A systematic review and meta-analysis of clinical trials assessing safety and efficacy of human extracellular vesicle-based therapy.

Nowadays, it has become clear that extracellular vesicles (EVs) are not a cellular waste disposal vesicle but are an essential part of an intercellular communication system. Besides the use of EVs in biomarker studies and diagnostics, the potential of EV-therapeutics has been seen by many. They provide unique properties for disease therapy, including strong immune-modulatory actions, the possibility of engineering, low immunogenicity, and the capability of crossing biological barriers. Proof-of-concept of EV-therapeutics for various pathologies has been achieved in preclinical studies. However, clinical trials with EVs have only been emerging slowly. Here, we aim to provide a comprehensive overview of the current state-of-the-art concerning clinical studies using EVs in human therapy. By approaching the current knowledge in a systematic manner, we were able to include 21 reports for meta-analysis of safety and evaluation of efficacy outcomes. Overall, we have shown that EV-based therapy is safe with a low incidence of serious adverse events (SAE; 0.7% (95%-CI: 0.1-5.2%), and adverse events (AE; 4.4% (95%-CI: 0.7-22.2%). Subgroup analysis showed no significant difference in SAE when comparing autologous versus allogeneic administration, as well as engineered versus non-engineered EV products. A significantly higher number of AE was seen in autologous versus allogeneic administration. However, the clinical relevance remains questionable. Evaluation of the clinical outcomes of immunostimulatory, immunosuppressive or regenerative EV-therapies indicated improvement in the majority of treated patients. Despite these promising results, data need to be approached with caution due to a high heterogeneity in the EVs manufacturing methods, study design, and reporting of (S)AE. Overall, we conclude that EV-based therapy is safe and presents a promising opportunity in therapy. More efforts are needed in the standardization and harmonization of reporting of EV isolation and characterization data as well as in the reporting of (S)AE to allow inter-study comparison.

Protocol of the LATFIA trial (Laser Assisted Treatment of Fistula in Ano): a multicentre, prospective, randomized controlled trial comparing fistula-tract laser closure (FiLaC™) with rectal advancement flap for high trans-sphincteric fistulas.

AIM: Anal fistula is one of the most common anal diseases, affecting between 1 and 3 per 10 000 people per year. Symptoms have a potentially severe effect on a patient's quality of life. Surgery is the mainstay of treatment, aiming to cure the fistula and preserve anal sphincter function. Rectal advancement flap (RAF) is currently the gold standard treatment but has recurrence rates varying between 20% and 50% and might lead to disturbance of continence. The aim of the trial described in this work is to discover if the minimally invasive fistula tract laser closure (FiLaC™) technique could achieve higher healing rates and a better functional outcome than RAF. METHOD: We will perform a randomized prospective multicentre noninferiority study of the treatment of high trans-sphincteric perianal fistulas, comparing FiLaC™ with RAF in terms of fistula healing, recurrence rate, functional outcome and quality of life. Primary and secondary fistula healing will be evaluated at 26 and 52 weeks' follow-up. Quality of life will be evaluated using the SF-36 questionnaire, the Faecal Incontinence Quality of Life Scale questionnaire and the Vaizey score at 3, 6, 12 and 26 weeks postoperatively. CONCLUSION: High trans-sphincteric fistulas have a potentially severe effect on a patient's quality of life. Classical treatment with RAF is a time-consuming invasive procedure. The LATFIA trial aims to compare FiLaC™ with the gold standard treatment with RAF. In case of noninferiority, FiLaC™ treatment could be standardized as a first line treatment for high trans-sphincteric fistulas. Better conservation of the patient's anal sphincter function could possibly be obtained. Likewise, we will report on the postoperative quality of life when applying these two techniques.

Insulin resistance and CGM-derived parameters in people with type 1 diabetes: are they associated?

