To compare the anatomic and functional efficacy and safety of half-dose photodynamic therapy (PDT) versus high-density subthreshold micropulse laser (HSML) treatment in patients with chronic central serous chorioretinopathy (cCSC). Open-label, multicenter, randomized controlled clinical trial. Patients with cCSC whose disease had to be confirmed by both clinical characteristics and findings on multimodal imaging. Eligible patients were randomized in a 1:1 allocation ratio. Treatment was evaluated during a follow-up visit, and the same treatment was repeated in patients who still demonstrated subretinal fluid (SRF). The primary end point was the complete disappearance of SRF at the first evaluation visit at 6 to 8 weeks after treatment. As a secondary outcome measure, we assessed this anatomic result at the final evaluation visit at 7 to 8 months after treatment. Other secondary outcomes covered functional improvement and included change in best-corrected visual acuity (BCVA; measured in Early Treatment Diabetic Retinopathy Study [ETDRS] letters), retinal sensitivity (measured using microperimetry), and vision-related quality of life using a validated questionnaire. Between November 2013 and September 2016, 179 patients were included: 89 patients were assigned randomly to half-dose PDT, and 90 were assigned randomly to HSML treatment. At their first evaluation visit, SRF had resolved in 51.2% and 13.8% of patients, respectively (P < 0.001). At their final evaluation visit, a significantly higher percentage of PDT-treated patients demonstrated no SRF (67.2% vs. 28.8%; P < 0.001). Moreover, at the first evaluation visit, the PDT-treated patients showed a significantly higher increase in BCVA (+4.60±6.62 ETDRS letters vs. +1.39±8.99 ETDRS letters; P = 0.011), and a significantly higher increase in retinal sensitivity on microperimetry (+2.01±3.04 dB vs. +0.92±3.65 dB; P = 0.046); however, the improvement in vision-related quality of life was similar (score of +2.87±8.35 vs. +2.56±7.36, respectively; P = 0.800). Half-dose PDT is superior to HSML for treating cCSC, leading to a significantly higher proportion of patients with complete resolution of SRF and functional improvement.

In a continuation of a prospective longitudinal cohort study in a healthy population on the course of skull shape from birth to 24 months, at 5 years of age, 248 children participated in a follow-up assessment using plagiocephalometry (ODDI—oblique diameter difference index, CPI—cranio proportional index). Data from the original study sampled at birth, 7 weeks, 6, 12, and 24 months were used in two linear mixed models. Main findings: (1) if deformational plagiocephaly (ODDI <104%) and/or positional preference at 7 weeks of age are absent, normal skull shape can be predicted at 5 years of age; (2) if positional preference occurs, ODDI is the highest at 7 weeks and decreases to a stable lowest value at 2 and 5 years of age; and (3) regarding brachycephaly, all children showed the highest CPI at 6 months of age with a gradual decrease over time. Conclusion: The course of skull deformation is favourable in most of the children in The Netherlands; at 5 years of age, brachycephaly is within the normal range for all children, whereas the severity of plagiocephaly is within the normal range in 80%, within the mild range in 19%, and within the moderate/severe range in 1%. Medical consumption may be reduced by providing early tailored counselling. What is Known: • Skull deformation prevalence increased after recommendations against Sudden Infant Death Syndrome, little is known about the longitudinal course. • Paediatric physical therapy intervention between 2 and 6 months of age reduces deformational plagiocephaly at 6 and 12 months of age. What is New: • The course of skull deformation is favourable in most of the children in The Netherlands; at 5 years of age, deformational brachycephaly is within the normal range for all children, whereas the severity of deformational plagiocephaly is within the normal range in 80%, within the mild range in 19%, and within the moderate to severe range in only 1%. • Paediatric physical therapy intervention does not influence the long-term outcome; it only influences the earlier decrease of the severity of deformational plagiocephaly.

Objective To perform a systematic review of published N-of-1 trials (e.g. single patient cross-over trials) in neurological disorders, including an assessment of methodological quality and reporting. Methods We searched PubMed, MEDLINE and Embase, from inception date - the first of December 2019, for reports on N-of-1 trials in neurological 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 using the CONSORT 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 neurological 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, nine N-of-1 trials studied a stable chronic symptom of a progressive or acute neurological disorder. Besides pharmacological interventions, electrical 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 methodological measures of quality and reporting across all N-of-1 trials Conclusions N-of-1 trials have been reported in numerous neurological 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. Methodological quality and reporting of N-of-1 trials were found suboptimal and can easily be improved in future trials by appropriately describing the methods of blinding and randomization and follow CENT guidelines. As most N-of-1 trials remain unreported in medical literature, this systematic review probably only represent the tip of the iceberg of conducted N-of-1 trials in neurological 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.

To obtain evidence for the clinical and cost-effectiveness of treatments for patients with rare diseases is a challenge. Non-dystrophic myotonia (NDM) is a group of inherited, rare muscle diseases characterized by muscle stiffness. The reimbursement of mexiletine, the expert opinion drug for NDM, has been discontinued in some countries due to a lack of independent randomized controlled trials (RCTs). It remains unclear however, which concessions can be accepted towards the level 1 evidence needed for coverage decisions, in rare diseases. Considering the large number of rare diseases with a lack of treatment evidence, more experience with innovative trial designs is needed. Both NDM and mexiletine are well suited for an N-of-1 trial design. A Bayesian approach allows for the combination of N-of-1 trials, which enables the assessment of outcomes on the patient and group level simultaneously. We will combine 30 individual, double-blind, randomized, placebo-controlled N-of-1 trials of mexiletine (600 mg daily) vs. placebo in genetically confirmed NDM patients using hierarchical Bayesian modeling. Our results will be compared and combined with the main results of an international cross-over RCT (mexiletine vs. placebo in NDM) published in 2012 that will be used as an informative prior. Similar criteria of eligibility, treatment regimen, end-points and measurement instruments are employed as used in the international cross-over RCT. The treatment of patients with NDM with mexiletine offers a unique opportunity to compare outcomes and efficiency of novel N-of-1 trial-based designs and conventional approaches in producing evidence of clinical and cost-effectiveness of treatments for patients with rare diseases. ClinicalTrials.gov Identifier: NCT02045667

Tightly-controlled dose reduction was possible during 1 year in psoriasis patients on adalimumab, etanercept or ustekinumab with low disease activity (CONDOR trial). Extended observation is needed ...

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 cost...