Trends and projections in fall death in the Netherlands from 1990 to 2045.

BACKGROUND: Increasing life expectancy in high-income countries has been linked to a rise in fall mortality. In the Netherlands, mortality rates from falls have increased gradually from the 1950s, with some indication of stabilisation in the 1990s. For population health and clinical practice, it is important to foresee the future fall mortality trajectories. METHODS: A graphical approach was used to explore trends in mortality by age, calendar period and cohorts born in the periods of 1915-1945. Population data and the numbers of people with accidental fall fatality as underlying cause of death from 1990 to 2021 were derived from Statistics Netherlands. Age-standardised mortality rates of unintentional falls per 100 000 population were calculated by year and sex. A log-linear model was used to examine the separate effects of age, period and cohort on the trend in mortality and to produce estimates of future numbers of fall deaths until 2045. RESULTS: While the total population increased by 17% between 1990 and 2021, absolute numbers of fall-related deaths rose by 230% (from 1584 to 5234), which was 251% (an increase of 576 deaths in 1990 to 2021 deaths in 2020) for men and 219% (from 1008 to 3213) for women. Age-standardised figures were higher for women than men and increased more over time. In 2020, 79% of those with death due to falls were over the age of 80, and 35% were 90 years or older. From 2020 to 2045, the observed and projected numbers of fall deaths were 2021 and 7073 for men (250% increase) and 3213 and 12 575 for women (291% increase). CONCLUSION: Mortality due to falls has increased in the past decades and will continue to rise sharply, mainly caused by growing numbers of older adults, especially those in their 80s and 90s. Contributing risk factors are well known, implementation of preventive measures is a much needed next step. An effective approach to managing elderly people after falls is warranted to reduce crowding in the emergency care and reduce unnecessary long hospital stays.

Adrenal fast-track and enhanced recovery in retroperitoneoscopic surgery for primary aldosteronism improving patient outcome and efficiency.

PURPOSE: No data exist on perioperative strategies for enhancing recovery after posterior retroperitoneoscopic adrenalectomy (PRA). Our objective was to determine whether a multimodality adrenal fast-track and enhanced recovery (AFTER) protocol for PRA can reduce recovery time, improve patient satisfaction and maintain safety. METHODS: Thirty primary aldosteronism patients were included. Fifteen patients were treated with 'standard-of-care' PRA and compared with 15 in the AFTER protocol. The AFTER protocol contains: a preoperative information video, postoperative oral analgesics, early postoperative mobilisation and enteral feeding, and blood pressure monitoring at home. The primary outcome was recovery time. Secondary outcomes were length of hospital stay, postoperative pain and analgesics requirements, patient satisfaction, perioperative complications and quality of life (QoL). RESULTS: Recovery time was much shorter in both groups than anticipated and was not significantly different (median 28 days). Postoperative length of hospital stay was significantly reduced in AFTER patients (mean 32 vs 42 h, CI 95%, p = 0.004). No significant differences were seen in pain, but less analgesics were used in the AFTER group. Satisfaction improved amongst AFTER patients for time of admission and postoperative visit to the outpatient clinic. There were no significant differences in complication rates or QoL. CONCLUSION: Despite no difference in recovery time between the two groups, probably due to small sample size, the AFTER protocol led to shorter hospital stays and less analgesic use after surgery, whilst maintaining and even enhancing patient satisfaction for several aspects of perioperative care. Complication rates and QoL are comparable to standard-of-care.

Impact of Expanding Eligibility Criteria for Cochlear Implantation - Dynamic Modeling Study.

