One-Stage Vs. Two-Step One Anastomosis Duodenal Switch (OADS/SADI-S): A Safety and Efficacy Single-Center Propensity-Score Matched Analysis.

INTRODUCTION: One Anastomosis Duodenal Switch (OADS/SADI-S) is used both as a one stage and a second-step procedure, either planned or revisional after a failed sleeve gastrectomy. However, there is lack of adjusted comparative evidence validating its use. MATERIAL AND METHODS: Propensity-score matched comparison between patients submitted to one-stage vs. two-step OADS, adjusted by age, gender, and initial body mass index (BMI). RESULTS: One hundred ninety-five patients (130 one-stage and 65 two-step OADS) were included, with mean initial BMI 52.4 kg/m2. Overall complication rate was 6.6% in the short-term (3.3% Clavien-Dindo ≥ III), and 7.3% in the long-term, with no differences between groups. Follow-up at 1 and 3 years was 83.6% and 61.5%. After one-stage OADS, total weight loss was 36.6 ± 8.2% at 1 year and 30.4 ± 10.3% at 3 years, vs. 30.2 ± 9.4% and 25.6 ± 10.2% after two-steps OADS (p = 0.021). Resolution rates of diabetes mellitus, hypertension, dyslipidemia, and obstructive sleep apnea were 86.4%, 80.4%, 78.0%, and 73.3%, with no differences between groups. CONCLUSION: One-stage OADS is a safe and effective bariatric technique for patients with grade III and IV obesity. The two-step strategy does not reduce postoperative risks and may compromise weight loss results at mid-term.

A Randomized Clinical Trial to Evaluate the Efficacy of an Oral Probiotic in Acne Vulgaris.

The relevance of the gut microbiota in some skin inflammatory diseases, including acne vulgaris, has been emphasized. Probiotics could play a role in the modulation of the microbiota, improving the clinical course of this disease. A 12-week randomized, double-blind, placebo-controlled, clinical trial with patients aged 12 to 30 years with acne vulgaris was conducted. The study product was a capsule composed of the probiotic Lacticaseibacillus rhamnosus (CECT 30031) and the cyanobacterium Arthrospira platensis (BEA_IDA_0074B). Patients with improvement in the Acne Global Severity Scale were 10/34 (29.41%) in the placebo group compared with 20/40 (50%) in the probiotic group (p = 0.03). A significant reduction (p = 0.03) in the number of non-inflammatory acne lesions was observed in the probiotic group (-18.60 [-24.38 to -12.82]) vs the placebo group (-10.54 [-17.43 to -3.66]). Regarding the number of total  lesions, a reduction almost reaching statistical significance (p = 0.06) was observed in the probiotic group (-27.94 [-36.35 to -19.53]) compared with the placebo group (-18.31 [-28.21 to -8.41]). In addition, patients with improvement attending the Global Acne Grading System were 7/34 (20.58%) in the placebo group vs 17/40 (42.50%) in the probiotic group (p = 0.02). The number of adverse events was similar in both groups. The probiotic used in this study was effective and well tolerated, and it should be considered for acne vulgaris patients.

Correction: Clinical outcomes in a primary-level non-communicable disease programme for Syrian refugees and the host population in Jordan: A cohort analysis using routine data.

[This corrects the article DOI: 10.1371/journal.pmed.1003279.].

Gastroschisis prevalence patterns in 27 surveillance programs from 24 countries, International Clearinghouse for Birth Defects Surveillance and Research, 1980-2017.

BACKGROUND: Gastroschisis is a serious birth defect with midgut prolapse into the amniotic cavity. The objectives of this study were to evaluate the prevalence and time trends of gastroschisis among programs in the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR), focusing on regional variations and maternal age changes in the population. METHODS: We analyzed data on births from 1980 to 2017 from 27 ICBDSR member programs, representing 24 countries and three regions (Europe+ (includes Iran) , Latin America, North America). Cases were identified using diagnostic codes (i.e., 756.7, 756.71, or Q79.3). We excluded cases of amniotic band syndrome, limb-body wall defect, and ruptured omphalocele. Programs provided annual counts for gastroschisis cases (live births, stillbirths, and legally permitted pregnancy terminations for fetal anomalies) and source population (live births, stillbirths), by maternal age. RESULTS: Overall, gastroschisis occurred in 1 of every 3268 births (3.06 per 10,000 births; 95% confidence intervals [CI]: 3.01, 3.11), with marked regional variation. European+ prevalence was 1.49 (95%CI: 1.44, 1.55), Latin American 3.80 (95%CI: 3.69, 3.92) and North American 4.32 (95%CI: 4.22, 4.42). A statistically significant increasing time trend was observed among six European+ , four Latin American, and four North American programs. Women <20 years of age had the highest prevalence in all programs except the Slovak Republic. CONCLUSIONS: Gastroschisis prevalence increased over time in 61% of participating programs, and the highest increase in prevalence was observed among the youngest women. Additional inquiry will help to assess the impact of the changing maternal age proportions in the birth population on gastroschisis prevalence.

