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.

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.

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.

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.

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.

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.

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.

Association between cholinesterase's inhibition and cognitive impairment: A basis for prevention policies of environmental pollution by organophosphate and carbamate pesticides in Chile.

BACKGROUND: In Chile organophosphate pesticides are widely used in the production of fruits. Pesticides use is regulated for professional practice but there is no regulation regarding exposure to the general population. OBJECTIVE: To relate exposure to cholinesterase's inhibitor pesticides during the spray season with neuropsychological impairment in occupationally exposed (OE) and environmentally exposed (EE) groups of people. METHODS: Exposure was assessed through inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity and neuropsychological outcomes were evaluated through a large battery of tests covering general mental status, language, memory, attention, executive function, praxis and psychomotricity. Evaluations were carried out firstly in a period of no/low organophosphate pesticide use and subsequently during the spray season. All parameters were calculated as the relative change from baseline to spray season. RESULTS: For this study in total 156 participants were recruited divided equally over participants with environmental exposures (EE) and participants with occupational exposure (OE). In the EE, BChE's enzyme activity inhibition ≥30% showed significant association with 10% or more decreased performance in several tests evaluating six of the eight cognitive areas (excepting psychomotricity and mood status); besides, for AChE inhibition in EE, the association was significant in three tests evaluating attention and one of executive function. Whereas, in OE, the inhibition of the BChE ≥30% was associated with a low performance of one attention test and for AChE the exceedance of the standard was associated with diminished performance in one test of memory and attention, respectively. The association between biomarkers of biological effect and cognitive impairment persisted among the EE group after removing confounders. No association was found between biomarkers of biological acute effect and decreased cognitive performance in the OE group. CONCLUSIONS: Increased exposure to pesticides was confirmed by increased inhibition of cholinesterase's in both exposure groups; which was associated with a diminished neuropsychological performance, mainly in the environmentally exposed study group. [310 words].

Patients' and gynecologists' views on sentinel lymph node mapping in low- and intermediate-risk endometrial cancer: a Dutch vignette study.

OBJECTIVE: Sentinel lymph node (SLN) mapping in endometrial cancer is gaining ground. However, patient views on this new technique are unknown. The aim of this study was to determine factors important to patients and gynecologists when considering SLN mapping in low- and intermediate-risk endometrial cancer. METHODS: We performed a vignette study. Patients who underwent a total hysterectomy for low- or intermediate-risk endometrial cancer between 2012 and 2015 were invited. Dutch gynecologists specializing in gynecologic oncology were also invited. We based the selection for attributes in the vignettes on literature and interviews: risk of complications of SLN mapping; chance of finding a metastasis; survival gain; risk of complications after radiotherapy; operation time; and hospital of surgery (travel time). We developed a questionnaire with 18 hypothetical scenarios. Each attribute level varied and for each scenario, participants were asked how strongly they would prefer SLN on a scale from 1 to 7. The strength of preference for each scenario was analyzed using linear mixed effects models. RESULTS: A total of 38% of patients (41/108) and 33% of gynecologists (42/126) participated in the study. Overall, they had a preference for SLN. The mean preference for patients was 4.29 (95% CI 3.72 to 4.85) and 4.39 (95% CI 3.99 to 4.78) for gynecologists. Patients' preferences increased from 3.4 in the case of no survival gain to 4.9 in the case of 3-year survival gain (P<0.05) and it decreased when travel time increased to >60 min (-0.4, P=0.024), or with an increased risk of complications after adjuvant radiotherapy (-0.6, P=0.002). For gynecologists all attributes except travel time were important. CONCLUSIONS: Overall, patients and gynecologists were in favor of SLN mapping in low- and intermediate-risk endometrial cancer. Most important to patients were survival gain, travel time, and complication risk after adjuvant radiotherapy. These preferences should be taken into account when counseling about SLN mapping.

Reduced neurobehavioral functioning in agricultural workers and rural inhabitants exposed to pesticides in northern Chile and its association with blood biomarkers inhibition.

