Development and validation of a new drug-focused predictive risk score for postoperative delirium in orthopaedic and trauma surgery patients.

BACKGROUND: Postoperative delirium (POD) is the most common complication following surgery in elderly patients. During pharmacist-led medication reconciliation (PhMR), a predictive risk score considering delirium risk-increasing drugs and other available risk factors could help to identify risk patients. METHODS: Orthopaedic and trauma surgery patients aged ≥ 18 years with PhMR were included in a retrospective observational single-centre study 03/2022-10/2022. The study cohort was randomly split into a development and a validation cohort (6:4 ratio). POD was assessed through the 4 A's test (4AT), delirium diagnosis, and chart review. Potential risk factors available at PhMR were tested via univariable analysis. Significant variables were added to a multivariable logistic regression model. Based on the regression coefficients, a risk score for POD including delirium risk-increasing drugs (DRD score) was established. RESULTS: POD occurred in 42/328 (12.8%) and 30/218 (13.8%) patients in the development and validation cohorts, respectively. Of the seven evaluated risk factors, four were ultimately tested in a multivariable logistic regression model. The final DRD score included age (66-75 years, 2 points; > 75 years, 3 points), renal impairment (eGFR < 60 ml/min/1.73m2, 1 point), anticholinergic burden (ACB-score ≥ 3, 1 point), and delirium risk-increasing drugs (n ≥ 2; 2 points). Patients with ≥ 4 points were classified as having a high risk for POD. The areas under the receiver operating characteristic curve of the risk score model were 0.89 and 0.81 for the development and the validation cohorts, respectively. CONCLUSION: The DRD score is a predictive risk score assessable during PhMR and can identify patients at risk for POD. Specific preventive measures concerning drug therapy safety and non-pharmacological actions should be implemented for identified risk patients.

Emulating a target trial of proton pump inhibitors and dementia risk using claims data.

BACKGROUND AND PURPOSE: Understanding the adverse effects of proton pump inhibitors (PPIs) is important due to their widespread use, but the available evidence for an increased dementia risk amongst patients taking PPIs is inconclusive. The present study aimed to estimate the causal effect of PPIs on the risk of dementia by target trial emulation and time-varying exposure modeling. METHODS: Using claims data of 2,698,176 insured people of a large German statutory health insurer, a target trial was conceptualized in which individuals aged 40 years and older were classified as PPI initiators or non-initiators between 2008 and 2018, and were followed until diagnosis of dementia, death, loss to follow-up or end of study. Incidence of dementia (International Classification of Diseases 10 codes F00, F01, F03, F05.1, G30, G31.0, G31.1, G31.9 and F02.8+G31.82) was defined applying a 1-year lag window. Weighted Cox models were used to estimate the effect of PPI initiation versus non-initiation on dementia risk and weighted pooled logistic regression was used to estimate the effect of time-varying use versus non-use. RESULTS: In all, 29,746 PPI initiators (4.4%) and 26,830 non-initiators (1.3%) were diagnosed with dementia. Comparing PPI initiation with no initiation, the hazard ratio for dementia was 1.54 (95% confidence interval 1.51-1.58). The hazard ratio for time-dependent PPI use versus non-use was 1.56 (95% confidence interval 1.50-1.63). Differentiated subtypes, including unspecified dementia, Alzheimer's disease and vascular dementia, showed increased risk by PPI initiation and time-varying PPI use. CONCLUSIONS: This study suggests that PPI initiation and time-varying PPI use may increase overall dementia risk.

Who gets prescriptions for proton pump inhibitors and why? A drug-utilization study with claims data in Bavaria, Germany, 2010-2018.

