Evidence-based definition of hypoprolactinemia in European men aged 40-86 years: the European male ageing study.

Empirical evidence for a low normal or reference interval for serum prolactin (PRL) is lacking for men, while the implications of very low PRL levels for human health have never been studied. A clinical state of "PRL deficiency" has not been defined except in relation to lactation. Using data from the European Male Ageing Study (EMAS), we analyzed the distribution of PRL in 3,369 community-dwelling European men, aged 40-80 years at phase-1 and free from acute illnesses. In total, 2,948 and 2,644 PRL samples were collected during phase-1 and phase-2 (3 to 5.7 years later). All samples were analysed in the same centre with the same assay. After excluding individuals with known pituitary diseases, PRL ≥ 35 ng/ml, and PRL-altering drugs including antipsychotic agents, selective serotonin reuptake inhibitors, or dopamine agonists, 5,086 data points (2,845 in phase-1 and 2,241 in phase-2) were available for analysis. The results showed that PRL declined minimally with age (slope = -0.02) and did not correlate with BMI. The positively skewed PRL distribution was log-transformed to a symmetrical distribution (skewness reduced from 13.3 to 0.015). Using two-sigma empirical rule (2[]SD about the mean), a threshold at 2.5% of the lower end of the distribution was shown to correspond to a PRL value of 2.98ng/ml. With reference to individuals with PRL levels of 5-34.9 ng/ml (event rate = 6.3%), the adjusted risk of developing type 2 diabetes increased progressively in those with PRL levels of 3-4.9 ng/ml: event rate = 9.3%, OR (95% CI) 1.59 (0.93-2.71), and more so with PRL levels of 0.3-2.9 ng/ml: event rate = 22.7%, OR 5.45 (1.78-16.62). There was also an increasing trend in prediabetes and diabetes based on fasting blood glucose levels was observed with lower categories of PRL. However, PRL levels were not associated with cancer, cardiovascular diseases, depressive symptoms or mortality. Our findings suggest that a PRL level below 3 ng/ml (64 mlU/l) significantly identifies European men with a clinically-important outcome (of type 2 diabetes), offering a lower reference-value for research and clinical practice.

Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold.

Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 - 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.

Number of CAG repeats and mortality in middle aged and older men.

DESIGN: The androgen receptor (AR) mediates peripheral effects of testosterone. Previous data suggests an association between the number of CAG repeats in exon-1 of the AR gene and AR transcriptional activity. The aim of this analysis was to determine the association between the number of AR CAG repeats and all-cause mortality in men and the influence of testosterone level on the association. PATIENTS AND MEASUREMENTS: Follow-up data to 27 January 2018 were available for men aged 40-79 years recruited across six countries of the European Male Aging Study between 2003 and 2005. Cox proportional hazards modelling was used to determine the association between CAG repeat number/mortality. Results were expressed as hazard ratios (HR)/95% confidence intervals (CI). RESULTS: One thousand nine hundred and seventy-seven men were followed up. Mean baseline age was 60 ± 11.1 years. Mean duration of follow-up was 12.2 years. At follow up 25.1% of men had died. CAG repeat length ranged from 6 to 39, with the highest proportion of CAG repeat number at 21 repeats (16.4%). In a multivariable model, compared to men with 22-23 AR CAG repeats: for men with <22 and >23 AR CAG HR, 95% CI for mortality were, <22 CAG repeats 1.17 (0.93-1.49) and >23 CAG repeats 1.14 (0.88-1.47). In a post-hoc analysis, the association was significant for men in the lowest tertile of baseline testosterone (<14.2 nmol/L) with >23 CAG repeats: in the adjusted model for <22 and >23 CAG repeats, respectively, 1.49 (0.97-2.27) and 1.68 (1.06-2.67) versus 22-23 repeats. CONCLUSIONS: Our European-wide cohort data overall found no association of androgen receptor CAG repeat number and mortality in men. However, post hoc analysis suggested that an association might be present in men with lower baseline testosterone concentrations, which merits further investigation.

Spatial decrease of synaptic density in amnestic mild cognitive impairment follows the tau build-up pattern.

