The Problem of Pain in Rheumatology: Variations in Case Definitions Derived From Chronic Pain Phenotyping Algorithms Using Electronic Health Records.

OBJECTIVE: The aim of this study was to investigate and compare different case definitions for chronic pain to provide estimates of possible misclassification when researchers are limited by available electronic health record and administrative claims data, allowing for greater precision in case definitions. METHODS: We compared the prevalence of different case definitions for chronic pain (N = 3042) in patients with autoimmune rheumatic diseases. We estimated the prevalence of chronic pain based on 15 unique combinations of pain scores, diagnostic codes, analgesic medications, and pain interventions. RESULTS: Chronic pain prevalence was lowest in unimodal pain phenotyping algorithms: 15% using analgesic medications, 18% using pain scores, 21% using pain diagnostic codes, and 22% using pain interventions. In comparison, the prevalence using a well-validated phenotyping algorithm was 37%. The prevalence of chronic pain also increased with the increasing number (bimodal to quadrimodal) of phenotyping algorithms that comprised the multimodal phenotyping algorithms. The highest estimated chronic pain prevalence (47%) was the multimodal phenotyping algorithm that combined pain scores, diagnostic codes, analgesic medications, and pain interventions. However, this quadrimodal phenotyping algorithm yielded a 10% overestimation of chronic pain compared to the well-validated algorithm. CONCLUSION: This is the first empirical study to our knowledge that shows that established common modes of phenotyping chronic pain can lead to substantially varying estimates of the number of patients with chronic pain. These findings can be a reference for biases in case definitions for chronic pain and could be used to estimate the extent of possible misclassifications or corrections in using datasets that cannot include specific data elements.

The Problem of Pain in Lupus: Epidemiological Profiles of Patients Attending Multidisciplinary Pain Clinics.

INTRODUCTION: Patients with systemic lupus erythematosus (SLE) bear a significant burden of pain. We aimed to identify factors that distinguish patients with SLE referred to comprehensive pain clinics and those who are not. Characterizing this patient population will identify unmet needs in SLE management and inform efforts to improve pain care in rheumatology. METHODS: Among patients with SLE with ≥2 rheumatology clinic visits in a large hospital system from 1998 to 2023 (n = 1319), we examined factors that distinguished those who had at least one visit to multidisciplinary pain clinics (n = 77, 5.8%) from those who did not have any visits (n = 1242, 94.2%) with a focus on biopsychosocial and socioeconomic characteristics. We extracted demographic data and ICD-9/ICD-10 codes from the EHR. RESULTS: Patients with SLE attending the pain clinics exhibited characteristics including average older age (mean age ± SD: 54.1 ± 17.9 vs. 48.4 ± 19.9), a higher likelihood of relying on public health insurance (50.7% vs. 34.2%), and a greater representation of Black patients (9.1% vs. 4.4%) compared to SLE patients not seen in pain clinics. Nearly all patients seen at the pain clinics presented with at least one chronic overlapping pain condition (96.1% vs. 58.6%), demonstrated a higher likelihood of having a mental health diagnosis (76.7% vs. 42.4%), and exhibited a greater number of comorbidities (mean ± SD: 6.0 ± 3.0 vs. 2.9 ± 2.6) compared to those not attending the pain clinic. CONCLUSION: We found notable sociodemographic and clinical differences between these patient populations. Patients presenting with multiple comorbidities might benefit from further pain screening and referral to pain clinics to provide comprehensive care, and earlier referral could mitigate the development and progression of multimorbidities.

Internet analytics of an innovative digital educational resource of type 1 diabetes HelloType1 in local languages for people living with diabetes families and healthcare professionals in Southeast Asia.