PURPOSE: The German annual drug prescription-report has indicated overuse of proton pump inhibitors (PPIs) for many years; however, little was known about the characteristics of people using PPIs. This study aimed to provide comprehensive utilization data and describe frequencies of potential on- and off-label PPI-indications in Bavaria, Germany. METHODS: Claims data of statutorily insured people from 2010 to 2018 were used. Defined daily doses (DDDs) of PPIs by type of drug, prevalence of PPI-use and DDDs prescribed per 1000 insured people/day were analyzed. For 2018, proportions of users and DDDs per 1000 insured people were calculated by age and sex. To elucidate changes in prescribing practices due to a suspected drug-drug interaction, we examined co-prescribing of clopidogrel and PPIs between 2010 and 2018. For PPI new users, sums of DDDs and frequencies of potential indications were examined. RESULTS: PPI prescribing increased linearly from 2010 to 2016 and gradually decreased from 2016 to 2018. In 2018, 14.7% of women and 12.2% of men received at least one prescription, and 64.8 DDDs (WHO-def.) per 1000 insured people/day were prescribed. Overall, omeprazole use decreased over the observation period and was steadily replaced by pantoprazole, especially when co-prescibed with clopidogrel. An on-label PPI-indication was not reported at first intake in 52.0% of new users. CONCLUSIONS: The utilization of prescribed PPIs has decreased since 2016. However, a large proportion of new PPI-users had no documentation of a potential indication, and the sums of DDDs prescribed often seemed not to comply with guidelines.

Impact of COVID-19 pandemic lockdown on myocardial infarction care.

The aim of this study was to evaluate the impact of the COVID-19 pandemic lockdown on acute myocardial infarction (AMI) care, and to identify underlying stressors in the German model region for complete AMI registration. The analysis was based on data from the population-based KORA Myocardial Infarction Registry located in the region of Augsburg, Germany. All cases of AMI (n = 210) admitted to one of four hospitals in the city of Augsburg or the county of Augsburg from February 10th, 2020, to May 19, 2020, were included. Patients were divided into three groups, namely pre-lockdown, strict lockdown, and attenuated lockdown period. An additional survey was conducted asking the patients for stress and fears in the 4 weeks prior to their AMI. The AMI rate declined by 44% in the strict lockdown period; in the attenuated lockdown period the rate was 17% lower compared to the pre-lockdown period. The downward trend in AMI rates during lockdown was seen in STEMI and NSTEMI patients, and independent of sex and age. The door-to-device time decreased by 70-80% in the lockdown-periods. In the time prior to the infarction, patients felt stressed mainly due to fear of infection with Sars-CoV-2 and less because of the restrictions and consequences of the lockdown. A strict lockdown due to the Covid-19 pandemic had a marked impact on AMI care even in a non-hot-spot region with relatively few cases of COVID-19. Fear of infection with the virus is presumably the main reason for the drop in hospitalizations due to AMI.

Lack of association between proton pump inhibitor use and brain aging: a cross-sectional study.

PURPOSE: Due to conflicting scientific evidence for an increased risk of dementia by intake of proton pump inhibitors (PPIs), this study investigates associations between PPI use and brain volumes, estimated brain age, and cognitive function in the general population. METHODS: Two surveys of the population-based Study of Health in Pomerania (SHIP) conducted in Northeast Germany were used. In total, 2653 participants underwent brain magnetic resonance imaging (MRI) and were included in the primary analysis. They were divided into two groups according to their PPI intake and compared with regard to their brain volumes (gray matter, white matter, total brain, and hippocampus) and estimated brain age. Multiple regression was used to adjust for confounding factors. Cognitive function was evaluated by the Verbal Learning and Memory Test (VLMT) and the Nuremberg Age Inventory (NAI) and put in relation to PPI use. RESULTS: No association was found between PPI use and brain volumes or the estimated brain age. The VLMT score was 1.11 lower (95% confidence interval: - 2.06 to - 0.16) in immediate recall, and 0.72 lower (95% CI: - 1.22 to - 0.22) in delayed recall in PPI users than in non-users. PPI use was unrelated to the NAI score. CONCLUSIONS: The present study does not support a relationship between PPI use and brain aging.

Prevalence, awareness, treatment, and control of hypertension in older people: results from the population-based KORA-age 1 study.