Next to amyloid and tau, synaptic loss is a key pathological hallmark in Alzheimer's disease, closely related to cognitive dysfunction and neurodegeneration. Tau is thought to cause synaptic loss, but this has not been experimentally verified in vivo. In a 2-year follow-up study, dual tracer PET-MR was performed in 12 amnestic MCI patients using 18F-MK-6240 for tau and 11C-UCB-J for SV2A as a proxy for synaptic density. Tau already accumulated in the neocortex at baseline with progression in Braak V/VI at follow-up. While synaptic loss was limited to limbic regions at baseline, it followed the specific tau pattern to stage IV/V regions two years later, indicating that tau spread might drive synaptic vulnerability. Moreover, synaptic density changes correlated to changes in cognitive function. This study shows for the first time in vivo that synaptic loss regionally follows tau accumulation after two years, providing a disease-modifying window of opportunity for (combined) tau-targeting therapies.

Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT): protocol of a cross-sequential study to explore the gut-muscle axis in the development and treatment of sarcopenia in community-dwelling older adults.

BACKGROUND: Gut microbiota (GM) might play a role in muscle metabolism and physiological processes through a hypothesized gut-muscle axis, influencing muscle mass and function and thus, sarcopenia. The Trial in Elderly with Musculoskeletal Problems due to Underlying Sarcopenia-Faeces to Unravel the Gut and Inflammation Translationally (TEMPUS-FUGIT) aims to explore the gut-muscle axis in sarcopenia. METHODS: First, in a cross-sectional case-control phase, 100 community-dwelling adults without sarcopenia will be compared to 100 community-dwelling adults (≥ 65 years) with sarcopenia of similar age-, gender and BMI-ratio, participating in the ongoing 'Exercise and Nutrition for Healthy AgeiNg' (ENHANce; NCT03649698) study. Sarcopenia is diagnosed according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. GM composition and intestinal inflammatory markers (fecal calprotectin, lactoferrin and S100A12) will be determined in fecal samples. Systemic inflammatory markers (hs-CRP, IL-4, IL-6, TNF-α, IL-13, IL-1ß and creatine kinase) will be determined in fasted blood samples. Both groups will be compared using appropriate statistical testing, whereas linear regression will be used for cross-sectional associations between gut, inflammatory and sarcopenia parameters. Second, in the longitudinal phase, sarcopenic older adults will be requested to deliver five fecal samples during the 12-week intervention to assess the effects of protein, omega-3 and a physical exercise program on the GM. DISCUSSION: TEMPUS-FUGIT aims to explore the gut-muscle axis by comparing GM composition between sarcopenic and non-sarcopenic older adults and to determine the association of GM with intestinal and systemic inflammatory markers and sarcopenia-defining parameters (muscle mass, muscle strength and physical performance). Furthermore, effects of single or combined, optimized and individualized anabolic interventions (exercise, protein and omega-3 supplementation), on GM will be explored in persons with sarcopenia. TEMPUS-FUGIT aims to impact clinical practice by clarifying the relationship between the gut-muscle axis and sarcopenia. TEMPUS-FUGIT is expected to contribute to the discovery of clinical and microbial biomarkers for sarcopenia and insights in its pathophysiology, opening possible future perspectives for novel sarcopenia treatment strategies targeting GM. TRIAL REGISTRATION: ClinicalTrails.gov NCT05008770, registered on August 17, 2021; first participant enrolled on September 21 2021.

The impact of a pharmacist intervention on post-discharge hypnotic drug discontinuation in geriatric inpatients: a before-after study.