BACKGROUND: Previous biomonitoring studies have shown that people in the rural population of Coquimbo, the major agricultural area in northern Chile are being occupationally and environmentally exposed to organophosphate/carbamate (OP/CB) pesticides. Given their harmful effects, this study had two aims; first, to evaluate the effect of cumulative or chronic exposure to OP/CB pesticides on the neurobehavioral performance of agricultural workers and rural inhabitants; second, to determine if changes in the neurobehavioral performance are associated to changes in blood biomarkers of OP/CB pesticides during the spray season, when exposure is higher. METHODS: For the first aim, a cross sectional study of neurobehavioral performance in adult volunteers (men and women, 18-50 years-old, right-handed) was carried out in the pre-spray season. Sampling was done by convenience and a questionnaire was used to categorize participants depending on their level of chronic exposure, as either: occupationally exposed (OE, n = 87), environmentally exposed (EE, n = 81), or non-exposed controls or reference group (RG, n = 100). A neurobehavioral test battery consisting of 21 tests to measure cognitive, motor and emotional state was applied. For the second aim, neurobehavioral measures were taken a second time from EE and OE groups during the spray season, and their exposure corroborated by blood-based biomarker inhibition. RESULTS: Lower neurobehavioral performance was observed in the pre-spray evaluation of EE and OE groups compared to the non-exposed, OE being the worst performing group. Seasonal exposure impaired performance in both exposure groups on all tests except those on attention and mood. Data modeling of the basal (pre-spray) measurements showed that the level of exposure was the best predictor of performance. During spraying, inhibition of BChE activity in the EE group was the best predictor of low performance in tests measuring logical, auditory and visual memory, inhibitory control of cognitive interference, constructional and planning abilities, executive functions, and motor speed and coordination. CONCLUSION: Long-term occupational or environmental exposure to pesticides caused impairment in neurobehavioral functioning, which worsened during the spraying season, mainly in EE. BChE inhibition was the best predictor for seasonal neurobehavioral changes in EE.

Disease and Treatment Characteristics in Geriatric Psoriasis: A Patient Survey Comparing Age Groups.

Little is known about psoriasis in geriatric patients, whereas treating this growing population can be challenging due to comorbidities, comedication and physical impairments. To compare disease and treatment characteristics of psoriasis patients ≥ 65 years old with patients < 65 years old, a self-assessment survey was sent to all members of the Dutch Psoriasis Association (n = 3,310). In total, 985 (29.7%) patients returned the survey, 414 (43.6%) respondents were ≥ 65 years old. Patients ≥ 65 years old had experienced erythrodermic psoriasis significantly more frequently than patients < 65 years old, other disease characteristics were highly comparable. Despite a significantly higher prevalence of comorbidities and comedication use in patients ≥ 65 years old, no difference was seen between the age groups regarding systemic antipsoriatic treatment (38.3% in ≥ 65 years old vs 42.3% in < 65 years old; p = 0.219). Remarkably, treatment-related side-effects were reported more frequently by patients < 65 years old. In conclusion, age alone should not be a limiting factor in psoriasis management, and proper attention must be paid to additional patient-related factors.

Health Economic Consequences of a Tightly Controlled Dose Reduction Strategy for Adalimumab, Etanercept and Ustekinumab Compared with Standard Psoriasis Care: A Cost-utility Analysis of the CONDOR Study.

A dose reduction strategy for adalimumab, etanercept and ustekinumab in patients with psoriasis who have stable and low disease activity has recently been compared with usual care in the CONDOR study (CONtrolled DOse Reduction) of biologics in patients with psoriasis with low disease activity. The aim of the current study was to perform a cost-utility analysis with a 12-month time horizon alongside this trial, using prospectively measured healthcare costs and quality-adjusted life years, based on Short-Form Six-Dimension utilities. Bootstrap analys-es were used to calculate the decremental cost-utility ratio and the incremental net monetary benefit. The dose reduction strategy resulted in a mean cost saving of €3,820 (95th percentile -€3,099 to -€4,509) per patient over a period of 12 months. There was an 83% chance that dose reduction would result in a reduction in quality adjusted life years (mean -0.02 (95th percentile -0.06 to 0.02). In conclusion, dose reduction of biologics resulted in substantial cost savings with an acceptable reduction in quality of life.

Impact of molecular point-of-care testing on clinical management and in-hospital costs of patients suspected of influenza or RSV infection: a modeling study.

