The role of qualification and quality management in the prescription of antipsychotics and potentially inappropriate medication (PIM) in nursing home residents in Germany: results of the HIOPP-3-iTBX study.

BACKGROUND: Nursing home residents (NHR) show high rates of polypharmacy. The HIOPP-3-iTBX study is the first cRCT on medication optimization in nursing homes (NH) in Germany. The intervention did not result in a reduction of PIM and/or antipsychotics. This analysis looks at structure quality in the HIOPP-3-iTBX study participants. AIMS: Evaluation of structure quality as part of a cluster-randomized controlled intervention study. METHODS: Structure quality in multiprofessional teams from n = 44 NH (n = 44 NH directors, n = 91 family doctors (FD), and n = 52 pharmacies with n = 62 pharmacists) was assessed using self-designed questionnaires at baseline. Main aspects of the questionnaires related to the qualification of participants, quality management, the medication process and size of the facilities. All completed questionnaires were included. number of PIM/antipsychotics was drawn from the baseline medication analysis in 692 NHR. Data were analyzed by descriptive statistics and mixed model logistic regression. RESULTS: The presence of a nurse with one of the additional qualifications pain nurse or Zertifiziertes Curriculum (Zercur) Geriatrie in the participating NH was associated with a lower risk for the prescription of PIM/antipsychotics. No association between any characteristic in the other participants at baseline was observed. CONCLUSIONS AND DISCUSSION: The results support the known role of nursing qualification in the quality and safety of care. Further studies need to look more closely at how use is made of the additional qualifications within the multiprofessional teams. Perspectively, the results can contribute to the development of quality standards in NH in Germany.

Drug Safety for Nursing-Home Residents-Findings of a Pragmatic, Cluster-Randomized, Controlled Intervention Trialin 44 Nursing Homes.

BACKGROUND: The safety of drug use by nursing-home residents can be impaired by polypharmacy, potentially inappropriate medications (PIM), and neuroleptics, as well as by a lack of adequate interprofessional coordination in the nursing home. The goal of the HIOPP-3-iTBX Trial was to improve drug safety in nursing-home residents, including a reduction of PIM and/or neu - roleptic use, by means of a complex interprofessional intervention. METHODS: This cluster-randomized, controlled trial was performed in nursing homes in Germany. Residents over age 65 were included in the trial. The intervention was carried out over six months and consisted of four elements: a drug review by trained pharmacists, educational sessions for general practitioners and nurses, a drug safety toolbox, and change management seminars for members of the three participating professions. The nursing homes in the control group continued to provide usual care. The primary endpoint was the prescription of at least one PIM and/or at least two neuroleptic drugs simultaneously. The secondary endpoints were the incidence of falls and hospitalizations, quality of life, and health-care costs. This trial is registered in the German Clinical Trials Registry (DRKS00013588). RESULTS: 44 nursing homes with 862 residents were randomized, 23 of them (with 452 residents) to the intervention group and 21 (with 410 residents) to the control group. 41% of all nursing-home residents initially took at least one PIM and/or at least two neuroleptic drugs simultaneously. Follow-up data (including, among other things, the current drug regimen) were obtained for 773 residents. The intention-to-treat analysis continued to show no difference between the intervention group and the control group with respect to the primary endpoint. CONCLUSION: This trial of an intervention to improve drug safety in nursing homes led neither to reduced prescribing of PIM and/or neuroleptic drugs, nor to any improvement in the overall health status of the nursing-home residents.

Non-random relations in drug use expressed as patterns comprising prescription and over-the-counter drugs in multimorbid elderly patients in primary care: Data of the exploratory analysis of the multicentre, observational cohort study MultiCare.

