Risk Factors for Falls Among Hospitalized Medical Patients - A Systematic Review and Meta-analysis.

OBJECTIVE: To identify and quantify risk factors for in-hospital falls in medical patients. DATA SOURCES: Six databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, CINAHL, and Google Scholar) were systematically screened until April 11, 2023, to identify relevant articles. STUDY SELECTION: All titles and abstracts of the retrieved articles were independently screened by 2 researchers who also read the full texts of the remaining articles. Quantitative studies that assessed risk factors for falls among adult patients acutely hospitalized were included in the review. Publications that did not capture internal medicine patients or focused on other specific populations were excluded. DATA EXTRACTION: Information on study characteristics and potential risk factors were systematically extracted. Risk of bias was assessed using the Quality in Prognosis Studies tool. Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analyses of Observational Studies in Epidemiology guidelines were followed for reporting. DATA SYNTHESIS: The main outcome was any in-hospital falls. Using a random-effects meta-analysis model, association measures for each risk factor reported in 5 or more studies were pooled. Separate analyses according to effect measure and studies adjusted for sex and age at least were performed. Of 5067 records retrieved, 119 original publications from 25 countries were included. In conclusion, 23 potential risk factors were meta-analyzed. Strong evidence with large effect sizes was found for a history of falls (odds ratio [OR], 2.54; 95% confidence interval [CI], 1.63-3.96; I2, 91%), antidepressants (pooled OR, 2.25; 95% CI, 1.92-2.65; I2, 0%), benzodiazepines (OR, 1.97; 95% CI, 1.68-2.31; I2, 0%), hypnotics-sedatives (OR, 1.90; 95% CI, 1.53-2.36; I2, 46%), and antipsychotics (OR, 1.61; 95% CI, 1.33-1.95; I2, 0%). Furthermore, evidence of associations with male sex (OR, 1.22, 95% CI, 0.99-1.50; I2, 65%) and age (OR, 1.17, 95% CI, 1.02-1.35; I2, 72%) were found, but effect sizes were small. CONCLUSIONS: The comprehensive list of risk factors, which specifies the strength of evidence and effect sizes, could assist in the prioritization of preventive measures and interventions.

Barriers, facilitators and needs to deprescribe benzodiazepines and other sedatives in older adults: a mixed methods study of primary care provider perspectives.

BACKGROUND: Benzodiazepines and other sedative hypnotic drugs (BSHs) are frequently prescribed for sleep problems, but cause substantial adverse effects, particularly in older adults. Improving knowledge on barriers, facilitators and needs of primary care providers (PCPs) to BSH deprescribing could help reduce BSH use and thus negative effects. METHODS: We conducted a mixed methods study (February-May 2023) including a survey, semi-structured interviews and focus groups with PCPs in Switzerland. We assessed barriers, facilitators and needs of PCPs to BSH deprescribing. Quantitative data were analyzed descriptively, qualitative data deductively and inductively using the Theoretical Domain Framework (TDF). Quantitative and qualitative data were integrated using meta-interferences. RESULTS: The survey was completed by 126 PCPs (53% female) and 16 PCPs participated to a focus group or individual interview. The main barriers to BSH deprescribing included patient and PCP lack of knowledge on BSH effects and side effects, lack of PCP education on treatment of sleep problems and BSH deprescribing, patient lack of motivation, PCP lack of time, limited access to cognitive behavioral therapy for insomnia and absence of public dialogue on BSHs. Facilitators included informing on side effects to motivate patients to discontinue BSHs and start of deprescribing during a hospitalization. Main PCP needs were practical recommendations for pharmacological and non-pharmacological treatment of sleep problems and deprescribing schemes. Patient brochures were wished by 69% of PCPs. PCPs suggested the brochures to contain explanations about risks and benefits of BSHs, sleep hygiene and sleep physiology, alternative treatments, discontinuation process and tapering schemes. CONCLUSION: The barriers and facilitators as well as PCP needs and opinions on patient material we identified can be used to develop PCP training and material on BSH deprescribing, which could help reduce the inappropriate use of BSHs for sleep problems.

[Deprescribing statinsand other cardiovascular medications Barriers and facilitators]. / Déprescription des statines et autres médicaments cardiovasculaires. Obstacles et facilitateurs.