BACKGROUND: Chronic use of hypnotic agents is prevalent in older adults, who as a result are at increased risk for certain adverse events, such as day-time drowsiness and falls. Multiple strategies to discontinue hypnotics have been tested in geriatric patients, but evidence remains scarce. Hence, we aimed to investigate a multicomponent intervention to reduce hypnotic drug use in geriatric inpatients. METHODS: A before-after study was performed on the acute geriatric wards of a teaching hospital. The before group (= control group) received usual care, while intervention patients (= intervention group) were exposed to a pharmacist-led deprescribing intervention, comprising education of health care personnel, access to standardized discontinuation regimens, patient education and support of transitional care. The primary outcome was hypnotic drug discontinuation at one month after discharge. Secondary outcomes among others were sleep quality and hypnotic use at one and two weeks after enrolment and at discharge. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) upon inclusion, two weeks after enrolment and one month after discharge. Determinants for the primary outcome were identified using regression analysis. RESULTS: A total of 173 patients were enrolled, with 70.5% of patients taking benzodiazepines. Average age was 85 years (interquartile range 81-88.5) and 28.3% were male. A higher discontinuation rate at one month after discharge was observed in favour of the intervention (37.7% vs. 21.9%, p = 0.02281). No difference in sleep quality was found between both groups (p = 0.719). The average sleep quality was 8.74 (95% confidence interval (CI): 7.98-9.49) and 8.57 (95% CI: 7.75-9.39) in the control and intervention groups respectively. Determinants for discontinuation at one month were: the intervention (odds ratio (OR) 2.36, 95% CI: 1.14-4.99), fall on admission (OR 2.05; 95% CI: 0.95-4.43), use of a z-drug (OR 0.54, 95% CI: 0.23-1.22), PSQI score on admission (OR 1.08, 95% CI: 0.97-1.19) and discontinuation prior to discharge (OR 4.71, 95% CI: 2.26-10.17). CONCLUSIONS: A pharmacist-led intervention in geriatric inpatients was associated with a reduction of hypnotic drug use one month after discharge, without any loss in sleep quality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05521971 (retrospectively registered on 29th of August 2022).

Are dietary intake and nutritional status of specific polyunsaturated fatty acids correlated with sarcopenia outcomes in community-dwelling older adults with sarcopenia? - Exploratory results from ENHANce.

AIMS: To explore the relationship between dietary polyunsaturated fatty acids (PUFAs) intake, nutritional PUFAs status and sarcopenia outcomes in sarcopenic older adults. METHODS: The Exercise and Nutrition for Healthy AgeiNg (ENHANce) is an ongoing 5-armed triple blinded randomized controlled trial, in sarcopenic older adults (> 65y) aiming to assess the effect of combined anabolic interventions (protein, omega-3 supplement and exercise) on physical performance in these adults, compared to single/placebo interventions. Baseline data were used for a secondary, exploratory, cross-sectional analysis. Dietary PUFAs intake was assessed with 4-day food records, status with RBC membrane fatty acids profiles. Spearman's rho(ρ) correlation coefficients were calculated to explore associations of PUFAs intake and status with sarcopenia-defining parameters (muscle strength, mass and physical performance), physical activity (step count) and quality of life (SF-36, SarQoL). RESULTS: In total, 29 subjects (9♂/20♀, mean age 76.3 ± 5.4y) were included. Total omega-3 intake of participants (1.99 ± 0.99 g/d) was below the recommended intake (♂:2.8-5.6 g/d; ♀:2.2-4.4 g/d). Intake and status of PUFAs were not correlated. Regarding correlations with outcomes, α-linolenic acid status was inversely associated with appendicular lean mass (aLM) (ρ:-0.439; p = 0.017), whereas docosahexaenoic acid status was positively associated with aLM (ρ:0.388; p = 0.038). Some omega-3 PUFAs intake and status markers were positively associated with step count, SF-36 and SarQoL scores, whereas gamma-linolenic acid status was inversely associated with SF-36 physical component summary score (ρ = -0.426; p = 0.024). CONCLUSIONS: Although intake of omega-3 and omega-6 was low, the present exploratory study generated new hypotheses for potential correlations of PUFAs intake and status with sarcopenia outcomes in older adults with sarcopenia.

Does testosterone influence the association between sleep and frailty in men: results from the European Male Aging Study.

