Inferring skin-brain-skin connections from infodemiology data using dynamic Bayesian networks.

The relationship between skin diseases and mental illnesses has been extensively studied using cross-sectional epidemiological data. Typically, such data can only measure association (rather than causation) and include only a subset of the diseases we may be interested in. In this paper, we complement the evidence from such analyses by learning an overarching causal network model over twelve health conditions from the Google Search Trends Symptoms public data set. We learned the causal network model using a dynamic Bayesian network, which can represent both cyclic and acyclic causal relationships, is easy to interpret and accounts for the spatio-temporal trends in the data in a probabilistically rigorous way. The causal network confirms a large number of cyclic relationships between the selected health conditions and the interplay between skin and mental diseases. For acne, we observe a cyclic relationship with anxiety and attention deficit hyperactivity disorder (ADHD) and an indirect relationship with depression through sleep disorders. For dermatitis, we observe directed links to anxiety, depression and sleep disorders and a cyclic relationship with ADHD. We also observe a link between dermatitis and ADHD and a cyclic relationship between acne and ADHD. Furthermore, the network includes several direct connections between sleep disorders and other health conditions, highlighting the impact of the former on the overall health and well-being of the patient. The average R 2 for a condition given the values of all conditions in the previous week is 0.67: in particular, 0.42 for acne, 0.85 for asthma, 0.58 for ADHD, 0.87 for burn, 0.76 for erectile dysfunction, 0.88 for scars, 0.57 for alcohol disorders, 0.57 for anxiety, 0.53 for depression, 0.74 for dermatitis, 0.60 for sleep disorders and 0.66 for obesity. Mapping disease interplay, indirect relationships, and the key role of mediators, such as sleep disorders, will allow healthcare professionals to address disease management holistically and more effectively. Even if we consider all skin and mental diseases jointly, each disease subnetwork is unique, allowing for more targeted interventions.

Bilateral Total Hip Prosthesis in Coxarthritis of Inflammatory Origin: Technical Features and Intraoperative Complications Encountered in Five Cases.

Total hip arthroplasty remains the treatment of last resort in inflammatory coxarthritis, where joint destruction is bilateral as well as the treatment which must be bilateral. We present in this work the experience of our orthopaedic department with a series of five cases (10 hips) operated for total hip arthroplasty. the first particularity observed in this series is the abnormal bone fragility present in 55% of the cases. For this reason, we had two other intraoperative complications that are related to this bone fragility, during the preparation of the acetabulum, we had a destruction of the medial wall by the burr that went unnoticed intraoperatively and was discovered during the patient's recovery from acute ischemia secondary to the burr, which led to an extensive rupture of the common femoral vein and partial sectioning of the common femoral artery. We also had an exceptional incident in a case with two ankylosed hips; in fact, when the approach was performed, the sciatic nerve was found pressed against the posterior surface of the greater trochanter, which was unusual but was explained by the retraction of the structures of the gluteal region secondary to prolonged immobilization. Thus, there was one case of cement shock manifested by hypotension occurring immediately after cement placement. In front of this inflammatory disease and ankylosis terrain, the surgeon must always be prepared for any complication and must keep in mind that he is operating on a hip that is anatomically not normal due to ankylosis and retraction of the vascular, nerve, and muscle structures.

Comparison of different skin care regimens in patients with moderate to severe atopic dermatitis receiving systemic treatment: A randomized controlled trial.