BACKGROUND: There is minimal data of health outcomes for Type 1 Diabetes (T1D) in Southeast Asia (SEA) where government funding of insulin and blood glucose monitoring either do not exist or is limited. The full impact of Covid-19 pandemic on the national economies of SEA remain unknown. In the midst of the pandemic, in 2021, HelloType1 was developed by Action4Diabetes (A4D), a non-government organisation charity in collaboration with Southeast Asia local healthcare professionals as an innovative digital educational resource platform of T1D in local languages. HelloType1 was launched in Cambodia, Vietnam, Thailand and Malaysia in 2021 to 2022 with Memorandums of Understandings (MOUs) signed between A4D and each country. Internet data analytics were undertaken between the 1st of January 2022 to 31st of December 2022. AIMS: The aims of this study were to explore the usability and internet data analytics of the HelloType1 online educational platform within each country. METHODS: The data analytics were extracted Google analytics that tracks data from the website hellotype1.com and Facebook analytics associated with the website. RESULTS: There was a 147% increase in the number of HelloType1 users between the first 6 months versus the latter 6 months in 2022 and a 15% increase in the number of pages visited were noted. The majority of traffic source were coming from organic searches with a significant increase of 80% growth in 2022. CONCLUSIONS: The results of the analytics provide important insights on how an innovative diabetes digital educational resource in local languages may be optimally delivered in low-middle income countries with limited resources.

Factor structure of the Mini-Maternal Behavior Q-Sort and associations with infant attachment: Informing precision in research and intervention.

We examined the factor structure of parental sensitivity to infants as assessed by the Mini-Maternal Behavior Q-Sort (Mini-MBQS), a 25-item short-form of the original 90-item MBQS. We aimed to: (1) identify latent factors of the Mini-MBQS; and (2) validate each factor by testing associations with infant attachment classifications. Data on parent-infant dyads (n = 313; 222 mothers with 281 children, 29 fathers with 32 children) were drawn from a three-generation Australian cohort study. Exploratory Factor Analysis and Exploratory Structural Equation Modelling examined the structure of the Mini-MBQS. Two latent Mini-MBQS factors were identified, requiring 8 of 25 original items: (1) Attention and Responsiveness and (2) Contingency in Interactions. Infants with insecure attachment classifications had parents with lower sensitivity across both factors relative to infants classified secure. In particular, infants with resistant attachment classifications had parents with notably low Contingency in Interactions scores. Infants with disorganised attachment classifications had parents with the lowest relative sensitivity across both factors, and in these dyads Attention and Responsiveness scores were especially low. Results provide an empirically derived factor structure for the Mini-MBQS. Two subscales, each with significant infant attachment associations, may improve precision in clinical intervention and research translation.

Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries.

BACKGROUND: Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control. METHODS: In a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007-2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG). RESULTS: Among 86,931 patients with type 2 diabetes (mean±SD age: 56.6±11.6 years; age at diagnosis of diabetes: 49.8±10.5 years), the prevalence of FamH ranged from 39.1% to 85.3% in different areas with FamH affecting mother being most common (32.5%). The FamH group (n=51,705; 59.5%) was diagnosed 4.6 years earlier than the non-FamH group [mean (95% CI): 47.9 (47.8-48.0) vs. 52.5 (52.4-52.6), logrank p<0.001]. In the FamH group, patients with both parents affected had the earliest age at diagnosis [44.6 (44.5-44.8)], followed by affected single parent [47.7 (47.6-47.8)] and affected siblings only [51.5 (51.3-51.7), logrank p<0.001]. The FamH plus ≥2 healthy lifestyle group had similar age at diagnosis [48.2 (48.1-48.3)] as the non-FamH plus <2 healthy lifestyle group [50.1 (49.8-50.5)]. The FamH group with affected parents had higher odds of hyperglycemia, hypertension, and dyslipidemia than the FamH group with affected siblings, with the lowest odds in the non-FamH group. Self-management (healthy lifestyles plus SMBG) was associated with higher odds of attaining HbA1c<7%, blood pressure<130/80mmHg, and LDL-C<2.6 mmol/L especially in the FamH group (FamH×self-management, pinteraction=0.050-0.001). CONCLUSIONS: In Asia, FamH was common and associated with young age of diagnosis which might be delayed by healthy lifestyle while self management  was associated with better control of  cardiometabolic risk factors especially in those with FamH.

Impact of a mindfulness-based school curriculum on emotion processing in Vietnamese pre-adolescents: An event-related potentials study.