BACKGROUND: Insulin resistance (IR) is increasingly more prevalent in people with type 1 diabetes (T1D). We investigated whether IR is associated with continuous glucose monitor (CGM)-derived parameters (glucometrics) such as time in range (TIR), time above range (TAR), time below range (TBR) and glycaemic variability (CV). METHODS: This is a retrospective analysis of two databases: IR was quantified according to the estimated glucose disposal rate (eGDR) (NCT04664036) and by performing a hyperinsulinaemic-euglycaemic clamp (HEC) (NCT04623320). All glucometrics were calculated over 28 days. RESULTS: A total of 287 subjects were included. Mean age was 46 ± 17 years, 55% were male, TIR was 57 ± 14% and eGDR was 7.6 (5.6 - 9.3) mg/kg min. The tertile of people with the lowest eGDR (highest level of IR) had a higher TAR compared to the tertile with the highest eGDR (39 ± 15% versus 33 ± 14, p = 0.043). Using logistic regression, a higher eGDR was associated with a higher chance to fall in a higher TIR- (OR 1.251, p < 0.001), a lower TAR- (OR 1.281, p < 0.001) and a higher TBR-tertile (OR 0.893, p = 0.039), adjusted for age, sex, diabetes duration, smoking status and alcohol intake. In the 48 people undergoing a HEC, no significant association between glucometrics and the HEC-determined glucose disposal rate (M-value) was observed. CONCLUSION: In people with T1D, an association between IR, measured by eGDR, and worse CGM profiles was observed.

Prophylactic Swallowing Therapy During Head-and-Neck Cancer Radiotherapy: Effect of Service-Delivery Mode and Overall Adherence Level on Swallowing Function and Muscle Strength-the PRESTO Trial.

Prophylactic swallowing exercises (PSE) during head-and-neck cancer (HNC) (chemo)radiotherapy (CRT) have a positive effect on swallowing function and muscle strength. Adherence rates to PSE are, however, moderate to low, undermining these effects. PRESTO already showed that the service-delivery mode (SDM), the way the exercises are offered, can influence adherence. The aim of this study was to investigate the effect of SDM on swallowing function and muscle strength during and post-CRT. In addition, the effect of overall adherence (OA), independent of SDM, was also investigated. A total of 148 HNC patients, treated with CRT, were randomly assigned to one of the three SDM's (paper-supported, app-supported, or therapist-supported PSE) and performed a 4-week PSE program. OA was calculated based on the percentage of completed exercises. Patients were divided into OA levels: the OA75+ and OA75- group performed respectively ≥ 75 and < 75% of the exercises. Swallowing function based on Mann Assessment of Swallowing Ability-Cancer (MASA-C), tongue and suprahyoid muscle strength during and up to 3 months after CRT were compared between the SDM's and OA levels. Linear Mixed-effects Models with post hoc pairwise testing and Bonferroni-Holm correction was used. No significant differences were found between the three SDMs. Significant time effects were found: MASA-C scores decreased and muscle strength increased significantly during CRT. By the end of CRT, the OA75+ showed significantly better swallowing function compared to OA75-. Muscle strength gain was significantly higher in the OA75+ group. SDM had no impact on swallowing function and muscle strength; however, significant effects were shown for OA level. Performing a high level of exercise repetitions is essential to benefit from PSE.Trial registration ISRCTN, ISRCTN98243550. Registered December 21, 2018-retrospectively registered, https://www.isrctn.com/ISRCTN98243550?q=gwen%20van%20nuffelen&filters=&sort=&offset=1&totalResults=2&page=1&pageSize=10&searchType=basic-search.

The impact of diabetes on mortality rates after lower extremity amputation.