Considering the growing problematic of polypharmacy, this article summarizes barriers and facilitators to deprescribing cardiovascular medications, from the point of view of physicians and patients. Patients seem to be more open to discontinue cardiovascular medications when their physician suggests to do so, or if they dislike the medication. Physicians tend to consider deprescribing more if they had positive experiences with deprescribing in the past, or if their patients ask them to. The most common barrier for patients is the fear of health deterioration. Patient desire to continue with their usual medication or past negative experiences with depresecribing are frequently reported as barriers by physicians.

Vu le problème croissant de la polypharmacie, cet article résume les différents obstacles et facilitateurs à la déprescription des médicaments cardiovasculaires, du point de vue des médecins et des patients. Ces derniers sont plus enclins à stopper des médicaments cardiovasculaires lorsque cela leur est proposé par leur médecin traitant ou s'ils n'aiment pas le médicament. Les médecins arrêtent plus facilement les traitements s'ils ont déjà eu des expériences positives de déprescription et si leurs patients le leur demandent. L'obstacle le plus fréquent pour les patients est la peur d'une détérioration de leur état de santé. Pour les médecins, la volonté du patient de poursuivre le traitement, ou une expérience passée négative avec la déprescription, sont des obstacles fréquents.

Perspectives of patients and clinicians on older patient mobility on acute medical wards: a qualitative study.

BACKGROUND: Low mobility during an acute care medical hospitalization is frequent and associated with adverse outcomes, particularly among older patients. Better understanding barriers and facilitators to improve mobility during hospitalization could help develop effective interventions. The goal of this study was to assess barriers and facilitators to older medical patients' hospital mobility, from the point of view of patients and clinicians, to develop a framework applicable in clinical practice. METHODS: We conducted a qualitative study in one university and two non-university hospitals of two different language and cultural regions of Switzerland, including 13 focus groups (FGs; five with patients, eight with clinicians). We included 24 adults aged 60 years or older hospitalized on an acute general internal medicine ward of one of the three participating hospitals during the previous years, and 34 clinicians (15 physicians, nine nurses/nursing assistants, 10 physiotherapists) working on those wards. The FG guides included open-ended questions exploring mobility experiences, expectations, barriers and facilitators to mobility, consequences of low mobility and knowledge on mobility. We applied an inductive thematic analysis. RESULTS: We identified four themes of barriers and facilitators to mobility: 1) patient-related factors; 2) clinician-related factors; 3) social interactions; and 4) non-human factors. Clinician-related factors were only mentioned in clinician FGs. Otherwise, subthemes identified from patient and clinician FGs were similar and codes broadly overlapped. Subthemes included motivation, knowledge, expectations, mental and physical state (theme 1); process, knowledge - skills, mental state - motivation (theme 2); interpersonal relationships, support (theme 3); hospital setting - organization (theme 4). CONCLUSIONS: From patients' and clinicians' perspectives, a broad spectrum of human and structural factors influences mobility of older patients hospitalized on an acute general internal medicine ward. New factors included privacy issues and role perception. Many of those factors are potentially actionable without additional staff resources. This study is a first step in participatory research to improve mobility of older medical inpatients.

Impact of an INtervention to increase MOBility in older hospitalized medical patients (INTOMOB): Study protocol for a cluster randomized controlled trial.

