Surgical decision-making in superior canal dehiscence syndrome with concomitant otosclerosis.

OBJECTIVE: The diagnosis and management of Superior Canal Dehiscence Syndrome (SCDS) with concomitant otosclerosis can be a challenge. Otosclerosis can mask SCDS symptoms and stapes surgery may reveal or exacerbate vestibular symptoms. Our aim is to present four cases of SCDS with concomitant otosclerosis and thereby informing the reader about the possibility of this dual occurrence and its implications for treatment. CASES: Four patients with SCDS and concomitant otosclerosis are presented. Two patients underwent surgical treatment for both SCDS and otosclerosis and two patients opted for conservative management. OUTCOMES: The main differences between surgically and non-surgically treated cases are the presence of autophony and pressure-induced vertigo and a more severe experience of symptoms in surgically treated cases. Surgically treated cases achieved a sizeable reduction in postoperative air-bone gap and resolution of vestibular symptoms. CONCLUSION: The subjective severity of symptoms in combination with shared decision-making is key in determining the appropriate treatment plan for SCDS and concomitant otosclerosis.

The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons.

Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11-2.16], p = .01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased ß1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.

Can artificial intelligence separate the wheat from the chaff in systematic reviews of health economic articles?

OBJECTIVES: Artificial intelligence-powered tools, such as ASReview, could reduce the burden of title and abstract screening. This study aimed to assess the accuracy and efficiency of using ASReview in a health economic context. METHODS: A sample from a previous systematic literature review containing 4,994 articles was used. Previous manual screening resulted in 134 articles included for full-text screening (FT) and 50 for data extraction (DE). Here, accuracy and efficiency was evaluated by comparing the number of identified relevant articles with ASReview versus manual screening. Pre-defined stopping rules using sampling criteria and heuristic criteria were tested. Robustness of the AI-tool's performance was determined using 1,000 simulations. RESULTS: Considering included stopping rules, median accuracy for FT articles remained below 85%, but reached 100% for DE articles. To identify all relevant articles, a median of 89.9% of FT articles needed to be screened, compared to 7.7% for DE articles. Potential time savings between 49 and 59 hours could be achieved, depending on the stopping rule. CONCLUSIONS: In our case study, all DE articles were identified after screening 7.7% of the sample, allowing for substantial time savings. ASReview likely has the potential to substantially reduce screening time in systematic reviews of health economic articles.

Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

PURPOSE: Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. METHODS: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC-MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. RESULTS: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07-5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. CONCLUSION: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed.

Cost-effectiveness of a stepped care program to prevent depression among primary care patients with diabetes mellitus type 2 and/or coronary heart disease and subthreshold depression in comparison with usual care.

BACKGROUND: Patients with diabetes mellitus type 2 (DM2) and/or coronary heart disease (CHD) are at high risk to develop major depression. Preventing incident major depression may be an important tool in reducing the personal and societal burden of depression. The aim of the current study was to assess the cost-effectiveness of a stepped care program to prevent major depression (Step-Dep) in diabetes mellitus type 2 and/or coronary heart disease patients with subthreshold depression in comparison with usual care. METHODS: An economic evaluation with 12 months follow-up was conducted alongside a pragmatic cluster-randomized controlled trial from a societal perspective. Participants received care as usual (n = 140) or Step-Dep (n = 96) which consisted of four sequential treatment steps: watchful waiting, guided self-help, problem solving treatment and referral to a general practitioner. Primary outcomes were quality-adjusted life years (QALYs) and cumulative incidence of major depression. Costs were measured every 3 months. Missing data was imputed using multiple imputation. Uncertainty around cost-effectiveness outcomes was estimated using bootstrapping and presented in cost-effectiveness planes and acceptability curves. RESULTS: There were no significant differences in QALYs or depression incidence between treatment groups. Secondary care costs (mean difference €1644, 95% CI €344; €3370) and informal care costs (mean difference €1930, 95% CI €528; €4089) were significantly higher in the Step-Dep group than in the usual care group. The difference in total societal costs (€1001, 95% CI €-3975; €6409) was not statistically significant. The probability of the Step-Dep intervention being cost-effective was low, with a maximum of 0.41 at a ceiling ratio of €30,000 per QALY gained and 0.32 at a ceiling ratio of €0 per prevented case of major depression. CONCLUSIONS: The Step-Dep intervention is not cost-effective compared to usual care in a population of patients with DM2/CHD and subthreshold depression. Therefore, widespread implementation cannot be recommended. TRIAL REGISTRATION: The trial was registered in the Netherlands Trial Register ( NTR3715 ).

