index, status 'frail'; disability: one question on need for human help with basic activities of daily living. Kaplan-Meier curves and Cox's proportional hazards regression were used for time-to-event analyses with shifting baseline. RESULTS: Sample size in 2007 was 2012, average age 76.2 years; ±6.5. Main results were as follows: (1) depression significantly increased the hazard of subsequent frailty (HR=1.581; 95% CI 1.257 to 1.988; p<0.001); (2) frailty significantly increased the hazard of subsequent depression (HR=2.324; 95% CI 1.703 to 3.172; p<0.001); (3) depression significantly increased the hazard of subsequent disability (HR=2.589; 95% CI 1.885 to 3.557; p<0.001) and (4) disability did not significantly increase the hazard of subsequent depression (HR=1.540; 95% CI 0.917 to 2.579; p=0.102). CONCLUSION: Our results suggest an interdependence of the processes of depression and frailty/disability rather than unidirectional dependencies. These observable processes may be representative of underlying unobservable profound life changes. Obviously, there is a need for early screening to initiate appropriate interventions.

What makes internal medicine attractive for the millennial generation? A survey of residents in internal medicine in Switzerland.

AIMS: A new generation of physicians, millennials (also known as Generation Y), are entering residency programmes in internal medicine, and these young men and women learn and work in ways that are different from those of past generations. The aim of the present study was to investigate aspects contributing to the attractiveness to young residents of a career in general internal medicine (GIM) compared with medical subspecialties (SUB). METHODS: In a cross-sectional online survey, we included residents working in residency facilities in GIM in German-speaking Switzerland. A total of 1818 junior residents were eligible. We looked for personal preferences, characteristics, and criteria influencing the choice of a career in GIM or SUB. RESULTS: 392 out of 1818 (22%) residents participated in the survey (66% females); they had been in clinical training for 35.5 months on average. 87% of the respondents aspired to a title in GIM, and 29% of these to a SUB title as well. 71% of the women chose GIM and not a SUB vs 58% of the men (p <0.019). GIM residents gave significantly higher ratings to “broad range of expertise,” “flexible work hours” (p = 0.007), “work-life balance”, and “reconciliation of work, family and private life” than residents aiming at a SUB. SUB residents evaluated career-related criteria as significantly more important (p <0.0001). With regard to career motivation, GIM residents and female residents rated extraprofessional concerns significantly higher than SUB residents did (p = 0.019). In contrast, SUB residents showed significantly higher intrinsic motivation than GIM residents (p = 0.025). Only 28.2% of GIM residents had a mentor, compared to 49.6% of SUB residents (p <0.0005). Concerning personal perceptions of the future within the next 5 years, GIM residents attached significantly more importance to part-time work (p = 0.001), whereas SUB residents attached more importance to getting a leading position as a main goal (p = 0.0001). CONCLUSIONS: There are considerable differences between GIM and SUB residents regarding career motivation and their views on working conditions and work-life balance. It is essential to understand the factors that motivate or deter the next generation in order to ensure the attractiveness of the profession of GIM.  .

[Effectiveness of "Active health promotion in old age" : Results regarding compression of morbidity by target groups in 13.8 years of observation in LUCAS]. / Wirksamkeit der "Aktiven Gesundheitsförderung im Alter" : Zielgruppenspezifische Ergebnisse bezüglich einer Kompression von Morbidität über 13,8 Jahre LUCAS Verlauf.