BACKGROUND: Low mobility during an acute hospitalization is frequent and associated with adverse effects, including persistent functional decline, institutionalization and death. However, we lack effective interventions to improve mobility that are scalable in everyday practice. The INTOMOB trial - INtervention to increase MOBility in older hospitalized medical patients - will test the effect of a multilevel intervention to improve mobility of older hospitalized patients on functional mobility. METHODS: The INTOMOB multicenter superiority parallel cluster randomized controlled trial will enroll in total 274 patients in Swiss hospitals. Community-dwelling adults aged ≥ 60 years, admitted to a general internal medicine ward with an anticipated length of hospital stay of ≥ 3 days, will be eligible for participation. Unit of randomization will be the wards. A multilevel mobility intervention will be compared to standard of care and target the patients (information and exercise booklets, mobility diary, iPad with exercise videos), healthcare professionals (e-learning, oral presentation, mobility checklist), and environment (posters and pictures on the wards). The primary outcome will be life-space level, measured by the University of Alabama at Birmingham Study of Aging Life-Space Assessment (LSA), at 30 days after enrollment. The LSA is a measure of functional mobility, i.e., how far participants move from bedroom to outside town. Secondary outcomes include, among others, LSA at 180 days, mobility and falls during hospitalization, muscle strength at discharge, and falls, emergency room visits, readmissions, and death within 180 days. DISCUSSION: This study has the potential to improve outcomes of older hospitalized patients through an intervention that should be scalable in clinical practice because it fosters patient empowerment and does not require additional resources. The tools provided to the patients can help them implement better mobility practices after discharge, which can contribute to better functional outcomes. The choice of a functional patient-reported outcome measure as primary outcome (rather than a "simple" objective mobility measure) reinforces the patient-centeredness of the study. TRIAL REGISTRATION: clinicaltrials.gov (NCT05639231, released on December 19 2022); Swiss National Clinical Trial Portal (SNCTP000005259, released on November 28 2022).

Type 2 Diabetes Management, Control and Outcomes During the COVID-19 Pandemic in Older US Veterans: an Observational Study.

BACKGROUND: The COVID-19 pandemic required a change in outpatient care delivery models, including shifting from in-person to virtual visits, which may have impacted care of vulnerable patients. OBJECTIVE: To describe the changes in management, control, and outcomes in older people with type 2 diabetes (T2D) associated with the shift from in-person to virtual visits. DESIGN AND PARTICIPANTS: In veterans aged ≥ 65 years with T2D, we assessed the rates of visits (in person, virtual), A1c measurements, antidiabetic deintensification/intensification, ER visits and hospitalizations (for hypoglycemia, hyperglycemia, other causes), and A1c level, in March 2020 and April-November 2020 (pandemic period). We used negative binomial regression to assess change over time (reference: pre-pandemic period, July 2018 to February 2020), by baseline Charlson Comorbidity Index (CCI; > 2 vs. <= 2) and A1c level. KEY RESULTS: Among 740,602 veterans (mean age 74.2 [SD 6.6] years), there were 55% (95% CI 52-58%) fewer in-person visits, 821% (95% CI 793-856%) more virtual visits, 6% (95% CI 1-11%) fewer A1c measurements, and 14% (95% CI 10-17%) more treatment intensification during the pandemic, relative to baseline. Patients with CCI > 2 had a 14% (95% CI 12-16%) smaller relative increase in virtual visits than those with CCI <= 2. We observed a seasonality of A1c level and treatment modification, but no association of either with the pandemic. After a decrease at the beginning of the pandemic, there was a rebound in other-cause (but not hypo- and hyperglycemia-related) ER visits and hospitalizations from June to November 2020. CONCLUSION: Despite a shift to virtual visits and a decrease in A1c measurement during the pandemic, we observed no association with A1c level or short-term T2D-related outcomes, providing some reassurance about the adequacy of virtual visits. Further studies should assess the longer-term effects of shifting to virtual visits in different populations to help individualize care, improve efficiency, and maintain appropriate care while reducing overuse.

Incidence of and predictors for antiseizure medication gaps in Medicare beneficiaries with epilepsy: a retrospective cohort study.

BACKGROUND: For the two-thirds of patients with epilepsy who achieve seizure remission on antiseizure medications (ASMs), patients and clinicians must weigh the pros and cons of long-term ASM treatment. However, little work has evaluated how often ASM discontinuation occurs in practice. We describe the incidence of and predictors for sustained ASM fill gaps to measure discontinuation in individuals potentially eligible for ASM withdrawal. METHODS: This was a retrospective cohort of Medicare beneficiaries. We included patients with epilepsy by requiring International Classification of Diseases codes for epilepsy/convulsions plus at least one ASM prescription each year 2014-2016, and no acute visit for epilepsy 2014-2015 (i.e., potentially eligible for ASM discontinuation). The main outcome was the first day of a gap in ASM supply (30, 90, 180, or 360 days with no pills) in 2016-2018. We displayed cumulative incidence functions and identified predictors using Cox regressions. RESULTS: Among 21,819 beneficiaries, 5191 (24%) had a 30-day gap, 1753 (8%) had a 90-day gap, 803 (4%) had a 180-day gap, and 381 (2%) had a 360-day gap. Predictors increasing the chance of a 180-day gap included number of unique medications in 2015 (hazard ratio [HR] 1.03 per medication, 95% confidence interval [CI] 1.01-1.05) and epileptologist prescribing physician (≥25% of that physician's visits for epilepsy; HR 2.37, 95% CI 1.39-4.03). Predictors decreasing the chance of a 180-day gap included Medicaid dual eligibility (HR 0.75, 95% CI 0.60-0.95), number of unique ASMs in 2015 (e.g., 2 versus 1: HR 0.37, 95% CI 0.30-0.45), and greater baseline adherence (> 80% versus ≤80% of days in 2015 with ASM pill supply: HR 0.38, 95% CI 0.32-0.44). CONCLUSIONS: Sustained ASM gaps were rarer than current guidelines may suggest. Future work should further explore barriers and enablers of ASM discontinuation to understand the optimal discontinuation rate.