BACKGROUND: Hypertension remains a significant modifiable risk factor for cardiovascular diseases and a major determinant of morbidity and mortality. We aimed to describe sex-stratified age-standardized estimates of prevalence, awareness, treatment and control of hypertension, and their associated factors in older adults. METHODS: The KORA-Age1 is a population-based cross-sectional survey carried out in 2008/2009 on individuals aged 65-94 years in Augsburg region, Germany. Blood pressure measurements were available for 1052 out of 1079 persons who participated in the physical examination. Factors associated with prevalence, awareness and control of hypertension were investigated by multivariable logistic regression. RESULTS: The overall prevalence of hypertension (≥140/90 mmHg) was 73.8% [95% confidence interval (CI), 69.3-77.9], representing 74.8% (95% CI, 68.4-80.2) in men and 73.5% (95% CI, 66.8-79.3) in women. Among those with hypertension, 80.2% (95% CI, 75.3-84.4) were aware of their hypertensive condition and 74.4% (95% CI, 69.2-79.1) were on treatment for hypertension. Among those aware of their hypertension status, 92.8% (95% CI, 88.8-95.6) were on treatment and 53.7% (95% CI, 47.0-60.1) had their blood pressure controlled. Hypertension was more frequent in individuals who were older, obese, or had diabetes. Higher education attainment or presence of comorbidities was associated with higher level of hypertension awareness. Individuals taking three antihypertensive drug classes were more likely to have controlled hypertension compared with those taking one antihypertensive drug class, odds ratio (OR), 1.85 (95% CI, 1.14-2.99). CONCLUSION: Our findings identified high prevalence of hypertension and relevant health gaps on awareness, treatment and suboptimal control of hypertension in older adults in Germany. Screening for hypertension should especially target older adults with low educational attainment and 'healthy' elderly with less contact to physicians.

Association of sleep disturbances within 4 weeks prior to incident acute myocardial infarction and long-term survival in male and female patients: an observational study from the MONICA/KORA Myocardial Infarction Registry.

BACKGROUND: Sleep-related investigations in acute myocardial infarction (AMI) patients are rare. The aim of this study was to examine sex-specific associations of patient-reported sleep disturbances within 4 weeks before AMI and long-term survival. METHODS: From a German population-based, regional AMI registry, 2511 men and 828 women, aged 28-74 years, hospitalized with a first-time AMI between 2000 and 2008 and still alive after 28 days, were included in the study (end of follow-up: 12/2011). Frequency of any sleep disturbances within 4 weeks before AMI was inquired by a 6-categorical item summarized to 'never', 'sometimes' and 'nightly'. Cox regression models were calculated. RESULTS: Over the median follow-up time of 6.1 years (IQR: 4.1) sleep disturbances were reported by 32.3% of male and 48.4% of female patients. During the observation period, 318 men (12.7%) and 131 women (15.8%) died. Men who 'sometimes' had sleep disturbances showed a 56% increased mortality risk compared to those without complaints in an age-adjusted model (HR 1.56; 95%-CI 1.21-2.00). Additional adjustment for confounding variables attenuated the effect to 1.40 (95%-CI 1.08-1.81). Corresponding HRs among women were 0.97 (95%-CI 0.65-1.44) and 0.99 (95%-CI 0.66-1.49). HRs for patients with nightly sleep disturbances did not suggest any association for both sexes. CONCLUSIONS: Our study found that nightly sleep disturbances have no influence on long-term survival in male and female AMI patients. Contrary to women, men who reported sometimes sleep disturbances had a higher mortality. Further investigations on this topic taking into account the role of obstructive sleep apnoea are needed.

Association between admission anemia and long-term mortality in patients with acute myocardial infarction: results from the MONICA/KORA myocardial infarction registry.

