BMC Medicine

Imaging is critical in the diagnosis and treatment of dementia, particularly in vascular cognitive impairment, due to the visualization of ischemic and hemorrhagic injury of gray and white matter. Magnetic resonance imaging (MRI) and positron emission tomography (PET) provide structural and functional information. Clinical MRI is both generally available and versatile – T2-weighted images show infarcts, FLAIR shows white matter changes and lacunar infarcts, and susceptibility-weighted images reveal microbleeds. Diffusion MRI adds another dimension by showing graded damage to white matter, making it more sensitive to white matter injury than FLAIR. Regions of neuroinflammatory disruption of the blood–brain barrier with increased permeability can be quantified and visualized with dynamic contrast-enhanced MRI. PET shows metabolism of glucose and accumulation of amyloid and tau, which is useful in showing abnormal metabolism in Alzheimer’s disease. Combining MRI and PET allows identification of patients with mixed dementia, with MRI showing white matter injury and PET demonstrating regional impairment of glucose metabolism and deposition of amyloid. Excellent anatomical detail can be observed with 7.0-Tesla MRI. Imaging is the optimal method to follow the effect of treatments since changes in MRI scans are seen prior to those in cognition. This review describes the role of various imaging modalities in the diagnosis and treatment of vascular cognitive impairment.

Preterm delivery is an independent risk factor for maternal cardiovascular disease. Little is known about the association between preterm delivery and maternal renal function. This study aimed to examine whether women who experience preterm delivery are at increased risk of subsequent chronic kidney disease (CKD) and end-stage kidney disease (ESKD). Using data from the Swedish Medical Birth Register, singleton live births from 1973 to 2012 were identified and linked to data from the Swedish Renal Register and National Patient Register (up to 2013). Gestational age at delivery was the main exposure and treated as a time-dependent variable. Primary outcomes were maternal CKD or ESKD. Cox proportional hazard regression models were used for analysis. The dataset included 1,943,716 women who had 3,760,429 singleton live births. The median follow-up was 20.6 (interquartile range 9.9–30.0) years. Overall, 162,918 women (8.4%) delivered at least 1 preterm infant (< 37 weeks). Women who had any preterm delivery (< 37 weeks) were at increased risk of CKD (adjusted hazard ratio (aHR) 1.39, 95% CI 1.32–1.45) and ESKD (aHR 2.22, 95% CI 1.90–2.58) compared with women who only delivered at term (≥ 37 weeks). Women who delivered an extremely preterm infant (< 28 weeks) were at increased risk of CKD (aHR 1.84, 95% CI 1.52–2.22) and ESKD (aHR 3.61, 95% CI 2.03–6.39). The highest risk of CKD and ESKD was in women who experienced preterm delivery + preeclampsia (vs. non-preeclamptic term deliveries, for CKD, aHR 2.81, 95% CI 2.46–3.20; for ESKD, aHR 6.70, 95% CI 4.70–9.56). However, spontaneous preterm delivery was also associated with increased risk of CKD (aHR 1.32, 95% CI 1.25–1.39) and ESKD (aHR 1.99, 95% CI 1.67–2.38) independent of preeclampsia or small for gestational age (SGA). Women with history of preterm delivery are at increased risk of CKD and ESKD. The risk is higher among women who had very preterm or extremely preterm deliveries, or whose preterm delivery was medically indicated. Women who experience spontaneous preterm delivery are at increased risk of long-term renal disease independent of preeclampsia or SGA. Preterm delivery may act as a risk marker for adverse maternal renal outcomes.

An update of the chapter on Mental, Behavioral and Neurodevelopmental Disorders in the International Classification of Diseases and Related Health Problems (ICD) is of great interest around the world. The recent approval of the 11th Revision of the ICD (ICD-11) by the World Health Organization (WHO) raises broad questions about the status of nosology of mental disorders as a whole as well as more focused questions regarding changes to the diagnostic guidelines for specific conditions and the implications of these changes for practice and research. This Forum brings together a broad range of experts to reflect on key changes and controversies in the ICD-11 classification of mental disorders. Taken together, there is consensus that the WHO’s focus on global applicability and clinical utility in developing the diagnostic guidelines for this chapter will maximize the likelihood that it will be adopted by mental health professionals and administrators. This focus is also expected to enhance the application of the guidelines in non-specialist settings and their usefulness for scaling up evidence-based interventions. The new mental disorders classification in ICD-11 and its accompanying diagnostic guidelines therefore represent an important, albeit iterative, advance for the field.