Impact of borderline personality disorder traits on the association between age and health-related quality of life: A cohort study in the general population.

BACKGROUND: Increasing age as well as borderline personality pathology are associated with a lower level of health-related quality of life (HR-QoL). Our objective was to investigate whether the presence of borderline personality traits modifies the association between age and HR-QoL in the general population. METHODS: Cross-sectional data from 5,303 respondents (aged 21-72 years) of the Netherlands Mental Health Survey and Incidence Study-2 were analyzed. Borderline personality traits were assessed with the International Personality Disorder Examination questionnaire. Mental and physical HR-QoL were measured with the Medical Outcomes Study Short Form Health Survey. Multiple linear regression analysis was used to examine the association of borderline personality traits, age and their interaction on mental as well as physical HR-QoL, adjusted for demographic variables as well as somatic and mental disorders. RESULTS: A total of 1,520 (28.7%) respondents reported one or more borderline personality traits of which 58 (1.1%) reported five or more indicative of a borderline personality disorder. A higher age was associated with lower physical HR-QoL. This negative association became significantly stronger in the presence of borderline personality traits. The association between increasing age and mental HR-QoL was positive in the absence of borderline personality traits and negative in the presence of borderline personality traits. CONCLUSION: Borderline personality traits negatively interfere with the association between age and HR-QoL irrespective of somatic and mental disorders. Attention of clinicians and researchers for subthreshold borderline personality pathology is needed in middle-aged and older persons.

European Society of Coloproctology: guidelines for the management of diverticular disease of the colon.

AIM: The goal of this European Society of Coloproctology (ESCP) guideline project is to give an overview of the existing evidence on the management of diverticular disease, primarily as a guidance to surgeons. METHODS: The guideline was developed during several working phases including three voting rounds and one consensus meeting. The two project leads (JKS and EA) appointed by the ESCP guideline committee together with one member of the guideline committee (WB) agreed on the methodology, decided on six themes for working groups (WGs) and drafted a list of research questions. Senior WG members, mostly colorectal surgeons within the ESCP, were invited based on publication records and geographical aspects. Other specialties were included in the WGs where relevant. In addition, one trainee or PhD fellow was invited in each WG. All six WGs revised the research questions if necessary, did a literature search, created evidence tables where feasible, and drafted supporting text to each research question and statement. The text and statement proposals from each WG were arranged as one document by the first and last authors before online voting by all authors in two rounds. For the second voting ESCP national representatives were also invited. More than 90% agreement was considered a consensus. The final phrasing of the statements with < 90% agreement was discussed in a consensus meeting at the ESCP annual meeting in Vienna in September 2019. Thereafter, the first and the last author drafted the final text of the guideline and circulated it for final approval and for a third and final online voting of rephrased statements. RESULTS: This guideline contains 38 evidence based consensus statements on the management of diverticular disease. CONCLUSION: This international, multidisciplinary guideline provides an up to date summary of the current knowledge of the management of diverticular disease as a guidance for clinicians and patients.

Meta-analysis of the effects of on-farm management strategies on milk yields of dairy cattle on smallholder farms in the Tropics.

Although East Africa is home to one of the most advanced dairy industries in Sub-Saharan Africa, regional annual milk production is insufficient to meet the demand. The challenge of increasing milk yields (MYs) among smallholder dairy cattle farmers (SDCFs) has received considerable attention and resulted in the introduction of various dairy management strategies (DMSs). Despite adoption of these DMSs, MYs remain low on-farm and there is a large discrepancy in the efficacy of DMSs across different farms. Therefore, the present study sought to: (1) identify on-farm DMSs employed by East African SDCFs to increase MYs and (2) summarize existing literature to quantify the expected MY changes associated with these identified DMSs. Data were collected through a comprehensive literature review and in-depth semi-structured interviews with 10 experts from the East African dairy sector. Meta-analysis of the literature review data was performed by deriving four multivariate regression models (i.e. models 1 to 4) that related DMSs to expected MYs. Each model differed in the weighting strategy used (e.g. number of observations and inverse of the standard errors) and the preferred model was selected based on the root estimated error variance and concordance correlation coefficient. Nine DMSs were identified, of which only adoption of improved cattle breeds and improved feeding (i.e. increasing diet quality and quantity) consistently and significantly (P < 0.05) increased daily MYs across the available studies. Improved breeds alongside adequate feeding explained ≤50% of the daily MYs observed in the metadata while improved feeding explained ≤30% of the daily MYs observed across the different models. Conversely, calf suckling significantly (P < 0.05) reduced MYs according to model 2. Other variables including days in milk, trial length and maximum ambient temperature (used as a proxy for heat stress) contributed significantly to decreasing MYs. These variables may explain some of the heterogeneity in MY responses to DMSs reported in the literature. Our results suggest that using improved cattle breeds alongside improved feeding is the most reliable strategy to increase MYs on-farm in East Africa. Nevertheless, these DMSs should not be considered as standalone solutions but as a pool of options that should be combined depending on the resources available to the farmer to achieve a balance between using dairy cattle genetics, proper husbandry and feeding to secure higher MYs.