Anaerobic hexadecane degradation by a thermophilic Hadarchaeon from Guaymas Basin.

Hadarchaeota inhabit subsurface and hydrothermally heated environments, but previous to this study, they had not been cultured. Based on metagenome-assembled genomes, most Hadarchaeota are heterotrophs that grow on sugars and amino acids, or oxidize carbon monoxide or reduce nitrite to ammonium. A few other metagenome-assembled genomes encode alkyl-coenzyme M reductases (Acrs), ß-oxidation, and Wood-Ljungdahl pathways, pointing toward multicarbon alkane metabolism. To identify the organisms involved in thermophilic oil degradation, we established anaerobic sulfate-reducing hexadecane-degrading cultures from hydrothermally heated sediments of the Guaymas Basin. Cultures at 70°C were enriched in one Hadarchaeon that we propose as Candidatus Cerberiarchaeum oleivorans. Genomic and chemical analyses indicate that Ca. C. oleivorans uses an Acr to activate hexadecane to hexadecyl-coenzyme M. A ß-oxidation pathway and a tetrahydromethanopterin methyl branch Wood-Ljungdahl (mWL) pathway allow the complete oxidation of hexadecane to CO2. Our results suggest a syntrophic lifestyle with sulfate reducers, as Ca. C. oleivorans lacks a sulfate respiration pathway. Comparative genomics show that Acr, mWL, and ß-oxidation are restricted to one family of Hadarchaeota, which we propose as Ca. Cerberiarchaeaceae. Phylogenetic analyses further indicate that the mWL pathway is basal to all Hadarchaeota. By contrast, the carbon monoxide dehydrogenase/acetyl-coenzyme A synthase complex in Ca. Cerberiarchaeaceae was horizontally acquired from Bathyarchaeia. The Acr and ß-oxidation genes of Ca. Cerberiarchaeaceae are highly similar to those of other alkane-oxidizing archaea such as Ca. Methanoliparia and Ca. Helarchaeales. Our results support the use of Acrs in the degradation of petroleum alkanes and suggest a role of Hadarchaeota in oil-rich environments.

Comparing binary efficacy outcomes for systemic immunomodulatory treatments for atopic dermatitis in a living systematic review and network meta-analysis.

BACKGROUND: Systemic treatments for atopic dermatitis (AD) are evaluated primarily in placebo-controlled trials with binary efficacy outcomes. In a living systematic review and network meta-analysis (NMA), we previously analysed continuous efficacy measures. OBJECTIVES: To compare binary efficacy outcomes of systemic treatments for AD. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Latin American and Caribbean Health Science Information (LILACS) database, Global Resource for Eczema Trials (GREAT) database and trial registries up to 1 March 2023. We included randomized trials examining ≥ 8 weeks of treatment with systemic immunomodulatory medications for moderate-to-severe AD. We screened titles, abstracts and full texts and abstracted data independently, in duplicate. Outcomes included the proportion of patients achieving at least 50%, 75% and 90% improvements in Eczema Area and Severity Index (EASI 50, EASI 75 and EASI 90, respectively) and Investigator Global Assessment (IGA) success. We performed random-effects Bayesian NMAs to calculate odds ratios (OR) and 95% credible intervals (CrIs) between each intervention for each outcome. RESULTS: Eighty-three trials with 22 122 participants were included in the systematic review. In analyses limited to trials of 8-16 weeks' duration with predominantly adult populations, abrocitinib 200 mg daily (OR 1.5, 95% CrI 1.1-2.2) and upadacitinib 15 mg daily (OR 1.7, 95% CrI 0.9-3.3) and 30 mg daily (OR 2.5, 95% CrI 1.3-5.0) were associated with higher odds of achieving EASI 50 vs. dupilumab. Abrocitinib 100 mg daily (OR 0.7, 95% CrI 0.5-1.0), baricitinib 2 mg daily (OR 0.4, 95% CrI 0.3-0.5) and 4 mg daily (OR 0.5, 95% CrI 0.3-0.7), and tralokinumab (OR 0.4, 95% CrI 0.3-0.6) were associated with lower odds of achieving EASI 50 vs. dupilumab. Results were similar for EASI 75, EASI 90 and IGA success. CONCLUSIONS: Supporting results for continuous outcome measures, upadacitinib 30 mg daily and abrocitinib 200 mg daily are the most efficacious with regard to binary efficacy endpoints up to 16 weeks in adults with moderate-to-severe AD, followed by upadacitinib 15 mg daily, dupilumab and abrocitinib 100 mg daily. Dupilumab and both doses of upadacitinib and abrocitinib are more efficacious than baricitinib 4 and 2 mg daily and tralokinumab.