The neurocognitive mechanisms associated with mindfulness training in children are not well understood. This randomised controlled study with active and passive control groups examined the impact of an 18-week mindfulness curriculum delivered by schoolteachers on emotion processing in Vietnamese 7- to 11-year-olds. Event-related potential markers indexed emotion processing while children were completing emotional Go/No-Go tasks before and after mindfulness training, and at 6-month follow-up. In an oddball Go/No-Go task with Caucasian faces no changes in P3b and LPP components were detected, but in a Go/No-Go task with Caucasian and Japanese faces changes were observed in P3b latencies and LPP mean amplitudes. Specifically, the P3b in response to angry non-targets for Japanese faces peaked later in the mindfulness training group (TG) at 6-months follow-up in comparison to the non-intervention control group (NCG). The LPP mean amplitudes for averaged Caucasian and Japanese angry non-targets were also attenuated in the TG at 6-month follow-up. In contrast, no changes in the LPP mean amplitudes were observed for the NCG over time. Together, these findings may indicate that mindfulness training in pre-adolescents enhances emotional non-reactivity to negative distractors. A fluctuating pattern of LPP mean amplitude modulations for angry targets was observed in the active control group (ACG) receiving social-emotional learning (SEL) training. Overall, findings from this study suggest that mindfulness training in pre-adolescents enhances emotional non-reactivity to negative distractors and some of the effects are culturally sensitive.

Association of PSORS1C3, CARD14 and TLR4 genotypes and haplotypes with psoriasis susceptibility.

Psoriasis is a common chronic, immune-mediated inflammatory disease of the skin. PSORS1C3 is a non-protein coding gene, of which the RNA transcript is found in psoriatic patients. CARD14 is mainly expressed in epidermal keratinocytes. TLR4 is a transmembrane protein to recognize microbial antigens. Our study aimed to assess the relationship among PSORS1C3, CARD14 and TLR4 polymorphisms, inflammatory expression and psoriasis susceptibility. To the end, 71 patients with psoriasis and 46 healthy individuals with the well-characterized clinical profiles were enrolled. Gene polymorphisms were determined by Sanger DNA sequencing and secretion of cytokines by ELISA. As a result, genetic analysis of PSORS1C3 gene identified nine SNPs and three haplotype blocks. Sequencing of the CARD14 gene determined eight SNPs and one haplotype block. Sequencing of TLR4 gene identified nine SNPs, in which a SNP rs1018673641 was found to exert deleterious effect. The linkage disequilibrium analysis showed that seven variants in PSORS1C3 gene and three SNPs in CARD14 gene were in tightly linked. More importantly, a significant association between IL-6 level and rs1018673641 AT genotype in TLR4 gene was detected in psoriatic patients. In conclusion, the PSORS1C3, CARD14 and TLR4 polymorphisms and haplotypes may be correlated with risk of suffering psoriasis and the IL-6-mediated chronic inflammation in psoriasis could be partially regulated by the TLR4 functional variant.

Real-world data reveal unmet clinical needs in insulin treatment in Asian people with type 2 diabetes: the Joint Asia Diabetes Evaluation (JADE) Register.

