Detection of Helicobacter pylori infection in children using rapid urease and histologic methods of diagnosis.

Objective: The study aimed to detect the presence of Helicobacter pylori infection in children using two investigative methods: the rapid urease test and histological methods. It also examined the relationship between socioeconomic status and Helicobacter pylori infection. Design: This was a cross-sectional study conducted in the paediatric theatre at Korle Bu Teaching Hospital in Accra, Ghana. Participants: Children who were scheduled for upper gastrointestinal endoscopy were recruited into the study. Main outcome measures: The presence of Helicobacter pylori in gastric biopsies was measured using a rapid urease test and histology. Results: Seventy-three children aged 2 years to 16 years were seen during the period. Both tests were positive at the same time in 36 (49.3%) out of the 73 children (p<0.0001). The positivity rates for the rapid urease test and histology were 57.5% and 53.4 %, respectively. Significant predictors of the histology presence of H. pylori were a large household size of at least 6 members (AOR: 4.03; p<0.013) and the presence of pets at home (AOR: 3.23; p<0.044). Conclusions: Substantial agreement was found between the rapid urease test and histology examination of gastric biopsies for the presence of H. pylori. Children from large households and those with pets at home appear to have increased odds of having H. pylori infection of the gastric mucosa. Funding: None declared.

Assessing Factors that Influence Pharmacy Student Burnout and Identifying Recommendations to Support Student Well-being.

OBJECTIVE: Literature indicates concerning rates of burnout and declining well-being among students. While well-being initiatives have increased, a gap exists in identifying factors that impact pharmacy student well-being. The purpose of this study was to explore factors students perceive influence their burnout and identify recommendations to improve student well-being. METHODS: First- (PY1), second- (PY2), and third-year (PY3) pharmacy students enrolled in the didactic curriculum were invited to participate in this exploratory study. Focus groups were organized by program year to explore experiences that may be unique to each group. A semi-structured interview format was used to discuss factors contributing to student burnout and fulfillment as well as solicit recommendations for strategies to improve student well-being. Inductive coding was used to identify themes. RESULTS: Twelve students participated in six sessions: one PY1 interview (n=1 student), one PY2 focus group (n=2 students) and one PY2 interview (n=1 student), and three PY3 focus groups (n=2-3 students/focus group). Common factors identified as contributing towards burnout included having too little time, overwhelming academic workload, competitive culture, and non-coursework commitments. Factors contributing to student fulfillment included life outside of pharmacy school, well-being resources, and activities aligned with future goals. Participants recommended several strategies to improve student well-being, including curricular changes (eg, course schedule layout, pass/fail grading), culture strategies, and well-being resources. CONCLUSION: Findings underscore the impact of workload and competitive culture on student burnout. This study fills a literature gap regarding factors influencing student burnout, and informs strategies for fostering student well-being in pharmacy education.

Management, Utilization, and Outcomes of Preterm Labor in an Integrated Health Care System.

OBJECTIVE: Fetal fibronectin (fFN) testing and transvaginal ultrasound (TVUS) are diagnostic tools used to predict impending spontaneous preterm birth (sPTB) among women presenting with preterm labor (PTL). We evaluated the association between fFN testing or TVUS cervical length (CL) measurement in predicting sPTB, respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, and sPTB-related costs. STUDY DESIGN: We conducted a retrospective cohort study using data from the Kaiser Permanente Southern California electronic health system (January 1, 2009-December 31, 2020) using diagnostic and procedure codes, along with a natural language processing algorithm to identify pregnancies with PTL evaluations. PTL evaluation was defined as having fFN and/or TVUS assessment. Outcomes were ascertained using diagnostic, procedural, and diagnosis-related group codes. Multivariable logistic regression assessed the association between fFN and/or TVUS results and perinatal outcomes. RESULTS: Compared with those without PTL evaluations, those with positive fFN tests had higher adjusted odds ratio (adj.OR) for sPTB (2.95, 95% confidence interval [CI]: 2.64, 3.29), RDS (2.34, 95% CI: 2.03, 2.69), and NICU admission (2.24, 95% CI: 2.01, 2.50). In contrast, those who tested negative had lower odds for sPTB (adj.OR: 0.75, 95% CI: 0.70, 0.79), RDS (adj.OR: 0.67, 95% CI: 0.61, 0.73), and NICU admission (adj.OR: 0.74, 95% CI: 0.70, 0.79). Among those with positive fFN results, the odds of sPTB was inversely associated with CL. Health care costs for mothers and neonates were lowest for those with fFN testing only. CONCLUSION: This study demonstrates that positive fFN results were associated with an increased odds of sPTB, RDS, and NICU admission and the association with sPTB was inversely proportional to CL. Additionally, negative fFN results were associated with decreased odds of sPTB, RDS, and NICU admissions. fFN testing may predict these and other sPTB-related adverse outcomes hence its utility should be explored further. Moreover, fFN testing has some cost savings over TVUS. KEY POINTS: · Patients with positive fFN tests had higher odds of sPTB, RDS, and NICU admission.. · Inverse relationship between sPTB and CL among those with positive fFN tests was observed.. · Health care costs for mothers and neonates were lowest for those with fFN testing only..