Prevalence of chronic pain or analgesic use in children and young people and its long-term impact on substance misuse, mental illness, and prescription opioid use: a retrospective longitudinal cohort study.

Background: Epidemiological studies suggest chronic and recurrent pain affects around a quarter of children, while 8% report intense and frequent pain. The long-term implications of chronic pain in childhood are uncertain. Using electronic health records (EHRs) we used both disease codes and medicines prescription records to investigate the scale of chronic pain and long-term analgesic use in children and young people (CYP), and if chronic pain and/or use of analgesic medicines at an early age is associated with substance misuse, use of prescription opioids, and poor mental health in adulthood. Methods: We conducted a cohort study using data from IQVIA Medical Research Data UK. We identified individuals aged 2-24 with exposure to either a diagnostic code indicating chronic pain (diagnosis-exposed), repeat prescription for medicines commonly used to treat pain (prescription-exposed), or both. Follow-up began at 25, and the unexposed population acted as comparators. We calculated hazard ratios (HR) for mental health and substance misuse outcomes, and rate ratios (RR) for opioid prescriptions in adulthood. Additionally, we investigated which diagnoses, if any, were over-represented in the prescription-exposed subgroup. Findings: The cohort constituted 853,625 individuals; 146,431 had one or more of the exposures of interest (diagnosis-exposed = 115,101, prescription-exposed = 20,298, both-exposed = 11,032), leaving 707,194 as comparators. Median age at index exposure was 18.7 years (IQR 14.7-22.3). On average during follow-up, the pooled exposed group had, respectively, a 31% and 17% higher risk of adverse mental health and substance misuse outcomes (adjusted HR [95% CI] of 1.31 [1.29-1.32] and 1.17 [1.11-1.24]). Exposed individuals also received prescription opioids at double the rate of unexposed individuals on average during follow-up (adjusted RR 2.01 [95% CI 1.95-2.10]). Outcomes varied between exposure subgroups, with prescription- and both-exposure tending to have worse outcomes. Unlike these two subgroups, in the diagnosis-exposed subgroup we did not detect a greater risk of substance misuse. Interpretation: Chronic pain in CYP is associated with increased prescription opioid use and adverse mental health outcomes in adulthood, as is repeat prescription for analgesic medicines, but only the latter is also associated with substance misuse in adulthood. It is essential to avoid the harms of under-treating pain in CYP while giving due consideration to the risks posed by analgesic medicines. Early recognition of chronic pain in CYP and utilising non-pharmacological management options may help minimise overprescribing, and long-term reliance on dependence-forming-drugs. Funding: AL is an NIHR funded academic clinical fellow, and was supported by funding from UCLH Charities while carrying out this work. RS and DS are part of the Advanced Pain Discovery Platform and were supported by a UKRI and Versus Arthritis grant (MR/W002566/1) as part of the Consortium Against Pain Inequality. AW was supported by the Wellcome Trust (220558/Z/20/Z).

Optimising prediction of mortality, stroke, and major bleeding for patients with atrial fibrillation: validation of the GARFIELD-AF tool in UK primary care electronic records.