BACKGROUND: The elderly population deals with multimorbidity (three chronic conditions) and increasinged drug use with age. A comprehensive characterisation of the medication - including prescription and over-the-counter (OTC) drugs - of elderly patients in primary care is still insufficient. OBJECTIVES: This study aims to characterise the medication (prescription and OTC) of multimorbid elderly patients in primary care and living at home by identifying drug patterns to evaluate the relationship between drugs and drug groups and reveal associations with recently published multimorbidity clusters of the same cohort. METHODS: MultiCare was a multicentre, prospective, observational cohort study of 3189 multimorbid patients aged 65 to 85 years in primary care in Germany. Patients and general practitioners were interviewed between 2008 and 2009. Drug patterns were identified using exploratory factor analysis. The relations between the drug patterns with the three multimorbidity clusters were analysed with Spearman-Rank-Correlation. RESULTS: Patients (59.3% female) used in mean 7.7 drugs; in total 24,535 drugs (23.7% OTC) were detected. Five drug patterns for men (drugs for obstructive pulmonary diseases (D-OPD), drugs for coronary heart diseases and hypertension (D-CHD), drugs for osteoporosis (D-Osteo), drugs for heart failure and drugs for pain) and four drug patterns for women (D-Osteo, D-CHD, D-OPD and drugs for diuretics and gout) were detected. Significant associations between multimorbidity clusters and drug patterns were detectable (D-CHD and CMD: male: ρ = 0.376, CI 0.322-0.430; female: ρ = 0.301, CI 0.624-0.340). CONCLUSION: The drug patterns demonstrate non-random relations in drug use in multimorbid elderly patients and systematic associations between drug patterns and multimorbidity clusters were found in primary care.

Home-based training program in patients with chronic heart failure and reduced ejection fraction: a randomized pilot study

OBJECTIVES: We aimed to compare the effects of home-and center-based exercise training programs on functional capacity, inspiratory muscle strength, daily physical activity level, and quality of life (QoL) in patients with chronic heart failure (CHF) over a 12-week period. METHODS: This study included 23 patients with CHF (left ventricular ejection fraction 31±6%) randomized to a home-based (n=11) or center-based (n=12) program. Patients underwent 12 weeks of aerobic training (60%-70% heart rate reserve): walking for the home-based and supervised cycling for the center-based group, both combined with resistance training (50% of 1 maximum repetition). At baseline and after 12 weeks of training, we assessed cardiopulmonary test variables, 6-min walk test distance (6 MWD), steps/day with accelerometry, and QoL (Minnesota Living with Heart Failure questionnaire). Maximal inspiratory pressure and handgrip strength were measured at baseline and after 4, 8, and 12 weeks of training. ClinicalTrials.gov: NCT03615157. RESULTS: There were no adverse events during training in either group. The home- and center-based training groups obtained similar improvements in peak oxygen uptake, maximal ventilation, and 6 MWD. However, there were significant between-group differences: center-based training was more effective in improving maximal inspiratory pressure (p=0.042), number of steps/day (p=0.001), and QoL (p=0.039). CONCLUSIONS: Home-based training is safe and can be an alternative to improve the exercise capacity of patients with stable CHF. However, center-based training was superior in improving inspiratory muscle strength, QoL, and daily physical activity.

Lifestyle Aspects As A Predictor Of Pain Among Oldest-Old Primary Care Patients - A Longitudinal Cohort Study.

PURPOSE: Dealing with the high prevalence of pain among the oldest-old (+75) is becoming a major health issue. Therefore, the aim of the study was to uncover health-related lifestyle behaviors (HLB) and age-related comorbidities which may predict, influence and prevent pain in old age. PATIENTS AND METHODS: In this longitudinal cohort study, data were obtained initially from 3.327 individuals aged 75+ from over 138 general practitioners (GP) during structured clinical interviews in 2003. Nine follow-ups (FU) were assessed until 2017. Available data from 736 individuals scoring in FU3 and FU7 were included in this analysis. Data were assembled in an ambulatory setting at participant's homes. Associations were tested using a linear regression model (model 1) and ordered logistic regression model (model 2). RESULTS: Statistical analyses revealed increased likelihood to experience pain for participants with comorbidities such as peripheral arterial disease (PAD) (coef. 13.51, P>t = 0.00) or chronic back pain (CBP) (coef. 6.64, P>t = 0.003) or higher body mass index (BMI) (coef. 0.57, P>t = 0.015) and, female gender (coef. 6.00, SE 3.0, t = 2.02, P>t = 0.044). Participants with medium education and former smokers showed significantly lower pain rating (coef. -5.05, P>t = 0.026; coef. -5.27, P>t = 0.026). Suffering from chronic back pain (OR = 2.03), osteoarthritis (OR = 1.49) or depressive symptoms (OR = 1.10) raised the odds to experience impairments in daily living due to pain. Physical activity showed no significant results. CONCLUSION: Chronic conditions such as PAD, or CBP, female gender and higher BMI may increase the risk of experiencing more pain while successful smoking cessation can lower pain ratings at old age. Early and consistent support through GPs should be given to older patients in order to prevent pain at old age.

