Daily CBCT-based dose calculations for enhancing the safety of dose-escalation in lung cancer radiotherapy.

PURPOSE: Dose-escalation in lung cancer comes with a high risk of severe toxicity. This study aimed to calculate the delivered dose in a Scandinavian phase-III dose-escalation trial. METHODS: The delivered dose was evaluated for 21 locally-advanced non-small cell lung cancer (LA-NSCLC) patients treated as part of the NARLAL2 dose-escalation trial. The patients were randomized between standard and escalated heterogeneous dose-delivery. Both treatment plans were created and approved before randomization. Daily cone-beam CT (CBCT) for patient positioning, and adaptive radiotherapy were mandatory. Standard and escalated plans, including adaptive re-plans, were recalculated on each daily CBCT and accumulated on the planning CT for each patient. Dose to the clinical target volume (CTV), organs at risk (OAR), and the effects of plan adaptions were evaluated for the accumulated dose and on each treated fraction scaled to full treatment. RESULTS: For the standard treatment, plan adaptations reduced the number of patients with CTV-T underdosage from six to one, and the total number of fractions with CTV-T underdosage from 161 to 56; while for the escalated treatment, the number of patients was reduced from five to zero and number of fractions from 81 to 11. For dose-escalation, three patients had fractions exceeding trial constraints for heart, bronchi, or esophagus, and one had an accumulated heart dose above the constraints. CONCLUSION: Dose-escalation for LA-NSCLC patients, using daily image guidance and adaptive radiotherapy, is dosimetrically safe for the majority of patients. Dose calculation on daily CBCTs is an efficient tool to monitor target coverage and OAR doses.

A value-based healthcare model for initiating and switching psoriasis therapies-Results from the prospective multicentre IMPROVE study.

BACKGROUND: Little is known about the therapeutic benefits of a value-based healthcare model compared to a traditional activity-based incentive model in psoriasis (PsO). OBJECTIVES: This prospective non-interventional study evaluated an outcome-based, patient-centred management model for patients with PsO. METHODS: In total, 49 patients with a Psoriasis Area and Severity Index (PASI) ≥3 who were starting or switching between treatments were included. Patients were assessed at baseline, 3 and 9 months. The patient benefit index (PBI) was calculated using predefined questionnaires. An expected PBI was calculated and adjusted for risk factors known to complicate treatment, that is overweight and smoking. The model remunerated the department on whether the observed PBI exceeded the expected PBI to incentivize over-performance. RESULTS: In total, 40 patients (80%) completed all three visits; 32.7% were smokers and 73.5% were overweight. Mean PASI at baseline was 11.5 (SD 9.1); PASI improved significantly from baseline through 3 months: mean reduction, 8.0 (SD 9.2), p < 0.001 and was maintained until 9 months: mean further reduction, 0.1 (SD 3.3), p = 0.893. The mean PBI was 2.5 (SD 1.3) and 2.8 (SD 1.1) at 3 and 9 months, respectively. A PBI ≥1 was achieved by 87.8% at 3 and 95.1% at 9 months. Overall, the department was remunerated a mean 2721.1 DKK (SD 4472.8) per patient. In subgroup analysis, the department was remunerated a mean of, respectively, 2428.6 (SD 5089.5), 2636.6 (SD 4471.3) and 3196.5 (SD 4497.1) DKK for patients with none, 1 or 2 risk factors, that is smoking or/and overweight. CONCLUSIONS: The model evaluated herein is the first value-based model to calculate remuneration from patient reported outcomes and showed to successfully predict the expected PBI and remunerate treatment based on whether the expected treatment goal was met or exceeded. This can be utilized in the patient-centred management of PsO.

Prevalence of and association between atopic dermatitis and food sensitivity, food allergy and challenge-proven food allergy: A systematic review and meta-analysis.

Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co-occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta-analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge-proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full-text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7-53.2), 32.7% (28.8-36.6) and 40.7% (34.1-47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3-56.2), 45.3% (41.4-49.3) and 54.9% (47.0-62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4-55.1)) and FA (31.4% (26.9-36.1)) prevalences than adults with AD (28.6% (13.4-46.8) and 24.1% (12.1-38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.