Association between SARS-CoV-2 Infection and Adverse Perinatal Outcomes by Race/Ethnicity in a Large Integrated Health Care System.

OBJECTIVE: Recent studies have reported associations between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection during pregnancy and adverse perinatal outcomes but the extent to which these associations vary by race/ethnicity remains uncertain. Therefore, we examined how the association between prenatal SARS-CoV-2 infection and adverse perinatal outcomes may be modified by race/ethnicity. STUDY DESIGN: A retrospective cohort study was performed using data on 67,986 pregnant women extracted from the Kaiser Permanente Southern California electronic health records between April 6, 2020, and December 31, 2021. Upon admission to labor and delivery, all women were routinely tested for coronavirus disease 2019 (COVID-19) using real-time reverse-transcriptase polymerase chain reaction test. Adjusted odds ratios (aORs) were used to estimate associations. RESULTS: During the study period, COVID-19 was diagnosed in 4,960 (7%) of singleton pregnancies, with the highest rates observed among Hispanics (9.4%) and non-Hispanic Blacks (6.2%). Compared with non-Hispanic Whites, Hispanics (aOR: 1.12, 95% CI: 1.03, 1.21) with SARS-CoV-2 infection had the highest odds of a pregnancy associated with nonreassuring fetal heart rate tracing. Neonates of all races/ethnicities, except for non-Hispanic Blacks, showed significantly increased odds of SARS-CoV-2 infection, with the highest risk observed among Asians/Pacific Islanders (aOR: 10.88, 95% CI: 1.33, 89.04). Non-Hispanic White mothers who tested positive were admitted to intensive care unit (ICU) at a higher rate at delivery and within 7 days of delivery (aOR: 34.77, 95% CI: 11.3, 107.04; aOR: 26.48, 95% CI: 9.55, 73.46, respectively). Hispanics were also at a significantly higher odds of admission to ICU (aOR: 4.62, 95% CI: 2.69, 7.94; aOR: 4.42, 95% CI: 2.58, 7.56, respectively). Non-Hispanic Black, Hispanic, and Asian/Pacific Islander mothers who tested positive for SARS-CoV-2 prenatally, were at increased risk for preeclampsia/eclampsia, and preterm birth as compared to non-Hispanic White mothers. CONCLUSION: The findings highlight racial/ethnic disparities in the association between SARS-CoV-2 infection and adverse perinatal outcomes. The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders. We also observed a remarkably high risk of ICU admission for non-Hispanic White mothers infected with SARS-CoV-2. KEY POINTS: · Race/ethnicity influences perinatal outcomes in pregnancies impacted by SARS-CoV-2.. · The risk of neonatal SARS-CoV-2 infection was highest for Asian/Pacific Islanders.. · White mothers had a notably high risk of ICU admission at delivery following SARS-CoV-2 infection..

Drug use and COVID-19 testing, vaccination, and infection among underserved, minority communities in Miami, Florida.