Health behaviour, social support, socio-economic status and the 5-year progression of multimorbidity: Results from the MultiCare Cohort Study.

BACKGROUND: Multimorbidity in elderly patients is a major challenge for physicians, because of a high prevalence of and associations with many adverse outcomes. However, the mechanisms of progressing multimorbidity are not well-understood. The aim of our study was to determine if the progression of multimorbidity is influenced by health behaviour and social support and to analyse if the patients' socio-economic status had an effect on these prognostic factors. METHODS: The study was designed as prospective cohort study based on interviews of 158 GPs and 3189 patients randomly selected from GP records (response rate: 46.2%). Patients were aged 65-85 years at recruitment and observed in four waves of data collection (dropout rate: 41.5%). Statistical analyses of the 'hot deck' imputed data included multilevel mixed-effects linear regression allowing for random effects at the study centre and GP practice within study centre level. RESULTS: Regarding cardiovascular and metabolic diseases, multimorbidity progressed more rapidly in patients who reported less physical activity (ß = -0.28; 95% confidence interval = -0.35 to -0.20), had more tobacco-related pack years (0.15; 0.07-0.22) and consumed less alcohol (-0.21; -0.31 to -0.12) at baseline. Multimorbidity related to psychiatric and pain-related disorders progressed more rapidly if the patients had less perceived social support (-0.31; -0.55 to -0.07) and reported less physical activity (-0.08; -0.15 to -0.02) at baseline. Education and income only slightly modified the effects of these variables. CONCLUSION: Depending on the multimorbidity cluster, different strategies should be used for slowing down the progression of multimorbidity. Changing lifestyle and increasing social support are beneficial for the entire group of elderly multimorbid patients - regardless of their socio-economic status. REGISTRATION: ISRCTN89818205.

Prevalence of pain and its associated factors among the oldest-olds in different care settings - results of the AgeQualiDe study.

BACKGROUND: The prevalence of pain is very common in the oldest age group. Managing pain successfully is a key topic in primary care, especially within the ageing population. Different care settings might have an impact on the prevalence of pain and everyday life. METHODS: Participants from the German longitudinal cohort study on Needs, Health Service Use, Costs and Health-related Quality of Life in a large Sample of Oldest-old Primary Care Patients (85+) (AgeQualiDe) were asked to rate their severity of pain as well as the impairment with daily activities. Besides gender, age, education, BMI and use of analgesics we focused on the current housing situation and on cognitive state. Associations of the dependent measures were tested using four ordinal logistic regression models. Model 1 and 4 consisted of the overall sample, model 2 and 3 were divided according to no cognitive impairment (NCI) and mild cognitive impairment (MCI). RESULTS: Results show a decline in pain at very old age but nonetheless a high prevalence among the 85+ year olds. Sixty-three per cent of the participants report mild to severe pain and 69% of the participants mild to extreme impairment due to pain with daily activities. Use of analgesics, depression and living at home with care support are significantly associated with higher and male gender with lower pain ratings. CONCLUSIONS: Sufficient pain management among the oldest age group is inevitable. Outpatient care settings are at risk of overlooking pain. Therefore focus should be set on pain management in these settings.

Membranous CD24 expression as detected by the monoclonal antibody SWA11 is a prognostic marker in non-small cell lung cancer patients.