AIMS: To explore the pattern of insulin use and glycaemic control in Asian people with type 2 diabetes, stratified by gender, young-onset diabetes (YOD; diagnosed before age 40 years), and diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 ). MATERIALS AND METHODS: We conducted a cross-sectional analysis of 97 852 patients from 11 Asian countries/regions (2007-2017) included in the prospective Joint Asia Diabetes Evaluation (JADE) Register. RESULTS: Among 18 998 insulin users (47% women, mean ± SD age 59.2 ± 11.7 years, diabetes duration 13.2 ± 8.3 years, glycated haemoglobin [HbA1c] 72 ± 21.4 mmol/mol [8.74 ± 1.95%], median total daily insulin dose [TDD] 0.27-0.82 units/kg), 25% and 29.5% had YOD and DKD, respectively. Premixed (44%) and basal-only (42%) insulin were the most common regimens. Despite being more commonly treated with these two regimens with higher insulin dosages, patients with YOD had worse HbA1c levels than their late-onset peers (73 ± 20.5 vs. 71 ± 21.2 mmol/mol [8.82 ± 1.87% vs. 8.66 ± 1.94%]; P < 0.001). Fewer women than men attained an HbA1c level < 53 mmol/mol (7%; 15.7% vs 17.1%; P = 0.018). Adjusting for age, diabetes duration, TDD, HbA1c, eGFR, and use of oral glucose-lowering drugs at baseline, the odds of self-reported hypoglycaemia were higher in women (vs. men: adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.05-1.28) and in patients with DKD treated with a premixed regimen (1.81 [95% CI 1.54-2.13] vs. 1.34 [95% CI 1.16-1.54] in non-DKD; Pinteraction < 0.001). Compared to basal-only regimens, premixed and basal-bolus regimens had similar HbA1c reductions but were independently associated with increased odds of hypoglycaemia (1.65 [95% CI 1.45-1.88] and 1.88 [95% CI 1.58-2.23], respectively). CONCLUSIONS: In this Asian population, there were varying patterns of insulin regimens with suboptimal glycaemic control, despite relatively high TDDs, which were influenced by gender, DKD, and YOD status.

Polymorphisms of ABCG2 and SLC22A12 Genes Associated with Gout Risk in Vietnamese Population.

Background and objective: Gout is a common form of inflammatory arthritis caused by the crystallization of uric acid. Previous studies have demonstrated that the genetic predisposition of gout varies in different ethnic populations. However the association study of genetic variants with gout remains unknown in the Vietnamese population. Our study aimed to assess the relationship between polymorphisms in ABCG2 and SLC22A12 and gout susceptibility in Vietnamese. Materials and methods: Genomic DNA was extracted from blood of a total of 170 patients with gout and 351 healthy controls. We genotyped single nucleotide polymorphisms (SNPs): rs72552713, rs12505410 of the ABCG2 gene and rs11231825, rs7932775 of the SLC22A12 gene using polymerase chain reaction⁻restriction fragment length polymorphism (PCR⁻RFLP) and then confirmed 10% of randomly selected subjects by Sanger sequencing. Results: Three SNPs (rs72552713 and rs12505410 and rs11231825) were in accordance with Hardy⁻Weinberg Equilibrium (HWE) (p > 0.05) while rs7932775 was not (p < 0.05). For rs72552713, CT genotype was significantly different between gout patient and control groups (p < 0.001) and the T allele was associated with an increased risk of gout (OR = 21.19; 95% CI: 3.00⁻918.96; p < 0.001). Serum uric acid and hyperuricemia differed significantly between CC and CT genotype groups (p = 0.004 and 0.008, respectively). For rs11231825, a protective effect against gout risk was identified in the presence of the C allele when compared with the T allele (OR = 0.712; 95% CI: 0.526⁻0.964 p = 0.0302). In contrast, no significant difference of allele frequencies between gout patients and controls was detected for rs12505410 (p > 0.05). However, significant differences in serum uric acid and systolic blood pressure were obtained among gout patients. Conclusion: Our results suggest that ABCG2 rs72552713 and SLC22A12 rs11231825 are likely associated with gout in the Vietnamese population in which T allele may be a risk factor for gout susceptibility.

Animal models of preeclampsia: translational failings and why.

Preeclampsia affects up to 8% of pregnancies worldwide and is a leading cause of both maternal and fetal morbidity and mortality. Our current understanding of the cause(s) of preeclampsia is far from complete, and the lack of a single reliable animal model that recapitulates all aspects of the disease further confounds our understanding. This is partially due to the heterogeneous nature of the disease, coupled with our evolving understanding of its etiology. Nevertheless, animal models are still highly relevant and useful tools that help us better understand the pathophysiology of specific aspects of preeclampsia. This review summarizes the various types and characteristics of animal models used to study preeclampsia, highlighting particular features of these models relevant to clinical translation. This review points out the strengths and limitations of these models to illustrate the importance of using the appropriate model depending on the research question.

Capacity building toward evidence-based medicine among healthcare professionals at the university of medicine and pharmacy, ho chi minh city, and its related institutes.