BACKGROUND AND OBJECTIVE: Healthy ageing as defined by the World Health Organization (WHO) is the development and maintenance of functional competence. Unfavourable ageing is described by the term frailty and is characterised by a decline in functional reserves. The frailty process can be influenced in a positive way. Previous interventions concerned mostly hospital patients and residents of nursing homes. In this study we examined the maintenance of functional competence in an urban community setting. MATERIAL AND METHODS: The programme "Active health promotion in old age" was carried out by a health advisory team with geriatric expertise for independent persons 60 years and older without disabilities. Its effectiveness was evaluated in the Longitudinal Urban Cohort Ageing Study (LUCAS) over a period of 13.8 years. Survival and disability-free survival were calculated separately for persons with a high level of functional competence (many reserves) and persons with few functional reserves, using Kaplan-Meier curves. Adjustments were made for unequal distribution of age, gender, educational level, chronic diseases and functional status using multivariate Cox regressions. This methodology facilitates the study of interrelationships between mortality and morbidity (compression of morbidity) including an impact from life style interventions. RESULTS: Participants with a high level of functional competence had longer disability-free lifes (p < 0.001), and their average proportion of life time with disability was shorter than either for non-participants, or those with low functional competence. CONCLUSION: There is evidence from these analyses on compression of morbidity that the health promotion programme had its strongest effects in persons with high functional competence, exactly those people for whom it has been developed.

Evidence-based design recommendations for prevalence studies on multimorbidity: improving comparability of estimates.

BACKGROUND: In aging populations, multimorbidity causes a disease burden of growing importance and cost. However, estimates of the prevalence of multimorbidity (prevMM) vary widely across studies, impeding valid comparisons and interpretation of differences. With this study we pursued two research objectives: (1) to identify a set of study design and demographic factors related to prevMM, and (2) based on (1), to formulate design recommendations for future studies with improved comparability of prevalence estimates. METHODS: Study data were obtained through systematic review of the literature. UsingPubMed/MEDLINE, Embase, CINAHL, Web of Science, BIOSIS, and Google Scholar, we looked for articles with the terms "multimorbidity," "comorbidity," "polymorbidity," and variations of these published in English or German in the years 1990 to 2011. We selected quantitative studies of the prevalence of multimorbidity (two or more chronic medical conditions) with a minimum sample size of 50 and a study population with a majority of Caucasians. Our database consisted of prevalence estimates in 108 age groups taken from 45 studies. To assess the effects of study design variables, we used meta regression models. RESULTS: In 58% of the studies, there was only one age group, i.e., no stratification by age. The number of persons per age group ranged from 136 to 5.6 million. Our analyses identified the following variables as highly significant: "mean age," "number of age groups", and "data reporting quality" (all p < 0.0001). "Setting," "disease classification," and "number of diseases in the classification" were significant (0.01 < p ≤ 0.03), and "data collection period" and "data source" were non-significant. A separate analysis showed that prevMM was significantly higher in women than men (sign test, p = 0.0015). CONCLUSIONS: Comparable prevalence estimates are urgently needed for realistic description of the magnitude of the problem of multimorbidity. Based on the results of our analyses of variables affecting prevMM, we make some design recommendations. Our suggestions were guided by a pragmatic approach and aimed at facilitating the implementation of a uniform methodology. This should aid progress towards a more uniform operationalization of multimorbidity.

Chronic Pain: How Challenging Are DDIs in the Analgesic Treatment of Inpatients with Multiple Chronic Conditions?

BACKGROUND: Chronic pain is common in multimorbid patients. However, little is known about the implications of chronic pain and analgesic treatment on multimorbid patients. This study aimed to assess chronic pain therapy with regard to the interaction potential in a sample of inpatients with multiple chronic conditions. METHODS AND FINDINGS: We conducted a retrospective study with all multimorbid inpatients aged ≥18 years admitted to the Department of Internal Medicine of University Hospital Zurich in 2011 (n = 1,039 patients). Data were extracted from the electronic health records and reviewed. We identified 433 hospitalizations of patients with chronic pain and analyzed their combinations of chronic conditions (multimorbidity). We then classified all analgesic prescriptions according to the World Health Organization (WHO) analgesic ladder. Furthermore, we used a Swiss drug-drug interactions knowledge base to identify potential interactions between opioids and other drug classes, in particular coanalgesics and other concomitant drugs. Chronic pain was present in 38% of patients with multimorbidity. On average, patients with chronic pain were aged 65.7 years and had a mean number of 6.6 diagnoses. Hypertension was the most common chronic condition. Chronic back pain was the most common painful condition. Almost 90% of patients were exposed to polypharmacotherapy. Of the chronic pain patients, 71.1% received opioids for moderate to severe pain, 43.4% received coanalgesics. We identified 3,186 potential drug-drug interactions, with 17% classified between analgesics (without coanalgesics). CONCLUSIONS: Analgesic drugs-related DDIs, in particular opioids, in multimorbid patients are often complex and difficult to assess by using DDI knowledge bases alone. Drug-multimorbidity interactions are not sufficiently investigated and understood. Today, the scientific literature is scarce for chronic pain in combination with multiple coexisting medical conditions and medication regimens. Our work may provide useful information to enable further investigations in multimorbidity research within the scope of potential interactions and chronic pain.