BACKGROUND: Previous studies have shown that the presence of anemia is associated with increased short- and long-term outcomes in patients with acute myocardial infarction (AMI). This study aims at examining the impact of admission anemia on long-term, all-cause mortality following AMI in patients recruited from a population-based registry. Contrary to most prior studies, we distinguished between patients with mild and moderate to severe anemia. METHODS: This prospective study was conducted in 2011 patients consecutively hospitalized for AMI that occurred between January 2005 and December 2008. Patients who survived more than 28 days after AMI were followed up until December 2011. Hemoglobin (Hb) concentration was measured at hospital admission and classified according to the World Health Organization (WHO). Mild anemia was defined as Hb concentration of 11 to < 12 g/dL in women and 11 to < 13 g/dL in men; moderate to severe anemia as Hb concentration of < 11 g/dL. Adjusted Cox regression models were calculated to compare survival in patients with and without anemia. RESULTS: Mild anemia and moderate to severe anemia was found in 183 (9.1%) and 100 (5%) patients, respectively. All-cause mortality after a median follow-up time of 4.2 years was 11.9%. The Cox regression analysis showed significantly increased mortality risks in both patients with mild (HR 1.74, 95% CI 1.23-2.45) and moderate to severe anemia (HR 2.05, 95% CI 1.37-3.05) compared to patients without anemia. CONCLUSION: This study shows that anemia adversely affects long-term survival following AMI. However, further studies are needed to confirm that anemia can solely explain worse long-term outcomes after AMI.

Neuropathic pain is not adequately treated in the older general population: Results from the KORA F4 survey.

PURPOSE: We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population. METHODS: The study included subjects aged 61 to 82 years from the KORA F4 survey (2006-2008). DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. Pain intensity was assessed with the painDETECT questionnaire. RESULTS: From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty-eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of ≥4 during the past 4 weeks received medical treatment, predominantly nonsteroidal anti-inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN. CONCLUSIONS: In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs.

Determinants of adherence and effects on health-related quality of life after myocardial infarction: a prospective cohort study.

BACKGROUND: Adherence to recommendations and medication is deemed to be important for effectiveness of case management interventions. Thus, reasons for non-adherence and effects on health-related quality of life (HRQoL) should be fully understood. The objective of this research was to identify determinants of non-adherence to medication and recommendations, and to test whether increased adherence improved HRQoL in patients after myocardial infarction (MI) in a case management intervention. METHODS: Data were obtained from the intervention group of the KORINNA study, a randomized controlled trail of a nurse-led case management intervention with targeted recommendations in the elderly after MI in Germany. Reasons for non-adherence were described. Logistic mixed effects models and OLS (ordinary least squares) were used to analyze the effect of recommendations on the probability of adherence and the association between adherence and HRQoL. RESULTS: One hundred and twenty-seven patients with 965 contacts were included. Frequent reasons for non-adherence to medication and recommendations were "forgotten" (22%; 11%), "reluctant" (18%; 18%), "side effects" (38%; 7%), "the problem disappeared" (6%; 13%), and "barriers" (0%; 13%). The probability of adherence was lowest for disease and self-management (38%) and highest for visits to the doctor (61%). Only if patients diverging from prescribed medication because of side effects were also considered as adherent, 3-year medication adherence was associated with a significant gain of 0.34 quality-adjusted life years (QALYs). CONCLUSIONS: Most important determinants of non-adherence to medication were side effects, and to recommendations reluctance. Recommended improvements in disease and self-management were least likely adhered. Medication adherence was associated with HRQoL. TRIAL REGISTRATION: Current Controlled Trials ISRCTN02893746 , retrospectively registered, date assigned 27/03/2009.

Muscular Strength is Independently Associated with Cystatin C: The KORA-Age Study.