Research capacity development enhances a country's ownership of activities aimed at strengthening its health system. In Vietnam, continuing medical education (CME) is attracting increasing attention with the establishment of legal and policy frameworks. During 2010-2013, the Japan International Cooperation Agency funded a research capacity building project targeting physicians in Ho Chi Minh City. The project had been developed in four previous courses that were conducted in collaboration with Fukushima Medical University and Ho Chi Minh City University of Medicine and Pharmacy (UMP). The project succeeded in obtaining accreditation as the city's CME course. A total of 262 physicians attended three courses that have a divided set of research competencies. Following the Kirkpatrick Model for evaluating the effectiveness of training programs, we confirmed the participants' positive reaction to the courses (Level 1 evaluation), their perceived increase in knowledge and confidence in research skills (Level 2 evaluation), and application of learned knowledge in their practice (Level 3 evaluation). Presented here is a step-by-step scaling-up model of health research capacity building. Strategies for the further expansion include: further capacity building of instructors; responding to clinicians' specific needs; building a recruiting system with authorization; and improving the Level 3 training evaluation.

A novel missense variant located within the zinc finger domain of the GLI3 gene was identified in a Vietnamese pedigree with index finger polydactyly.

BACKGROUND: Polydactyly, particularly of the index finger, remains an intriguing anomaly for which no specific gene or locus has been definitively linked to this phenotype. In this study, we conducted an investigation of a three-generation family displaying index finger polydactyly. METHODS: Exome sequencing was conducted on the patient, with a filtration to identify potential causal variation. Validation of the obtained variant was conducted by Sanger sequencing, encompassing all family members. RESULTS: Exome analysis uncovered a novel heterozygous missense variant (c.1482A>T; p.Gln494His) at the zinc finger DNA-binding domain of the GLI3 protein within the proband and all affected family members. Remarkably, the variant was absent in unaffected individuals within the pedigree, underscoring its association with the polydactyly phenotype. Computational analyses revealed that GLI3 p.Gln494His impacts a residue that is highly conserved across species. CONCLUSION: The GLI3 zinc finger DNA-binding region is an essential part of the Sonic hedgehog signaling pathway, orchestrating crucial aspects of embryonic development through the regulation of target gene expression. This novel finding not only contributes valuable insights into the molecular pathways governing polydactyly during embryonic development but also has the potential to enhance diagnostic and screening capabilities for this condition in clinical settings.

Re-evaluating the gender gap: a cross-sectional analysis of accepted American Academy of Neurology annual meeting abstracts in 2020 and 2021.

Background and objective: Prior studies reveal that invited speaker panels, editorial boards, authors of practice guidelines, and senior authors of published articles are disproportionately male in the neurology field. We aimed to analyze a gender gap in authorship of accepted abstracts to the American Academy of Neurology annual meetings in 2020 and 2021. Design/methods: This is a cross-sectional study evaluating the proportions of female first and senior abstract authors in 2020 and 2021. Abstracts were reviewed manually (n = 3,211 in 2020; n = 2,178 in 2021). Data were collected regarding the gender of first and senior authors, subspecialties, and origin of research (USA, international, or corporate-affiliated). Then, we compared the percentages of female first and senior authors in the 2 years to assess for any short-term effects of the COVID-19 pandemic. Results: Accepted abstracts with female first and senior authors comprised 46%, 34% in 2020, and the same in 2021, without change. Female senior authors had a significantly higher proportion of female first authors than their male senior author counterparts. The analysis of subspecialties with more than 100 abstracts showed the lowest percentages of female senior authors was oncology (24.7%), sleep (25.5%), headache (28.7%), and cerebrovascular disease (29%) in 2020. Cerebrovascular disease (29%) and behavioral neurology (24.7%) had the lowest percentage of female senior authors in 2021. In the analysis of the origin of research, corporate-affiliated authors had the lowest percentages of female first (34 and 36%) and senior authors (22.6 and 27.6%). Conclusion: The gender gap in neurology was reaffirmed in regards to female senior authorship overall and in subgroups of abstracts including cerebrovascular disease, headache, behavioral neurology, sleep, oncology, and corporate-affiliated research.