[Comparability of studies of epidemiological research on aging : Results from the Longitudinal Urban Cohort Ageing Study (LUCAS) and three representative Hamburg cross-sectional studies of healthy aging]. / Vergleichbarkeit von Studien epidemiologischer Alternsforschung : Ergebnisse aus der Longitudinalen Urbanen Cohorten-Alters-Studie (LUCAS) und drei repräsentativen Hamburger Querschnitt-Studien zur Gesundheit im Alter.

BACKGROUND: Participants of the Longitudinal Urban Cohort Ageing Study (LUCAS) were recruited from patients 60 years and older from general practitioner's offices in Hamburg. This is different from the usual methods of drawing representative samples. OBJECTIVES: The research question addressed the comparability of LUCAS results with those from cross-sectional surveys with participants randomly chosen from a population list. Therefore, the LUCAS data collected in four waves during the first 12 years were compared with data (age, gender) from the Hamburg Statistics Office (HSO), and selected characteristics (socio-demography, health, mobility) from three representative cross-sectional surveys in older Hamburg citizens. METHODS: First, HSO data compiled in population pyramids for older men and women were compared with equivalent pyramids based on the LUCAS data at recruitment (2000/01) and in waves 2 to 4. Second, characteristics worded identically in the cross-sectional surveys and the simultaneous LUCAS waves were compared. RESULTS: The LUCAS population pyramids were in good accordance at all time points with those of the general older population in Hamburg (except ages 60-64 in men in 2000). Good comparability was also found for health related characteristics from the three representative studies and simultaneous LUCAS waves (e. g. need of nursing care in 2012: LUCAS 7.1 %; Hamburg 7.4 %). CONCLUSIONS: Information on health in old age generated periodically in the LUCAS cohort was largely comparable with that from representative cross-sectional studies and statistics registries. Older people are frequently under-represented in epidemiological studies. Therefore, the LUCAS data may provide useful information for Hamburg and similar metropolitan areas in Germany.

Long-term prediction of changes in health status, frailty, nursing care and mortality in community-dwelling senior citizens­results from the Longitudinal Urban Cohort Ageing Study (LUCAS).