OBJECTIVES: Eligibility criteria for cochlear implantation (CI) are shifting due to technological and surgical improvements. The aim of this study was to explore the impact of further expanding unilateral CI criteria in those with severe hearing loss (HL) (61-80 dBHL) in terms of number of CI recipients, costs, quality of life, and cost-effectiveness. METHODS: A dynamic population-based Markov model was constructed mimicking the Dutch population in three age categories over a period of 20 years. Health states included severe HL (61-80 dBHL), profound HL (>81 dBHL), CI recipients, and no-CI recipients. Model parameters were based on published literature, (national) databases, expert opinion, and model calibration. RESULTS: If persons with severe HL would qualify and opt for CI similar to those with profound HL now, this would lead to a 6-7 times increase of new CI recipients and an associated increase in costs (€550 million) and QALYs (54.000) over a 20-year period (incremental cost utility ratio: 10.771 euros/QALY [2.5-97.5 percentiles: 1.252-23.171]). One-way-sensitivity analysis indicated that model outcomes were most sensitive to regaining employment, utility associated with having a CI, and costs of surgery and testing. CONCLUSION: Our findings suggest that expanding eligibility for CI to persons with severe HL could be a cost-effective use of resources. Clearly, however, it would require a significant increase in diagnostic, operative, and rehabilitative capacity. Our quantitative estimates can serve as a basis for a wider societal deliberation on the question whether such an increase can and should be pursued. LEVEL OF EVIDENCE: NA Laryngoscope, 133:924-932, 2023.

Challenges in Noninvasive Skin Biomarker Measurements in Daily Practice: A Longitudinal Study on Skin Surface Protein Detection by the Transdermal Analysis Patch in Pediatric Psoriasis.

INTRODUCTION: Skin surface proteins are potential biomarkers in psoriasis and can be measured noninvasively with the transdermal analysis patch (TAP). This study aimed to assess markers measured by TAP over time in daily clinical practice, explore their correlation with disease severity in pediatric psoriasis, and compare the TAP and tape stripping detection capability. METHODS: In this prospective observational daily clinical practice study, pediatric psoriasis patients (aged >5 to <18 years) were followed during 1 year. At each visit, TAPs were applied to lesional (n = 2), peri-lesional (n = 2), and non-lesional (n = 1) sites. Post-lesional skin was sampled if all lesions on the arms, legs, or trunk cleared. Treatment and psoriasis severity data were collected. IL-1RA, hBD-2, IL-1α, IL-8, VEGF, CXCL-1/2, CCL-27, IL-23, hBD-1, IL-22, IL-17A, KLK-5, and IL-4 levels were quantified by spot-ELISA. For the statistical analysis, Wilcoxon signed rank tests, Mann-Whitney U tests, and Spearman correlations were used. Detection capability of the TAP was compared to tape stripping in a separate cohort of adult psoriasis patients. RESULTS: 32 patients (median age 15.0 years, median Psoriasis Area and Severity Index [PASI] 5.2) were followed for a mean of 11.3 (±3.4) months with a total of 104 visits. In lesional skin (n = 197), significantly higher IL-1RA, hBD-2, IL-8, VEGF, CXCL-1/2, IL-23, hBD-1, IL-22, CCL-27, and IL-17A levels were found compared to non-lesional skin (n = 104), while IL-1α was higher in non-lesional skin. Marker levels were highly variable over time and did not correlate with disease severity measured by PASI or SUM scores. Comparison of the TAP and tape strip detection capability in adult psoriasis patients (n = 10) showed that lesional hBD-2, IL1-α, IL-8, and VEGF and non-lesional IL-1RA, hBD-2, IL-8, and VEGF were more frequently detected in tape extracts than TAPs. CONCLUSION: Due to the lack of correlation with clinical disease severity and the current detection capability of the markers measured by TAP in psoriasis, its use in regular practice is still a bridge too far.

CXCR4-directed [68Ga]Ga-PentixaFor PET/CT versus adrenal vein sampling performance: a study protocol for a randomised two-step controlled diagnoStic Trial Ultimately comparing hypertenSion outcome in primary aldosteronism (CASTUS).