A National Cross-Sectional Survey of EMG Physician Volume.

Background and Objectives: This study presents results from a survey of physicians performing electrodiagnostic studies to assess average volume. We also assessed how different factors (trainees, technologists, age of the physician, and case complexity) affected volume. Productivity is an important factor for physicians across practice settings. However, unlike evaluation and management services for neurologists, there are no published data for benchmarks of average volume of electrodiagnostic studies. Methods: A 34-question survey was designed collecting information on demographics, electrodiagnostic study volume, technologists, trainees, referrals, and case complexity. The anonymous survey was disseminated through a QR code or hyperlink to multiple online neurology, physical medicine and rehabilitation, electromyography, and neuromuscular forums. The primary outcome was EMG volume including number of EMGs per half-day and EMG volume per year. We conducted bivariate association analysis between primary outcomes and respondent characteristics using the Pearson χ2 test. Multivariable regression models determined factors associated with each of our outcome variables. Results: A total of 201 respondents initiated the survey. 71% were certified in adult neurology, 19.6% in physical medicine and rehabilitation, and 2.7% in pediatric neurology. 37.5% practiced in academic medicine. The remaining respondents were from private practice, group, solo, hospital employed, or other. 83% of respondents allotted a dedicated half-day to performing EMGs. The median number of EMGs scheduled during a half-day was within 3-4 (45%). 30% and 7% scheduled 5-6 or more than 7 patients per half-day, respectively. The median number of EMGs performed per year was within 251-500 (37%). Discussion: This national, cross-sectional survey evaluates average metrics of EMG volume. Our survey showed that the median number of EMGs annually lies between 251 and 500 studies (37%). In addition, for those respondents who allotted a dedicated half-day to performing EMGs, the median number of EMG studies scheduled per half-day lies between 3 and 4 studies (45%). In multivariate analysis, respondent characteristics of age of the physician (older than 45), working with nerve conduction technologists, and holding the position of EMG director were associated with increased EMG volume.

Analysis of Inflammatory Markers in Response to Induction of Reprometabolic Syndrome by a Eucaloric High Fat Diet in Normal Weight Women.

Obesity is associated with chronic low-level inflammation and is known to contribute to metabolic dysfunction and hypogonadotropic hypogonadism, which we have previously termed the 'Reprometabolic Syndrome.' To investigate potential factors involved in obesity-related reproductive endocrine dysfunction, we conducted a secondary analysis of inflammatory markers in a sample of normal weight women exposed to a one-month eucaloric high-fat diet (HFD), which, as reported earlier, induced the relative hypogonadotropic hypogonadism characteristic of Reprometabolic Syndrome. Eighteen healthy women with a BMI between 18.0-24.9 kg/m2 and regular menstrual cycles participated in the study. Frequent blood sampling was performed during the early follicular phase before and after the one-month eucaloric HFD intervention (48% of calories from fat). Serum samples pooled from each participant were analyzed using immunoassay to measure levels of 30 cytokines, interleukins, and chemokines. Differences between pre- and post-HFD intervention measures were examined by one-sample t-tests. Exposure to the eucaloric HFD did not result in changes in body weight. HFD-induction of Reprometabolic Syndrome in normal weight women was associated with a significant elevation only in the anti- inflammatory cytokine IL-10 (p = 0.04). Eotaxin, IL-6 and MIP-1ß also increased in response to the HFD, but not statistically significantly (p = 0.07). Results suggest that the increase in multiple inflammatory markers, typically associated with obesity, are not primary mediators of the relative hypogonadotropic hypogonadism of Reprometabolic Syndrome. Clinical Trials Registration Number: NCT02653092; Date of Registration: January 6, 2016.

Trends in Patient Representation in Low Back Pain Pharmacological Randomized Clinical Trials, 2011 to 2020: A Systematic Review.