BACKGROUND: The GARFIELD-AF tool is a novel risk tool that simultaneously assesses the risk of all-cause mortality, stroke or systemic embolism, and major bleeding in patients with atrial fibrillation (AF). AIM: To validate the GARFIELD-AF tool using UK primary care electronic records. DESIGN AND SETTING: A retrospective cohort study using the Clinical Practice Research Datalink (CPRD) linked with Hospital Episode Statistics data and Office for National Statistics mortality data. METHOD: Discrimination was evaluated using the area under the curve (AUC) and calibration was evaluated using calibration-in-the-large regression and calibration plots. RESULTS: A total of 486 818 patients aged ≥18 years with incident diagnosis of non-valvular AF between 2 January 1998 and 31 July 2020 were included; 50.6% (n = 246 425/486 818) received anticoagulation at diagnosis The GARFIELD- AF models outperformed the CHA2DS2VASc and HAS-BLED scores in discrimination ability of death, stroke, and major bleeding at all the time points. The AUC for events at 1 year for the 2017 models were: death 0.747 (95% confidence interval [CI] = 0.744 to 0.751) versus 0.635 (95% CI = 0.631 to 0.639) for CHA2DS2VASc; stroke 0.666 (95% CI = 0.663 to 0.669) versus 0.625 (95% CI = 0.622 to 0.628) for CHA2DS2VASc; and major bleeding 0.602 (95% CI = 0.598 to 0.606) versus 0.558 (95% CI = 0.554 to 0.562) for HAS- BLED. Calibration between predicted and Kaplan- Meier observed events was inadequate with the GARFIELD-AF models. CONCLUSION: The GARFIELD-AF models were superior to the CHA2DS2VASc score for discriminating stroke and death and superior to the HAS-BLED score for discriminating major bleeding. The models consistently underpredicted the level of risk, suggesting that a recalibration is needed to optimise its use in the UK population.

Potential for the anaerobic oxidation of benzene and naphthalene in thermophilic microorganisms from the Guaymas Basin.

Unsubstituted aromatic hydrocarbons (UAHs) are recalcitrant molecules abundant in crude oil, which is accumulated in subsurface reservoirs and occasionally enters the marine environment through natural seepage or human-caused spillage. The challenging anaerobic degradation of UAHs by microorganisms, in particular under thermophilic conditions, is poorly understood. Here, we established benzene- and naphthalene-degrading cultures under sulfate-reducing conditions at 50°C and 70°C from Guaymas Basin sediments. We investigated the microorganisms in the enrichment cultures and their potential for UAH oxidation through short-read metagenome sequencing and analysis. Dependent on the combination of UAH and temperature, different microorganisms became enriched. A Thermoplasmatota archaeon was abundant in the benzene-degrading culture at 50°C, but catabolic pathways remained elusive, because the archaeon lacked most known genes for benzene degradation. Two novel species of Desulfatiglandales bacteria were strongly enriched in the benzene-degrading culture at 70°C and in the naphthalene-degrading culture at 50°C. Both bacteria encode almost complete pathways for UAH degradation and for downstream degradation. They likely activate benzene via methylation, and naphthalene via direct carboxylation, respectively. The two species constitute the first thermophilic UAH degraders of the Desulfatiglandales. In the naphthalene-degrading culture incubated at 70°C, a Dehalococcoidia bacterium became enriched, which encoded a partial pathway for UAH degradation. Comparison of enriched bacteria with related genomes from environmental samples indicated that pathways for benzene degradation are widely distributed, while thermophily and capacity for naphthalene activation are rare. Our study highlights the capacities of uncultured thermophilic microbes for UAH degradation in petroleum reservoirs and in contaminated environments.

Candidatus Alkanophaga archaea from Guaymas Basin hydrothermal vent sediment oxidize petroleum alkanes.

Methanogenic and methanotrophic archaea produce and consume the greenhouse gas methane, respectively, using the reversible enzyme methyl-coenzyme M reductase (Mcr). Recently, Mcr variants that can activate multicarbon alkanes have been recovered from archaeal enrichment cultures. These enzymes, called alkyl-coenzyme M reductase (Acrs), are widespread in the environment but remain poorly understood. Here we produced anoxic cultures degrading mid-chain petroleum n-alkanes between pentane (C5) and tetradecane (C14) at 70 °C using oil-rich Guaymas Basin sediments. In these cultures, archaea of the genus Candidatus Alkanophaga activate the alkanes with Acrs and completely oxidize the alkyl groups to CO2. Ca. Alkanophaga form a deep-branching sister clade to the methanotrophs ANME-1 and are closely related to the short-chain alkane oxidizers Ca. Syntrophoarchaeum. Incapable of sulfate reduction, Ca. Alkanophaga shuttle electrons released from alkane oxidation to the sulfate-reducing Ca. Thermodesulfobacterium syntrophicum. These syntrophic consortia are potential key players in petroleum degradation in heated oil reservoirs.