OBJECTIVE: To assess the impact of diabetes, amputation level, sex and age on mortality rates after lower extremity amputation (LEA) in Belgium, and to assess temporal trends in one-year survival rates from 2009 to 2018. METHODS: Nationwide data on individuals who underwent minor and major LEA from 2009 to 2018 were collected. Kaplan-Meier survival curves were constructed. A Cox regression model with time-varying coefficients was used to estimate the likelihood of mortality after LEA in individuals with or without diabetes. Matched amputation-free individuals with or without diabetes were used for comparison. Time trends were analysed. RESULTS: Amputations 41,304 were performed: 13,247 major and 28,057 minor. Five-year mortality rates in individuals with diabetes were 52% and 69% after minor and major LEA, respectively (individuals without diabetes: 45% and 63%, respectively). In the first six postoperative months, no differences in mortality rates were found between individuals with or without diabetes. Later, hazard ratios (HRs) for mortality in individuals with diabetes (compared with no diabetes) after minor LEA ranged from 1.38 to 1.52, and after major LEA from 1.35 to 1.46 (all p ≤ 0.005). Among individuals without LEA, HRs for mortality in diabetes (versus no diabetes) were systematically higher compared to the HRs for mortality in diabetes (versus no diabetes) after minor and major LEA. One-year survival rates did not change for individuals with diabetes. CONCLUSIONS: In the first six postoperative months, mortality rates after LEA were not different between individuals with or without diabetes; later, diabetes was significantly associated with increased mortality. However, as HRs for mortality were higher in amputation-free individuals, diabetes impacts mortality less in the minor and major amputation groups relative to the comparison group of individuals without LEA.

Impact of diabetes on medical costs in the pre- and postoperative year of lower extremity amputations in Belgium.

AIMS: To compare the medical costs of individuals undergoing lower extremity amputation (LEA) in Belgium with those of amputation-free individuals. METHODS: Belgian citizens undergoing LEAs in 2014 were identified. The median costs per capita in euros for the 12 months preceding and following minor and major LEAs were compared with those of matched amputation-free individuals. RESULTS: A total of 3324 Belgian citizens underwent LEAs (2295 minor, 1029 major), 2130 of them had diabetes. The comparison group included 31,716 individuals. Amputation was associated with high medical costs (individuals with diabetes: major LEA €49,735, minor LEA €24,243, no LEA €2,877 in the year preceding amputation; €45,740, €21,445 and €2,284, respectively, in the post-amputation year). Significantly higher costs were observed in the individuals with (versus without) diabetes in all groups. This difference diminished with higher amputation levels. Individuals undergoing multiple LEAs generated higher costs (individuals with diabetes: €39,313-€89,563 when LEAs preceded index amputation; €46,629-€92,877 when LEAs followed index amputation). Individuals dying in the year after a major LEA generated remarkably lower costs. CONCLUSIONS: LEA-related medical costs were high. Diabetes significantly impacted costs, but differences in costs diminished with higher amputation levels. Individuals with multiple amputations generated the highest costs.

Belgian Endothelial Surgical Transplant of the Cornea (BEST cornea) protocol: clinical and patient-reported outcomes of Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) versus Descemet Membrane Endothelial Keratoplasty (DMEK) - a multicentric, randomised, parallel group pragmatic trial in corneal endothelial decompensation.

OBJECTIVES: Corneal blindness is the third most frequent cause of blindness globally. Damage to the corneal endothelium is a leading indication for corneal transplantation, which is typically performed by lamellar endothelial keratoplasty. There are two conventional surgical techniques: Ultra-Thin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK). The purpose of this study is to compare both techniques. METHODS AND ANALYSIS: The trial compares UT-DSAEK and DMEK in terms of clinical and patient reported outcomes using a pragmatic, parallel, multicentric, randomised controlled trial with 1:1 allocation with a sample size of 220 participants across 11 surgical centres. The primary outcome is the change in best-corrected visual acuity at 12 months. Secondary outcomes include corrected and uncorrected vision, refraction, proportion of high vision, quality of life (EQ-5D-5L and VFQ25), endothelial cell counts and corneal thickness at 3, 6 and 12 months follow-up appointments. Adverse events will also be compared 12 months postoperatively. ETHICS AND DISSEMINATION: The protocol was reviewed by ethical committees of 11 participating centres with the sponsor centre issuing the final definitive approval. The results will be disseminated at clinical conferences, by patient partner groups and open access in peer-reviewed journals. GOVERNANCE OF THE TRIAL: Both, trial management group and trial steering committee, are installed with representatives of all stakeholders involved including surgeons, corneal bankers, patients and external experts. TRIAL REGISTRATION NUMBER: NCT05436665.

Disease Perception Is Correlated with Health-Related Quality of Life in Patients Suffering from Myelodysplastic Syndromes: Results of the Belgian Be-QUALMS Study.

