Antipsychotic prescribing and drug-related readmissions in multimorbid older inpatients: a post-hoc analysis of the OPERAM population.

BACKGROUND: Limited data are available on characteristics associated with antipsychotic use in multimorbid older adults. AIM: Primary: to identify patient characteristics associated with antipsychotic prescribing in a multimorbid population of older inpatients with polypharmacy. Secondary: (1) to observe if antipsychotics use during an index hospitalisation was associated with a drug related admission (DRA) within one year, and (2) to describe these cases of antipsychotic-related readmissions. METHOD: This was a secondary analysis of the OPERAM randomized controlled trial. Multivariate analysis assessed the association between characteristics and comorbidities with antipsychotic use. An expert team assessed DRA occurring during the one-year follow-up. RESULTS: Antipsychotics were prescribed to 5.5% (n = 110) patients upon admission while 7.7% (n = 154) inpatients received antipsychotics at any time (i.e. upon admission, during hospitalisation, and/or at discharge). The most frequently prescribed antipsychotics were quetiapine (n = 152), haloperidol (n = 48) and risperidone (n = 22). Antipsychotic prescribing was associated with dementia (OR = 3.7 95%CI[2.2;6.2]), psychosis (OR = 26.2 [7.4;92.8]), delirium (OR = 6.4 [3.8;10.8]), mood disorders (OR = 2.6 [1.6;4.1]),  ≥ 15 drugs a day (OR = 1.7 [1.1;2.6]), functional dependency (Activities of Daily Living score < 50/100) (OR = 3.9 [2.5;6.1]) and < 2 units of alcohol per week (OR = 2.2 [1.4;3.6]). DRA occurred in 458 patients (22.8%) within one year. Antipsychotic prescribing at any time was not associated with DRA (OR = 1.0 [0.3;3.9]) however contributed to 8 DRAs, including 3 falls. CONCLUSION: In this European multimorbid polymedicated older inpatients, antipsychotics were infrequently prescribed, most often at low dosage. Besides neuro-psychiatric symptoms, risk factors for inhospital antipsychotic prescribing were lower functional status and polymedication.

Male-female differences in thoracic aortic diameters at presentation of acute type A aortic dissection.

Background: Acute type A aortic dissection (ATAAD) is a highly lethal event, associated with aortic dilatation. It is not well known if patient height, weight or sex impact the thoracic aortic diameter (TAA) at ATAAD. The study aim was to identify male-female differences in TAA at ATAAD presentation. Methods: This retrospective cross-sectional study analysed all adult patients who presented with ATAAD between 2007 and 2017 in two tertiary care centres and underwent contrast enhanced computed tomography (CTA) before surgery. Absolute aortic diameters were measured at the sinus of Valsalva (SoV), ascending (AA) and descending thoracic aorta (DA) using double oblique reconstruction, and indexed for body surface area (ASI) and height (AHI). Z-scores were calculated using the Campens formula. Results: In total, 59 % (181/308) of ATAAD patients had CT-scans eligible for measurements, with 82 female and 99 male patients. Females were significantly older than males (65.5 ± 12.4 years versus 60.3 ± 2.3, p = 0.024). Female patients had larger absolute AA diameters than male patients (51.0 mm [47.0-57.0] versus 49.0 mm [45.0-53.0], p = 0.023), and larger ASI and AHI at all three levels. Z-scores for the SoV and AA were significantly higher for female patients (2.99 ± 1.66 versus 1.34 ± 1.77, p < 0.001 and 5.27 [4.38-6.26] versus 4.06 [3.14-5.02], p < 0.001). After adjustment for important clinical factors, female sex remained associated with greater maximal TAA (p = 0.019). Conclusion: Female ATAAD patients had larger absolute ascending aortic diameters than males, implying a distinct timing in disease presentation or selection bias. Translational studies on the aortic wall and studies on growth patterns should further elucidate these sex differences.