INTRODUCTION: Primary aldosteronism (PA) is the most common form of secondary hypertension. It is caused by overproduction of aldosterone by either a unilateral aldosterone-producing adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction is crucial, because PA is cured by adrenalectomy in APA and is treated by mineralocorticoid receptor antagonists in BAH. The distinction is currently made by adrenal vein sampling (AVS). AVS is a costly, invasive and complex technical procedure with limited availability and is not superior in terms of outcomes to CT scan-based diagnosis. Thus, there is a need for a cheaper, non-invasive and readily available diagnostic tool in PA. We propose a new diagnostic imaging modality employing the positron emission tomography (PET) tracer [68Ga]Ga-PentixaFor. This tracer has high focal uptake in APAs, whereas low uptake was shown in patients with normal adrenals. Thus, [68Ga]Ga-PentixaFor PET/CT is an imaging modality with the potential to improve subtyping of PA. It is readily available, safe and, as an out-patient procedure, much cheaper diagnostic method than AVS. METHODS AND ANALYSIS: We present a two-step randomised controlled trial (RCT) protocol in which we assess the accuracy of [68Ga]Ga-PentixaFor PET/CT in the first step and compare [68Ga]Ga-PentixaFor PET/CT to AVS in the second step. In the first step, the concordance will be determined between [68Ga]Ga-PentixaFor PET/CT and AVS and a concordance probability is calculated with a Bayesian prediction model. In the second step, we will compare [68Ga]Ga-PentixaFor PET/CT and AVS for clinical outcome and intensity of hypertensive drug use defined as daily defined doses in a RCT. ETHICS AND DISSEMINATION: Ethics approval was acquired from the medical ethical committee East-Netherlands (METC Oost-Nederland). Results will be disseminated through peer-reviewed articles. TRIAL REGISTRATION NUMBER: NL9625.

Real-world Methotrexate Use in a Prospective Cohort of Paediatric Patients with Plaque Psoriasis: Effectiveness, Adverse Events and Folic Acid Regimen.

In paediatric psoriasis, few studies have evaluated methotrexate effectiveness, adverse events and folic acid regimen. Therefore this study prospectively assessed methotrexate adverse events and effectiveness in paediatric patients with psoriasis in a real-world setting. Furthermore, gastrointestinal adverse events and methotrexate effectiveness were compared between folic acid regimens (5 mg once weekly vs 1 mg 6 times weekly). Data for paediatric patients with psoriasis treated with methotrexate from September 2008 to October 2020 were extracted from Child-CAPTURE, a prospective, daily clinical practice registry. Effectiveness was determined by Psoriasis Area and Severity Index (PASI). Comparison of persistent gastrointestinal adverse events between folic acid regimens were assessed through Kaplan-Meier analysis. A total of 105 paediatric patients with plaque psoriasis (41.0% male, mean age 14.1 years) were included. At week 24 and 48, an absolute PASI ≤ 2.0 was achieved by approximately one-third of all patients. During follow-up, 46.7% reported ≥ 1 persistent adverse events. After 1 and 2 years, approximately one-quarter of patients achieved a PASI ≤ 2.0 without persistent adverse events. Although non-significant, a possible trend towards lower occurrence of gastrointestinal adverse events was found for folic acid 1 mg 6 times weekly (p = 0.196), with similar effectiveness between folic acid regimens. These findings show that a subgroup of paediatric patients with psoriasis responded well to methotrexate treatment without considerable side-effects during a 2-year follow-up.

Direct Comparison of Real-world Effectiveness of Biologics for Psoriasis using Absolute and Relative Psoriasis Area and Severity Index Scores in a Prospective Multicentre Cohort.

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.

Serum drug levels and anti-drug antibodies in the context of dose tapering by interval prolongation of adalimumab, etanercept and ustekinumab in psoriasis patients: results of the CONDOR trial.

BACKGROUND: Biologics for psoriasis are registered in standard dosages. In patients with low disease activity, reduction of the dose by interval prolongation can prevent overtreatment, and lower risks and costs. However, fear for increased anti-drug antibody (ADA) formation due to interval prolongation of biologics is an important barrier. OBJECTIVE: To investigate the course of serum drug concentrations, ADA levels, and predictors for successful dose reduction of adalimumab, ustekinumab, and etanercept for psoriasis. METHODS: Patients were randomized to dose reduction (DR) or usual care (UC) and followed for one year. The course and extent of detectable ADA levels were expressed as proportions/relative risks for DR vs. UC. Association of baseline characteristics with successful tapering was investigated with log-binomial regression analysis. RESULTS: In total, 118 patients were included. In adalimumab-treated patients, no significant difference in the proportion of patients with relevant ADA levels in DR vs. UC was seen. For ustekinumab, relevant ADA development was absent in both groups. Baseline trough levels were not predictive for successful DR. CONCLUSIONS: Immunogenicity may not increase by interval prolongation in psoriasis patients with low disease activity. This pilot provides important and reassuring insight into the pharmacological changes after dose tapering of adalimumab, etanercept, and ustekinumab.