The purpose of this study was to investigate if there is a link between muscular strength (MS) and markers of chronic kidney disease (CKD) among older adults. The cross-sectional analysis based on 1041 men and women, aged 65-94 years, who participated in the KORA-Age study. Participants underwent an interview and extensive examinations including anthropometric measurements, diseases and drug intake registration, determination of health-related behaviors, collection of blood samples for measurements of cystatin C and maximal muscle strength evaluation. One-Way ANOVA revealed significant differences in both mean cystatin C (1.16±0.37 vs. 1.03±0.29 vs. 0.93±0.24 mg/L, p<0.001) and mean eGFRcysC (63.61±18.61 vs. 72.14±18.92 vs. 79.87±18.19 ml/min/1.73 m2, p<0.05) across thirds of maximal muscular strength (from lowest to highest). MS in the lowest third was significantly associated with increased odds of having elevated cystatin C (OR: 1.70, 95% CI: 1.01-2.85, p=0.043) after controlling for age, gender, fat mass, fat-free mass, alcohol intake, smoking status, number of regularly used medications, multimorbidity status, hs-CRP, telomere length and levels of physical activity. Lower levels of MS are independently associated with higher concentrations of cystatin C and lower eGFRcysC in older individuals. Increasing the levels of muscular strength may be useful to prevent the age-related CKD disease of older adults.

Admission serum potassium concentration and long-term mortality in patients with acute myocardial infarction: results from the MONICA/KORA myocardial infarction registry.

BACKGROUND: Conflicting with clinical practice guidelines, recent studies demonstrated that serum potassium concentrations (SPC) of ≥4.5 mEq/l were associated with increased mortality in patients with acute myocardial infarction (AMI). This study examined the association between SPC and long-term mortality following AMI in patients recruited from a population-based registry. METHODS: Included in the study were 3347 patients with AMI aged 28-74 years consecutively hospitalized between 1 January 2000 and 31 December 2008 and followed up until 31 December 2011. Patients were categorized into five SPC groups (<3.5, 3.5 to <4.0, 4.0 to <4.5, 4.5 to <5.0, and ≥5.0 mEq/l). The outcome of the study was all-cause mortality. Cox regression models adjusted for risk factors, co-morbidities and in-hospital treatment were constructed. RESULTS: In our study population, 249 patients (7.4%) had a low SPC (<3.5 mEq/l) and 134 (4.0%) patients had a high SPC (≥5.0 mEq/l). Patients with SPC of ≥5.0 mEq/l had the highest long-term mortality (29.9%) and in the adjusted model, their risk of dying was significantly increased (HR 1.46, 95% CI 1.03 to 2.07) compared to patients with SPC between 4.0 and <4.5 mEq/l. Analyses of increasing observation periods showed a trend towards a higher risk of dying in patients with SPC between 4.5 and <5.0 mEq/l. CONCLUSION: An admission SPC of ≥5.0 mEq/l might be associated with an increased mortality risk in patients with AMI. Patients with an admission SPC between 4.5 and <5.0 mEq/l might have an increased mortality risk in the first few years following AMI.

Factors Associated With Emergency Services Use by Patients With Recurrent Myocardial Infarction: From the Monitoring Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg Myocardial Infarction Registry.

BACKGROUND: Although emergency medical services (EMS) use is the recommended mode of transport in case of acute coronary symptoms, many people fail to use this service. OBJECTIVE: The objective of this study was to determine factors associated with EMS use in a population-based sample of German patients with recurrent acute myocardial infarction (AMI). METHODS: The sample consisted of 998 persons with a first and recurrent AMI, recruited from 1985 to 2011. Logistic regression modeling adjusted for sociodemographic, situational, and clinical variables, previous diseases, and presenting AMI symptoms was applied. RESULTS: Emergency medical services was used by 48.8% of the patients at first, and 62.6% at recurrent AMI. In first AMI, higher age, history of hyperlipidemia, ST-segment elevation AMI, more than 4 presenting symptoms, symptom onset in daytime, and later year of AMI were significantly related with EMS use. Pain in the upper abdomen and pain between the shoulder blades were significantly less common in EMS users. In recurrent AMI, EMS use at first AMI, presence of any other symptom except chest pain, ST-segment elevation myocardial infarction, and later year of AMI were significantly related with EMS use. Significant predictors of EMS use in recurrent AMI in patients who failed to use EMS at first AMI were unmarried, experience of any symptom except chest symptoms at reinfarction, bundle branch block (first AMI), any in-hospital complication (first AMI), longer duration between first and recurrent AMI, and later year of reinfarction. CONCLUSIONS: Patients with AMI and their significant others may profit by education about the benefits of EMS use.