BACKGROUND: Moderate to severe AD can be successfully managed by systemic treatments. Current guidelines also recommend emollients or emollients 'plus' and eudermic cleansers for all AD patients to improve the skin barrier and provide anti-irritant and anti-pruritic effects. OBJECTIVES: To investigate the efficacy of skin care (in addition to systemic treatment) with an Emollient 'plus' balm designed to improve the skin barrier and skin microbiome plus a corresponding syndet compared to usual commercial emollients and cleansers. METHODS: In a randomized controlled multicenter study, patients with moderate to severe AD (Severity scoring of atopic dermatitis [SCORAD] score ≥ 40) receiving systemic treatment (cyclosporin A, dupilumab or a Janus kinase inhibitor) were randomized 1:1 to apply twice daily for 10 weeks Emollient 'plus' after pre-cleaning with the syndet (Emollient 'plus' group) or to continue with their usual emollient and cleanser (Control group). Assessments included SCORAD, pruritus on a Visual Analog Scale, Dermatology quality of life questionnaire (DLQI), efficacy and tolerance questionnaires. RESULTS: Included were 57 patients with mean age of 38 years (range 19-70 years). The mean amount of emollient used after 10 weeks was 447.3 g (range 29-1099 g) and 613.2 g (range 97-2565 g) for the Emollient 'plus' versus the Control, respectively (p = 0.0277). After 10 weeks, subjects in the Emollient 'plus' had a significantly greater reduction in current pruritus (p = 0.0277) and a greater reduction in some DLQI items compared to the Control group. CONCLUSIONS: In patients with moderate to severe AD receiving systemic treatment, the Emollient 'plus' regimen significantly improved pruritus and quality of life items compared to the control, while using 23% less product over a 10-week period. These results stress the importance of daily use of emollients, especially emollients 'plus' to improve signs, symptoms and quality of life in patients with AD.

Algerian Registry for Inborn Errors of Immunity in Children: Report of 887 Children (1985-2021).

INTRODUCTION: Inborn errors of immunity (IEI) represent a heterogeneous large group of genetic disorders characterized by susceptibility of affected individuals to recurrent infections, autoimmune/inflammatory diseases, allergy, and malignancy. We aimed to report for the first time the Algerian registry for IEI in children. METHODS: We described the characteristics of IEI in Algerian children from the data collected in the Algerian registry for IEI between 1985 and 2021. RESULTS: Over a period of 37 years, we included 887 children (530 male, 59.6%) with a mean age at diagnosis of 3.23 years and a mean diagnosis delay of 2 years. The prevalence rate was estimated at 1.97/100,000 inhabitants or 5.91/100,000 children. The parental consanguinity was found in 52.6%. The most prevalent category was combined immunodeficiencies (CID) (35.5%), followed by predominantly antibody deficiencies (24.5%) and CID with syndromic features (18.3%). The most predominant diseases were severe CID (134 cases), MHC II deficiency (99 cases), agammaglobulinemia (82 cases), common variable immunodeficiency (78 cases), hyper IgE syndromes (61 patients), ataxia-telangiectasia (46 patients), Wiskott-Aldrich syndrome (40 patients) and chronic granulomatous disease (39 cases). The clinical presentation was dominated by lower respiratory tract infections (69%), failure to thrive (38.3%), and chronic diarrhea (35.2%). Genetic analysis was performed in 156 patients (17.6%). The global mortality rate was 28.4% mainly caused by CID. CONCLUSION: This is the first report of the Algerian registry for IEI in children. Data is globally similar to that of the Middle East and North African (MENA) registries with high consanguinity, predominance of CID, and significant mortality. This registry highlights the weak points that should be improved in order to provide better patient care.

Prevalence of Skin Reactions and Self-Reported Allergies in 5 Countries with Their Social Impact Measured through Quality of Life Impairment.

BACKGROUND: The prevalence of allergies increases worldwide. Allergies may increase the risk of skin reactions. OBJECTIVE: To evaluate the prevalence of allergies and skin reactions in the adult population, the strength of their relationship, and their impact on the quality of life. METHODS: An online survey was conducted in a representative population of 11,067 adults from China, USA, Brazil, Russia, and France. RESULTS: Overall, 35.6% of respondents reported having allergies, they were predominantly fair-skinned women, and younger than responders reporting no allergy. Among patients reporting allergies, 68.6% declared that their allergy makes their skin reacts. A strong association between allergy and major skin reactions was observed, which were associated with skin discomforts such as itching, burning, and pain. Skin discomforts were associated with an increased risk of quality of life alteration. CONCLUSIONS: Quantifying the prevalence and the association of allergies with skin reactions and discomfort sensations is critical to evaluating the impact on quality of life. Since skin barrier alteration is hypothesized as a risk factor and a route of sensitization for allergy development, the daily use of topical treatments, such as moisturizers, could help prevent allergic skin reactions, discomfort and impaired quality of life in individuals with an altered skin barrier.