Hearing-Related Quality of Life in 75 Patients With a Percutaneous Bone Conduction Device.

OBJECTIVE: To evaluate long-term hearing-related quality of life (HRQoL) and device use in bone conduction (BCD) users. Furthermore, to assess differences between indications and changes in HRQoL over time. STUDY DESIGN: Prospective questionnaire survey. SETTING: Tertiary referral center. PATIENTS: Seventy-five patients with a percutaneous BCD. MAIN OUTCOME MEASURES: Glasgow Benefit Inventory (GBI) at 3 and 12 months postoperatively, Glasgow Health Status Inventory (GHSI) preoperatively, and 6 and 36 months postoperatively, device use at 6, 12, and 36 months. Changes over time were assessed and outcomes were compared between indications. RESULTS: After implantation, 97% of all patients reported a positive benefit on the GBI total. The GHSI total had improved with median 15 points (Interquartile range [IQR] 12). At 36 months, median device use was 15 hours/day (IQR 10) and one nonuser was reported. Patients with bilateral hearing loss (BHL) showed greater improvement on the GHSI total (median 18 vs 14, p < 0.0001) and used their devices more frequently (median 16 vs 8 h/day, p < 0.0001) than patients with unilateral HL (UHL). Postoperative GHSI and GBI scores were consistent over time, in the entire patient population and for every indication. Between 6 and 36 months, device use was stable over time, except for patients with single-sided deafness (SSD; median -6.4 h/day, p = 0.009). CONCLUSION: The BCD improves HRQoL in patients with BHL, in patients with unilateral conductive/mixed hearing loss and in patients with SSD. Patients with BHL experienced a greater improvement in hearing status compared to patients with UHL. Although use decreased over time in SSD patients, device use was high for every indication.

N-of-1 Trials in Neurology: A Systematic Review.

BACKGROUND AND OBJECTIVES: To perform a systematic review of published N-of-1 trials (e.g., single patient crossover trials) in neurologic disorders, including an assessment of methodologic quality and reporting. METHODS: We searched PubMed, MEDLINE, and Embase from inception date to the December 1, 2019, for reports on N-of-1 trials in neurologic disorders. Basic trial information on design, disease, intervention, analysis, and treatment success was extracted. Strengths and weaknesses of the N-of-1 trials were assessed with the Consolidated Standards of Reporting Trials extension for N-of-1 trials (CENT) 2015 criteria checklist and the Jadad score as measures of quality and reporting. RESULTS: We retrieved 40 reports of N-of-1 trials in neurologic disorders (19 individual N-of-1 trials, 21 series of N-of-1 trials). Most N-of-1 trials were performed in neuromuscular and neurodegenerative/movement disorders. Unlike the majority of trials that studied the main symptom(s) of a chronic stable condition, 9 N-of-1 trials studied a stable chronic symptom of a progressive or acute neurologic disorder. Besides pharmacologic interventions, electric stimulation protocols and nutritional products were studied. A mean total CENT score of 20.88 (SD 9.10, range 0-43) and mean total Jadad score of 2.90 (SD 2.15, range 0-5) were found as methodologic measures of quality and reporting across all N-of-1 trials. DISCUSSION: N-of-1 trials have been reported in numerous neurologic disorders, not only in chronic stable disorders, but also in progressive or acute disorders with a stable symptom. This indicates the emerging therapeutic area of N-of-1 trials in neurology. Methodologic quality and reporting of N-of-1 trials were found to be suboptimal and can easily be improved in future trials by appropriately describing the methods of blinding and randomization and following CENT guidelines. Because most N-of-1 trials remain unreported in medical literature, this systematic review probably represents only the tip of the iceberg of conducted N-of-1 trials in neurologic disorders. In addition to conventional trial designs, N-of-1 trials can help to bridge the gap between research and clinical care by providing an alternative, personalized level 1 evidence base for suitable treatments.

Perfusion measured by laser speckle contrast imaging as a predictor for expansion of psoriasis lesions.