BACKGROUND: The detection of incipient functional decline in elderly persons is not an easy task. Here, we propose the self-reporting Functional Ability Index (FA index) suitable to screen functional competence in senior citizens in the community setting. Its prognostic validity was investigated in the Longitudinal Urban Cohort Ageing Study (LUCAS). METHODS: This index is based equally on both, resources and risks/functional restrictions which precede ADL limitations. Since 2001, the FA index was tested in the LUCAS cohort without any ADL restrictions at baseline (n = 1,679), and followed up by repeated questionnaires in Hamburg, Germany. RESULTS: Applying the index, 1,022 LUCAS participants were initially classified as Robust (60.9%), 220 as postRobust (13.1%), 172 as preFrail (10.2%) and 265 as Frail (15.8%). This classification correlated with self-reported health, chronic pain and depressive mood (rank correlations 0.42, 0.26, 0.21; all p < .0001). Survival analyses showed significant differences between these classes as determined by the FA index: the initially Robust survived longest, the Frail shortest (p < .0001). Analyses of the time to need of nursing care revealed similar results. Significant differences persisted after adjustment for age, sex and self-reported health. CONCLUSIONS: Disability free lifetime and its development over time are important topics in public health. In this context, the FA index presented here provides answers to two questions. First, how to screen the heterogeneous population of community-dwelling senior citizens, i.e. for their functional ability/competence, and second, how far away they are from disability/dependency. Furthermore, the index provides a tool to address the urgent question whether incipient functional decline/incipient frailty can be recognized early to be influenced positively. The FA index predicted change in functional status, future need of nursing care, and mortality in an unselected population of community-dwelling seniors. It implies an operational specification of the classification into Robust, postRobust, preFrail and Frail. Based on a self-administered questionnaire, the FA index allows easy screening of elderly persons for declining functional competence. Thereby, incipient functional decline is recognized, e.g. in GPs' practices and senior community health centers, to initiate early appropriate preventive action.

Overcoming cut-off restrictions in multimorbidity prevalence estimates.

BACKGROUND: Presently, there is no consensus on how to define multimorbidity. In this paper we investigate the connection between prevalence estimates for two or more and three or more chronic conditions to improve comparability of multimorbidity studies with different cut-offs. METHODS: In a systematic review of the literature published between January, 1990 and December, 2011, we found 52 suitable studies, many providing prevalence estimates for several age groups. A total of 31 studies reported both the prevalence for multimorbidity based on two or more chronic conditions and three or more chronic conditions, which were analysed in this study. Our research question was whether there is a systematic interrelation between these two prevalence estimates, and how this could be used to improve the comparability of studies on the burden of multimorbidity. RESULTS: Actually, we found a tight relationship between the prevalence of two or more and three or more chronic conditions. Moreover, each of these estimates can be predicted from the other. I.e. the cut-offs of two or three for the number of chronic conditions produce essentially the same information on prevalence. CONCLUSIONS: Our study shows a way to enhance and improve the comparability of prevalence estimates from different multimorbidity studies.

Patient characteristics and patterns of intoxication: one-time and repeated use of emergency ambulance services.

OBJECTIVE: The aim of this study was to investigate the utilization of ambulance services that resulted from alcohol and drug intoxication over a period of 1 year in a metropolitan area, with an emphasis on characteristic differences between patients with one-time versus repeated use. METHOD: All ambulance-service report forms filed in 2010 were systematically screened for utilizations in which alcohol intoxication or intoxication resulting from consumption of illicit or legal drugs other than alcohol was the chief complaint (N = 2,341 patients; 65% male). RESULTS: Repeat users differed from persons with one-time use in their characteristics and patterns of intoxication. On average, patients with repeated ambulance use were almost 8 years older and had a different pattern of ambulance use over the course of the week with no clear peak on any specific day. The mean number of ambulance services in patients with repeated use was 2.8 (SD = 1.517) in the 1-year study period. Repeat users were less likely to be injured than patients with one-time ambulance-service use and more often showed aggression or uncooperative behavior toward paramedics. All cases of death associated with intoxication involved patients with one-time ambulance use. CONCLUSIONS: The ambulance-service users' generally slight impairment of consciousness and the high proportion of intoxicated patients without any injuries raise the question of how many of these patients could be adequately cared for in a sobering center. Sobering centers might relieve hospital emergency departments of patients not requiring acute emergency care and, in addition, could provide intervention services to prevent relapses.

The Longitudinal Urban Cohort Ageing Study (LUCAS): study protocol and participation in the first decade.