The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately impacted people who use drugs (PWUD). This study explored relationships between drug use, COVID-19 testing, vaccination, and infection. This cross-sectional study was conducted in Miami, Florida between March 2021 and October 2022 as part of the National Institutes of Health (NIH) Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) initiative and the Miami Adult Studies on HIV (MASH) cohort. Users of cannabis, cocaine/crack, heroin/fentanyl, methamphetamines, hallucinogens, and/or prescription drug misuse in the previous 12 months were considered PWUD. Sociodemographic data, COVID-19 testing history, and vaccination-related beliefs were self-reported. Vaccinations were confirmed with medical records and positivity was determined with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Statistical analyses included chi-square tests and logistic regression. Of 1,780 participants, median age was 57 years, 50.7% were male, 50.2% Non-Hispanic Black, and 66.0% reported an annual income less than $15,000. Nearly 28.0% used drugs. PWUD were less likely than non-users to self-report ever testing positive for SARS-CoV-2 (14.7% vs. 21.0%, p = 0.006). However, 2.6% of participants tested positive for SARS-CoV-2, with no significant differences between PWUD and non-users (3.7% vs. 2.2%, p = 0.076). PWUD were more likely than non-users to experience difficulties accessing testing (10.2% vs. 7.1%, p = 0.033), vaccine hesitancy (58.9% vs. 43.4%, p = 0.002) and had lower odds of receiving any dose of a COVID-19 vaccine compared to non-users (aOR, 0.63; 95% CI, 0.49-0.81; p<0.001). PWUD presented with greater difficulties accessing COVID-19 testing, greater vaccine hesitancy, and lower odds of vaccination. Testing and immunization plans that are tailored to the needs of PWUD and consider access, trust-building campaigns, and education may be needed.

Prostate Tissue Microbiome in Patients with Prostate Cancer: A Systematic Review.

Some researchers have speculated that the prostatic microbiome is involved in the development of prostate cancer (PCa) but there is no consensus on certain microbiota in the prostatic tissue of PCa vs. healthy controls. This systematic review aims to investigate and compare the microbiome of PCa and healthy tissue to determine the microbial association with the pathogenesis of PCa. We searched MEDLINE, Embase, and Scopus databases. Articles were screened by two independent and blinded reviewers. Literature that compared the prostatic tissue microbiome of patients with PCa with benign controls was included. We found that PCa may be associated with increased Propionibacterium acnes, the herpesviridae and papillomaviridae families, and Mycoplasma genitalium, but definitive conclusions cannot be drawn from the existing data. Challenges include the difficulty of obtaining uncontaminated tissue samples and securing tissue from healthy controls. As a result, methods are varied with many studies using cancerous and "healthy" tissue from the same prostate. The organisms chosen for each study were also highly variable, making it difficult to compare studies. These issues have led to lower confidence in our results. Overall, further work is warranted to better understand the implications of the prostatic microbiome in the pathogenesis of PCa.

Rising Trends of Childhood Attention-Deficit/Hyperactivity Disorder in a Large Integrated Healthcare Delivery System in Southern California, 2010-2021.

OBJECTIVE: To evaluate trends of attention-deficit/hyperactivity disorder (ADHD) diagnosis rates among children aged 5-17 years over the past decade (2010-2021) and to investigate whether there have been differences in temporal changes based on race and ethnicity, sex, or income. STUDY DESIGN: Childhood ADHD diagnosis was ascertained from electronic health records using International Classification of Diseases ninth revision (314.xx) and International Classification of Diseases tenth revision (F90.x) codes. Data were stratified by child's sex, race and ethnicity, and household income, and rates of ADHD were estimated before and after adjustment for potential confounders. RESULTS: The overall ADHD diagnosis rates increased from 3.5% in 2010 to 4.0% in 2021. ADHD diagnosis was most prevalent among White children (6.1%), then Black (4.6%), Other/multiple (3.7%), Hispanic (3.1%), and Asian/Pacific Islander (PI) (1.7%). ADHD was also highly prevalent among boys (73.3%) or family income≥$70,000 (50.0%). ADHD diagnosis increased among Black (4.2% to 5.1%), Hispanic (2.8% to 3.6%), and Asian/PI children (1.5% to 2.0%) but remained stable for White (6.2% to 6.1%) and Other/multiple race/ethnic children (3.7% to 3.7%). Increases in the prevalence among girls were also observed. CONCLUSION: The prevalence of ADHD in children has risen with the largest increases observed for Black, Hispanic, and Asian/PI children. Rates among less affluent families and girls have also been increasing, narrowing the gaps in diagnosis rates previously observed. These increases may reflect improvements in screening and provision of care among demographics where ADHD has been historically underdiagnosed.