BACKGROUND: Skin microvasculature changes are crucial in psoriasis development and correlate with perfusion. The noninvasive Handheld Perfusion Imager (HAPI) examines microvascular skin perfusion in large body areas using laser speckle contrast imaging (LSCI). OBJECTIVES: To (i) assess whether increased perilesional perfusion and perfusion inhomogeneity are predictors for expansion of psoriasis lesions and (ii) assess feasibility of the HAPI system in a mounted modality. METHODS: In this interventional pilot study in adults with unstable plaque psoriasis, HAPI measurements and color photographs were performed for lesions present on one body region at week 0, 2, 4, 6 and 8. The presence of increased perilesional perfusion and perfusion inhomogeneity was determined. Clinical outcome was categorized as increased, stable or decreased lesion surface between visits. Patient feedback was collected on a 10-point scale. RESULTS: In total, 110 lesions with a median follow-up of 6 (IQR 6.0) weeks were assessed in 6 patients with unstable plaque psoriasis. Perfusion data was matched to 281 clinical outcomes after two weeks. A mixed multinomial logistic regression model revealed a predictive value of perilesional increased perfusion (OR 9.90; p < 0.001) and perfusion inhomogeneity (OR 2.39; p = 0.027) on lesion expansion after two weeks compared to lesion stability. HAPI measurements were considered fast, patient-friendly and important by patients. CONCLUSION: Visualization of increased perilesional perfusion and perfusion inhomogeneity by noninvasive whole field LSCI holds potential for prediction of psoriatic lesion expansion. Furthermore, the HAPI is a feasible and patient-friendly tool.

Treatment goals and preferences of pediatric psoriasis patients, young adults, and parents.

BACKGROUND: Treatment needs of young psoriasis patients and parents are not widely studied and could advance patient-centered care. OBJECTIVE: To explore treatment goals and preferences of pediatric psoriasis patients, young adults, and parents. METHODS: A web-based survey among Dutch psoriasis patients aged ≥6 to ≤30 years and parents included multiple-choice, open-ended, and 4-point Likert scale questions. Treatment goals and characteristic preferences of pediatric patients (≤17 years) were compared to young adults (≥18 years) and parents. RESULTS: 195 young patients (20.2 ± 6.3 years) and 45 parents were included. The most important treatment goals were 'preventing lesions', 'reducing lesions', 'no itch', and 'no lesions'. Regarding treatment characteristics, 'long-term safety', 'high effectiveness', and 'short-term safety' were most important. We found differences by age, gender, and current treatment. Pediatric patients rated 'not sticky', 'quick results', and 'no/few blood samples needed' higher than parents and/or young adults. Young adults rated 'feeling more confident' and 'better quality of sleep' higher than pediatric patients. Parents considered safety most important. Psychosocial goals were more important for women and patients on biologics. CONCLUSION: Young psoriasis patients and parents mainly strive to clear lesions and itch with effective and safe treatment. However, revealed differences underline the relevance of addressing individual needs.

Risk of candidiasis associated with interleukin-17 inhibitors: A real-world observational study of multiple independent sources.

BACKGROUND: Biologics directed against the T-helper (Th)-17 pathway have been approved for several inflammatory diseases. Interleukin (IL)-17 is involved in anti- Candida host defense, and clinical trials suggested increased candidiasis incidence during IL-17 inhibitor therapy. We describe the worldwide epidemiology of candidiasis during Th17 inhibitor therapy, and immunological mechanisms involved in candidiasis susceptibility. METHODS: A comprehensive analysis of multiple independent sources reporting Candida adverse events during biologics inhibiting the Th17 pathway was performed. Association between Th17 inhibitors and candidiasis was assessed using safety reports of (1) WHO and (2) EMA, (3) a population-based prescriptions registry, and (4) a psoriasis cohort. In a cohort of psoriasis patients experiencing candidiasis during Th17 inhibitors, Candida killing by immune cells and serum inflammatory proteome were analyzed. FINDINGS: A strong association between IL-17 inhibitors and candidiasis (ROR 10·20) was found in the WHO database, particularly for cutaneous (ROR 12·28), oropharyngeal (ROR 19·18), and esophageal candidiasis (ROR 21·20). Risk was higher relative to TNF-α inhibitors (4-10-fold, depending on candidiasis type), confirmed by EMA reports (16-33-fold), prescriptions registry (2-42-fold), and a psoriasis cohort (3-25-fold). After start of IL-17 inhibitors, patients' risk of candidiasis requiring antifungals increased 2-16 fold. In the psoriasis cohort, 58% of IL-17 treatment episodes were associated with candidiasis. In Th17 inhibitor recipients, proteins involved in anti- Candida immunity and Candida killing by mononuclear leukocytes were impaired. INTERPRETATION: IL-17 inhibitors are associated with an increased risk of oropharyngeal, esophageal, and cutaneous candidiasis, posing a significant disease burden for IL-17 inhibitor recipients. FUNDING: RadboudUMC.