Although extensive research exists on informal long-term care, little work has examined the clinical significance of transitions in family caregiving due to a lack of established clinical cut-points on key measures. The objectives of this study were to determine whether clinically significant changes in symptoms of burden and depression occur among caregivers within 12 months of nursing home admission (NHA) of their relatives with dementia, and to identify key predictors of clinically persistent burden and depression in the first year after institutionalization. Secondary longitudinal analysis of dementia caregivers were recruited from eight catchment areas in the United States with 6- and 12-month post-placement follow-up data. The sample included data on 1,610 dementia caregivers with pre- and six-month post-placement data and 1,116 with pre-placement, six-month, and 12-month post-placement data. Burden was measured with a modified version of the Zarit Burden Inventory. Depressive symptoms were assessed with the Geriatric Depression Scale. Chi-square analyses found significant (P < .05) reductions in the number of caregivers who reported clinically significant burden and depressive symptoms after NHA compared to pre-placement. Logistic regression models revealed that wives and daughters were most likely to experience clinically persistent burden and husbands were most likely to experience clinically significant depression after NHA. In addition to suggesting that clinically significant decreases in caregiver burden and depression are likely to occur following institutionalization, the results reveal particular subsets of caregivers who are at continued risk of distress. Such findings can facilitate development of screening processes to identify families at-risk following institutionalization.

Dietary interventions targeting the gut microbiota have been proposed as innovative strategies to improve obesity-associated metabolic disorders. Increasing physical activity (PA) is considered as a key behavioral change for improving health. We have tested the hypothesis that changing the PA status during a nutritional intervention based on prebiotic supplementation can alter or even change the metabolic response to the prebiotic. We confirm in obese subjects and in high-fat diet fed mice that performing PA in parallel to a prebiotic supplementation is necessary to observe metabolic improvements upon inulin. A randomized, single-blinded, multicentric, placebo-controlled trial was conducted in obese participants who received 16 g/day native inulin versus maltodextrin, coupled to dietary advice to consume inulin-rich versus -poor vegetables for 3 months, respectively, in addition to dietary caloric restriction. Primary outcomes concern the changes on the gut microbiota composition, and secondary outcomes are related to the measures of anthropometric and metabolic parameters, as well as the evaluation of PA. Among the 106 patients who completed the study, 61 patients filled a questionnaire for PA before and after intervention (placebo: n = 31, prebiotic: n = 30). Except the dietitian (who provided dietary advices and recipes book), all participants and research staff were blinded to the treatments and no advices related to PA were given to participants in order to change their habits. In parallel, a preclinical study was designed combining both inulin supplementation and voluntary exercise in a model of diet-induced obesity in mice. Obese subjects who increased PA during a 3 months intervention with inulin-enriched diet exhibited several clinical improvements such as reduced BMI (− 1.6 kg/m2), decreased liver enzymes and plasma cholesterol, and improved glucose tolerance. Interestingly, the regulations of Bifidobacterium, Dialister, and Catenibacterium genera by inulin were only significant when participants exercised more. In obese mice, we highlighted a greater gut fermentation of inulin and improved glucose homeostasis when PA is combined with prebiotics. We conclude that PA level is an important determinant of the success of a dietary intervention targeting the gut microbiota. ClinicalTrials.gov, NCT03852069 (February 22, 2019 retrospectively registered).