BACKGROUND: At hospital admission, patients suspected of infection with influenza or respiratory syncytial virus (RSV) are placed in isolation, pending the outcome of diagnostics. In a significant number, isolated care proves unnecessary. We investigated the potential impact of molecular point-of-care (POC) diagnostics on patient management and in-hospital costs. METHOD: Prospective collection of data on resource utilization within the hospital from consecutive patients 18 years or older presenting at our university medical center with symptoms of respiratory tract infection from December 2016 to April 2017. A cost analysis was conducted using Markov modeling comparing the actual course of events (on the basis of routine diagnostic tests) with two hypothetical scenarios: when POC would impact time to diagnosis only (scenario 1) or on discharge from the hospital, too (scenario 2). RESULTS: A total of 283 patients were included, of whom 217 (76.7%) were admitted. Influenza and RSV were detected in 31% and 7% of the patients, respectively. Fifty-four percent of patients tested negative, of which 79% were kept in isolated care waiting for test results, with a median duration of 24 hours. Median length of stay was 6.0 days. Mean total in-hospital costs per patient were € 5243. Introducing POC would lower mean costs per patient to € 4904 (scenario 1) and € 4206 (scenario 2). At the hospital level, this would result in a total cost reduction of € 95 937 to € 293 471 in a single influenza season. CONCLUSIONS: Introducing POC testing for patients presenting with symptoms of viral respiratory tract infection can reduce time-to-diagnosis, hospital stay and, thereby, in-hospital costs.

Nail Involvement as a Predictor of Disease Severity in Paediatric Psoriasis: Follow-up Data from the Dutch ChildCAPTURE Registry.

Little is known about the relationship between nail psoriasis and psoriasis severity in children, and there has been no longitudinal assessment of psoriasis severity related to nail psoriasis. The aim of this study was to assess whether nail psoriasis could serve as a predictor for a more severe disease course. De-identified data were obtained from the ChildCAPTURE registry, a daily clinical practice cohort of children with psoriasis, from September 2008 to November 2015. Cross-sectional analyses were performed at baseline. Longitudinal data until 2-year follow-up were analysed by linear mixed models. Nail psoriasis was present in 19.0% of all 343 patients at baseline and cross-sectionally associated with higher Psoriasis Area and Severity Index (PASI) (p = 0.033). Longitudinal analysis demonstrated higher PASI (p <0.001) during 2-year follow-up in patients with nail involvement at baseline. These findings suggest that nail psoriasis is a potential clinical predictor for more severe disease course over time in paediatric psoriasis.

Substantial clinical benefit for Neck Disability Index revisited: establishing the goal for treatment?

PURPOSE: It is difficult for clinicians to inform patients about the success rate of a treatment as a cervical anterior discectomy procedure. Ideally, a proportion of good outcome as rated by patients is known. Patient-reported outcome measurements are helpful. The purpose is to relate the difference in Neck Disability Index (NDI) after a cervical anterior discectomy procedure for single level cervical degenerative disc disease with the patients' rating of their actual clinical situation after long-term follow-up to define the substantial clinical benefit (SCB). METHODS: After completion of the NDI, patients who were surgically treated for cervical single level degenerative disease were asked to complete a five-item Likert scale to rate their clinical situation. After dichotomisation of the outcome in good versus less than good, a cut-off value was defined by determining the value of the difference of NDI with the highest specificity and sensitivity. Funding was not obtained. RESULTS: SCB for NDI after surgery for cervical single level degenerative disease should be set at ten with area under the curve (AUC) of 0.71 for sensitivity as well specificity. CONCLUSIONS: The goal for each treatment is a good outcome. While comparing treatments for cervical degenerative disc disease only those with an SCB of ten will be relevant for the patient, as patients who achieved this difference in NDI rated their actual situation at long-term follow-up as good.

Effect of Mexiletine on Muscle Stiffness in Patients With Nondystrophic Myotonia Evaluated Using Aggregated N-of-1 Trials.