Trends and projections in the incidence of oesophageal cancer in the Netherlands: An age-period-cohort analysis from 1989 to 2041.

In Western populations, the incidence of oesophageal squamous cell carcinoma (OSCC) has been declining, whereas the incidence of oesophageal adenocarcinoma (OAC) has been increasing. Our study examines temporal trends in the incidence of oesophageal cancer in the Netherlands between 1989 and 2016, in addition to predicting future trends through 2041. Data from the Netherlands Cancer Registry and Statistics Netherlands were collected to obtain incidence trends of OSCC and OAC for the period 1989 to 2016. Age-period-cohort (APC) modelling was used to estimate the contribution of age, calendar period and birth cohort on the observed incidence trends. To predict the future numbers of new cases of both OSCC and OAC from 2017 to 2041, log-linear APC models were fitted to the trends of 1989 to 2016. The age-standardised incidence rates of OSCC have decreased slightly for men and increased slightly for women. In contrast, a marked increase in the incidence of OAC was observed, ranging from 2.8 per 100 000 persons in 1989 to 10.1 in 2016. This increase in OAC incidence was more prominent in men, and it will result in an increased risk of OAC for successive generations. Future projections indicate that the incidence of OAC will further increase to 13.1 per 100 000 persons in 2037 to 2041, meaning that there will be 13 259 cases of OAC in 2037 to 2041, as compared to 9386 diagnoses in 2017 to 2021. The changing epidemiologic trends in oesophageal cancer in the Netherlands should be reflected in the development of prevention, early detection and treatment strategies.

Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER): Protocol for a Longitudinal Observational Study.

BACKGROUND: One in three patients with psoriasis will develop psoriatic arthritis (PsA). If left untreated, this can lead to pain, impaired function, and irreversible joint damage. Timely recognition and referral to a rheumatologist are therefore key. However, current methods used to screen patients with psoriasis for those who might benefit from referral to a rheumatologist are not performing well enough. OBJECTIVE: The Discovery of Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) study is designed to determine the prevalence of PsA in a psoriasis population and to find parameters that can be used to develop a new or enhance an existing instrument for a rheumatological referral. METHODS: DAPPER is a longitudinal observational study with a 1-year follow-up. Patients with psoriasis (N=300) who are treated at an outpatient dermatological clinic will be screened extensively for signs and symptoms of PsA by a trained rheumatologist. If there is clinical suspicion of PsA and the patient is not yet treated by a rheumatologist, referral to the Department of Rheumatology will follow for confirmation of the diagnosis and further care. After 1 year, data on changes in quality of life and PsA and psoriasis disease activity will be collected from the referred patients. The screening visit will be used to gather demographical and medical data, which can later be used to develop the aforementioned screening instrument. RESULTS: Inclusion started in June 2019 and finished in June 2021. Follow-up with newly discovered patients with PsA is ongoing. CONCLUSIONS: The DAPPER study is specifically designed to improve the detection of existing PsA in a dermatologic outpatient setting. Although internal validity will be tested, external validity will have to be checked using a second validation cohort. To predict the development of PsA in the future, longitudinal/prospective data collection is required and will be performed in a follow-up study (DAPPER-i). TRIAL REGISTRATION: Dutch Trial Register NTR7604; https://www.trialregister.nl/trial/7397. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/31647.

Translating Evidence to Advanced Parkinson's Disease Patients: A Systematic Review and Meta-Analysis.