BACKGROUND: Previous studies have suggested an association between sleep disturbance and frailty. The mechanism is unknown, although it has been suggested that hormonal factors may play a role. METHODS: The aim was to determine the association between sleep duration, sleep quality and frailty, and to determine whether testosterone influenced this association. Males aged 40-79 years were recruited from eight European centres to the European Male Aging Study (EMAS). Subjects completed an interviewer-assisted questionnaire including questions regarding sleep quality and duration. Sleep quality was scored 0-20 and categorised as 0-4, 5-9, 10-14, and 15-20, with higher scores indicating poorer quality. A 39-component frailty index (FI) was constructed. Total testosterone levels were measured. The association between sleep duration, sleep quality and the FI was assessed using negative binomial regression, with adjustment for putative confounders including testosterone level. RESULTS: Two thousand three hundred ninety-three participants contributed data to the analysis. The mean age was 63.3 years and mean sleep duration was 7.01 h. The mean frailty index was 0.15. Mean testosterone levels declined with decreasing sleep quality. After adjustment, compared to those with a sleep score of 0-4, the FI was 57% (95% CI 38%, 78%) higher among those with a sleep score of 15-20. After adjustment compared to those with normal sleep duration (6-9 h), those with a short (< 6 h) and long (≥ 9 h) sleep duration had a 16% (95% CI 6%, 28%) and 11% (95% CI 0%, 23%) higher FI, respectively. Adjustment for testosterone did not influence the strength of either association. CONCLUSION: Frailty is associated with impaired sleep quality and sleep duration. The association cannot, however, be explained by variation in testosterone levels.

Pharmacokinetics of 2 oral paracetamol formulations in hospitalized octogenarians.

AIMS: It is currently unclear how paracetamol should be dosed in order to increase its efficacy while warranting safety in very old adults. The objective was to evaluate the pharmacokinetics of 2 oral paracetamol formulations and its metabolites in hospitalized octogenarians. METHODS: Geriatric inpatients aged 80 years and older received a 1000-mg paracetamol tablet or granulate at 08.00, 14.00 and 20.00. After at least 4 consecutive gifts, plasma samples were collected around the 08.00 dose (trough, +0.5, +1, +2, +4, +5 and +6 h). Plasma concentrations of paracetamol and its metabolites were determined and individual pharmacokinetic parameters were derived. The Edmonton Frail Scale was used to assess frailty. An analgesic plasma target was defined as an average plasma concentration (Cavg ) of 10 mg/L. RESULTS: The mean (±standard deviation) age was 86.78 (±4.20) years. The majority (n = 26/36, 72%) received the tablet, 10 (28%) the granulate. Thirty patients (85%) were classified with moderate to severe frailty. Seven (21%) patients had a Cavg above 10 mg/L. The median [interquartile range] time to reach the peak concentration was 50.5 [31.50-92.50] and 42.50 [33.75-106.75] min for the tablet and granulate, respectively. The coefficient of variation was 95% for time to reach the peak concentration and 30% for Cavg of paracetamol. A correlation of Cavg of paracetamol was observed with female sex and total serum bilirubin. CONCLUSION: Large interindividual differences were found for pharmacokinetic parameters of oral paracetamol in frail inpatients after multiple dosing. Female sex and higher total serum bilirubin concentrations were associated with paracetamol exposure. No significant differences were observed between the tablet and granulate.

Erectile dysfunction predicts mortality in middle-aged and older men independent of their sex steroid status.

BACKGROUND: erectile dysfunction is associated with mortality, whereas the association between low testosterone (T) and higher mortality remains controversial. Sexual dysfunction and low T often coexist, but the relative importance of sexual symptoms versus low T in predicting mortality is not known. We studied the interrelationships between sex steroids and sexual symptoms with all-cause mortality in a large prospective cohort of European men. DESIGN: survival status was assessed in 1,788 community-dwelling men, aged 40-79, who participated in the European Male Ageing Study (EMAS). Sexual symptoms were evaluated via a validated questionnaire (EMAS-SFQ). Sex steroids were measured by mass spectrometry. Cox proportional hazard models were used to study the association between hormones, sexual symptoms and mortality. RESULTS: about 420 (25.3%) men died during a mean follow-up of 12.6 ± 3.1 years. Total T levels were similar in both groups, but free T was lower in those who died. Men with three sexual symptoms (erectile dysfunction, reduced morning erections and lower libido) had a higher mortality risk compared with men with none of these symptoms (adjusted hazard ratio (HR) and 95% confidence intervals: 1.75 (1.28-2.40, P = 0.001)). Particularly, erectile dysfunction and poor morning erections, but not lower libido, were associated with increased mortality (HR 1.40 (1.13-1.74, P = 0.002), 1.28 (1.04-1.59, P = 0.023) and 1.12 (0.90-1.39, P = 0.312), respectively). Further adjusting for total T, free T or oestradiol did not influence the observed risk. CONCLUSIONS: sexual symptoms, in particular erectile dysfunction, predict all-cause mortality independently of sex steroids and can be an early warning sign of a poor health status.