Importance: In rare diseases it is difficult to achieve high-quality evidence of treatment efficacy because of small cohorts and clinical heterogeneity. With emerging treatments for rare diseases, innovative trial designs are needed. Objective: To investigate the effectiveness of mexiletine in nondystrophic myotonia using an aggregated N-of-1 trials design and compare results between this innovative design and a previously conducted RCT. Design, Setting, and Participants: A series of aggregated, double-blind, randomized, placebo-controlled N-of-1-trials, performed in a single academic referral center. Thirty Dutch adult patients with genetically confirmed nondystrophic myotonia (38 patients screened) were enrolled between February 2014 and June 2015. Follow-up was completed in September 2016. Interventions: Mexiletine (600 mg daily) vs placebo during multiple treatment periods of 4 weeks. Main Outcomes and Measures: Reduction in daily-reported muscle stiffness on a scale of 1 to 9, with higher scores indicating more impairment. A Bayesian hierarchical model aggregated individual N-of-1 trial data to determine the posterior probability of reaching a clinically meaningful effect of a greater than 0.75-point difference. Results: Among 30 enrolled patients (mean age, 43.4 [SD, 15.24] years; 22% men; 19 CLCN1 and 11 SCN4A genotype), 27 completed the study and 3 dropped out (1 because of a serious adverse event). In 24 of the 27 completers, a clinically meaningful treatment effect was found. In the Bayesian hierarchical model, mexiletine resulted in a 100% posterior probability of reaching a clinically meaningful reduction in self-reported muscle stiffness for the nondystrophic myotonia group overall and the CLCN1 genotype subgroup and 93% posterior probability for the SCN4A genotype subgroup. In the total nondystrophic myotonia group, the median muscle stiffness score was 6.08 (interquartile range, 4.71-6.80) at baseline and was 2.50 (95% credible interval [CrI], 1.77-3.24) during the mexiletine period and 5.56 (95% CrI, 4.73-6.39) during the placebo period; difference in symptom score reduction, 3.06 (95% CrI, 1.96-4.15; n = 27) favoring mexiletine. The most common adverse event was gastrointestinal discomfort (21 mexiletine [70%], 1 placebo [3%]). One serious adverse event occurred (1 mexiletine [3%]; allergic skin reaction). Using frequentist reanalysis, mexiletine compared with placebo resulted in a mean reduction in daily-reported muscle stiffness of 3.12 (95% CI, 2.46-3.78), consistent with the previous RCT treatment effect of 2.69 (95% CI, 2.12-3.26). Conclusions and Relevance: In a series of N-of-1 trials of mexiletine vs placebo in patients with nondystrophic myotonia, there was a reduction in mean daily-reported muscle stiffness that was consistent with the treatment effect in a previous randomized clinical trial. These findings support the efficacy of mexiletine for treatment of nondystrophic myotonia as well as the feasibility of N-of-1 trials for assessing interventions in some chronic rare diseases. Trial Registration: ClinicalTrials.gov Identifier: NCT02045667.

Identification of the Best Direct-Acting Antiviral Regimen for Patients With Hepatitis C Virus Genotype 3 Infection: A Systematic Review and Network Meta-analysis.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective in the treatment of chronic hepatitis C virus (HCV) infection, although results for patients infected with genotype 3 are suboptimal. There are several regimens available, however, direct comparisons have not been made and are unlikely to occur. We aimed to identify the most effective DAA regimen for patients infected with HCV genotype 3 and to assess the role of ribavirin. METHODS: We conducted a systematic search of PubMed, Embase, and Web of Science databases through March 2016. We performed a Bayesian network meta-analysis using a random-effects model to indirectly compare regimens in patients with and without cirrhosis. We calculated mean estimated sustained virologic response (SVR) with 95% credible intervals (95% CrI) per regimen and effect of ribavirin as odds ratio. We focused on current recommended regimens and regimens under evaluation by regulatory authorities. RESULTS: Our search identified 2167 articles; 27 studies (comprising 3415 patients) were included. Among patients without cirrhosis, the greatest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir with ribavirin (99%; 95% CrI, 98%-100%) and without ribavirin (97%; 95% CrI, 95%-99%), sofosbuvir + daclatasvir + ribavirin (96%; 95% CrI, 92%-98%), and sofosbuvir + peginterferon + ribavirin (95%; 95% CrI, 91%-98%), all for 12 weeks. Among patients with cirrhosis, the highest rates of SVR were estimated for those receiving sofosbuvir + velpatasvir for 24 weeks (96%; 95% CrI, 92%-99%), sofosbuvir + daclatasvir + ribavirin for 24 weeks (94%; 95% CrI, 87%-98%), and sofosbuvir + velpatasvir + ribavirin for 12 weeks (94%; 95% CrI, 86%-98%). Ribavirin increases efficacy in patients with and without cirrhosis (odds ratio, 2.6-4.5). CONCLUSIONS: An indirect comparison of DAA-based treatments, using Bayesian network meta-analysis, found regimens containing sofosbuvir and velpatasvir to be the best option for patients with HCV genotype 3 infection. Our analyses indicated that ribavirin significantly increases SVR rates and should be considered if tolerated.