BACKGROUND: Lung cancer is one of the most common malignant neoplasms worldwide and has a high mortality rate. To enable individualized therapy regimens, a better understanding of the molecular tumor biology has still to be elucidated. The expression of the cell surface protein CD24 has already been claimed to be associated with shorter patient survival in non-small cell lung cancer (NSCLC), however, the prognostic value and applicability of CD24 immunostaining in paraffin embedded tissue specimens has been questioned due to the recent acknowledgement of restricted epitope specificity of the commonly used antibody SN3b. METHODS: A cohort of 137 primary NSCLC cases was immunostained with a novel CD24 antibody (clone SWA11), which specifically recognizes the CD24 protein core and the resulting expression data were compared with expression profiles based on the monoclonal antibody SN3b. Furthermore, expression data were correlated to clinico-pathological parameters. Univariate and multivariate survival analyses were conducted with Kaplan Meier estimates and Cox regression, respectively. RESULTS: CD24 positivity was found in 34 % resp. 21 % (SN3b) of NSCLC with a membranous and/or cytoplasmic staining pattern. Kaplan-Meier analyses revealed that membranous, but not cytoplasmic CD24 expression (clone SWA11) was associated with lympho-nodular spread and shorter overall survival times (both p < 0.05). CD24 expression established by SN3b antibodies did not reveal significant clinicopathological correlations with overall survival, neither for cytoplasmic nor membranous CD24 staining. CONCLUSIONS: Membranous CD24 immunoreactivity, as detected with antibody clone SWA11 may serve as a prognostic factor for lymphonodular spread and poorer overall survival. Furthermore, these results corroborate the importance of a careful distinction between membranous and cytoplasmic localisation, if CD24 is to be considered as a potential prognostic biomarker.

Is the Short Form of the Mini-Mental State Examination (MMSE) a better screening instrument for dementia in older primary care patients than the original MMSE? Results of the German study on ageing, cognition, and dementia in primary care patients (AgeCoDe).

The aim of the study was to investigate the psychometric properties of a Short Form of the Mini-Mental State Examination (SMMSE) for the screening of dementia in older primary care patients. Data were obtained from a large longitudinal cohort study of initially nondemented individuals recruited via primary care chart registries and followed at 18-month intervals. Item and scale parameters for MMSE and SMMSE scores were analyzed and cross-validated for 2 follow-up assessments (n1 = 2,657 and n2 = 2,274). Binary logistic regression and receiver-operating-characteristic (ROC) curve analyses were conducted in order to assess diagnostic accuracy parameters for MMSE and SMMSE scores. Cross-sectional differentiation between dementia-free and dementia patients yielded moderate to good results for MMSE and SMMSE scores. With regard to most diagnostic accuracy parameters, SMMSE scores did not outperform the MMSE scores. The current study provides first evidence regarding the psychometric properties of the SMMSE score in a sample of older primary care patients. However, our findings do not confirm previous findings that the SMMSE is a more accurate screening instrument for dementia than the original MMSE. Further studies are needed in order to assess and to develop short, reliable and valid instruments for routine cognitive screening in clinical practice and primary care settings.

Risk of dementia in elderly patients with the use of proton pump inhibitors.

Drugs that modify the risk of dementia in the elderly are of potential interest for dementia prevention. Proton pump inhibitors (PPIs) are widely used to reduce gastric acid production, but information on the risk of dementia is lacking. We assessed association between the use of PPIs and the risk of dementia in elderly people. Data were derived from a longitudinal, multicenter cohort study in elderly primary care patients, the German Study on Aging, Cognition and Dementia in Primary Care Patients (AgeCoDe), including 3,327 community-dwelling persons aged ≥ 75 years. From follow-up 1 to follow-up 4 (follow-up interval 18 months), we identified a total of 431 patients with incident any dementia, including 260 patients with Alzheimer's disease. We used time-dependent Cox regression to estimate hazard ratios of incident any dementia and Alzheimer's disease. Potential confounders included in the analysis comprised age, sex, education, the Apolipoprotein E4 (ApoE4) allele status, polypharmacy, and the comorbidities depression, diabetes, ischemic heart disease, and stroke. Patients receiving PPI medication had a significantly increased risk of any dementia [Hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.04-1.83] and Alzheimer's disease (HR 1.44, 95% CI 1.01-2.06) compared with nonusers. Due to the major burden of dementia on public health and the lack of curative medication, this finding is of high interest to research on dementia and provides indication for dementia prevention.