Randomized double-blind placebo-controlled clinical trial to evaluate the effect of a mixture of probiotic strains on symptom severity and use of corticosteroids in children and adolescents with atopic dermatitis.

BACKGROUND: The intestinal microbiota is altered in patients with atopic dermatitis (AD) when compared with those of the healthy population. Some interventions with specific probiotic preparations already demonstrate a change in composition of this microbiota accompanied by improvement in the disease. OBJECTIVES: This research work was designed to evaluate clinical efficacy of the probiotic preparation, and to measure the effect of the intervention on the total dose of corticosteroids administered to subjects. METHODS: This double-blind, randomized, placebo-controlled clinical trial including 70 participants with AD aged 4-17 years was designed to evaluate the clinical effect, compared with placebo, of a probiotic mixture of Bifidobacterium lactis, Bifidobacterium longum and Lactobacillus casei at a total daily consumption of 1 × 109 colony-forming units per capsule, over 12 weeks. After randomization and exclusion, 35 patients were allocated to probiotic and 35 to placebo. Clinical variables analysed were SCORAD (SCORing of Atopic Dermatitis) and Investigator Global Assessment (IGA) indices; effect on the amount of topical corticosteroids used; and assessment of safety. RESULTS: Mean SCORAD index at 12 weeks showed a statistically significant difference of -5.43 (95% confidence interval -10.65 to -0.21) between probiotic (SCORAD 13.52) and placebo groups (SCORAD 18.96); P = 0.04. Comparison between groups showed a statistically significant difference in the number of patients with IGA score improvement over the 12-week intervention: 29 of 32 (90.5%) in the probiotic group vs. 17 of 30 (56.7%) in the placebo group (P < 0.002). A comparison between groups of the proportions of days using corticosteroids and the total dose (g) of corticosteroids between baseline and end of study showed no significant difference, but between weeks 6 and 12 there was a statistically significant reduction in the probiotic group when compared with the placebo group in both variables. Numbers of adverse events were similar in both groups of treatment. CONCLUSIONS: The probiotic mix used in this clinical trial demonstrated efficacy on the change in activity index of AD compared with placebo. Furthermore, the total number of days and total amount of topical corticosteroids required by participants in the probiotic group showed a significant reduction compared with placebo between 6 and 12 weeks.

BioBlocksLab: A portable DIY Bio Lab using BioBlocks language.

Standard molecular biology laboratories are usually made with complex, sophisticated, and expensive equipment. Unfortunately, most of these labs are not affordable for everyone. In this paper, we show how we built a portable bio lab BioBlocksLab, made of four modules: a centrifuge, a thermocycler, electrophoresis, and an incubator. We also propose a new version of a blockly programming language to describe experimental lab protocols, called BioBlocks 2.0, which is based on the Microsoft MakeCode platform from the open-source project Microsoft Programming Experience Toolkit (PXT). We run BioBlocks programs of real lab protocols to control different hardware modules with biological reagents and get positive results. We offer an easy, affordable, and open-source way for everyone to do experiments with Do-It-Yourself (DIY) portable bio-labs.

Fixed dose combination drugs for cardiovascular disease in a prolonged humanitarian crisis in Lebanon: an implementation study.