Polypharmacy composition and patient- and provider-related variation in patients with epilepsy.

OBJECTIVE: To describe polypharmacy composition, and the degree to which patients versus providers contribute to variation in medication fills, in people with epilepsy. METHODS: We performed a retrospective study of Medicare beneficiaries with epilepsy (antiseizure medication plus diagnostic codes) in 2014 (N = 78,048). We described total number of medications and prescribers, and specific medications. Multilevel models evaluated the percentage of variation in two outcomes (1. number of medications per patient-provider dyad, and 2. whether a medication was filled within thirty days of a visit) due to patient-to-patient differences versus provider-to-provider differences. RESULTS: Patients filled a median of 12 (interquartile range [IQR] 8-17) medications, from median of 5 (IQR 3-7) prescribers. Twenty-two percent filled an opioid, and 61% filled at least three central nervous system medications. Levetiracetam was the most common medication (40%), followed by hydrocodone/acetaminophen (27%). The strongest predictor of medications per patient was Charlson comorbidity index (7.5 [95% confidence interval (CI) 7.2-7.8] additional medications for index 8+ versus 0). Provider-to-provider variation explained 36% of variation in number of medications per patient, whereas patient-to-patient variation explained only 2% of variation. Provider-to-provider variation explained 57% of variation in whether a patient filled a medication within 30 days of a visit, whereas patient-to-patient variation explained only 30% of variation. CONCLUSION: Patients with epilepsy fill a large number of medications from a large number of providers, including high-risk medications. Variation in medication fills was substantially more related to provider-to-provider rather than patient-to-patient variation. The better understanding of drivers of high-prescribing practices may reduce avoidable medication-related harms.

Barriers and facilitators to mobility of patients hospitalised on an acute medical ward: a systematic review.

BACKGROUND: low patient mobility is common during hospitalisation and is associated with adverse outcomes. To change practice, interventions should address barriers and facilitators to mobility. Our aim was to systematically review the literature to provide a synthesised overview of patient-, health care professional (HCP)- and environment-/system-related barriers and facilitators to mobility of patients hospitalised on an acute care medical ward. METHODS: we searched Medline, Embase, PsycInfo, Web of Science Core Collection, Cochrane CENTRAL, CINHAHL and Google Scholar (inception to 18 October 2021) to identify studies reporting barriers and/or facilitators to mobility of adults hospitalised on an acute medical ward. We applied a deductive and inductive thematic analysis to classify barriers and facilitators into themes and subthemes relevant for clinical practice. RESULTS: among 26 studies (16 qualitative, 7 quantitative and 3 mixed methods), barriers and facilitators were categorised into 10 themes: patient situation, knowledge, beliefs, experiences, intentions, emotions, social influences, role/identity, implementation/organisation and environment/resources. Barriers included patient characteristics (e.g. impaired cognitive/physical status) and symptoms, HCPs prioritising other tasks over mobility, HCPs labelling patients as 'too sick', fear of injury, lack of time, lack of clarity about responsibility, patient medical devices and non-encouraging environment. Facilitators included knowledge of mobility importance, HCP skills, interdisciplinarity, documentation and unit expectations, encouraging staff, goal individualisation, activity programme, family/visitor/volunteer support and availability of equipment. CONCLUSION: this synthesised overview of patient-, HCP- and environment-/system-related barriers and facilitators to mobility of adults hospitalised on an acute medical ward can help researchers and clinicians focus on what can realistically be influenced to improve mobility. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42021285954.