SARC-F Is Inaccurate to Identify Geriatric Rehabilitation Inpatients at Risk for Sarcopenia: RESORT.

INTRODUCTION: Sarcopenia is highly prevalent in geriatric rehabilitation inpatients; screening using the Strength, Assistance in walking, Rise from a chair, Climb stairs, Falls history questionnaire (SARC-F) has been recommended. This study assessed the diagnostic accuracy of the SARC-F in identifying sarcopenia according to the European Working Group on Sarcopenia in Older People (EWGSOP), EWGSOP2, and Asian Working Group for Sarcopenia (AWGS) definitions in geriatric rehabilitation inpatients. METHODS: REStOring health of acutely unwell adulTs (RESORT) is an observational, longitudinal cohort of geriatric rehabilitation inpatients. The SARC-F was completed for 2 time-points, status at preadmission (1 month before admission) and at admission; a score ≥4 was considered at risk for sarcopenia. Muscle mass (bioelectrical impedance analysis), handgrip strength (handheld dynamometry), and gait speed (4-m walk test) were measured at admission. Diagnostic accuracy was determined by sensitivity, specificity, and area under the curve (AUC). RESULTS: The sarcopenia prevalence (n = 290, median age 84.0 years [IQR 79.0-89.0], 56.9% female) was 40.3% (EWGSOP1), 25.4% (EWGSOP2), and 38.8% (AWGS). For preadmission and admission status, respectively, the SARC-F identified 67.9 and 82.1% (EWGSOP), 66.0 and 81.0% (EWGSOP2), and 67.5 and 81.6% (AWGS) inpatients at risk for sarcopenia. The SARC-F showed fair sensitivity (67-74%), poor specificity (32-37%), and poor AUC (0.411-0.474) to identify inpatients at risk for sarcopenia at preadmission status, and fair-good sensitivity (79-84%), poor specificity (17-20%), and poor AUC (0.401-0.432) to identify inpatients at risk for sarcopenia at admission, according to EWGSOP, EWGSOP2, and AWGS definitions. CONCLUSION: The SARC-F showed poor diagnostic accuracy in identifying sarcopenia in geriatric rehabilitation inpatients. Assessment of sarcopenia is recommended without screening.

How to implement geriatric co-management in your hospital? Insights from the G-COACH feasibility study.

BACKGROUND: Geriatric co-management is advocated to manage frail patients in the hospital, but there is no guidance on how to implement such programmes in practice. This paper reports our experiences with implementing the 'Geriatric CO-mAnagement for Cardiology patients in the Hospital' (G-COACH) programme. We investigated if G-COACH was feasible to perform after the initial adoption, investigated how well the implementation strategy was able to achieve the implementation targets, determined how patients experienced receiving G-COACH, and determined how healthcare professionals experienced the implementation of G-COACH. METHODS: A feasibility study of the G-COACH programme was performed using a one-group experimental study design. G-COACH was previously implemented on two cardiac care units. Patients and healthcare professionals participating in the G-COACH programme were recruited for this evaluation. The feasibility of the programme was investigated by observing the reach, fidelity and dose using registrations in the electronic patient record and by interviewing patients. The success of the implementation reaching its targets was evaluated using a survey that was completed by 48 healthcare professionals. The experiences of 111 patients were recorded during structured survey interviews. The experiences of healthcare professionals with the implementation process was recorded during 6 semi-structured interviews and 4 focus groups discussions (n = 27). RESULTS: The programme reached 91% in a sample of 151 patients with a mean age of 84 years. There was a high fidelity for the major components of the programme: documentation of geriatric risks (98%), co-management by specialist geriatrics nurse (95%), early rehabilitation (80%), and early discharge planning (74%), except for co-management by the geriatrician (32%). Both patients and healthcare professionals rated G-COACH as acceptable (95 and 94%) and feasible (96 and 74%). The healthcare professionals experienced staffing, competing roles and tasks of the geriatrics nurse and leadership support as important determinants for implementation. CONCLUSIONS: The implementation strategy resulted in the successful initiation of the G-COACH programme. G-COACH was perceived as acceptable and feasible. Fidelity was influenced by context factors. Further investigation of the sustainability of the programme is needed. TRIAL REGISTRATION: ISRCTN22096382 (21/05/2020).