OBJECTIVES: This pre-post implementation study evaluated the introduction of fixed dose combination (FDC) medications for atherosclerotic cardiovascular disease (ASCVD) secondary prevention into routine care in a humanitarian setting. SETTING: Two Médecins sans Frontières (MSF) primary care clinics serving Syrian refugee and host populations in north Lebanon. PARTICIPANTS: Consenting patients ≥18 years with existing ASCVD requiring secondary prevention medication were eligible for study enrolment. Those with FDC contraindication(s) or planning to move were excluded. Of 521 enrolled patients, 460 (88.3%) were retained at 6 months, and 418 (80.2%) switched to FDC. Of these, 84% remained on FDC (n=351), 8.1% (n=34) discontinued and 7.9% (n=33) were lost to follow-up by month 12. INTERVENTIONS: Eligible patients, enrolled February-May 2019, were switched to Trinomia FDC (atorvastatin 20 mg, aspirin 100 mg, ramipril 2.5/5/10 mg) after 6 months' usual care. During the study, the COVID-19 pandemic, an economic crisis and clinic closures occurred. OUTCOME MEASURES: Descriptive and regression analyses compared key outcomes at 6 and 12 months: medication adherence, non-high density lipoprotein cholesterol (non-HDL-C) and systolic blood pressure (SBP) control. We performed per-protocol, intention-to-treat and secondary analyses of non-switchers. RESULTS: Among 385 switchers remaining at 12 months, total adherence improved 23%, from 63% (95% CI 58 to 68) at month 6, to 86% (95% CI 82 to 90) at month 12; mean non-HDL-C levels dropped 0.28 mmol/L (95% CI -0.38 to -0.18; p<0.0001), from 2.39 (95% CI 2.26 to 2.51) to 2.11 mmol/L (95% CI 2.00 to 2.22); mean SBP dropped 2.89 mm Hg (95% CI -4.49 to -1.28; p=0.0005) from 132.7 (95% CI 130.8 to 134.6) to 129.7 mm Hg (95% CI 127.9 to 131.5). Non-switchers had smaller improvements in adherence and clinical outcomes. CONCLUSION: Implementing an ASCVD secondary prevention FDC improved adherence and CVD risk factors in MSF clinics in Lebanon, with potential for wider implementation by humanitarian actors and host health systems.

The effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis: Results from the global SECURE-AD registry.

BACKGROUND: Limited data are available on the effects of systemic immunomodulatory treatments on COVID-19 outcomes in patients with atopic dermatitis (AD). OBJECTIVE: To investigate COVID-19 outcomes in patients with AD treated with or without systemic immunomodulatory treatments, using a global registry platform. METHODS: Clinicians were encouraged to report cases of COVID-19 in their patients with AD in the Surveillance Epidemiology of Coronavirus Under Research Exclusion for Atopic Dermatitis (SECURE-AD) registry. Data entered from 1 April 2020 to 31 October 2021 were analysed using multivariable logistic regression. The primary outcome was hospitalization from COVID-19, according to AD treatment groups. RESULTS: 442 AD patients (mean age 35.9 years, 51.8% male) from 27 countries with strongly suspected or confirmed COVID-19 were included in analyses. 428 (96.8%) patients were treated with a single systemic therapy (n = 297 [67.2%]) or topical therapy only (n = 131 [29.6%]). Most patients treated with systemic therapies received dupilumab (n = 216). Fourteen patients (3.2%) received a combination of systemic therapies. Twenty-six patients (5.9%) were hospitalized. No deaths were reported. Patients treated with topical treatments had significantly higher odds of hospitalization, compared with those treated with dupilumab monotherapy (odds ratio (OR) 4.65 [95%CI 1.71-14.78]), including after adjustment for confounding variables (adjusted OR (aOR) 4.99 [95%CI 1.4-20.84]). Combination systemic therapy which did not include systemic corticosteroids was associated with increased odds of hospitalization, compared with single agent non-steroidal immunosuppressive systemic treatment (OR 8.09 [95%CI 0.4-59.96], aOR 37.57 [95%CI 1.05-871.11]). Hospitalization was most likely in patients treated with combination systemic therapy which included systemic corticosteroids (OR 40.43 [95%CI 8.16-207.49], aOR 45.75 [95%CI 4.54-616.22]). CONCLUSIONS: Overall, the risk of COVID-19 complications appears low in patients with AD, even when treated with systemic immunomodulatory agents. Dupilumab monotherapy was associated with lower hospitalization than other therapies. Combination systemic treatment, particularly combinations including systemic corticosteroids, was associated with the highest risk of severe COVID-19.

Comparison of real-world treatment outcomes of systemic immunomodulating therapy in atopic dermatitis patients with dark and light skin types.