Multimorbidity and long-term disability and physical functioning decline in middle-aged and older Americans: an observational study.

BACKGROUND: Multimorbidity is highly prevalent and associated with several adverse health outcomes, including functional limitations. While maintaining physical functioning is relevant for all adults, identifying those with multimorbidity at risk for faster rates of physical functioning decline may help to target interventions to delay the onset and progression of disability. We quantified the association of multimorbidity with rates of long-term disability and objective physical functioning decline. METHODS: In the Health and Retirement Study, we computed the Multimorbidity-Weighted Index (MWI) by assigning previously validated weights (based on physical functioning) to each chronic condition. We used an adjusted negative binomial regression to assess the association of MWI with disability (measured by basic and instrumental activities of daily living [ADLs, IADLs]) over 16 years, and linear mixed effects models to assess the association of MWI with gait speed and grip strength over 8 years. RESULTS: Among 16,616 participants (mean age 67.3, SD 9.7 years; 57.8% women), each additional MWI point was associated with a 10% increase in incidence rate of disability (IRR: 1.10; 95%CI: 1.09, 1.10). In 2,748 participants with data on gait speed and grip strength, each additional MWI point was associated with a decline in gait speed of 0.004 m/s (95%CI: -0.006, -0.001). The association with grip strength was not statistically significant (-0.01 kg, 95%CI: -0.73, 0.04). The rate of decline increased with time for all outcomes, with a significant interaction between time and MWI for disability progression only. CONCLUSION: Multimorbidity, as weighted on physical functioning, was associated with long-term disability, including faster rates of disability progression, and decline in gait speed. Given the importance of maintaining physical functioning and preserving functional independence, MWI is a readily available tool that can help identify adults to target early on for interventions.

Adding a New Medication Versus Maximizing Dose to Intensify Hypertension Treatment in Older Adults : A Retrospective Observational Study.

BACKGROUND: There are 2 approaches to intensifying antihypertensive treatment when target blood pressure is not reached, adding a new medication and maximizing dose. Which strategy is better is unknown. OBJECTIVE: To assess the frequency of intensification by adding a new medication versus maximizing dose, as well as the association of each method with intensification sustainability and follow-up systolic blood pressure (SBP). DESIGN: Large-scale, population-based, retrospective cohort study. Observational data were used to emulate a target trial with 2 groups, new medication and maximizing dose, who underwent intensification of their drug regimen. SETTING: Veterans Health Administration (2011 to 2013). PATIENTS: Veterans aged 65 years or older with hypertension, an SBP of 130 mm Hg or higher, and at least 1 antihypertensive medication at less than the maximum dose. MEASUREMENTS: The following 2 intensification approaches were emulated: adding a new medication, defined as a total dose increase with new medication, and maximizing dose, defined as a total dose increase without new medication. Inverse probability weighting was used to assess the observational effectiveness of the intensification approach on sustainability of intensified treatment and follow-up SBP at 3 and 12 months. RESULTS: Among 178 562 patients, 45 575 (25.5%) had intensification by adding a new medication and 132 987 (74.5%) by maximizing dose. Compared with maximizing dose, adding a new medication was associated with less intensification sustainability (average treatment effect, -15.2% [95% CI, -15.7% to -14.6%] at 3 months and -15.1% [CI, -15.6% to -14.5%] at 12 months) but a slightly larger reduction in mean SBP (-0.8 mm Hg [CI, -1.2 to -0.4 mm Hg] at 3 months and -1.1 mm Hg [CI, -1.6 to -0.6 mm Hg] at 12 months). LIMITATION: Observational data; largely male population. CONCLUSION: Adding a new antihypertensive medication was less frequent and was associated with less intensification sustainability but slightly larger reductions in SBP. Trials would provide the most definitive support for our findings. PRIMARY FUNDING SOURCE: National Institute on Aging and Veterans Health Administration.

[Should dyslipidemia be treated in the elderly and very old people?] / Faut-il traiter les dyslipidémies chez les personnes âgées et très âgées ?