Adults with concomitant atopic dermatitis and asthma have more frequent urgent healthcare utilization and less frequent scheduled follow-up visits than adults with atopic dermatitis or asthma only: a nationwide cohort study.

BACKGROUND: Atopic dermatitis (AD) and asthma often co-occur in the same patient, and healthcare utilization is related to disease severity of these diseases. OBJECTIVE: The objective of the study was to investigate differences in healthcare utilization in adults with concomitant AD and asthma compared to patients with asthma or AD only. METHODS: All Danish adults with a hospital diagnosis of AD, asthma or concomitant AD, and asthma recorded in national registries were included. Healthcare utilization data were obtained in 3-month intervals from 2 years prior to index date (the date of the first hospital diagnosis) and to 5 years after. RESULTS: A total of 12 409 patients with AD were included (11 590 with AD only and 819 with concomitant AD and asthma), and 65 539 with asthma only. Adults with concomitant AD and asthma had higher risk of hospitalization for AD (OR 1.38, 95% CI (1.15-1.67), P = 0.001) and asthma (OR 1.16, 95% CI (1.00-1.35), P = 0.047) compared to patients with only AD and asthma, respectively. These patients also had fewer visits in outpatient clinics for AD (OR 0.10, 95% CI (0.08-0.12), P < 0.001) and asthma (OR 0.34, 95% CI (0.29-0.39), P < 0.001) compared to patients with only AD or asthma. Outpatient clinic visits for rhinitis were more frequent among patients with concomitant AD and asthma compared to patients with only AD or asthma. CONCLUSION: Adults with concomitant AD and asthma had different patterns of healthcare utilization compared to adults with AD or asthma alone, suggesting that improvements in management and monitoring may reduce unscheduled healthcare visits and lower healthcare costs.

PDE concept for controlling cleaning agent residues in pharmaceuticals- A critical analysis.

Cleaning agents (CAs) are used in multipurpose facilities to control carryover contamination of active pharmaceutical ingredients (APIs) to scientifically justified limits. While this is often done with the PDE methodology used for API impurities, it is unclear if it is justifiable and necessary for cleaning agents, which generally represent a comparatively lower health risk. Comparing calculated oral PDE values for CA ingredients (CAIs) from four companies with PDEs of a selected number of small-molecule APIs showed that the toxicity of CAIs is several orders of magnitude lower. Furthermore, a critical review of the toxicity and everyday exposure to the general population of the main CAIs functional groups showed that the expected health risks are generally negligible. This is particularly true if the associated mode of actions cause local toxicity that is usually irrelevant at the concentration of potential residue carryover. This work points towards alternative approaches to the PDE concept to control CAIs' contamination and provides some guidance on grouping and identifying compounds with lower health risks based on exposure and mode of action reasoning. In addition, this work supports the concept that limit values should only be set for CAIs of toxicological concern.

Antimicrobial peptides in hidradenitis suppurativa: a systematic review.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, inflammatory skin disease of the hair follicle defined by recurrent nodules, tunnels and scarring involving the intertriginous regions. HS is associated with microbial dysbiosis and immune dysregulation. In HS, an increasing number of studies have investigated antimicrobial peptides (AMPs). OBJECTIVES: To provide an overview of the literature on AMPs in HS, and to discuss the potential role of AMPs in the pathogenesis of HS. METHODS: PubMed, Embase and the Cochrane Library were searched. The titles, abstracts and full texts of all articles were manually screened. Additionally, the reference lists of the included articles were screened and hand searched for relevant studies. RESULTS: The final literature sample comprised 18 retrospective and prospective studies (no reviews or commentaries) published between 2009 and 2020. CONCLUSIONS: This review demonstrates the multitude of AMPs in HS. Although the methodology of the studies varied, the included studies indicate a consistent overexpression of human ß-defensin (hBD)-2, S100A7, S100A8 and S100A9 at both the mRNA and protein levels, and a decreased expression of hBD-1. Overall, the studies point to a dysregulation of AMPs in both lesional and nonlesional HS skin.