Patients with myelodysplastic syndromes suffer from an impaired quality of life that is only partially explained by physical symptoms. In an observational study, we aimed to investigate the impact of current MDS treatments and the influence of disease perception on quality of life. Serial measurement of health-related quality of life was performed by 'the QUALMS', a validated MDS-specific patient reported outcome tool. Disease perception was evaluated by means of the Brief Illness Perception Questionnaire (B-IPQ). We prospectively collected data on 75 patients that started on a new treatment and could not demonstrate a significant change in QUALMS score or B-IPQ score during treatment. Six out of eight items evaluated in the B-IPQ correlated significantly with QUALMS score. In this small sample, no significant difference in QUALMS score was found between lower vs. higher risk MDS patients or other studied variables, e.g., targeted hemoglobin showed no correlation with QUALMS score. In daily practice attention must be paid to initial formation of disease perception as it correlates independently with health-related quality of life and does not change during treatment (clinicaltrials.gov identifier: NCT04053933).

Does the Tacrolimus Trough Level Adequately Predict Drug Exposure in Patients Requiring a High Tacrolimus Dose?

Tacrolimus (Tac) has a narrow therapeutic range. Dosing is generally targeted at Tac trough levels (C 0), notwithstanding conflicting reports on the correlation between Tac C 0 and systemic exposure measured by the area-under-the-concentration-over-time curve (AUC). The Tac dose required to meet the target C 0 varies highly among patients. We hypothesized that patients requiring a relatively high Tac dose for a certain C 0 may show a higher AUC. Methods: We retrospectively analyzed data from 53 patients in which a 24-h Tac AUC24 estimation was performed at our center. Patients were divided into those taking a low (≤0.15 mg/kg) or high (>0.15 mg/kg) once-daily Tac dose. Multiple linear regression models were used to investigate if the association between C 0 and AUC24 changes according to dose level. Results: Despite the large difference in mean Tac dose between the low- and high-dose group (7 versus 17 mg/d), C 0 levels were similar. However, the mean AUC24 was substantially higher in the high-dose group (320 ± 96 h·µg/L versus 255 ± 81 h·µg/L, P < 0.001). This difference remained significant after adjusting for age and race. For a same C 0, every 0.01 mg/kg increase in Tac dose resulted in an AUC24 increase of 3.59 h·µg/L. Conclusions: This study challenges the general belief that C 0 levels are sufficiently reliable to estimate systemic drug exposure. We demonstrated that patients requiring a relatively high Tac dose to attain therapeutic C 0 levels have higher drug exposure and could therefore potentially be overdosed.

Insights into barriers and facilitators in PrEP uptake and use among migrant men and transwomen who have sex with men in Belgium.

BACKGROUND: PrEP uptake is low among non-Belgian men and transwomen who have sex with men, although the HIV epidemic among men who have sex with men in Belgium is diversifying in terms of nationalities and ethnicity. We lack an in-depth understanding of this gap. METHODS: We conducted a qualitative study using a grounded theory approach. The data consists of key informants interviews and in-depth interviews with migrant men or transwomen who have sex with men. RESULTS: We identified four underlying determinants which shape our participants' experiences and contextualize the barriers to PrEP use. These include (1) the intersectional identities of being migrant and men and transwomen who have sex with men, (2) migration related stressors, (3) mental health and (4) socio-economic vulnerability. Identified barriers include: the accessibility of services; availability of information, social resources and providers' attitudes. These barriers influence PrEP acceptance and mediated by individual agency this influences their PrEP uptake. CONCLUSION: An interplay of several underlying determinants and barriers impacts on PrEP uptake among migrant men and transwomen who have sex with men, illustrating a social gradient in access to PrEP. We need equitable access to the full spectrum of HIV prevention and care for all priority populations, including undocumented migrants. We recommend social and structural conditions that foster exercising these rights, including adapting PrEP service delivery, mental health and social support.

Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study.