Perineal trauma during childbirth affects millions of women worldwide every year. The aim of the Perineal Assessment and Repair Longitudinal Study (PEARLS) was to improve maternal clinical outcomes following childbirth through an enhanced cascaded multiprofessional training program to support implementation of evidence-based perineal management. This was a pragmatic matched-pair cluster randomized controlled trial (RCT) that enrolled women (n = 3681) sustaining a second-degree perineal tear in one of 22 UK maternity units (clusters), organized in 11 matched pairs. Units in each matched pair were randomized to receive the training intervention either early (group A) or late (group B). Outcomes within each cluster were assessed prior to any training intervention (phase 1), and then after the training intervention was given to group A (phase 2) and group B (phase 3). Focusing on phase 2, the primary outcome was the percentage of women who had pain on sitting or walking at 10 to 12 days post-natal. Secondary outcomes included use of pain relief at 10 to 12 days post-natal, need for suture removal, uptake and duration of exclusive breastfeeding, and perineal wound infection. Practice-based measures included implementation of evidence into practice to promote effective clinical management of perineal trauma. Cluster-level paired t-tests were used to compare groups A and B. There was no significant difference between the clusters in phase 2 of the study in the average percentage of women reporting perineal pain on sitting and walking at 10 to 12 days (mean difference 0.7%; 95% CI −10.1% to 11.4%; P = 0.89). The intervention significantly improved overall use of evidence-based practice in the clinical management of perineal trauma. Following the training intervention, group A clusters had a significant reduction in mean percentages of women reporting perineal wound infections and of women needing sutures removed. PEARLS is the first RCT to assess the effects of a ‘training package on implementation of evidence-based perineal trauma management. The intervention did not significantly improve the primary outcome but did significantly improve evidence-based practice and some of the relevant secondary clinical outcomes for women. ISRCTN28960026 NIHR UKCRN portfolio no: 4785.

The number of patients living with co-existing diseases is growing. This study aimed to assess the extent of multimorbidity, medication use, and drug- and gene-based interactions in patients following a non-ST elevation acute coronary syndrome (NSTE-ACS). In 1456 patients discharged from hospital for a NSTE-ACS, comorbidities and multimorbidity (≥ 2 chronic conditions) were assessed. Of these, 698 had complete drug use recorded at discharge, and 652 (the ‘interaction’ cohort) had drug use and actionable genotypes available for CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, DPYD, F5, SLCO1B1, TPMT, UGT1A1, and VKORC1. The following drug interactions were investigated: pharmacokinetic drug-drug (DDIs) involving CYPs (CYPs above, plus CYP1A2, CYP2C8, CYP3A4), SLCO1B1, and P-glycoprotein; drug-gene (DGIs); drug-drug-gene (DDGIs); and drug-gene-gene (DGGIs). Interactions predicted to be ‘substantial’ were defined as follows: DDIs due to strong inhibitors/inducers, DGIs due to variant homozygous/compound heterozygous genotypes, and DDGIs/DGGIs where the constituent DDI/DGI(s) both influenced the victim drug in the same direction. In the whole cohort, 727 (49.9%) patients had multimorbidity. Non-linear relationships between age and increasing comorbidities and decreasing coronary intervention were observed. There were 98.1% and 39.8% patients on ≥ 5 and ≥ 10 drugs, respectively (from n = 698); women received more non-cardiovascular drugs than men (median (IQR) 3 (1–5) vs 2 (1–4), p = 0.014). Overall, 98.7% patients had at least one actionable genotype. Within the interaction cohort, 882 interactions were identified in 503 patients (77.1%), of which 346 in 252 patients (38.7%) were substantial: 59.2%, 11.6%, 26.3%, and 2.9% substantial interactions were DDIs, DGIs, DDGIs, and DGGIs, respectively. CYP2C19 (49.5% of all interactions) and SLCO1B1 (18.4%) were involved in the largest number of interactions. Multimorbidity (p = 0.019) and number of drugs (p = 9.8 × 10−10) were both associated with patients having ≥ 1 substantial interaction. Multimorbidity (HR 1.76, 95% CI 1.10–2.82, p = 0.019), number of drugs (HR 1.10, 95% CI 1.04–1.16, p = 1.2 × 10−3), and age (HR 1.05, 95% CI 1.03–1.07, p = 8.9 × 10−7), but not drug interactions, were associated with increased subsequent major adverse cardiovascular events. Multimorbidity, polypharmacy, and drug interactions are common after a NSTE-ACS. Replication of results is required; however, the high prevalence of DDGIs suggests integrating co-medications with genetic data will improve medicines optimisation.