[Case of hepatotoxicity of atorvastatin: the search for a possible etiology]. / Casus over hepatotoxiciteit door atorvastatine: de zoektocht naar mogelijke etiologie.

We describe a case of a geriatric patient with repeated hepatotoxicity after (re)start of atorvastatin. We also noticed an increased effect, a fast decline of LDL-cholesterol, after intake of atorvastatin. The intake of rosuvastatin or low dose lovastatin was not associated with hepatotoxicity. Multiple hypotheses were investigated and applied on the case. Genetic testing of statin transporters and CYP-enzymes and medication interactions could not explain the hepatotoxicity.

Self-Reported Shorter Than Desired Ejaculation Latency and Related Distress-Prevalence and Clinical Correlates: Results From the European Male Ageing Study.

BACKGROUND: Few data have looked at the occurrence and clinical correlates of self-reported shorter than desired ejaculation latency (rapid ejaculation, RE) and its related distress in the general population. AIM: To determine the prevalence and clinical correlates of self-reported RE and RE- related distress in middle age and older European men. METHODS: Subjects were recruited from population samples of men aged 40-79 years across 8 European centers. OUTCOMES: Self-reported RE and its related distress were derived from the European male Aging Study (EMAS) sexual function questionnaire (EMAS-SFQ). Beck's depression Inventory (BDI) was used for the quantification of depressive symptoms, the Short Form 36 health survey (SF-36) for the assessment of the quality of life, the International Prostate Symptom Score (IPSS) for the evaluation of lower urinary tract symptoms. RESULTS: About 2,888 community dwelling men aged 40-79 years old (mean 58.9 ± 10.8 years) were included in the analysis. Among the subjects included, 889 (30.8%) self-reported RE. Among them, 211 (7.3%) claimed to be distressed (5.9% and 1.4% reported mild or moderate-severe distress, respectively). Increasing levels of RE-related distress were associated with a progressive worse sexual functioning, higher risk of ED and with couple impairment, along with a higher prevalence of depressive symptoms (all P < 0.05). Furthermore, a worse quality of life and higher IPSS score were associated with RE-related distress (all P < 0.05). The aforementioned results were confirmed even when patients using drugs possibly interfering with ejaculation or those without a stable relationship were excluded from the analysis. CLINICAL IMPLICATIONS: RE is a frequent condition in men from the general population; however, its related distress is relatively modest. Nonetheless, men with any degree of self-reported RE show increasing levels of depression, worse quality of life and worse couple satisfaction. STRENGTHS & LIMITATIONS: This is the first study estimating the prevalence of self-reported RE and its related distress, along with their biological and psychological correlates, in a population sample of European middle age and older men. However, is should be recognized that the diagnosis of RE was derived from patient reports and not supported by Intra-ejaculatory-Latency-Time (IELT) measurements. CONCLUSION: Self-reported RE is relatively common in European men aged more than 40 years. The reported limited RE-related distress may explain the relatively low number of medical consultations for RE. RE-related distress is associated with worse sexual function, couple impairment, and more LUTS resulting in a worse quality of life and mood disturbances. Corona G, Rastrelli G, Bartfai G, et al. Self-Reported Shorter Than Desired Ejaculation Latency and Related Distress-Prevalence and Clinical Correlates: Results From the European Male Ageing Study. J Sex Med Rev 2021;18:908-919.

Diagnosing serious infections in older adults presenting to ambulatory care: a systematic review.