BACKGROUND: We present concept, study protocol and selected baseline data of the Longitudinal Urban Cohort Ageing Study (LUCAS) in Germany. LUCAS is a long-running cohort study of community-dwelling seniors complemented by specific studies of geriatric patients or diseases. Aims were to (1) Describe individual ageing trajectories in a metropolitan setting, documenting changes in functional status, the onset of frailty, disability and need of care; (2) Find determinants of healthy ageing; (3) Assess long-term effects of specific health promotion interventions; (4) Produce results for health care planning for fit, pre-frail, frail and disabled elderly persons; (5) Set up a framework for embedded studies to investigate various hypotheses in specific subgroups of elderly. METHODS/DESIGN: In 2000, twenty-one general practitioners (GPs) were recruited in the Hamburg metropolitan area; they generated lists of all their patients 60 years and older. Persons not terminally ill, without daily need of assistance or professional care were eligible. Of these, n = 3,326 (48 %) agreed to participate and completed a small (baseline) and an extensive health questionnaire (wave 1). In 2007/2008, a re-recruitment took place including 2,012 participants: 743 men, 1,269 women (647 deaths, 197 losses, 470 declined further participation). In 2009/2010 n = 1,627 returned the questionnaire (90 deaths, 47 losses, 248 declined further participation) resulting in a good participation rate over ten years with limited and quantified dropouts. Presently, follow-up data from 2007/2008 (wave 2) and 2009/2010 (wave 3) are available. Data wave 4 is due in 2011/2012, and the project will be continued until 2013. Information on survival and need of nursing care was collected continuously and cross-checked against official records. We used Fisher's exact test and t-tests. The study served repeatedly to evaluate health promotion interventions and concepts. DISCUSSION: LUCAS shows that a cohort study of older persons is feasible and can maintain a good participation rate over ten years, even when extensive self-reported health data are collected repeatedly through self-filled questionnaires. Evidently individual health developments of elderly persons can be tracked quantifying simultaneously behaviour, co-morbidity, functional competence and their changes. In future, we expect to generate results of significance about the five study aims listed above.

Ten-year trends in intoxications and requests for emergency ambulance service.

BACKGROUND: Intoxication, whether from alcohol, drugs, or alcohol and drugs in combination, remains a challenging burden on emergency departments. The increasing alcohol consumption among adolescents and young adults, particularly heavy episodic drinking, and the resulting increase in the use of health care resources for alcohol intoxication has been a widely discussed topic. OBJECTIVE: The aim of our study was to assess and characterize the use of emergency ambulance services that was required as a result of alcohol and drug intoxication in a major metropolitan area. METHODS: We conducted a retrospective, longitudinal study over a 10-year period in the greater metropolitan area of Zurich, Switzerland. The study population included intoxicated patients assessed and initially treated by paramedics of the emergency ambulance service. Data were extracted from the ambulance service reports. The primary outcomes measured were trends over time in the numbers and types of intoxication and trends with respect to gender and age distributions of intoxicated patients. RESULTS: An annual increase of about 5% in the number of intoxicated patients requiring emergency ambulance service was observed over the study period. Alcohol use was present in 73% of the cases. The highest number of cases was among patients 25-44 years of age. The greatest increase in the number of cases over time was among patients under 25 years of age. Women comprised 41% of the patients under 25 years of age but only about 35% of older patients. The number of severe injuries and suicide attempts was small, but the number of suicide attempts increased at a higher rate than the overall number of cases of intoxication. There was a significant increase (17.64% per year on average) in the incidence of aggressive behavior toward paramedics from intoxicated patients, although still small in numbers. CONCLUSIONS: Our findings suggest two main vulnerable groups: young persons under 25 years of age, with a particular focus on women, having the greatest increase over time, and middle-aged men, having the greatest proportion among all cases observed. Intervention efforts should include a high-risk approach to reduce alcohol-related problems. Key words: alcohol intoxication; substance-related disorders; aggression; injuries; emergency medical services.

Clinical competence of biopsychosocially trained physicians and controls.