Acute myocardial infarction in the elderly: Treatment strategies and 28-day-case fatality from the MONICA/KORA myocardial infarction registry.

OBJECTIVES: Aim of this observational study was to analyze today's real-life treatment strategies in elderly patients with an acute myocardial infarction (AMI) and to assess the association between 28-day-case fatality and invasive strategy (percutaneous coronary intervention/coronary artery bypass grafting). BACKGROUND: Elderly patients increasingly constitute a large proportion of the AMI population. METHODS: The present study is an analysis of all patients aged 75-84 years, who were enrolled in the German population-based MONICA/KORA MI registry between 2009 and 2012 and who were defined as nonfatal at least 24 hours surviving AMI cases according to MONICA definition. Multivariable logistic regression analyses were conducted for the total study population and stratified by type of AMI (ST-segment elevation MI [STEMI], Non-ST-segment elevation MI [NSTEMI], and bundle branch block [BBB]). RESULTS: Out of the 1,191 elderlies, 61.9% were treated invasively. In the multivariable analysis, the odds ratio (OR) for 28-day-case fatality in patients treated with invasive versus conservative strategy was 0.43 (95% CI 0.27-0.69). Stratified analyses revealed an OR of 0.27 (95% CI 0.13-0.56) for patients with NSTEMI. In patients with STEMI or BBB also a positive trend for invasive strategy was observed (OR 0.40; 95% CI 0.13-1.27 and OR 0.76; 95% CI 0.16-3.66, respectively). CONCLUSIONS: Invasive revascularization therapy was independently associated with short-term survival in elderly patients, particularly in those with NSTEMI.

Variables associated with disability in male and female long-term survivors from acute myocardial infarction. Results from the MONICA/KORA Myocardial Infarction Registry.

Increasing attention is paid on functional limitations and disability among people with chronic diseases. However, only few studies have explored disability in persons with acute myocardial infarction (AMI). The objective of this study was to provide a description of disability and to identify determinants of disability in a population-based sample of long-term AMI survivors. The sample consisted of 1943 persons (35-85years) with AMI from the German population-based MONICA/KORA Myocardial Infarction Registry, who responded to a postal follow-up survey in 2011. Disability was assessed with the 12-item version of the World Health Organization Disability Schedule (WHODAS). Multivariate linear regression models were established in order to identify socioeconomic and clinical factors, risk factors and comorbidities which are associated with disability. The mean WHODAS score for the total sample was 7.86±9.38. The regression model includes 26 variables that explained 37.2% of the WHODAS variance. Most of the explained variance could be attributed to the presence of depression, female sex, joint disorders, digestive disorders, and stroke. Depression was the most important determinant of disability in both sexes. Replacement of single comorbidities by the total number of comorbidities resulted in a model with 15 variables explaining 31.9% of the WHODAS variance. Most of the variance was explained by the number of comorbidities. Further significant determinants of disability were female sex, low education level, angina pectoris, and no revascularization therapy. In AMI patients, the number of comorbidities and particularly the presence of depression are important determinants of disability and should be considered in post-AMI health care.

Predictors of non-invasive therapy and 28-day-case fatality in elderly compared to younger patients with acute myocardial infarction: an observational study from the MONICA/KORA Myocardial Infarction Registry.