BACKGROUND: The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular (CV) immune-related adverse events (irAEs). The current follow-up guidelines are based on anecdotal evidence and expert opinions, due to a lack of solid data and prospective studies. As many questions remain unanswered, cardiac monitoring, in patients receiving ICIs, is not always implemented by oncologists. Hence, an urgent need to investigate the possible short- and long-term CV effects of ICIs, as ICI approval is continuing to expand to the (neo)adjuvant setting. METHODS: We have initiated a prospective, multicenter study, i.e., the CAVACI trial, in which a minimum of 276 patients with a solid tumor, eligible for ICI treatment, will be enrolled. The study consists of routine investigations of blood parameters (troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, in particular) and a thorough CV follow-up (electrocardiograms, transthoracic echocardiograms, and coronary calcium scoring) at fixed time points for a total period of two years. The primary endpoint is the cumulative incidence of troponin elevation in the first three months of ICI treatment, compared to baseline levels. Furthermore, secondary endpoints include incidence above the upper limit of normal of both troponin and NT-proBNP levels, evolution in troponin and NT-proBNP levels, the incidence of CV abnormalities/major adverse cardiac events, evaluation of associations between patient characteristics/biochemical parameters and CV events, transthoracic echocardiography parameters, electrocardiography parameters, and progression of coronary atherosclerosis. Recruitment of patients started in January 2022. Enrolment is ongoing in AZ Maria Middelares, Antwerp University Hospital, AZ Sint-Vincentius Deinze, and AZ Sint-Elisabeth Zottegem. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05699915, registered 26 January 2023.

Urinary epidermal growth factor reflects vascular health in boys with either obesity or type 1 diabetes. A role for renin, or beyond?

An increased blood pressure is a known comorbidity of both type 1 diabetes (T1DM) and obesity in children. Increasing evidence suggests a subtle interplay between epidermal growth factor (EGF) and renin along the juxtaglomerular system, regulating the impact of blood pressure on kidney health and the cardiovascular system. In this study, we investigated the relation between urinary EGF, serum renin and blood pressure in children with obesity or T1DM. 147 non-obese children with T1DM and 126 children with obesity, were included. Blood pressure was measured and mean arterial pressure (MAP) and the pulse pressure (PP) were calculated. Serum renin and urinary EGF levels were determined with a commercial ELISA kit. Partial Spearman rank correlation coefficients and multiple linear regression models were used to study the association between renin, the urinary EGF/urinary creatinine ratio and blood pressure parameters. The urinary EGF/urinary creatinine ratio is correlated with the SBP and the MAP in boys with obesity as well as in boys with T1DM. Multiple regression analysis showed that sex and pulse pressure in male subjects were found to be independently associated with renin. Sex, the presence of diabetes, age, the glomerular filtration rate and both pulse pressure and mean arterial pressure in male subjects were independently associated with urinary EGF/urinary creatinine. In conclusion, in boys with either obesity or diabetes, pulse pressure and mean arterial pressure are negatively associated with the functional integrity of the nephron, which is reflected by a decreased expression of urinary EGF.

Impact of hearing impairment and cochlear implantation on productivity and social well-being in a professionally active but severely hearing-impaired group: protocol of the 'Hear again, work again' longitudinal prospective cohort study.

INTRODUCTION: Severe hearing loss is a sensory deficit with considerable impact on the patient's daily life and on society. Previous research has established occupational obstacles in professionally active patients with hearing loss. However, studies investigating the impact of severe hearing loss and cochlear implantation (CI) on work performance using a quantitative and longitudinal study design and validated questionnaires are lacking. This study aims to answer the following research question: 'What is the impact of unilateral and bilateral severe hearing loss and CI on the cost for society, health state, employment, productivity and social well-being?'. We hypothesise hearing impairment to influence work performance. After establishing the impact, we will be able to enhance the support of hearing impaired patients to maintain employed. METHODS AND ANALYSIS: A total of 200 professionally active adults between 18 and 65 years old with severe hearing loss will be included for assessment at baseline and reassessment at 3, 6 and 12 months. The following four study groups are included: bilateral severely hearing impaired participants without CI (1) and with CI (2) and unilateral severely hearing impaired participants in acute (3) and chronic (4) setting. The primary outcome of this study is the change in index score on the Work Limitations Questionnaire, which evaluates the degree of limitations and health-related productivity loss. Secondary outcome measures include audiometric and cognitive evaluations and validated questionnaires evaluating employment, work productivity, quality of life and direct healthcare costs. Linear mixed models will assess the evolution in time and the difference in evolution between groups. ETHICS AND DISSEMINATION: This study protocol (project ID 2021-0306) received ethical approval from the ethics committee of the Antwerp University Hospital on 22 November 2021. Our findings will be disseminated by peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05196022.