OBJECTIVES: to summarise all available evidence on the accuracy of clinical features and blood tests for diagnosing serious infections in older patients presenting to ambulatory care. METHODS: systematic review, searching seven databases using a comprehensive search strategy. We included cross-sectional prospective diagnostic studies on (1) clinical features, (2) diagnostic prediction rules based on clinical features alone, (3) blood tests and (4) diagnostic prediction rules combining clinical features and blood tests. Study participants had to be community-dwelling adults aged ≥65 years, in whom a physician suspected an infection. We used QUADAS-2 to assess risk of bias. We calculated measures of diagnostic accuracy and present descriptive statistics. RESULTS: out of 13,757 unique articles, only six studies with a moderate to high risk of bias were included. There was substantial clinical heterogeneity across these studies. Clinical features had LR- ≥0.61 and LR+ ≤4.94. Twelve prediction rules using clinical features had LR- ≥0.30 and LR+ ≤2.78. There was evidence on four blood tests of which procalcitonin was the most often investigated: levels <0.37 ng/ml (LR- = 0.20; 95%CI 0.10-0.42) were suitable to rule out sepsis in moderately high prevalence situations. Two diagnostic prediction rules combining clinical features and procalcitonin had LR- of ≤0.12 (95%CI 0.05-0.33) and LR+ of maximum 1.39 (95%CI 1.30-1.49). CONCLUSIONS: we found few studies on the diagnostic accuracy of clinical features and blood tests to detect serious infections in older people presenting to ambulatory care. The risk of bias was mostly moderate to high, leading to substantial uncertainty.

Burden of infections on older patients presenting to general practice: a registry-based study.

BACKGROUND: Estimates on the incidence rates of infections are needed to assess the burden of disease in the community. OBJECTIVE: To assess incidence rates of potentially serious infections in patients aged 65 years and over presenting to Flemish general practice from 2000 to 2015, and to describe patient characteristics. METHODS: We performed a retrospective study, based on data provided by the Intego morbidity registry of the KU Leuven, which includes the electronic medical records of 111 general practitioners. Incidence rates were calculated taking person-time at risk into account, and longitudinal trends from 2000 to 2015 were analysed using autoregressive time-series analyses. RESULTS: On average, a person aged 65 years or older has an 8.0% risk of getting a potentially serious infection each year. Acute cystitis was the most often occurring potentially serious infection [39.8/1000 person-years; 95% confidence interval (CI): 39.4-40.2], followed by influenza like illness (ILI, 24.3/1000 person-years; 95% CI: 24.0-24.6) and pneumonia (9.7/1000 person-years; 95% CI: 9.5-9.9). The incidence rates of pneumonia were higher in older age groups and in men, whereas they were markedly lower for ILI at older ages, in both genders. From 2000 to 2015, overall incidence rates decreased significantly for ILI, while they increased in women for pneumonia, acute cystitis and pyelonephritis. Common chronic comorbidities were non-insulin dependent diabetes, chronic obstructive pulmonary disease, asthma, heart failure and chronic renal insufficiency. CONCLUSIONS: Potentially serious infections are quite common in an older patient population presenting to primary care. They are accompanied by several chronic comorbidities, which may differ by infection type.

Polypharmacy and excessive polypharmacy in community-dwelling middle aged and aged adults between 2011 and 2015.

AIMS: We aimed to assess the prevalence, components and evolution of polypharmacy and to evaluate risk factors associated with polypharmacy. METHODS: A retrospective dynamic cohort study was performed, using a primary healthcare database comprising Flemish community-dwelling adults aged ≥40 years between 2011 and 2015. Polypharmacy and excessive polypharmacy were defined as the use of 5-9 or minimum 10 different medications during 1 year, respectively. Temporal changes were analysed using an autoregressive error model. Risk factors for polypharmacy were evaluated using logistic regression. RESULTS: In total, 68 426 patients were included in the analysis. The prevalence of polypharmacy was 29.5% and 16.1% for excessive polypharmacy in 2015. The age-standardised prevalence rate of patients using minimum five medications increased with 1.3% per year (95% confidence interval (CI): 0.1968-2.4279). The mean number of unplanned hospital admissions was 0.07 (standard deviation (SD) 0.33) for polypharmacy patients and 0.19 (SD 0.53) for excessive polypharmacy patients. Four risk factors were found to be significantly correlated with polypharmacy: age (odds ratio (OR) 1.015; 95% CI: 1.013-1.017), female gender (OR 1.161; 95% CI: 1.108-1.216), number of chronic diseases (OR 1.126; 95% CI: 1.114-1.139) and number of general practitioner contacts (OR 1.283; 95% CI: 1.274-1.292). CONCLUSION: The prevalence of polypharmacy increased between 2011 and 2015. Polypharmacy and excessive polypharmacy patients appeared to differ based on our observations of characteristics, drug therapy and outcomes. Age, female gender, number of chronic diseases and number of general practitioner contacts were associated with polypharmacy.