Dysregulation of Glucocorticoid Receptor Homeostasis and Glucocorticoid-Associated Genes in Umbilical Cord Endothelial Cells of Diet-Induced Obese Pregnant Sheep.

Maternal obesity (MO) is associated with offspring cardiometabolic diseases that are hypothesized to be partly mediated by glucocorticoids. Therefore, we aimed to study fetal endothelial glucocorticoid sensitivity in an ovine model of MO. Rambouillet/Columbia ewes were fed either 100% (control) or 150% (MO) National Research Council recommendations from 60 d before mating until near-term (135 days gestation). Sheep umbilical vein and artery endothelial cells (ShUVECs and ShUAECs) were used to study glucocorticoid receptor (GR) expression and function in vitro. Dexamethasone dose-response studies of gene expression, activation of a glucocorticoid response element (GRE)-dependent luciferase reporter vector, and cytosolic/nuclear GR translocation were used to assess GR homeostasis. MO significantly increased basal GR protein levels in both ShUVECs and ShUAECs. Increased GR protein levels did not result in increased dexamethasone sensitivity in the regulation of key endothelial gene expression such as endothelial nitric oxide synthase, plasminogen activator inhibitor 1, vascular endothelial growth factor, or intercellular adhesion molecule 1. In ShUVECs, MO increased GRE-dependent transactivation and FKBP prolyl isomerase 5 (FKBP5) expression. ShUAECs showed generalized glucocorticoid resistance in both dietary groups. Finally, we found that ShUVECs were less sensitive to dexamethasone-induced activation of GR than human umbilical vein endothelial cells (HUVECs). These findings suggest that MO-mediated effects in the offspring endothelium could be further mediated by dysregulation of GR homeostasis in humans as compared with sheep.

District health management and stillbirth recording and reporting: a qualitative study in the Ashanti Region of Ghana.

BACKGROUND: Despite global efforts to reduce maternal and neonatal mortality, stillbirths remain a significant public health challenge in many low- and middle-income countries. District health systems, largely seen as the backbone of health systems, are pivotal in addressing the data gaps reported for stillbirths. Available, accurate and complete data is essential for District Health Management Teams (DHMTs) to understand the burden of stillbirths, evaluate interventions and tailor health facility support to address the complex challenges that contribute to stillbirths. This study aims to understand stillbirth recording and reporting in the Ashanti Region of Ghana from the perspective of DHMTs. METHODS: The study was conducted in the Ashanti Region of Ghana. 15 members of the regional and district health directorates (RHD/DHD) participated in semi-structured interviews. Sampling was purposive, focusing on RHD/DHD members who interact with maternity services or stillbirth data. Thematic analyses were informed by an a priori framework, including theme 1) experiences, perceptions and attitudes; theme 2) stillbirth data use; and theme 3) leadership and support mechanisms, for stillbirth recording and reporting. RESULTS: Under theme 1, stillbirth definitions varied among respondents, with 20 and 28 weeks commonly used. Fresh and macerated skin appearance was used to classify timing with limited knowledge of antepartum and intrapartum stillbirths. For theme 2, data quality checks, audits, and the district health information management system (DHIMS-2) data entry and review are functions played by the DHD. Midwives were blamed for data quality issues on omissions and misclassifications. Manual entry of data, data transfer from the facility to the DHD, limited knowledge of stillbirth terminology and periodic closure of the DHIMS-2 were seen to proliferate gaps in stillbirth recording and reporting. Under theme 3, perinatal audits were acknowledged as an enabler for stillbirth recording and reporting by the DHD, though audits are mandated for only late-gestational stillbirths (> 28 weeks). Engagement of other sectors, e.g., civil/vital registration and private health facilities, was seen as key in understanding the true population-level burden of stillbirths. CONCLUSION: Effective district health management ensures that every stillbirth is accurately recorded, reported, and acted upon to drive improvements. A large need exists for capacity building on stillbirth definitions and data use. Recommendations are made, for example, terminology standardization and private sector engagement, aimed at reducing stillbirth rates in high-mortality settings such as Ghana.