Targeted Next-Generation Sequencing in Children With Bilateral Sensorineural Hearing Loss: Diagnostic Yield and Predictors of a Genetic Cause.

OBJECTIVE: To investigate the diagnostic yield of targeted next-generation sequencing using hearing loss panels and to identify patient-related factors that are associated with a definite genetic cause. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Children with congenital or late-onset, bilateral sensorineural hearing loss. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: The number of patients with a definite genetic diagnosis. RESULTS: We report on 238 patients with hearing loss: 130 were male and 108 were female. About 55% had congenital hearing loss. A genetic cause was identified in 94 of the patients (39.5%), with 72.3% of these showing nonsyndromic and 27.6% showing syndromic hearing loss. The diagnostic yield was highest among North African patients (66.7%). A multiple linear regression model shows that profound hearing loss, family history of hearing loss, congenital hearing loss, and North African ethnicity are significantly related to identifying a genetic cause. CONCLUSIONS: Targeted next-generation sequencing using a panel of hearing loss genes identified a genetic diagnosis in almost 40% of children with bilateral sensorineural hearing loss. We describe the predictors of a genetic diagnosis, and this information may be used during genetic counseling.

Is Polyomavirus-Associated Nephropathy More Common in Kidney Transplant Recipients Exposed to Valganciclovir? A Retrospective Single Center Analysis.

BACKGROUND: BK polyomavirus-associated nephropathy (PVAN) is a frequent complication in the early phase after kidney transplantation. The most important risk factor for PVAN is the intensity of immunosuppression. A recent study suggests that exposure to valganciclovir (VGC) could also be a risk factor. METHODS: We performed a retrospective, single-center study to investigate the effect of valganciclovir exposure on the risk for PVAN during the first 100 days post transplant. Cytomegalovirus (CMV) seronegative recipients of a CMV seropositive donor kidney received VGC prophylaxis, whereas CMV seropositive recipients were managed by a pre-emptive CMV strategy. Cox regression analysis was used to identify risk factors for PVAN development with VGC treatment and strength of immunosuppressive therapy as time-dependent variables. RESULTS: A total of 211 adults who received a kidney transplant between 2014 and 2019 were included. Eighteen (9%) developed PVAN. Multivariate regression analysis showed that women have a lower risk of developing PVAN (hazard ratio [HR] 0.08 (confidence interval [CI] 0.01-0.58), P = .013), whereas age was associated with an increased risk for PVAN (HR 1.04 for every additional year [CI 1.00-1.08], P = .029). There was a trend toward a lower risk of PVAN for patients on reduced immunosuppressive therapy (HR 0.44 [CI 0.15-1.24], P = .12). VGC use was not associated with the risk for PVAN (HR 0.99 [CI 0.35-2.78], P = .98). CONCLUSIONS: In our study, VGC exposure was not associated with the risk for PVAN. Our study is the first to reassess in depth the hypothesis that VGC treatment increases the risk of PVAN. The unique strength of this study is the correction for the degree of immunosuppression and the statistical use of time-dependent covariates. This methodological approach can provide a foundation for further studies needed to confirm our findings.

Safety of the bag-in-the-lens implantation regarding the development of clinically significant pseudophakic cystoid macular edema: A retrospective case series study.