In the advanced stages of Parkinson's disease (PD), patients frequently experience disabling motor complications. Treatment options include deep brain stimulation (DBS), levodopa-carbidopa intestinal gel (LCIG), and continuous subcutaneous apomorphine infusion (CSAI). Choosing among these treatments is influenced by scientific evidence, clinical expertise, and patient preferences. To foster patient engagement in decision-making among the options, scientific evidence should be adjusted to their information needs. We conducted a systematic review from the patient perspective. First, patients selected outcomes for a treatment choice: quality of life, activities of daily living, ON and OFF time, and adverse events. Second, we conducted a systematic review and meta-analysis for each treatment versus best medical treatment using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE). Finally, the evidence was transformed into comprehensible and comparable information. We converted the meta-analysis results into the number of patients (per 100) who benefit clinically from an advanced treatment per outcome, based on the minimal clinically important difference and the cumulative distribution function. Although this approach allows for a comparison of outcomes across the three device-aided therapies, they have never been compared directly. The interpretation is hindered by the relatively short follow-up time in the included studies, usually less than 12 months. These limitations should be clarified to patients during the decision-making process. This review can help patients integrate the evidence with their own preferences, and with their clinician's expertise, to reach an informed decision. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The Additional Effect of Individualized Prescriber-Focused Feedback on General Guideline Instruction in Reducing Antipsychotic Polypharmacy in Inpatients.

PURPOSE/BACKGROUND: Antipsychotic polypharmacy (APP) is the concurrent use of more than one antipsychotic by a patient. Multiple antipsychotics are often prescribed, although all relevant guidelines discourage this practice. These recommendations are based on a lack of evidence for effectiveness and an increased risk of serious adverse events with APP. Studies on the effects of educational interventions targeted at physicians have demonstrated inconclusive results. Moreover, it is unclear how individualized these interventions need to be. In this study, we aimed to assess the effect of a general intervention and the additional impact of an individualized, prescriber-focused intervention on guidelines adherence, that is, the prescription of APP. METHODS/PROCEDURES: We conducted a 36-month 2-step serial intervention study with 4 stages of 9 months each (baseline, general intervention, addition of an individualized intervention, and follow-up) including all 20 inpatient units of one regional mental health organization. The primary outcome was the proportion of patients with regular prescriptions for APP ≥30 consecutive days across all patients with a prescription of at least one antipsychotic. The secondary outcome was the proportion of patient days on APP over the total number of patient days on at least one antipsychotic. FINDINGS/RESULTS: The general intervention was ineffective on both outcome measures. Addition of an individualized intervention decreased the proportion of patients with prescriptions for episodes of persistent APP significantly by 49.6%. The proportion of patient days on APP significantly decreased by 35.4%. IMPLICATIONS/CONCLUSIONS: In contrast to a general intervention, the addition of an individualized intervention was effective in improving adherence to guidelines with respect to APP prescription in inpatients.

Trends and projections in cutaneous melanoma death in the Netherlands from 1950 to 2045.

ABSTRACT: Child sun protection has recently been linked to the future disappearance of fatal melanoma in adults in successive generations. In the Netherlands, however, mortality rates from melanoma have increased gradually from the 1950s, with some indication of stabilisation since 2010, which may be compatible with a birth cohort effect by sun-protective measures and screening. To study the trajectories ahead a trend analysis was applied. Numbers of people with cutaneous melanoma as underlying cause of death from 1950 to 2018 and population data were derived from Statistics Netherlands. A graphical approach was used to explore trends in mortality by age, calendar period, and cohorts born in the successive periods of 1889 to 1979. Age-period-cohort modelling outcomes and population forecasts provided projections of mortality until 2045. Based on 24,151 cases of melanoma death (13,256 men, 10,895 women), age-standardised mortality rates were similar from 1950 to 1989 for both genders, and increased thereafter more in men. The age-curve patterns changed gradually towards higher death rates at older age, implying the existence of a birth cohort effect. The age-period-cohort models showed an increase in melanoma mortality rates in successive generations. For women, the birth cohort effect plateaued for generations born since the mid-1980s. The projected total mortality number was predicted to rise in the next 3 decades.It is concluded that a small future decline of mortality in younger generations can be expected in the Netherlands, but mortality is still rising for the total population.