Prediction of treatment effect perception in cosmetics using machine learning.

Perception of treatment effect (TE) in cosmetics is multifaceted and influenced by multiple parameters that need to be considered simultaneously when evaluating TE. Here we provide a global approach to predicting TE perception using Random Forest (RF) classifier. Data from three randomized double-blind clinical studies with a total of 50 subjects were used. Different products were applied to each facial cheek of subjects at each visit, and post-application photographs were taken. Nine primary endpoints relating to skin pores were assessed by a specific image analysis algorithm. Twenty judges evaluated the relative pore visibility in all possible pairs of cheek photographs. RF was used to construct a prediction model for TE perception based on the primary endpoints and judge's evaluation. Intra-study product ranking was done using the Bradley-Terry model on mean judges' predicted preference. RF demonstrated overall good accuracy in predicting TE perception. Applying RF technique not only addresses issues of multiplicity, nonlinearity and interactions between multiple criteria but also focuses decision-making on one discrete parameter thereby simplifying interpretability and allowing for more consumer-centered claim substantiation in clinical trials.Abbreviations: RF: Random Forest classifier; FDA: The US Food and Drug Agency; ID: Identifier; MCID: Minimal clinical important difference; Param: Parameter; PGIC: Patients' Global Impression of Change; TE: Treatment effect; TRT: Treatment.

Developing a new device for continuously recording, in vivo, the excretion rate of sweat (perspiration) in humans.

BACKGROUND: Some methodologies used for evaluating sweat production and antiperspirants are of a stationary aspect, that is, most often performed under warm (38°C) but resting conditions in a rather short period of time. The aim is to develop an electronic sensor apt at continuously recording sweat excretion, in vivo, during physical exercises, exposure to differently heated environments, or any other stimuli that may provoke sweat excretion. MATERIAL AND METHODS: A sensor (20 cm2 ) is wrapped under a double-layered textile pad. Fixed onto the armpits, these two arrays of electrodes are connected to electronic system through an analog multiplexer. A microcontroller is used to permanently record changes in the conductance between two electrodes during exposure of subjects to different sweat-inducing conditions or to assess the efficacy of applied aluminum hydrochloride (ACH)-based roll-ons at two concentrations (5% and 15%). RESULTS: In vitro calibration, using a NaCl 0.5% solution, allows changes in mV to be related with progressively increased volumes. In vivo, results show that casual physical exercise leads to sweat excretions much higher than in warm environment (37 or 45°C). Only, an exposure to a 50°C environment induced comparable sweat excretion. In this condition, sweat excretions were found similar in both armpits and both genders. Decreased sweat excretions were recorded following applications of ACH, with a dose effect. CONCLUSION: Developing phases of this new approach indicate that usual method or guidelines used to determine sweat excretions in vivo do not reflect true energy expenditure processes. As a consequence, they probably over-estimate the efficacy of antiperspirant agents or formulae.

Random main effects of treatment: A case study with a network meta-analysis.

If the number of treatments in a network meta-analysis is large, it may be possible and useful to model the main effect of treatment as random, that is to say as random realizations from a normal distribution of possible treatment effects. This then constitutes a third sort of random effect that may be considered in connection with such analyses. The first and most common models treatment-by-trial interaction as being random and the second, rather rarer, models the main effects of trial as being random and thus permits the recovery of intertrial information. Taking the example of a network meta-analysis of 44 similar treatments in 10 trials, we illustrate how a hierarchical approach to modeling a random main effect of treatment can be used to produce shrunk (toward the overall mean) estimates of effects for individual treatments. As a related problem, we also consider the issue of using a random-effect model for the within-trial variances from trial to trial. We provide a number of possible graphical representations of the results and discuss the advantages and disadvantages of such an approach.