PURPOSE: To determine the incidence of clinically significant pseudophakic cystoid macular edema (CSPME) after phacoemulsification using the 'bag-in-the-lens' lens (BIL) implantation technique and to examine the influence of associated risk factors for clinically significant pseudophakic macular edema (CSPME), both ocular and systemic. METHODS: This retrospective study included 2419 first-operated eyes of 2419 adults who underwent phacoemulsification cataract surgery using the BIL implantation technique between January 2013 and December 2018 in the Antwerp University Hospital, Belgium. The significance of several risk factors (age, gender, previous history, intra- and postoperative complications) was examined by extraction of electronic medical files. RESULTS: The 3-month incidence of CSPME in the subgroup without risk factors was 0.00% (95% CI: 0.00 -NA). The 3-month incidence of CSPME in the subgroup with risk factors was 0.57% (95% CI 0.22-1.29%). The 3-month incidence of CSPME in the total population of 2419 patients was 0.29% (95% CI: 0.11-0.65%). The risk factors most significantly associated with CSPME included renal insufficiency (hazard ration [HR]: 5.42; 95% CI: 1.69-17.44; P = .014), exudative age-related macular degeneration (HR: 74.50, 95% CI: 25.75-215.6; P < .001) and retinal vein occlusion (HR: 22.48, 95% CI: 4.55-111.02; P = .005). CONCLUSIONS: In the absence of risk factors, the incidence of CSPME was zero. We can conclude that Primary Posterior Continuous Curvilinear Capsulorhexis (PPCCC) does not increase the risk for CSPME. Non-inferiority of the BIL implantation regarding the development of CSPME, relative to the traditional 'lens-in-the-bag' (LIB) implantation, confirms that BIL is a safe surgical technique. This study also illustrates a previously undescribed risk factor for developing CSPME, namely renal insufficiency.

Transferring nursing home residents to emergency departments by emergency physician-staffed emergency medical services: missed opportunities to avoid inappropriate care?

BACKGROUND: The decision to transfer a nursing home (NH) resident to an emergency department (ED) is multifactorial and challenging but many of the emergency physician-staffed emergency medical service (EP-EMS) interventions and ED transfers are probably inappropriate. METHODS: We conducted a retrospective, cross-sectional study in three EP-EMSs in Belgium over a period of three years. We registered indicators that are potentially associated with inappropriate transfers: patient characteristics, availability of written do not resuscitate (DNR) orders or treatment restrictions, involvement of a general practitioner (GP) and availability of transfer notes. We also explored the association between age, the Charlson Comordity Index (CCI), polypharmacy, dementia, and the availability of DNR documents. RESULTS: We registered 308 EP-EMS interventions in NH residents. In 98% the caller was a health-care professional. In 75% there was no GP present and 40% had no transfer note. Thirty-two percentage of the patients had dementia, 45% had more than two comorbidities and 68% took five medications or more. In 6% cardiopulmonary resuscitation was performed. DNR orders were available in 25%. Eighty-eight percentage of the NH residents were transferred to the ED. Forty-four percent had a CCI >5. In patients of ≥90 years, with a CCI >5, with dementia and with polypharmacy, DNR orders were not available in 81%, 67%%,and 69%, respectively. CONCLUSIONS: Improved EMS dispatch centre-NH caller interaction, more involvement of GP's, higher availability of DNR orders and better communication between GPs/NHs and EP-EMS could prevent inappropriate interventions, futile prehospital aactions,and ED transfers.

Increasing Adherence to Prophylactic Swallowing Exercises During Head and Neck Radiotherapy: The Multicenter, Randomized Controlled PRESTO-Trial.