OBJECTIVE: To assess and compare clinical observations and interpretations by physicians trained in biopsychosocial internal medicine (group A) and a control group (C) of physicians with no such special training. METHODS: A verbatim first-interview of a 36-year old woman, seen for consultation by RHA, was presented to both groups (A, trained physicians: n = 30, and C, controls: n = 29). The patient's symptoms included: shaky knees, strange sensations in the abdomen and chest, insecurity and dizziness. The symptoms had begun before her final nursing- exam and exacerbated on her mother's 60th birthday two months later. The patient's mother is the sole caretaker for the patient's sister, who also attended the birthday party. The patient's sister is 19 and had been diagnosed with storage disease and is wheelchair-bound. The doctors were asked to record their observations and interpretations while reviewing the case report. RESULTS: Group A-physicians mentioned and interpreted the physician-patient relationship and the patient's body language as described in the case report more often (p = 0.002, Wilcoxon-Mann-Whitney rank sum test (RS)), mentioned physical symptoms more often (p = 0.0099, Fisher's exact test (FE)) and more often interpreted illness settings with respect to the patient's fear and guilt (Fisher's exact test, p = 0.007 and p = 0.015). A precise integrative diagnosis (life events leading to stress, the latter evoking fear and guilt, leading to symptoms of the fight-flight reaction) was suggested by 7 of group A and 4 of group C. Extensive laboratory work-up and requests for consultations were more frequently asked for by the C group (p = 0.048, RS). CONCLUSION: Residency training in biopsychosocial medicine in an Internal Medicine Department increased sensitivity to and interpretation of biological and psychosocial data many years after the training and decreased the extent of work-up and consultation costs. However it only tended to enhance psychosomatic conceptualisation with respect to anxiety/guilt/hyperventilation and conversion symptoms.

A simple approach to fairer hospital benchmarking using patient experience data.

OBJECTIVE: To determine the factors contributing most to variability in patient experience in order to present approaches for fairer benchmarking of hospitals and for quality improvement. DESIGN: Secondary analysis of data from a widely used survey on patient experience. SETTING: Inpatients from all 24 acute hospitals in the Canton of Bern in Switzerland. Data collection followed the standardized and validated Picker Institute methodology for a period of 13 weeks in the fall/winter of 2005. PARTICIPANTS: Inpatients age 18 years and older (n = 14 089), discharged within the sampling period. MAIN OUTCOME MEASURES: 'Patient experience', measured by the total Picker Problem Score (PPS) and by six domain scores (care, communication, respect, cooperation, organization, discharge management). RESULTS: In regression analysis, the patient factors self-reported health, age and education explained the highest proportion of variability in the PPS (4.8, 2.2 and 0.7%, respectively). Multiple linear adjustment for factors associated with patients removed between 29 and 33% of variability between hospital categories. The domain score means varied from under 5% for 'respect towards the patient' to 34% for 'discharge management'. Ranking of hospitals by domain scores differed from the ranking based on the total PPS. CONCLUSIONS: Statistical adjustment for patient mix and additional stratification for some hospital factors make benchmarking using patient survey data fairer and more transparent. Use of our approach for presenting quality data may make interpretation easier for the different target groups and may enhance the relevance of such information for decision-making.

Adverse event assessment of antimuscarinics for treating overactive bladder: a network meta-analytic approach.

BACKGROUND: Overactive bladder (OAB) affects the lives of millions of people worldwide and antimuscarinics are the pharmacological treatment of choice. Meta-analyses of all currently used antimuscarinics for treating OAB found similar efficacy, making the choice dependent on their adverse event profiles. However, conventional meta-analyses often fail to quantify and compare adverse events across different drugs, dosages, formulations, and routes of administration. In addition, the assessment of the broad variety of adverse events is dissatisfying. Our aim was to compare adverse events of antimuscarinics using a network meta-analytic approach that overcomes shortcomings of conventional analyses. METHODS: Cochrane Incontinence Group Specialized Trials Register, previous systematic reviews, conference abstracts, book chapters, and reference lists of relevant articles were searched. Eligible studies included randomized controlled trials comparing at least one antimuscarinic for treating OAB with placebo or with another antimuscarinic, and adverse events as outcome measures. Two authors independently extracted data. A network meta-analytic approach was applied allowing for joint assessment of all adverse events of all currently used antimuscarinics while fully maintaining randomization. RESULTS: 69 trials enrolling 26'229 patients were included. Similar overall adverse event profiles were found for darifenacin, fesoterodine, transdermal oxybutynin, propiverine, solifenacin, tolterodine, and trospium chloride but not for oxybutynin orally administered when currently used starting dosages were compared. CONCLUSIONS: The proposed generally applicable transparent network meta-analytic approach summarizes adverse events in an easy to grasp way allowing straightforward benchmarking of antimuscarinics for treating OAB in clinical practice. Most currently used antimuscarinics seem to be equivalent first choice drugs to start the treatment of OAB except for oral oxybutynin dosages of ≥ 10 mg/d which may have more unfavorable adverse event profiles.