The role of collaborative, multistakeholder partnerships in reshaping the health management of patients with noncommunicable diseases during and after the COVID-19 pandemic.

BACKGROUND: Policies to combat the COVID-19 pandemic have disrupted the screening, diagnosis, treatment, and monitoring of noncommunicable (NCD) patients while affecting NCD prevention and risk factor control. AIMS: To discuss how the first wave of the COVID-19 pandemic affected the health management of NCD patients, identify which aspects should be carried forward into future NCD management, and propose collaborative efforts among public-private institutions to effectively shape NCD care models. METHODS: The NCD Partnership, a collaboration between Upjohn and the European Innovation Partnership on Active and Healthy Ageing, held a virtual Advisory Board in July 2020 with multiple stakeholders; healthcare professionals (HCPs), policymakers, researchers, patient and informal carer advocacy groups, patient empowerment organizations, and industry experts. RESULTS: The Advisory Board identified barriers to NCD care during the COVID-19 pandemic in four areas: lack of NCD management guidelines; disruption to integrated care and shift from hospital-based NCD care to more community and primary level care; infodemics and a lack of reliable health information for patients and HCPs on how to manage NCDs; lack of availability, training, standardization, and regulation of digital health tools. CONCLUSIONS: Multistakeholder partnerships can promote swift changes to NCD prevention and patient care. Intra- and inter-communication between all stakeholders should be facilitated involving all players in the development of clinical guidelines and digital health tools, health and social care restructuring, and patient support in the short-, medium- and long-term future. A comprehensive response to NCDs should be delivered to improve patient outcomes by providing strategic, scientific, and economic support.

Motion Sensor-Based Detection of Outlier Days Supporting Continuous Health Assessment for Single Older Adults.

The aging population has resulted in interest in remote monitoring of elderly individuals' health and well being. This paper describes a simple unsupervised monitoring system that can automatically detect if an elderly individual's pattern of presence deviates substantially from the recent past. The proposed system uses a small set of low-cost motion sensors and analyzes the produced data to establish an individual's typical presence pattern. Then, the algorithm uses a distance function to determine whether the individual's observed presence for each day significantly deviates from their typical pattern. Empirically, the algorithm is validated on both synthetic data and data collected by installing our system in the residences of three older individuals. In the real-world setting, the system detected, respectively, five, four, and one deviating days in the three locations. The deviating days detected by the system could result from a health issue that requires attention. The information from the system can aid caregivers in assessing the subject's health status and allows for a targeted intervention. Although the system can be refined, we show that otherwise hidden but relevant events (e.g., fall incident and irregular sleep patterns) are detected and reported to the caregiver.

Efficacy and safety of non-benzodiazepine and non-Z-drug hypnotic medication for insomnia in older people: a systematic literature review.

PURPOSE: Insomnia is highly prevalent in older persons and significantly impacts quality of life, functional abilities, and health status. It is frequently treated with benzodiazepines or Z-drugs. Due to adverse events, an increased use of alternative sedative medications has been observed in older adults. We aimed to study the efficacy and safety of alternative sedative medications for treating insomnia in older people, excluding benzodiazepines and Z-drugs. METHODS: We conducted a systematic search of MEDLINE (PubMed), EMBASE, and the Cochrane Central register of Controlled Trials databases. We included randomized controlled trials and prospective and retrospective quasi-experimental studies, conducted in patients older than 65 years, without psychiatric or neurological comorbidities. RESULTS: The systematic search yielded 9483 articles, of which 24 were included in this review, describing nine different sleep medications in total. No clear beneficial impact on sleep could be demonstrated in studies investigating the impact of melatonin (n = 10), paroxetine (n = 1), diphenhydramine (n = 1), tiagabine (n = 2), and valerian (n = 1). Ramelteon slightly improved sleep latency (n = 4), while doxepin was found to provide a sustained sleep improvement with a safety profile that was comparable to placebo (n = 3). Suvorexant showed an improved sleep maintenance with only mild side effects (n = 1). One study detected increased adverse effects of trazodone after 3 months but did not evaluate the effect on sleep. CONCLUSIONS: The overall level of evidence was limited, making it difficult to draw robust conclusions. Preliminary evidence points towards suvorexant, doxepin, and possibly ramelteon as effective and safe pharmacological alternatives for treating insomnia in older adults.