People's perception of changes in their abortion attitudes over the life course: A mixed methods approach.

Research examining the extent that people's attitudes toward abortion vary across the life course is mixed. Some studies do not show a strong relationship between abortion attitudes and life stage, while others do find strong associations in both directions-older age associated with both more and less favorable attitudes toward legal abortion. Taken together, these findings suggest that individual attitudes toward abortion are static for some but malleable for others. Little is known about the prevalence, reasons, and directionality of attitude changes. This explanatory sequential mixed methods study investigates people's perceptions of whether, how, why, and for whom their abortion attitudes may have changed over their life course. We qualitatively investigated the reasons (e.g., experiences, life events) that triggered changes in respondents' abortion attitudes and quantitatively explored the sociodemographic factors associated with the perceived direction of those changes. The quantitative data come from a 2020 online survey completed by 1501 English and Spanish-speaking adults in the US. Qualitative data were collected from a subsample (n = 24) of the survey respondents who indicated interest in a follow-up in-depth interview. Our findings indicate that access to information and knowledge played an important role in changing abortion attitudes across a spectrum of support or opposition. For those who indicated becoming more opposed to abortion over time, experiencing parenthood was an important trigger for change and family/religious upbringing were key to shaping attitudes. For those who became more supportive of abortion over time, empathy for women was an important trigger for change and disagreeing with or distancing oneself from family/religious upbringing were key to shaping their attitudes. If attitudinal change occurs, becoming more supportive of abortion over the life-course is more common than becoming more opposed, however there are some nuances across age and gender. Understanding the different factors that influence attitudinal change regarding abortion has important implications for public opinion research and possible ramifications for abortion legality.

Food as medicine: a quasi-randomized control trial of two healthy food interventions for chronic disease management among ambulatory patients at an urban academic center.

BACKGROUND: Globally, poor nutrition is a driver of many chronic diseases and is responsible for more deaths than any other risk factor. Accordingly, there is growing interest in the direct provision of healthy foods to patients to tackle diet-linked chronic diseases and mortality. AIM: To assess the effect of two healthy food interventions in conjunction with nutrition counseling and education on select chronic disease markers, food insecurity, diet quality, depression, and on self-efficacy for healthy eating, healthy weight, and chronic disease management. METHODS: This parallel-arm quasi-randomized control trial will be conducted between January 2022 and December 2023. Seventy adult patients recruited from a single academic medical center will be randomly assigned to receive either: i) daily ready-made frozen healthy meals or ii) a weekly produce box and recipes for 15 weeks. Participants will, additionally, take part in one individual nutrition therapy session and watch videos on healthy eating, weight loss, type 2 diabetes, and hypertension. Data on weight, height, glycated hemoglobin, blood pressure, and diabetes and blood pressure medications will be collected in-person at the baseline visit and at 16 weeks from baseline and via medical chart review at six months and 12 months from enrollment. The primary outcome of the study is weight loss at 16 weeks from baseline. Pre- and post-intervention survey data will be analyzed for changes in food insecurity, diet quality, depression, as well as self-efficacy for health eating, healthy weight, and chronic disease management. Through retrospective chart review, patients who received standard of care will be matched to intervention group participants as controls based on body mass index, type 2 diabetes, and/or hypertension. FINDINGS: By elucidating the healthy food intervention with better health outcomes, this study aims to offer evidence that can guide providers in their recommendations for healthy eating options to patients.

SIRT1 Prevents R-Loops during Chronological Aging by Modulating DNA Replication at rDNA Loci.