Hospital physicians' and older patients' agreement with individualised STOPP/START-based medication optimisation recommendations in a clinical trial setting.

OBJECTIVE: To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. METHODS: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. RESULTS: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9-14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30-50 ml/min/1.73 m2; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients' reluctance to discontinue or initiate medication. CONCLUSION: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations. CLINICAL TRIAL REGISTRATION: Trial Registration Number NCT02986425.

Risk of cerebrovascular events in elderly users of antipsychotics.

It has been shown that elderly patients with dementia treated with atypical and conventional antipsychotics have a twofold increased risk of cerebrovascular adverse events (CVAEs). To investigate the temporal relationship between exposure to antipsychotics and the risk of CVAE, a case-control analysis nested within a cohort of 26,157 community-dwelling patients (mean age 76 +/- 9.7) with at least one antipsychotic prescription was conducted. Data were used from Dutch community pharmacies and hospital discharge records. Five hundred and eighteen cases of hospital admission for CVAE were identified. For each case, four randomly selected controls matched by sex and age were sampled from the cohort. To evaluate the temporal relationship between antipsychotic use and the occurrence of CVAE, two measures were used: the first being a current, recent or past user, and the second for the current users, the duration of use up to the index date. In addition, the cumulative exposure was assessed. Current and recent exposure to antipsychotics were associated with an increased risk of CVAE compared with non-users (odds ratio [OR] 1.7, CI 1.4-2.2). A strong temporal relationship was found; the OR for a history of use less than a week is 9.9 (5.7-17.2). The risk decreases in time and is comparable to non-users after 3 months of use (OR 1.0, CI 0.7-1.3). Cumulative exposure was not associated with an increase in risk. The risk of CVAE in elderly patients associated with antipsychotics is elevated especially during the first weeks of treatment. This risk decreases over time and is back on base level after 3 months of treatment. Chronic use is not associated with CVAE.

[Metformin-related lactic acidosis in an 85-year-old woman]. / Lactaatacidose bij een 85-jarige vrouw door behandeling met metformine.

An 85-year-old woman presented at the emergency ward. She had had shortness of breath for several days and no bowel movements for 3 days. On the day ofhospitalisation she experienced sudden abdominal pain and collapsed as she went to the toilet. She was being treated for multiple conditions, including type-2 diabetes. She appeared to have lactic acidosis. At first, the symptoms were not attributed to metformin because she was receiving a low dose and serum-creatinine concentrations were within the normal range (98 micromol/l). Bowel ischaemia was suspected and surgery was performed but no defects were found. She was subsequently treated for metformin-related lactic acidosis but died shortly thereafter due in part to postoperative complications. Lactic acidosis is a rare side effect of metformin. In this patient, the retrospectively calculated glomerular filtration rate (GFR) was extremely low (23 ml/min). The serum-creatinine concentration was normal because the patient's body weight was low (40 kg). Impaired renal function is a risk factor for metformin-related lactic acidosis. Renal function can appear to be normal when measured by serum-creatinine concentration in older patients with reduced muscle mass, but calculation of GFR often reveals impairment. Metformin is contraindicated in patients with poor renal function. The increasing use of metformin in older patients for the treatment of diabetes mellitus warrants renewed attention to this severe side effect.

Landscape ecological assessment: a tool for integrating biodiversity issues in strategic environmental assessment and planning.