The beneficial effect of statins on the risk of recurrence of cardiovascular disease (secondary prevention) is well demonstrated. In primary prevention (no symptomatic cardiovascular disease), the benefit of statins after the age of 70 years is less clear and elderly patients with comorbidities have often been excluded from large, randomized trials. Some ongoing clinical trials will provide more information on the potential benefits and risks of starting or stopping statins in older adults. In clinical practice, the decision to treat with statins needs to take into account age, comorbidities, life expectancy, functional and cognitive status and patient preferences (shared decision), but statin discontinuation is only recommended in the context of a clinical trial, as reviewed in this article.

L'effet bénéfique des statines sur le risque de récidive de maladie cardiovasculaire (prévention secondaire) est bien démontré. En prévention primaire (pas de maladie cardiovasculaire symptomatique), le bénéfice des statines après 70 ans est moins clair et les patients âgés avec des comorbidités ont souvent été exclus des grandes études randomisées. Des essais cliniques sont en cours et apporteront plus d'informations sur les potentiels effets bénéfiques et risques de débuter ou d'arrêter les statines chez les personnes âgées. Dans la pratique, en sus de l'âge, la décision de traiter par statine nécessite de prendre en compte les comorbidités, l'espérance de vie, l'état fonctionnel et cognitif et les souhaits du patient (décision partagée), mais un arrêt n'est recommandé que dans le cadre d'un essai clinique, comme revu dans cet article.

Cardiovascular disease risk, awareness, and treatment in people with epilepsy.

OBJECTIVE: To evaluate whether cardiovascular risk, risk awareness, and guideline concordant treatment differ in individuals with versus without epilepsy. METHODS: This was a retrospective cross-sectional study using the National Health and Nutrition Examination Survey. We included participants ≥18 years for 2013-2018. We classified participants as having epilepsy if reporting ≥1 medication treating seizures. We calculated 10-year atherosclerotic cardiovascular disease (ASCVD) risk using the revised pooled cohort equation. We compared unadjusted and adjusted risk for participants with versus without epilepsy. We then assessed hypertension and diabetes disease awareness and control, plus statin guideline-concordance. We assessed mediators for both ASCVD risk and cardiovascular disease awareness. RESULTS: Of 17,961 participants, 154 (0.9%) had epilepsy. Participants with epilepsy reported poorer diet (p = 0.03), fewer minutes of moderate-vigorous activity per day (p < 0.01), and increased frequency of cardiovascular conditions (e.g. coronary heart disease, myocardial infarction, stroke). There was no difference in control of individual examination and laboratory risk factors between groups (A1c, systolic blood pressure, diastolic blood pressure, high-density lipoprotein, low-density lipoprotein, total cholesterol). However, epilepsy was associated with 52% (95% confidence interval [CI]: 0-130%) increase in ASCVD risk, which became nonsignificant after adjusting for health behaviors. No single studied variable (income, Patient Health Questionnaire-9 (PHQ-9), diet, smoking) had a significant indirect effect. Participants with epilepsy reported increased hypertension awareness which was trivially but significantly mediated by having a routine place of healthcare (indirect effect: 1% absolute increase (95% CI: 0-1%), and they reported increased rates of hypertension treatment and guideline-concordant statin therapy. Participants with versus without epilepsy reported similar rates of blood pressure control and diabetes awareness, treatment, and control. CONCLUSIONS: Participants with epilepsy had increased ASCVD risk, despite similar or better awareness, treatment, and control of individual risk factors such as diabetes and hypertension. Our results suggest that epilepsy is associated with numerous health behaviors leading to cardiovascular disease, though the causal pathway is complex as these variables (income, depression, diet, exercise, smoking) generally served as confounders rather than mediators.

Diabetic foot ulcer management in a multidisciplinary foot centre: one-year healing, amputation and mortality rate.