In metazoans, the largest sirtuin, SIRT1, is a nuclear protein implicated in epigenetic modifications, circadian signaling, DNA recombination, replication, and repair. Our previous studies have demonstrated that SIRT1 binds replication origins and inhibits replication initiation from a group of potential initiation sites (dormant origins). We studied the effects of aging and SIRT1 activity on replication origin usage and the incidence of transcription-replication collisions (creating R-loop structures) in adult human cells obtained at different time points during chronological aging and in cancer cells. In primary, untransformed cells, SIRT1 activity declined and the prevalence of R-loops rose with chronological aging. Both the reduction in SIRT1 activity and the increased abundance of R-loops were also observed during the passage of primary cells in culture. All cells, regardless of donor age or transformation status, reacted to the short-term, acute chemical inhibition of SIRT1 with the activation of excessive replication initiation events coincident with an increased prevalence of R-loops. However, cancer cells activated dormant replication origins, genome-wide, during long-term proliferation with mutated or depleted SIRT1, whereas, in primary cells, the aging-associated SIRT1-mediated activation of dormant origins was restricted to rDNA loci. These observations suggest that chronological aging and the associated decline in SIRT1 activity relax the regulatory networks that protect cells against excess replication and that the mechanisms protecting from replication-transcription collisions at the rDNA loci manifest as differentially enhanced sensitivities to SIRT1 decline and chronological aging.

Knowledge, attitudes, and practices of caregivers on childhood immunization in Okaikoi sub-metro of Accra, Ghana.

Background: Immunization remains one of the most cost-effective health interventions. However, there are still issues of vaccine hesitancy especially in caregivers who are required to protect their children from vaccine-preventable diseases. This thwarts the overall vaccine coverage in disease-endemic areas such as sub-Saharan Africa. Therefore, to determine the factors that promote vaccine hesitancy in caregivers, this study sought to assess the knowledge, attitude, and practices of caregivers on childhood immunization in Okaikoi, a sub-metro of Accra in Ghana. Methods: A cross-sectional study on childhood immunization was conducted to determine the knowledge, attitudes, and practices of caregivers. A total of 120 caregivers with infants aged 12 months to 23 months were interviewed with a structured questionnaire containing open-ended and closed-ended queries. Results: From the community, infants whose caregivers had adhered completely to immunization constituted 53.3% while the rest were partially immunized. The two main deterrents to complete immunization were time constraints (25.8%) and forgetfulness (17.5%). It was observed that vaccination uptake and maternal level of education, as well as vaccination adverse reaction, did not impact the completion of the EPI program by these caregivers. Unfortunately, it was noted that caregivers with higher education levels were unable to complete their vaccination schedules due to their busy work schedules. Nonetheless, the main deterrent to adhering to complete childhood immunization was poor maternal knowledge (58%). Conclusion: The study revealed that, the caregivers in the community had poor knowledge on vaccination and its benefits, and therefore, with no strict adherence to vaccination schedules. This promoted the incomplete immunization of children in the community by their caregivers. Also, since the main source of information with regard to immunization in the sub-metro was through the antenatal and postnatal child welfare clinics and the media, we recommend that the health workers collaborate with media personnel to ensure that standardized information is disseminated.

Voltage-Gated Na+ Channels in Alzheimer's Disease: Physiological Roles and Therapeutic Potential.

Alzheimer's disease (AD) is the most common cause of dementia and is classically characterized by two major histopathological abnormalities: extracellular plaques composed of amyloid beta (Aß) and intracellular hyperphosphorylated tau. Due to the progressive nature of the disease, it is of the utmost importance to develop disease-modifying therapeutics that tackle AD pathology in its early stages. Attenuation of hippocampal hyperactivity, one of the earliest neuronal abnormalities observed in AD brains, has emerged as a promising strategy to ameliorate cognitive deficits and abate the spread of neurotoxic species. This aberrant hyperactivity has been attributed in part to the dysfunction of voltage-gated Na+ (Nav) channels, which are central mediators of neuronal excitability. Therefore, targeting Nav channels is a promising strategy for developing disease-modifying therapeutics that can correct aberrant neuronal phenotypes in early-stage AD. This review will explore the role of Nav channels in neuronal function, their connections to AD pathology, and their potential as therapeutic targets.