To achieve a sustainable development, impacts on biodiversity of urbanisation, new infrastructure projects and other land use changes must be considered on landscape and regional scales. This requires that important decisions are made after a systematic evaluation of environmental impacts. Landscape ecology can provide a conceptual framework for the assessment of consequences of long-term development processes like urbanisation on biodiversity components, and for evaluating and visualising the impacts of alternative planning scenarios. The aim of this paper was to develop methods for integrating biodiversity issues in planning and strategic environmental assessment in an urbanising environment, on landscape and regional levels. In order to test developed methods, a case study was conducted in the region of Stockholm, the capital of Sweden, and the study area embraced the city centre, suburbs and peri-urban areas. Focal species were tested as indicators of habitat quality, quantity and connectivity in the landscape. Predictive modelling of habitat distribution in geographic information systems involved the modelling of focal species occurrences based on empirical data, incorporated in a landscape ecological decision support system. When habitat models were retrieved, they were applied on future planning scenarios in order to predict and assess the impacts on focal species. The scenario involving a diffuse exploitation pattern had the greatest negative impacts on the habitat networks of focal species. The scenarios with concentrated exploitation also had negative impacts, although they were possible to mitigate quite easily. The predictions of the impacts on habitats networks of focal species made it possible to quantify, integrate and visualise the effects of urbanisation scenarios on aspects of biodiversity on a landscape level.

Kombucha fermentation and its antimicrobial activity.

Kombucha was prepared in a tea broth (0.5% w/v) supplemented with sucrose (10% w/v) by using a commercially available starter culture. The pH decreased steadily from 5 to 2.5 during the fermentation while the weight of the "tea fungus" and the OD of the tea broth increased through 4 days of the fermentation and remained fairly constant thereafter. The counts of acetic acid-producing bacteria and yeasts in the broth increased up to 4 days of fermentation and decreased afterward. The antimicrobial activity of Kombucha was investigated against a number of pathogenic microorganisms. Staphylococcus aureus, Shigella sonnei, Escherichia coli, Aeromonas hydrophila, Yersinia enterolitica, Pseudomonas aeruginosa, Enterobacter cloacae, Staphylococcus epidermis, Campylobacter jejuni, Salmonella enteritidis, Salmonella typhimurium, Bacillus cereus, Helicobacterpylori, and Listeria monocytogenes were found to be sensitive to Kombucha. According to the literature on Kombucha, acetic acid is considered to be responsible for the inhibitory effect toward a number of microbes tested, and this is also valid in the present study. However, in this study, Kombucha proved to exert antimicrobial activities against E. coli, Sh. sonnei, Sal. typhimurium, Sal. enteritidis, and Cm. jejuni, even at neutral pH and after thermal denaturation. This finding suggests the presence of antimicrobial compounds other than acetic acid and large proteins in Kombucha.

A sequential study of intravenous and oral Fleroxacin for 7 or 14 days in the treatment of complicated urinary tract infections.

OBJECTIVE: To compare 1 and 2-weeks of sequential intravenous and oral treatment for complicated urinary tract infection. DESIGN: Randomized, clinical trial. SETTING: 2 secondary and 1 tertiary care hospital in the Netherlands. PATIENTS: Patients (54) were randomly assigned, after 3 days Fleroxacin 400 mg iv once daily, to receive oral fleroxacin (400 mg OD,) either during 4 (total 7) days (n = 26), or during 11 (total 14) days (n = 28). Thirty-four patients were evaluable for efficacy. Complicated urinary tract infection was defined as the presence of an anatomical or functional abnormality of the urinary tract, urinary tract instrumentation, patients presenting with clinical signs and symptoms of pyelonephritis or a serious illness such as diabetes mellitus, immunosuppression or renal failure. Complicated urinary tract infection was defined as the presence of an anatomical or functional abnormality of the urinary tract, urinary tract instrumentation, patients presenting with clinical signs and symptoms of pyelonephritis or a serious illness such as diabetes mellitus, immunosuppression or renal failure. RESULTS: A bacteriological cure was seen in 22 of 34 (65%) patients at 4-6 weeks after therapy. Overall, a favorable bacteriological response was obtained in 26 of 34 (76%) patients. No significant difference could be found among the two dosage groups (7 days: 14 18 = 78 %; 14 days: 12 16 = 75 %). CONCLUSIONS: Sequential iv and oral treatment with fleroxacin in complicated UTI is a satisfactory treatment modality. Larger trials should be done in a more homogeneous population, studying shorter treatment durations in complicated UTI.