A randomized trial of effects of health risk appraisal combined with group sessions or home visits on preventive behaviors in older adults.

BACKGROUND: To explore effects of a health risk appraisal for older people (HRA-O) program with reinforcement, we conducted a randomized controlled trial in 21 general practices in Hamburg, Germany. METHODS: Overall, 2,580 older patients of 14 general practitioners trained in reinforcing recommendations related to HRA-O-identified risk factors were randomized into intervention (n = 878) and control (n = 1,702) groups. Patients (n = 746) of seven additional matched general practitioners who did not receive this training served as a comparison group. Patients allocated to the intervention group, and their general practitioners, received computer-tailored written recommendations, and patients were offered the choice between interdisciplinary group sessions (geriatrician, physiotherapist, social worker, and nutritionist) and home visits (nurse). RESULTS: Among the intervention group, 580 (66%) persons made use of personal reinforcement (group sessions: 503 [87%], home visits: 77 [13%]). At 1-year follow-up, persons in the intervention group had higher use of preventive services (eg, influenza vaccinations, adjusted odds ratio 1.7; 95% confidence interval 1.4-2.1) and more favorable health behavior (eg, high fruit/fiber intake, odds ratio 2.0; 95% confidence interval 1.6-2.6), as compared with controls. Comparisons between intervention and comparison group data revealed similar effects, suggesting that physician training alone had no effect. Subgroup analyses indicated favorable effects for HRA-O with personal reinforcement, but not for HRA-O without reinforcement. CONCLUSIONS: HRA-O combined with physician training and personal reinforcement had favorable effects on preventive care use and health behavior.

Patient-recorded outcome to assess therapeutic efficacy in protoporphyria-induced dermal phototoxicity: a proposal.

BACKGROUND: Protoporphyria (PP) resulting from two rare, inherited diseases of heme biosynthesis leads to dermal phototoxicity by accumulation of the heme precursor protoporphyrin IX. No standardized tools to quantify the degree of PP-related phototoxicity and its change by medical intervention have been published. METHODS: Results from a questionnaire completed by 17 affected individuals were used to determine the relative importance of two main components of PP-related phototoxicity, skin pain and sunlight exposure time, with respect to the effectiveness of any particular medical treatment. RESULTS: Inter-rater reliability was 0.71 (n = 490), repeated estimates by four identical individuals showed high reproducibility (Slope = 1, intercept = 0, n = 136, Passing-Bablock).Six different models were developed, three of them showed good correlation with effectiveness estimates. Data from an unpublished trial indicated that the model with highest potential of responsiveness was the so called "Exposure times [multiplied by] Freedom from Pain" (ETFP). The minimal clinically important difference (MID) was 15 (10.2-20.4) ETFP scores, representing 28% of the standard deviation of the clinical trial data and 2.9% of its total range. CONCLUSIONS: Among the six models proposed to assess the effectiveness of therapeutic interventions in PP the ETFP model demonstrates the highest sensitivity using the existing data from a clinical trial of afamelanotide in PP. The results of this study have provided sufficient validation of the ETFP model that is likely to prove useful in future clinical trials.