BACKGROUND: Prophylactic swallowing exercises (PSE) during radiotherapy can significantly reduce dysphagia after radiotherapy in head and neck cancer (HNC). However, its positive effects are hampered by low adherence rates during the burdensome therapy period. Hence, the main goal of this multicenter randomized controlled trial (RCT) was to investigate the effect of 3 different service-delivery modes on actual patients' adherence. METHODS: A total of 148 oropharyngeal cancer patients treated with primary (chemo)radiotherapy were randomly assigned to a 4 weeks PSE program, either diary-supported (paper group; n = 49), app-supported (app group; n = 49) or therapist-supported (therapist group; n = 50). Participants practiced 5 days/week, daily alternating tongue strengthening exercises with chin tuck against resistance exercises. Adherence was measured as the percentage of completed exercise repetitions per week (%reps). Statistical analysis was performed by means of SPSSv27, using Linear Mixed-effects Models with post hoc pairwise testing and Bonferroni-Holm correction. RESULTS: Adherence and evolution of adherence over time was significantly different between the three groups (p < .001). Adherence rates decreased in all three groups during the 4 training weeks (p < .001). During all 4 weeks, the therapist group achieved the highest adherence rates, whilst the app group showed the lowest adherence rates. CONCLUSIONS: PSE adherence decreased during the first 4 radiotherapy weeks regardless of group, but with a significant difference between groups. The therapist group achieved the highest adherence rates with a rather limited decline, therefore, increasing the face-to-face contact with a speech-language therapist can overcome the well-known problem of low adherence to PSE in this population. TRIAL REGISTRATION: Trial registration: ISRCTN, ISRCTN98243550. Registered December 21, 2018 - retrospectively registered, https://www.isrctn.com/ISRCTN98243550?q=gwen%20van%20nuffelen&filters=&sort=&offset=1&totalResults=2&page=1&pageSize=10&searchType=basic-search .

Neurocognitive correlates of probable posttraumatic stress disorder following traumatic brain injury.

Introduction: Neurocognitive problems associated with posttraumatic stress disorder (PTSD) can interact with impairment resulting from traumatic brain injury (TBI). Research question: We aimed to identify neurocognitive problems associated with probable PTSD following TBI in a civilian sample. Material and methods: The study is part of the CENTER-TBI project (Collaborative European Neurotrauma Effectiveness Research) that aims to better characterize TBI. For this cross-sectional study, we included patients of all severities aged over 15, and a Glasgow Outcome Score Extended (GOSE) above 3. Participants were assessed at six months post-injury on the PTSD Checklist-5 (PCL-5), the Trail Making Test (TMT), the Rey Auditory Verbal Learning Test (RAVLT) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Primary analysis was a complete case analysis. Regression analyses were performed to investigate the association between the PCL-5 and cognition. Results: Of the 1134 participants included in the complete case analysis, 13.5% screened positive for PTSD. Probable PTSD was significantly associated with higher TMT-(B-A) (OR â€‹= â€‹1.35, 95% CI: 1.14-1.60, p â€‹< â€‹.001) and lower RAVLT-delayed recall scores (OR â€‹= â€‹0.74, 95% CI: 0.61-0.91, p â€‹= â€‹.004) after controlling for age, sex, psychiatric history, baseline Glasgow Coma Scale and education. Discussion and conclusion: Poorer performance on cognitive tests assessing task switching and, to a lesser extent, delayed verbal recall is associated with probable PTSD in civilians who have suffered TBI.

Follow-up blood cultures in Staphylococcus aureus bacteremia: a probability-based optimization.

Staphylococcus aureus bacteremia (SAB) is a relevant finding which prompts a thorough diagnostic work-up. Follow-up blood cultures (BC) are essential in this work-up. We investigate the probability of detecting an ongoing bacteremia after initiation of active therapy according to the number of BC taken at key time points. A retrospective analysis of all patients with SAB in a 6-year period was performed. Total number of BCs taken and the positivity was registered for each day after start of therapy. A positivity-rate was corrected using a logistic mixed effects model. Observed detection frequencies were applied to calculate detection probabilities using binomial distributions. Three hundred and seventeen cases were withheld for analysis. A BC bottle positivity rate of 66.7% was found 1 day after initiation of active therapy, which decreased to 48.5% on day 4. When using 1 set of FU-BC, 73.4% of persisting SABs are detected. To maintain a probability of detection of ≥ 90%, 2 BC sets should be taken on day 2 and day 4 after start of therapy. In 10 of 109 patients with positive FU-BC, skip phenomena were registered, with a significant higher proportion in patients with < 4 BC bottles taken (14%) than when ≥ 4 BC bottles were taken (4.1%). We recommend taking 2 BC sets on days 2 and 4 after start of therapy in order to detect ≥ 90% of persisting SABs, limiting skip phenomena and blood volume required. We strongly advice against taking a single BC set as follow-up for SAB.