Background: Few data exist on differences in treatment effectiveness and safety in atopic dermatitis patients of different skin types. Objective: To investigate treatment outcomes of dupilumab, methotrexate, and ciclosporin, and morphological phenotypes in atopic dermatitis patients, stratified by Fitzpatrick skin type. Methods: In an observational prospective cohort study, pooling data from the Dutch TREAT (TREatment of ATopic eczema) NL (treatregister.nl) and UK-Irish A-STAR (Atopic eczema Systemic TherApy Register; astar-register.org) registries, data on morphological phenotypes and treatment outcomes were investigated. Results: A total of 235 patients were included (light skin types [LST]: Fitzpatrick skin type 1-3, n = 156 [Ethnicity, White: 94.2%]; dark skin types [DST]: skin type 4-6, n = 68 [Black African/Afro-Caribbean: 25%, South-Asian: 26.5%, and Hispanics: 0%]). DST were younger (19.5 vs 29.0 years; P < .001), more often had follicular eczema (22.1% vs 2.6%; P < .001), higher baseline Eczema Area and Severity Index (EASI) scores (20.1 vs 14.9; P = .009), less allergic contact dermatitis (30.9% vs 47.4%; P = .03), and less previous phototherapy use (39.7% vs 59.0%; P = .008). When comparing DST and LST corrected for covariates including baseline EASI, DST showed greater mean EASI reduction between baseline and 6 months with only dupilumab (16.7 vs 9.7; adjusted P = .032). No differences were found for adverse events for any treatments (P > .05). Limitations: Unblinded, non-randomized. Conclusion: Atopic dermatitis differs in several characteristics between LST and DST. Skin type may influence treatment effectiveness of dupilumab.

Novel multimorbidity clusters in people with eczema and asthma: a population-based cluster analysis.

Eczema and asthma are allergic diseases and two of the commonest chronic conditions in high-income countries. Their co-existence with other allergic conditions is common, but little research exists on wider multimorbidity with these conditions. We set out to identify and compare clusters of multimorbidity in people with eczema or asthma and people without. Using routinely-collected primary care data from the U.K. Clinical Research Practice Datalink GOLD, we identified adults ever having eczema (or asthma), and comparison groups never having eczema (or asthma). We derived clusters of multimorbidity from hierarchical cluster analysis of Jaccard distances between pairs of diagnostic categories estimated from mixed-effects logistic regressions. We analysed 434,422 individuals with eczema (58% female, median age 47 years) and 1,333,281 individuals without (55% female, 47 years), and 517,712 individuals with asthma (53% female, 44 years) and 1,601,210 individuals without (53% female, 45 years). Age at first morbidity, sex and having eczema/asthma affected the scope of multimorbidity, with women, older age and eczema/asthma being associated with larger morbidity clusters. Injuries, digestive, nervous system and mental health disorders were more commonly seen in eczema and asthma than control clusters. People with eczema and asthma of all ages and both sexes may experience greater multimorbidity than people without eczema and asthma, including conditions not previously recognised as contributing to their disease burden. This work highlights areas where there is a critical need for research addressing the burden and drivers of multimorbidity in order to inform strategies to reduce poor health outcomes.

Association between practice coding of chronic kidney disease (CKD) in primary care and subsequent hospitalisations and death: a cohort analysis using national audit data.

OBJECTIVE: To examine the association between practice percentage coding of chronic kidney disease (CKD) in primary care with risk of subsequent hospitalisations and death. DESIGN: Retrospective cohort study using linked electronic healthcare records. SETTING: 637 general practitioner (GP) practices in England. PARTICIPANTS: 167 208 patients with CKD stages 3-5 identified by 2 measures of estimated glomerular filtration rate <60 mL/min/1.73 m2, separated by at least 90 days, excluding those with coded initiation of renal replacement therapy. MAIN OUTCOME MEASURES: Hospitalisations with cardiovascular (CV) events, heart failure (HF), acute kidney injury (AKI) and all-cause mortality RESULTS: Participants were followed for (median) 3.8 years for hospital outcomes and 4.3 years for deaths. Rates of hospitalisations with CV events and HF were lower in practices with higher percentage CKD coding. Trends of a small reduction in AKI but no substantial change in rate of deaths were also observed as CKD coding increased. Compared with patients in the median performing practice (74% coded), patients in practices coding 55% of CKD cases had a higher rate of CV hospitalisations (HR 1.061 (95% CI 1.015 to 1.109)) and HF hospitalisations (HR 1.097 (95% CI 1.013 to 1.187)) and patients in practices coding 88% of CKD cases had a reduced rate of CV hospitalisations (HR 0.957 (95% CI 0.920 to 0.996)) and HF hospitalisations (HR 0.918 (95% CI 0.855 to 0.985)). We estimate that 9.0% of CV hospitalisations and 16.0% of HF hospitalisations could be prevented by improving practice CKD coding from 55% to 88%. Prescription of antihypertensives was the most dominant predictor of a reduction in hospitalisation rates for patients with CKD, followed by albuminuria testing and use of statins. CONCLUSIONS: Higher levels of CKD coding by GP practices were associated with lower rates of CV and HF events, which may be driven by increased use of antihypertensives and regular albuminuria testing, although residual confounding cannot be ruled out.