BACKGROUND: A substantial proportion of patients with acute myocardial infarction (AMI) did not receive invasive therapy, defined as percutaneous coronary intervention and/or coronary artery bypass grafting. Aims of this study were to evaluate predictors of non-invasive therapy in elderly compared to younger AMI patients and to assess the association between invasive therapy and 28-day-case fatality. METHODS: From the German population-based registry, 3475 persons, consecutively hospitalized with an AMI between 2009 and 2012 were included. Data were collected by standardized interviews and chart review. All-cause mortality was assessed on a regular basis. Multivariable logistic regression analyses were conducted. RESULTS: The sample consisted of 1329 patients aged 28-65 years (age category [AC] 1), 1083 aged 65-74 years (AC 2), and 1063 aged 75-84 years (AC 3). The proportion of patients receiving non-invasive therapy was 10.7, 17.7, and 35.8 % in AC 1, 2, and 3, respectively. Predictors of non-invasive therapy in all ACs were non-ST segment elevation MI, bundle branch block, reduced left ventricular ejection fraction, prior stroke, absence of hyperlipidemia, and low creatine kinase. Elderly women (≥65 years) were less likely to receive invasive therapy. Stratifying the models by type of AMI revealed fewer predictors in patients with ST segment elevation MI. Regarding 28-day-case fatality, strong inverse relations with invasive therapy were seen in all AC: odds ratio of 0.35 (95 % confidence interval [CI] 0.15-0.84), 0.45 (95 % CI 0.22-0.92), and 0.39 (95 % CI 0.24-0.63) in AC 1, 2 and 3, respectively. CONCLUSION: In today's real-life patient care we found that predictors of non-invasive therapy were predominantly the same in all age groups, but differed particularly by type of AMI. Further research is necessary to investigate the real reasons for non-invasive therapy, especially among elderly women. Moreover, we confirmed that receiving invasive therapy was inversely associated with 28-day-case fatality independent of age.

Association of obesity and long-term mortality in patients with acute myocardial infarction with and without diabetes mellitus: results from the MONICA/KORA myocardial infarction registry.

BACKGROUND: Paradoxically, beneficial effects of overweight and obesity on survival have been found in patients after cardiovascular events such as acute myocardial infarction (AMI). This obesity paradox has not been analyzed in AMI patients with diabetes even though their cardiovascular morbidity and mortality is increased compared to their counterparts without diabetes. Therefore, the objective of this long-term study was to analyze the association between body mass index (BMI) and all-cause mortality in AMI patients with and without diabetes mellitus. METHODS: Included in the study were 1190 patients with and 2864 patients without diabetes, aged 28-74 years, recruited from a German population-based AMI registry. Patients were consecutively hospitalized between 1 January 2000 and 31 December 2008 with a first ever AMI and followed up until December 2011. Data collection comprised standardized interviews and chart reviews. To assess the association between BMI and long-term mortality from all causes, Cox proportional hazards models were calculated adjusted for risk factors, co-morbidities, clinical characteristics, in-hospital complications as well as medical and drug treatment. RESULTS: AMI patients of normal weight (BMI 18.5-24.9 kg/m(2)) had the highest long-term mortality rate both in patients with and without diabetes with 50 deaths per 1000 person years and 26 deaths per 1000 person years, respectively. After adjusting for a selection of covariates, a significant, protective effect of overweight and obesity on all-cause mortality was found in AMI patients without diabetes (overweight: hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.58-0.93; p=0.009; obesity: HR 0.64, 95% CI 0.47-0.87; p=0.004). In contrast, an obesity paradox was not found in AMI patients with diabetes. However, stratified analyses showed survival benefits in overweight AMI patients with diabetes who had been prescribed statins prior to AMI (HR 0.51, 95% CI 0.29-0.89, p=0.018) or four evidence-based medications at hospital-discharge (HR 0.52, 95% CI 0.34-0.80, p=0.003). CONCLUSION: In contrast to AMI patients without diabetes, AMI patients with diabetes do not experience a survival benefit from an elevated BMI. To investigate the underlying reasons for these findings, further studies stratifying their samples by diabetes status are needed.

Does marital status contribute to the explanation of the hypercholesterolemia paradox in relation to long term mortality in myocardial infarction? Findings from the MONICA/KORA Myocardial Infarction Registry.