Cardiovascular disease (CVD) caused by air pollution poses a considerable burden on public health. We aim to examine whether lifestyle factors mediate the associations of air pollutant exposure with the risk of CVD and the extent of the interaction between lifestyles and air pollutant exposure regarding CVD outcomes. We included 7000 participants in 2011–2012 and followed up until 2018. The lifestyle evaluation consists of six factors as proxies, including blood pressure, blood glucose, blood lipids, body mass index, tobacco exposure, and physical activity, and the participants were categorized into three lifestyle groups according to the number of ideal factors (unfavorable, 0–1; intermediate, 2–4; and favorable, 5–6). Satellite-based spatiotemporal models were used to estimate exposure to ambient air pollutants (including particles with diameters ≤ 1.0 μm [PM1], ≤ 2.5 μm [PM2.5], ≤ 10 μm [PM10], nitrogen dioxide [NO2], and ozone [O3]). Cox regression models were used to examine the associations between air pollutant exposure, lifestyles and the risk of CVD. The mediation and modification effects of lifestyle categories on the association between air pollutant exposure and CVD were analyzed. After adjusting for covariates, per 10 μg/m3 increase in exposure to PM1 (HR: 1.09, 95% CI: 1.05–1.14), PM2.5 (HR: 1.04, 95% CI: 1.00–1.08), PM10 (HR: 1.05, 95% CI: 1.03–1.08), and NO2 (HR: 1.11, 95% CI: 1.05–1.18) was associated with an increased risk of CVD. Adherence to a healthy lifestyle was associated with a reduced risk of CVD compared to an unfavorable lifestyle (HR: 0.65, 95% CI: 0.56–0.76 for intermediate lifestyle and HR: 0.41, 95% CI: 0.32–0.53 for favorable lifestyle). Lifestyle played a significant partial mediating role in the contribution of air pollutant exposure to CVD, with the mediation proportion ranging from 7.4% for PM10 to 14.3% for PM2.5. Compared to an unfavorable lifestyle, the relative excess risk due to interaction for a healthier lifestyle to reduce the effect on CVD risk was − 0.98 (− 1.52 to − 0.44) for PM1, − 0.60 (− 1.05 to − 0.14) for PM2.5, − 1.84 (− 2.59 to − 1.09) for PM10, − 1.44 (− 2.10 to − 0.79) for NO2, and − 0.60 (− 1.08, − 0.12) for O3. Lifestyle partially mediated the association of air pollution with CVD, and adherence to a healthy lifestyle could protect middle-aged and elderly people from the adverse effects of air pollution regarding CVD.

Older adults hospitalized with fragility fractures are at high risk of negative events that can culminate in re-presentations to hospital emergency departments or readmissions to hospital. This systematic review aimed to identify patient, clinical, or hospital-related factors that are identifiable at the index admission and that may be associated with re-presentations to hospital emergency departments or hospital readmissions in older adults following fragility fractures. Four electronic databases (PubMed, CINAHL, Embase, and Scopus) were searched. A suite of search terms identified peer-reviewed English-language articles that examined potential correlates of hospital re-presentation in older adults (mean age ≥ 65 years) who were discharged from hospital following treatment for fragility fractures. A three-stage screening process (titles, abstracts, full text) was conducted by two researchers independently. Participant characteristics, study design, potential correlates examined, analyses, and findings were extracted for studies included in the review. Quality and risk of bias were assessed with the Effective Public Health Practice Project Quality Assessment Tool. The strength of evidence was incorporated into a best evidence synthesis, and meta-analysis was conducted where effect pooling was possible. Eleven of 35 eligible studies were categorized as high quality studies. These studies reported that age, higher Cumulative Illness Rating scores, American Society of Anesthesiologists scores > 3, longer length of stay, male sex, cardiovascular disease, low post-operative hemoglobin, kidney disease, dementia and cancer were factors identified at the index admission that were predictive of subsequent re-presentation to hospital. Age was the only predictor for which pooling of effects across studies was possible: pooling was conducted for re-presentation ≤ 30 days (pooled OR, 1.27; 95 % CI, 1.14–1.43) and > 30 days (pooled OR, 1.23; 95 % CI, 1.01–1.50). The best-evidence synthesis, in addition to the meta-analysis, identified a range of factors that may have utility in guiding clinical practice and policy guidelines for targeted interventions to reduce the need for re-presentation to hospital among this frail clinical population. The paucity of studies investigating re-presentations to hospital emergency departments without admission was an important gap in the literature identified in this review. Key limitations were exclusion of non-English language studies and grey literature. PROSPERO CRD42015019379 .