OBJECTIVE: To describe the rates of healing, major amputation and mortality after 12 months in patients with a new diabetic foot ulcer (DFU) and their care in a French diabetic foot service (DFS). METHOD: A prospective single-centre study including patients from March 2009 to December 2010. The length of time to healing, minor amputation, major amputation and mortality rate after inclusion were analysed using the Kaplan-Meier method. RESULTS: Some 347 patients were included (3% lost to follow-up), with a median follow-up (IQR) of 19 (12-24) months. The mean (SD) age was 65±12 years, 68% were male, and the median duration of the ulcer was 49 (19-120) days. Complications of the DFU were ischaemia (70%), infection (55%) and osteomyelitis (47%). Of the patients, 50% were inpatients in the DFS at inclusion (median duration of hospitalisation 26 (15-41) days). The rate of healing at one year was 67% (95% confidence interval (CI): 61-72); of major amputation 10% (95% CI: 7-17); of minor amputation 19% (95% CI: 14-25), and the death rate was 9% (95% CI: 7-13). Using an adjusted hazard ratio, the predictive factors of healing were perfusion and the area of the wound. The risk factors for a major amputation were active smoking and osteomyelitis. The risk factors for mortality were perfusion and age. CONCLUSION: This study confirms the need to treat DFUs rapidly, in a multidisciplinary DFS.

Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism.

BACKGROUND: The use of levothyroxine to treat subclinical hypothyroidism is controversial. We aimed to determine whether levothyroxine provided clinical benefits in older persons with this condition. METHODS: We conducted a double-blind, randomized, placebo-controlled, parallel-group trial involving 737 adults who were at least 65 years of age and who had persisting subclinical hypothyroidism (thyrotropin level, 4.60 to 19.99 mIU per liter; free thyroxine level within the reference range). A total of 368 patients were assigned to receive levothyroxine (at a starting dose of 50 µg daily, or 25 µg if the body weight was <50 kg or the patient had coronary heart disease), with dose adjustment according to the thyrotropin level; 369 patients were assigned to receive placebo with mock dose adjustment. The two primary outcomes were the change in the Hypothyroid Symptoms score and Tiredness score on a thyroid-related quality-of-life questionnaire at 1 year (range of each scale is 0 to 100, with higher scores indicating more symptoms or tiredness, respectively; minimum clinically important difference, 9 points). RESULTS: The mean age of the patients was 74.4 years, and 396 patients (53.7%) were women. The mean (±SD) thyrotropin level was 6.40±2.01 mIU per liter at baseline; at 1 year, this level had decreased to 5.48 mIU per liter in the placebo group, as compared with 3.63 mIU per liter in the levothyroxine group (P<0.001), at a median dose of 50 µg. We found no differences in the mean change at 1 year in the Hypothyroid Symptoms score (0.2±15.3 in the placebo group and 0.2±14.4 in the levothyroxine group; between-group difference, 0.0; 95% confidence interval [CI], -2.0 to 2.1) or the Tiredness score (3.2±17.7 and 3.8±18.4, respectively; between-group difference, 0.4; 95% CI, -2.1 to 2.9). No beneficial effects of levothyroxine were seen on secondary-outcome measures. There was no significant excess of serious adverse events prespecified as being of special interest. CONCLUSIONS: Levothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, NCT01660126 .).

Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study.

BACKGROUND: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes. METHODS: Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model. RESULTS: At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (ß coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00-1.04, p < 0.001), triglycerides (0.11, 0.03-0.20, p = 0.007), log(RANKL) (0.07, 0.02-0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15-0.57, p = 0.001), statin use (0.39, 0.06-0.72, p = 0.023) and duration of follow up (0.04, 0.01-0.06, p = 0.004). CONCLUSION: In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234.

Polypharmacy in patients with epilepsy: A nationally representative cross-sectional study.