Deep-branching ANME-1c archaea grow at the upper temperature limit of anaerobic oxidation of methane.

In seafloor sediments, the anaerobic oxidation of methane (AOM) consumes most of the methane formed in anoxic layers, preventing this greenhouse gas from reaching the water column and finally the atmosphere. AOM is performed by syntrophic consortia of specific anaerobic methane-oxidizing archaea (ANME) and sulfate-reducing bacteria (SRB). Cultures with diverse AOM partners exist at temperatures between 12°C and 60°C. Here, from hydrothermally heated sediments of the Guaymas Basin, we cultured deep-branching ANME-1c that grow in syntrophic consortia with Thermodesulfobacteria at 70°C. Like all ANME, ANME-1c oxidize methane using the methanogenesis pathway in reverse. As an uncommon feature, ANME-1c encode a nickel-iron hydrogenase. This hydrogenase has low expression during AOM and the partner Thermodesulfobacteria lack hydrogen-consuming hydrogenases. Therefore, it is unlikely that the partners exchange hydrogen during AOM. ANME-1c also does not consume hydrogen for methane formation, disputing a recent hypothesis on facultative methanogenesis. We hypothesize that the ANME-1c hydrogenase might have been present in the common ancestor of ANME-1 but lost its central metabolic function in ANME-1c archaea. For potential direct interspecies electron transfer (DIET), both partners encode and express genes coding for extracellular appendages and multiheme cytochromes. Thermodesulfobacteria encode and express an extracellular pentaheme cytochrome with high similarity to cytochromes of other syntrophic sulfate-reducing partner bacteria. ANME-1c might associate specifically to Thermodesulfobacteria, but their co-occurrence is so far only documented for heated sediments of the Gulf of California. However, in the deep seafloor, sulfate-methane interphases appear at temperatures up to 80°C, suggesting these as potential habitats for the partnership of ANME-1c and Thermodesulfobacteria.

A systematic review of statistical methodology used to evaluate progression of chronic kidney disease using electronic healthcare records.

BACKGROUND: Electronic healthcare records (EHRs) are a useful resource to study chronic kidney disease (CKD) progression prior to starting dialysis, but pose methodological challenges as kidney function tests are not done on everybody, nor are tests evenly spaced. We sought to review previous research of CKD progression using renal function tests in EHRs, investigating methodology used and investigators' recognition of data quality issues. METHODS AND FINDINGS: We searched for studies investigating CKD progression using EHRs in 4 databases (Medline, Embase, Global Health and Web of Science) available as of August 2021. Of 80 articles eligible for review, 59 (74%) were published in the last 5.5 years, mostly using EHRs from the UK, USA and East Asian countries. 33 articles (41%) studied rates of change in eGFR, 23 (29%) studied changes in eGFR from baseline and 15 (19%) studied progression to binary eGFR thresholds. Sample completeness data was available in 44 studies (55%) with analysis populations including less than 75% of the target population in 26 studies (33%). Losses to follow-up went unreported in 62 studies (78%) and 11 studies (14%) defined their cohort based on complete data during follow up. Methods capable of handling data quality issues and other methodological challenges were used in a minority of studies. CONCLUSIONS: Studies based on renal function tests in EHRs may have overstated reliability of findings in the presence of informative missingness. Future renal research requires more explicit statements of data completeness and consideration of i) selection bias and representativeness of sample to the intended target population, ii) ascertainment bias where follow-up depends on risk, and iii) the impact of competing mortality. We recommend that renal progression studies should use statistical methods that take into account variability in renal function, informative censoring and population heterogeneity as appropriate to the study question.