Adherence to therapy of ixekizumab and secukinumab in psoriatic arthritis patients using first- or second-line IL-17A inhibitor treatment: A Danish population-based cohort study.

OBJECTIVES: To assess the effectiveness and tolerability of first- and second-line interleukin (IL)-17A inhibitor treatment in patients with psoriatic arthritis (PsA) from 2014 to 2021, using data from the Danish Rheumatology Registry (DANBIO) by investigating adherence to therapy. METHOD: PsA patients recorded in DANBIO who received a first- or second-line IL-17A inhibitor treatment were included in this study. All patients included had previously received ≥1 TNFi treatment. Baseline characteristics were analyzed in subgroups: first-line IL-17A inhibitor treatment and second-line IL-17A inhibitor treatment. adherence to therapy of first- or second-line IL-17A inhibitor treatments were reported as Kaplan-Meier plots. RESULTS: 534 patients were included in the study; first-line switchers: 534 (secukinumab: 510, ixekizumab: 24), second-line switchers: 102 (secukinumab: 35, ixekizumab: 67). Baseline characteristics showed a similar Health Assessment questionnaire (HAQ) and Visual Analogue Scale (VAS) pain. VAS global, Disease Assessment Score-28CRP and previous number of bDMARD treatments are similar with a greater value for second-line switchers. First-line ixekizumab treated patients present a younger age, greater percentage of females, a lower disease duration and a lower CRP value. Concomitant MTX use was greater for the first-line secukinumab treated patients. First- and second-line switchers had a similar adherence to therapy. Second-line secukinumab and second-line ixekizumab switchers showed a similar adherence to treatment. CONCLUSION: PsA patients receiving first- or second-line IL-17A inhibitors showed homogeneous baseline characteristics and similar adherence to therapy. Treatment failure of the first IL-17A inhibitor treatment should not preclude a second-line IL-17A inhibitor treatment.

Drug Survival of Adalimumab, Secukinumab, and Ustekinumab in Psoriasis as Determined by Either Dose Escalation or Drug Discontinuation during the First 3 Years of Treatment - a Nationwide Cohort Study.

The real-world efficacy of biologics may be insufficiently assessed through common drug survival studies. The objective was thus to examine the real-world performance of biologics in the treatment of psoriasis using the composite endpoint of either discontinuation or off-label dose escalation. Using a prospective nationwide registry (DERMBIO, 2007-2019), we included patients with psoriasis treated with adalimumab, secukinumab, and/or ustekinumab, which have all been used as first-line therapy during the inclusion period. The primary endpoint was a composite of either off-label dose escalation or discontinuation of treatment, whereas the secondary outcomes were dose escalation and discontinuation, respectively. Kaplan-Meier curves were used for the presentation of unadjusted drug survival curves. Cox-regression models were used for risk assessment. In 4,313 treatment series (38.8% women, mean age 46.0 years, and 58.3% bio-naivety), we found that the risk of the composite endpoint was lower for secukinumab when compared with ustekinumab (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.59-0.76), but higher for adalimumab (HR 1.15, 95% CI 1.05-1.26). However, the risk of discontinuation was higher for secukinumab (HR 1.24, 95% CI 1.08-1.42) and adalimumab (HR 2.01, 95% CI 1.82-2.22). For bio-naive patients treated with secukinumab, the risk of discontinuation was comparable to that of ustekinumab (HR 0.95, 95% CI 0.61-1.49).

Diagnosis of Occult Infection Using Fracture-Related Infection Criteria at the Time of Nonunion Repair.