OBJECTIVE: The objective of the study was to characterize the prevalence of polypharmacy and central nervous system (CNS)-acting medications in patients with epilepsy, and particular types of medications. METHODS: This was a retrospective cross-sectional study using data from the nationally representative National Health and Nutrition Examination Survey (NHANES). We included patients who reported taking at least one prescription medication in order to treat seizures or epilepsy during NHANES survey years 2013-2016. We assessed the number and types of drugs and predictors of total number of medications using a negative binomial regression. We then assessed prevalence of polypharmacy (≥5 medications), CNS polypharmacy (≥3 CNS-acting medications) and additional CNS-acting medications, and drugs that lower the seizure threshold (i.e., bupropion and tramadol), and extrapolated prevalence to estimated affected US population. RESULTS: The NHANES contained 20,146 participants, of whom 135 reported taking ≥1 antiseizure medication (ASM) for seizures or epilepsy representing 2,399,520 US citizens using NHANES's sampling frame. Patients reported taking a mean 5.3 (95% confidence interval (CI): 4.3-6.3) prescription medications. Adjusting for race, sex, and uninsurance, both age and number of chronic conditions predicted increased number of medications (incident rate ratio (IRR) per decade: 1.16, 95% CI: 1.04-1.28; IRR per chronic condition: 1.19, 95% CI: 1.11-1.27). Polypharmacy was reported by 47% (95% CI: 38%-57%) of patients, CNS polypharmacy by 34% (23%-47%), benzodiazepine use by 21% (14%-30%), opioid use by 16% (11%-24%), benzodiazepine plus opioid use by 6% (3%-14%), and 6% (2%-15%) reported a drug that lowers the seizure threshold. Twelve percent (7%-20%) took an opioid with either a benzodiazepine or gabapentinoid. CONCLUSIONS: Polypharmacy is common in patients with epilepsy. Patients taking ASMs frequently reported also taking other CNS-acting medications (i.e., opioids, benzodiazepines, seizure threshold-lowering medications), and medication combinations with black box warnings. Central nervous system polypharmacy poses health risks. Future research is needed to explore drivers of polypharmacy and strategies to help mitigate potentially harmful prescription use in this high-risk population.

Diabetic foot ulcer management in a multidisciplinary foot centre: one-year healing, amputation and mortality rate.

OBJECTIVE: To describe the rates of healing, major amputation and mortality after 12 months in patients with a new diabetic foot ulcer (DFU) and their care in a French diabetic foot service (DFS). METHOD: A prospective single-centre study including patients from March 2009 to December 2010. The length of time to healing, minor amputation, major amputation and mortality rate after inclusion were analysed using the Kaplan-Meier method. RESULTS: Some 347 patients were included (3% lost to follow-up), with a median follow-up (IQR) of 19 (12-24) months. The mean (SD) age was 65±12 years, 68% were male, and the median duration of the ulcer was 49 (19-120) days. Complications of the DFU were ischaemia (70%), infection (55%) and osteomyelitis (47%). Of the patients, 50% were inpatients in the DFS at inclusion (median duration of hospitalisation 26 (15-41) days). The rate of healing at one year was 67% (95% confidence interval (CI): 61-72); of major amputation 10% (95% CI: 7-17); of minor amputation 19% (95% CI: 14-25), and the death rate was 9% (95% CI: 7-13). Using an adjusted hazard ratio, the predictive factors of healing were perfusion and the area of the wound. The risk factors for a major amputation were active smoking and osteomyelitis. The risk factors for mortality were perfusion and age. CONCLUSION: This study confirms the need to treat DFUs rapidly, in a multidisciplinary DFS.

[Controversies concerning screening and treatment of primary dyslipidemias in 2020]. / Controverses sur le dépistage et la prise en charge des dyslipidémies familiales en 2020.

Familial dyslipidemia is rare compared to polygenetic causes. Nevertheless, it is important not to miss this diagnosis, as it is more strongly associated with an increased risk of early cardiovascular disease and scores for calculating cardiovascular risk are not valid in this population. Early detection and management based on lifestyle optimization and treatment of cardiovascular risk factors can delay the onset of cardiovascular complications and thus improve patients' quality of life. A LDL-Cholesterol of 4,9 mmol/l has recently been suggested as the cut-off for starting lipid lowering therapy, but remains controversial because the majority of people above this threshold do not have primary monogenic dyslipidemia. The age at which therapy should be initiated as well as the targets for treatment are also controversial.

Les dyslipidémies familiales sont plus rares que les causes communes, mais il est important de ne pas les manquer vu qu'elles sont liées à un risque augmenté de maladie cardiovasculaire précoce et que les scores de risque ne sont pas valables chez ces patients. Un dépistage et une prise en charge précoces reposant sur une optimisation de l'hygiène de vie et une éviction des facteurs de risque cardiovasculaire permettent de retarder la survenue des complications cardiovasculaires et ainsi d'améliorer la qualité de vie des patients. Un seuil de LDL de 4,9 mmol/l pour débuter un traitement hypolipémiant a récemment été proposé, mais reste controversé car la majorité des patients au-dessus de ce seuil n'a pas une forme familiale. L'âge de début d'un traitement et les cibles de traitement sont également controversés.