On the evaluation of reliability, repeatability, and reproducibility of instrumental evaluation methods and measurement systems.

Validation of instrumental evaluation methods or measurement systems plays an important role in both pharmaceutical and cosmetic research and development. In practice, it is suggested that validation should be performed according to performance characteristics as described in the United States Pharmacopedia and National Formulary (USP/NF, 2000) for analytical methods validation. A validated method or measurement system is expected to achieve a certain degree of accuracy and reliability. However, it is a concern whether the test results obtained are repeatable (with similar test samples) and/or reproducible (under similar but slightly different experimental conditions). In this article, reliability and repeatability/reproducibility of a measurement system estimated within a mixed-effects nested design are monitored by relevant variability acceptance limits. A method based on the concept of empirical power (reproducibility) is used to determine these acceptance limits and thus ensure that there is a high probability of repeatability/reproducibility of the tests results. Formulas or procedures for sample size requirements for comparing the variabilities between products are derived. An example is presented to illustrate the use of the proposed method.

Relative efficacy and tolerability of vortioxetine versus selected antidepressants by indirect comparisons of similar clinical studies.

INTRODUCTION: Vortioxetine is an antidepressant with multimodal activity which has shown efficacy in major depressive disorder (MDD) patients in six of ten short-term, randomized, placebo-controlled trials (completed end 2012). METHODS: We performed meta-regression analyses to indirectly compare vortioxetine to seven marketed antidepressants with different mechanisms of action. To ensure study comparability, only experimental drug and placebo arms from placebo-controlled registration studies were included in primary analyses. The main outcomes were efficacy (standardized mean difference in change from baseline to 2 months on primary endpoint [MADRS/HAM-D]), and tolerability (withdrawal rate due to adverse events). RESULTS: For efficacy, estimates of treatment effect (negative estimates favor vortioxetine) for vortioxetine versus comparators were: agomelatine, -0.16 (p = 0.11); desvenlafaxine, 0.03 (p = 0.80); duloxetine, 0.09 (p = 0.42); escitalopram, -0.05 (p = 0.70); sertraline, -0.04 (p = 0.83); venlafaxine IR/XR, 0.12 (p = 0.33); and vilazodone, -0.25 (p = 0.11). For tolerability, all but one combination was numerically in favor of vortioxetine (odds ratio < 1), although not all differences were statistically significant: agomelatine, 1.77 (p = 0.03); desvenlafaxine, 0.58 (p = 0.04); duloxetine, 0.75 (p = 0.26); escitalopram, 0.67 (p = 0.28); sertraline, 0.30 (p = 0.01); venlafaxine, 0.47 (p = 0.01); and vilazodone, 0.64 (p = 0.18). Sensitivity analyses did not significantly alter antidepressant effect estimates or relative ranking. CONCLUSION: These meta-regression data show that vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD. Alternative methods like mixed-treatment comparison and inclusion of all randomized studies and active reference arms may provide complementary information to this analysis (more evidence but also more heterogeneity). Key messages: Indirect comparisons based on registration studies allow a useful comparison between a recently approved antidepressant and an approved drug. Vortioxetine offers a comparable or favorable combination of efficacy (measured by MADRS/HAM-D assessments) and tolerability (measured by withdrawal rate due to adverse events) versus other antidepressants in registration studies in MDD.

Bacteriological and chemical quality of swimming pools water in developing countries: a case study in the West Bank of Palestine.

Monitoring was carried out during summer 2000 in all the swimming pools in the West Bank of Palestine. Fifty-eight water samples, collected from 46 swimming pools, were examined for Coliforms and bacterial species including Streptococci, Salmonellae, and Staphylococcus. Salmonellae were isolated in 21 out of 23 samples. All of the examined samples from the swimming pools water were unacceptable according to the Palestinian and WHO standards. Extensive efforts are required to improve the water quality of the swimming pools in the West Bank, mainly public awareness, training of governmental inspectors, operators and owners of the swimming pools, in addition to a strict system for monitoring of the water quality.