Observational versus antibiotic treatment for uncomplicated diverticulitis: an individual-patient data meta-analysis.

BACKGROUND: Two RCTs (AVOD and DIABOLO) demonstrated no difference in recovery or adverse outcomes when antibiotics for acute uncomplicated diverticulitis were omitted. Both trials showed non-significantly higher rates of complicated diverticulitis and surgery in the non-antibiotic groups. This meta-analysis of individual-patient data aimed to explore adverse outcomes and identify patients at risk who may benefit from antibiotic treatment. METHODS: Individual-patient data from those with uncomplicated diverticulitis from two RCTs were pooled. Risk factors for adverse outcomes and the effect of observational management were assessed using logistic regression analyses. P < 0·025 was considered statistically significant owing to multiple testing adjustment. RESULTS: In total, 545 patients in the observational group and 564 in the antibiotics group were included. No statistical differences were found in 1-year follow-up rates of ongoing diverticulitis (7·2 versus 5·0 per cent in observation versus antibiotics groups respectively; P = 0·062), recurrent diverticulitis (8·6 versus 9·6 per cent; P = 0·610), complicated diverticulitis (4·0 versus 2·1 per cent; P = 0·079) and sigmoid resection (5·0 versus 2·5 per cent; P = 0·214). An initial pain score greater than 7, white blood cell count exceeding 13·5 × 109 /l and previous diverticulitis at presentation were risk factors for adverse outcomes. Antibiotic treatment did not prevent adverse outcomes in patients at high risk of adverse events. CONCLUSION: Observational management of acute uncomplicated diverticulitis is safe. Some statistical uncertainty remains, depending on the thresholds of clinical relevance, owing to small differences, but no subgroup that would benefit from antibiotic treatment was apparent.

ANTECEDENTES: Dos ensayos clínicos aleatorizados y controlados (randomized controlled trials, RCTc) (AVOD y DIABOLO) no mostraron diferencias en la recuperación ni en los resultados adversos al tratar la diverticulitis aguda no complicada sin antibióticos. Ambos ensayos mostraron tasas más altas, estadísticamente no significativas, de diverticulitis complicada y cirugía en los grupos sin antibióticos. Este metaanálisis de datos individuales de pacientes tuvo como objetivo explorar resultados adversos e identificar pacientes en riesgo que pudieran beneficiarse del tratamiento con antibióticos. MÉTODOS: Se agruparon los datos individuales de pacientes con diverticulitis no complicada de dos RCT. Los factores de riesgo para los resultados adversos y el efecto del tratamiento observacional (sin antibióticos) se evaluaron mediante un análisis de regresión logística. Una P < 0,025 se consideró estadísticamente significativa debido al ajuste de múltiples comparaciones. RESULTADOS: En total, se incluyeron 545 pacientes en el grupo de observación y 564 pacientes en el grupo de tratamiento antibiótico. No se encontraron diferencias estadísticamente significativas (observación versus antibióticos, respectivamente) en el seguimiento a 1 año en los porcentajes de diverticulitis persistente (7,2% versus 5,0%; P = 0,062), diverticulitis recurrente (8,6% versus 9,6%; P = 0,610), diverticulitis complicada (4,0% versus 2,1%; P = 0,079) y resección sigmoidea (5,0% versus 2,5%; P = 0,214). Una puntuación de dolor inicial > 7, un recuento leucocitario > 13,5 x 109 /L y los antecedentes de diverticulitis fueron factores de riesgo para un resultado adverso. El tratamiento con antibióticos no previno los resultados adversos en pacientes con alto riesgo. CONCLUSIÓN: El tratamiento de la diverticulitis aguda no complicada basado en la observación es seguro. No obstante, persiste una cierta incertidumbre desde el punto de vista estadístico, dependiendo de los umbrales de relevancia clínica, debido a pequeñas diferencias, pero no fue evidente ningún subgrupo que se pudiera beneficiar del tratamiento con antibióticos.