Obesity and associated lifestyle in a large sample of multi-morbid German primary care attendees.

BACKGROUND: Obesity and the accompanying increased morbidity and mortality risk is highly prevalent among older adults. As obese elderly might benefit from intentional weight reduction, it is necessary to determine associated and potentially modifiable factors on senior obesity. This cross-sectional study focuses on multi-morbid patients which make up the majority in primary care. It reports on the prevalence of senior obesity and its associations with lifestyle behaviors. METHODS: A total of 3,189 non-demented, multi-morbid participants aged 65-85 years were recruited in primary care within the German MultiCare-study. Physical activity, smoking, alcohol consumption and quantity and quality of nutritional intake were classified as relevant lifestyle factors. Body Mass Index (BMI, general obesity) and waist circumference (WC, abdominal obesity) were used as outcome measures and regression analyses were conducted. RESULTS: About one third of all patients were classified as obese according to BMI. The prevalence of abdominal obesity was 73.5%. Adjusted for socio-demographic variables and objective and subjective disease burden, participants with low physical activity had a 1.6 kg/m2 higher BMI as well as a higher WC (4.9 cm, p<0.001). Current smoking and high alcohol consumption were associated with a lower BMI and WC. In multivariate logistic regression, using elevated WC and BMI as categorical outcomes, the same pattern in lifestyle factors was observed. Only for WC, not current but former smoking was associated with a higher probability for elevated WC. Dietary intake in quantity and quality was not associated with BMI or WC in either model. CONCLUSIONS: Further research is needed to clarify if the huge prevalence discrepancy between BMI and WC also reflects a difference in obesity-related morbidity and mortality. Yet, age-specific thresholds for the BMI are needed likewise. Encouraging and promoting physical activity in older adults might a starting point for weight reduction efforts.

Tuberous-sclerosis complex-related cell signaling in the pathogenesis of lung cancer.

BACKGROUND: Hamartin (TSC1) and tuberin (TSC2), encoded by the tuberous sclerosis complex (TSC) genes, form a tumor-suppressor heterodimer which is implicated in PI3K-Akt signaling and acts as a functional inhibitor of the mammalian target of rapamycin (mTOR). Dysregulation of mTOR has been assigned to carcinogenesis and thus may be involved in cancer development. We have addressed the role of hamartin, phospho-tuberin (p-TSC2) and phospho-mTOR (p-mTOR) in a series of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) samples. METHODS: We collected 166 NSCLC and SCLC samples for immunohistochemical studies and performed western blot analyses in NSCLC and SCLC cell lines as well as comparative analyses with EGFR phosphorylation and downstream effectors. RESULTS: In cell lines we found an inverse correlation between hamartin and p-mTOR expression. In surgical specimens cytoplasmic hamartin expression was observed in more than 50% of adenocarcinoma (AC) and squamous cell carcinoma (SCC) compared to 14% of SCLC. P-mTOR and p-TSC2 staining was found in a minority of cases.There was a significant correlation between p-EGFR Tyr-1068, p-EGFR Tyr-992 and hamartin, and also between p-mTOR and p-EGFR Tyr-1173 in AC. In SCC an inverse correlation between hamartin and p-EGFR Tyr-992 was detected. Phosphorylation of TSC2 was associated with expression of MAP-Kinase. Hamartin, p-TSC2 and p-mTOR expression was not dependant of the EGFR mutation status. Hamartin expression is associated with poorer survival in SCC and SCLC. CONCLUSIONS: Our findings confirm the inhibitory role of the tuberous sclerosis complex for mTOR activation in lung cancer cell lines. These results reveal hamartin expression in a substantial subset of NSCLC and SCLC specimens, which may be due to EGFR signaling but is not dependant on EGFR mutations. Our data provide evidence for a functional role of the tuberous sclerosis complex in lung cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9274845161175223.