Self-Reported Pain Alleviating Methods in Patients with Hidradenitis Suppurativa. / Métodos referidos por los pacientes para aliviar el dolor asociado a la hidradenitis supurativa.

BACKGROUND: Pain is a common, important symptom negatively affecting the well-being and quality of life of patients with hidradenitis suppurativa (HS). The aim of this study was to examine self-reported pain alleviating methods among outpatients attending a tertiary referral center. METHODS: Consecutive patients with HS were invited to complete a questionnaire regarding their self-reported pain alleviating methods for HS associated pain. Additionally, the patients filled out the Dermatology Life Quality Index questionnaire and a visual analog scale for overall distress related to HS and for boil-associated pain in the past month. Information on disease severity and onset was obtained by interview and clinical examination. RESULTS: A total of 134 patients with a mean age of 38.3 years (SD 12.8) participated; 32% (n=43) had Hurley stage i, 52% (n=70) had Hurley stage ii, and 16% (n=21) had Hurley stage iii. Overall, to achieve pain relief, 82% (n=110) of the patients had previously drained pus from the lesions by manual pressure. Compared to patients who did not alleviate pain, patients who attempted to alleviate pain had a higher mean overall disease related distress score (7.43 [SD 2.81] vs. 5.47 [SD 3.37], P<.003), and a higher boil-associated pain score in the past month (6.56 [SD 3.07] vs. 4.39 [SD 3.88], P=.007). CONCLUSION: This study demonstrates that a large proportion of HS patients attempt to alleviate pain through various alternative and homespun methods. These results may reflect a major role of pain in HS and its potential insufficient management by dermatologists.

Maximal strength training in patients with Parkinson's disease: impact on efferent neural drive, force-generating capacity, and functional performance.

Parkinson's disease (PD) is characterized by progressive neurological deterioration, typically accompanied by reductions in skeletal muscle force-generating capacity (FGC) and functional performance. Physical activity has the potential to counteract this debilitating outcome, however, it is elusive if high-intensity strength training included in conventional treatment may improve results. Therefore, we randomly assigned 22 PD patients (74 ± 9 yr) to conventional rehabilitation with or without maximal strength training (MST) performed as leg press and chest press at ~90% of one repetition maximum (1RM), five times per week for 4 wk. FGC, physical performance, and efferent neural drive assessed as evoked potentials (V-wave normalized to M-wave in m. soleus) were measured following training. Results revealed that only MST improved 1RM leg press (101 ± 23 to 118 ± 18 kg) and chest press (36 ± 15 to 41 ± 15 kg), plantar flexion maximal voluntary contraction (235 ± 125 to 293 ± 158 N·m), and rate of force development (373 ± 345 to 495 ± 446 N·m·s-1; all P < 0.05; different from controls P < 0.05). FGC improvements were accompanied by an increased efferent neural drive to maximally contracting musculature (V-to-M ratio: 0.17 ± 0.12 to 0.24 ± 0.15; P < 0.05; different from controls P < 0.05), improved physical performance (stair climbing: 21.0 ± 9.2 to 14.4 ± 5.2 s; timed up and go: 7.8 ± 3.3 to 6.2 ± 2.5 s; both P < 0.05), and self-perceived improvement in health (3.1 ± 0.5 to 2.6 ± 0.9) and social activities functioning (2.2 ± 1.0 to 1.5 ± 1.1; both P < 0.05). No changes were observed in the control group. In conclusion, this study shows that MST improves FGC, neuromuscular function, and functional performance and advocates that high-intensity strength training should be implemented as an adjunct therapy in the treatment of PD patients.NEW & NOTEWORTHY This randomized, controlled trial documents that supervised high-intensity strength training improves efferent neural drive, maximal muscle strength, rate of force development, and functional performance in patients with Parkinson's disease (PD). In contrast, no differences were observed in these outcome variables in patients receiving conventional treatment consisting of recreational physical activity with low-to-medium intensity. Consequently, this study advocates that high-intensity strength training should be implemented in the clinical treatment of PD patients.