OBJECTIVES: To apply the recently developed fracture-related infection criteria to patients presenting for repair of fracture nonunion and determine the incidence and associated organisms of occult infection in these patients. DESIGN: Retrospective study. SETTING: Tertiary referral trauma center. PATIENTS AND PARTICIPANTS: Patients presenting with fracture nonunion after operative intervention. MAIN OUTCOME MEASUREMENTS: Demographic variables, injury characteristics, culture results, and physical examination and laboratory values at the time of presentation. RESULTS: A total of 270 nonunion patients were identified. Sixty-eight percent (n = 184) had no clinical or laboratory signs of infection at presentation before nonunion repair. After operative intervention, 7% of these clinically negative patients (n = 12/184) had positive intraoperative cultures indicating occult infection. The most common organisms causing occult infection were low-virulence coagulase-negative Staphylococcu s (83%) and Cutibacterium acnes (17%). Thirty-two percent of patients (n = 86/270) presented with clinical and/or laboratory signs of infection at presentation before nonunion repair, with 19% of these patients (n = 16/86) having negative cultures. The most common organisms in this group of patients with positive clinical signs and intraoperative cultures were methicillin-resistant Staphylococcus Aureus (21%) and gram-negative rods (29%). Patients with nonunion of the tibia were significantly more likely to have high-virulence organism culture results ( P < 0.001). CONCLUSIONS: Based on this analysis, occult infection occurs in 7% of patients presenting with nonunion and no clinical or laboratory signs of infection. We recommend that all patients should be carefully evaluated for infection with intraoperative cultures regardless of presentation. Organisms associated with occult infection at the time of nonunion repair were almost exclusively of low virulence ( CoNS and C. Acnes ) and were more likely to present in the upper extremity. Patients with nonunion of the tibia were more likely to have infection secondary to high-virulence organisms and demonstrate clinical or laboratory signs of infection at the time of presentation. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Exploring disease comorbidities and temporal disease progression of psoriasis: an observational, retrospective, multi-database, cohort study.

BACKGROUND: Comorbidities associated with psoriasis are well documented. However, few studies have explored the comorbidity trajectories that patients with psoriasis commonly experience over time. This study reports the 5-year comorbidity trajectories of patients with psoriasis. OBJECTIVES: To determine the long-term comorbidity trajectories of patients with psoriasis in Denmark. METHODS: This observational cohort study explored the Danish National Patient Registry (DNPR) between 1999 and 2013 to identify comorbidities diagnosed 5 years prior to or after a psoriasis diagnosis. Comorbidity occurrence in patients with psoriasis (psoriasis cohort) was compared with patients without psoriasis (the N group). Comparison groups, each the same size as the psoriasis cohort, were created by selecting random patients from the N group. If a comorbidity occurrence was higher in more than nine comparison groups than in the psoriasis cohort, it was not analysed and only comorbidities that occurred in ≥ 0·8% of the psoriasis cohort were analysed. The strength of association between a psoriasis diagnosis and a comorbidity diagnosis was measured using relative risk (RR). All psoriasis and comorbidity pairs that achieved RR > 1 (P < 0·001) (known as a Diagnosed Pair) were tested for directionality to identify the sequence of diagnoses using a binomial test. Diagnosed Pairs with a statistically significant direction (Bonferroni corrected P-value < 0·025) were then used to create comorbidity trajectory clusters 5 years before and after a psoriasis diagnosis. RESULTS: A total of 17 683 patients with psoriasis were compared with 10 000 comparison groups. A total of 121 comorbidities met the minimum criteria that ≥ 0·8% of the psoriasis cohort were diagnosed with the comorbidity within 5 years (before or after) of their psoriasis diagnosis. Thirty-eight of these comorbidities achieved RR > 1 (P < 0·001) with psoriasis, of which 19 achieved a significant direction from psoriasis to a comorbidity (including psoriasis to hypothyroidism), and four achieved a significant direction from a comorbidity diagnosis to a psoriasis diagnosis (including Crohn disease to psoriasis); four of five comorbidity trajectories with three sequential diagnoses achieved an RR > 1 (P < 0·001) and a significant direction from psoriasis to the first comorbidity to the second comorbidity (including psoriasis to hypertension to atrial fibrillation and flutter). CONCLUSIONS: Comorbidity trajectories may support clinicians in conducting disease risk analyses of patients with psoriasis and help plan optimal treatment to prevent future high-risk comorbidities.