Conceitos fisiológicos de importância para a compreensão das variáveis envolvidas no teste ergométrico e no teste ergométrico e no teste cardiopulmonar / Relevant physiological concepts for the undertanding of variables involved in exercise tests and cardiopulmonary exercise tests

Há muitos anos a utilização de testes com exercício programado ganhou importância e destaque como método auxiliar diagnóstico e prognóstico. Considerando-se o grande desenvolvimento tecnológico das últimas décadas, a associação de novos métodos de investigação e provas de esforço definitivamente se configura como ferramenta de relevância no manejo clínico, permitindo a obtenção de informações inquestionáveis no seguimento de pacientes com doenças cardíovasculares. Adicionalmente presta-se à caracterização e avaliação evolutiva da aptidão física em indivíduos saudáveis e atletas que procuram se aprimorar por meio de programas específicos de treinamento. Nesse contexto, o teste cardiopulmonar ou ergoespirométrico destaca-se como método de importante valor agregado por permitir a análise de variáveis clínicas, eletrocardiográficas, hemodinâmicas e respiratórias, que refletem os ajustes cardiovasculares e respiratórios desencadeados pelo exercício...

At-risk alcohol drinking in primary care patients aged 75 years and older.

BACKGROUND: Little is known about the prevalence and risk factors of alcohol problems among older people (especially those aged 75 years and more). The aims of this study were to report alcohol consumption patterns and to determine their association with socio-demographic variables and health characteristics. METHOD: 3224 non-demented subjects aged 75 and over and attending general practitioners (GPs) (n = 138) in an urban area of Germany were studied by structured clinical interviews including detailed assessment of alcohol consumption patterns distinguishing between abstainers, moderate drinkers and at-risk drinkers (>20 g of alcohol for women and >30 g of alcohol for men). RESULTS: A high proportion (50.1%) of the sample were abstainers, 43.4% were moderate drinkers. The prevalence of at-risk alcohol consumption was 6.5% (95% CI 5.6-7.4). Rates were significantly higher for men (12.1%; 95% CI 10.2-14.0) compared to women (3.6%; 95% CI 2.8-4.4). After full adjustment for confounding variables we found that compared to moderate drinking abstaining from alcohol was significantly associated with female gender, lower education, and mobility impairment. Compared to moderate drinking at-risk drinking was significantly higher among men, individuals with a liver disease, and current smokers. CONCLUSIONS: Multivariate analysis revealed that, apart from liver disease, at-risk drinking in a non-demented population aged 75 and over was associated with relatively good physical and mental health. Nevertheless, public prevention measures should focus on at-risk drinkers to make them aware of potential risks of high alcohol consumption in old age.

No limiar anaeróbico ventilatório o exercício pode causar isquemia em programa de reabilitação cardiovascular (parte I) / At anaerobic threshold, exercise may cause myocardial ischemia in cardiac rehabilitation programs

Fundamentos: isquemia miocárdica pode ocorrer durante uma sessão de atividade física em programa de reabilitação cardovascular. Não está descrito , no entanto, se ela pode se desenvolvida quando da prescrição do exercício com base na frequencia cardíaca correspondene ao limiar anaeróbico ventilatório obtido pelo teste cardiopulmonar. Objetivos: verificar a ocorrência de isquemia miocárdica na prescrição de exercício com base no limiar anaeróbicoventilatório em programa de reabilitação cardiovascular, utilizando a cintilografia miocárdica. Métodos: foram avaliados 39 coronariopatas (35 homens e quatro mulheres)com idade entre 45 e 75 anos (média= 59,76) com diagnóstico de doença comprovada por cinecoronariografia e cintilografia miocárdica de esforço com MIBI-99TC pela técnica Gated-Spect associada a um primeiro teste cardiopulmonar...