OBJECTIVE: A recent study found long-term mortality after first acute myocardial infarction (AMI) to be particularly reduced among married individuals with hypercholesterolemia. This study explores, whether statin treatments during the last week prior to AMI offer an explanation to this phenomenon. METHODS: Data were retrieved 2000-2008 from the population-based KORA myocardial infarction registry, located in Bavaria, Germany. The sample included 3162 individuals, alive 28days after first AMI, who received statins both in hospital and at discharge. Associations with long-term mortality were examined via multivariable Cox regression. Among patients with hypercholesterolemia, individuals with and without prior statin treatment were each tested against the reference group "neither (hypercholesterolemia nor statin)" and tested for interaction with "marital status". RESULTS: Among patients with and without prior statins, hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46-0.93 and HR 0.72, 95% CI 0.55-0.94, were observed, respectively. Mortality reductions diminished after introduction of the following interaction terms with marital status: HR 0.49, p 0.042 for patients with and HR 0.77, p 0.370, for patients without prior statins. CONCLUSIONS: Prior statin treatments appear to be an underlying factor for long-term mortality reduction in married AMI-survivors with hypercholesterolemia. Confirmation of our results in further studies is warranted.

Use of rivaroxaban in Germany: a database drug utilization study of a drug started in hospital.

PURPOSE: The purpose of this drug utilization study was to describe the use of rivaroxaban in Germany during a time period in which approval was limited to the prevention of venous thromboembolism following hip or knee replacement. Additionally, we explored the feasibility of reconstructing inpatient drug use of rivaroxaban in a database where with a few exceptions inpatient prescribing information is not available. METHODS: Source of data was one statutory health insurance providing data on about seven million insurants throughout Germany. Analyses were based on a cohort of rivaroxaban users from launch (October 2008) to December 2009 and encompassed potential indications for rivaroxaban use, treatment duration, and co-prescribing of potentially interacting drugs. Start of rivaroxaban treatment was defined by the date of surgery. RESULTS: During the study period, 425 rivaroxaban users were identified contributing 440 treatment periods. For more than 82% of these episodes labelled indications could be determined. Treatment durations exceeded recommendations in 95% of the episodes following knee replacement whereas rivaroxaban use after elective hip surgery was found to be longer than recommended in 56%. Prescribing of potentially interacting medication was rare except for non-steroidal anti-inflammatory drugs. CONCLUSIONS: Overall, no important off-label use of rivaroxaban was identified. Based on several assumptions that have to be considered in the interpretation of the results our study describes a database approach to reconstruct inpatient drug use for a drug started after a coded hospital procedure, when treatment continues after hospital discharge and no change in drug use is expected in the outpatient setting.

Prescribing of endothelin receptor antagonists and riociguat in women of childbearing age in a large German claims database study.

Use of endothelin receptor antagonists (ERAs) and riociguat, approved for treatment of pulmonary hypertension (PH), is contraindicated during pregnancy due to reported teratogenicity in animals. We aimed to investigate prescribing of these drugs in girls/women of childbearing age and to explore - as a secondary aim - the occurrence of pregnancies exposed to these drugs. Using the German Pharmacoepidemiological Research Database (GePaRD, claims data from 20% of the German population) we conducted cross-sectional analyses to determine prescribing prevalence of ERAs and riociguat between 2004 and 2019 and to characterize users and prescribing patterns. In a cohort analysis, we assessed the occurrence of pregnancies exposed to these drugs in the critical time window. Overall, we identified 407 women with ≥ 1 dispensation of bosentan between 2004 and 2019; the respective number was 73 for ambrisentan, 182 for macitentan, 31 for sitaxentan, and 63 for riociguat. In nearly all years, more than 50% of the girls/women were ≤ 40 years. Age-standardized prevalence was highest for bosentan (0.04/1000) in 2012 and 2013, followed by macitentan (0.03/1000) in 2018 and 2019. We observed 10 exposed pregnancies: 5 to bosentan, 3 to ambrisentan, and 2 to macitentan. The increased prevalence of macitentan and riociguat from 2014 onwards might reflect changes in PH treatment. Even though PH is a rare disease and pregnancy should be avoided in women with PH, particularly if they use ERAs, we identified pregnancies exposed to ERAs. Multi-database studies will be needed to assess the risk of these drugs on the unborn child.