Low back pain (LBP) significantly affects global health, with associated detrimental outcomes such as physical impairment, emotional distress, and exacerbated mental health symptoms. This study evaluated the representation of marginalized groups, including racialized, gender minority, pregnant/lactating, and elderly individuals in randomized controlled trials for pharmacological interventions treating LBP from 2011 to 2020. We searched Embase, MEDLINE, and CINAHL in December 2021, and 139 studies were eligible. Most trials (n = 113, 81%) reported participant sex; however, no study collected data on sexual and gender minorities, and the majority (n = 99, 71%) excluded pregnant/lactating individuals. Most trials (n = 105, 76%) reported no data on participant race or ethnicity. We limited within-country analyses of race and ethnicity to US-based trials because US-based trials were more likely to report race and/or ethnicity (48%) compared to non-US-based trials (8%). Black participants were the only racialized group whose composition was comparable to US Census estimates. About half (n = 73, 53%) of all trials had an upper age limit for eligibility (range: 40-85 years old) and 24% (n = 33) excluded adults aged >65 years. Our findings confirm that trials for pharmacological LBP interventions underreport demographic data, and the trials that include this data have unrepresentative samples. There is an urgent need for more inclusive and representative patient samples to ensure generalizability and equitable benefits. Standardizing demographic data reporting and integrating community-based participatory research methods can help foster inclusive research practices. This review was registered with prospective register of systematic reviews (PROSPERO), ID 296017. PERSPECTIVE: This systematic review investigates patient representation in pharmacological-based clinical trials for low back pain, LBP, the most prevalent pain condition worldwide. Improvements in reporting demographic data and recruiting diverse participant populations-across different racialized, gender and sexual minority, and age groups-will help clinical research generalizability and provide equitable benefits.

Comparing Anesthesia and Surgery Controlled Time for Primary Total Knee and Hip Arthroplasty Between an Academic Medical Center and a Community Hospital: Retrospective Cohort Study.

BACKGROUND: Osteoarthritis is a significant cause of disability, resulting in increased joint replacement surgeries and health care costs. Establishing benchmarks that more accurately predict surgical duration could help to decrease costs, maximize efficiency, and improve patient experience. We compared the anesthesia-controlled time (ACT) and surgery-controlled time (SCT) of primary total knee (TKA) and total hip arthroplasties (THA) between an academic medical center (AMC) and a community hospital (CH) for 2 orthopedic surgeons. OBJECTIVE: This study aims to validate and compare benchmarking times for ACT and SCT in a single patient population at both an AMC and a CH. METHODS: This retrospective 2-center observational cohort study was conducted at the University of Colorado Hospital (AMC) and UCHealth Broomfield Hospital (CH). Cases with current procedural terminology codes for THA and TKA between January 1, 2019, and December 31, 2020, were assessed. Cases with missing data were excluded. The primary outcomes were ACT and SCT. Primary outcomes were tested for association with covariates of interest. The primary covariate of interest was the location of the procedure (CH vs AMC); secondary covariates of interest included the American Society of Anesthesiologists (ASA) classification and anesthetic type. Linear regression models were used to assess the relationships. RESULTS: Two surgeons performed 1256 cases at the AMC and CH. A total of 10 THA cases and 12 TKA cases were excluded due to missing data. After controlling for surgeon, the ACT was greater at the AMC for THA by 3.77 minutes and for TKA by 3.58 minutes (P<.001). SCT was greater at the AMC for THA by 11.14 minutes and for TKA by 14.04 minutes (P<.001). ASA III/IV classification increased ACT for THA by 3.76 minutes (P<.001) and increased SCT for THA by 6.33 minutes after controlling for surgeon and location (P=.008). General anesthesia use was higher at the AMC for both THA (29.2% vs 7.3%) and TKA (23.8% vs 4.2%). No statistically significant association was observed between either ACT or SCT and anesthetic type (neuraxial or general) after adjusting for surgeon and location (all P>.05). CONCLUSIONS: We observed lower ACT and SCT at the CH for both TKA and THA after controlling for the surgeon of record and ASA classification. These findings underscore the efficiency advantages of performing primary joint replacements at the CH, showcasing an average reduction of 16 minutes in SCT and 4 minutes in ACT per case. Overall, establishing more accurate benchmarks to improve the prediction of surgical duration for THA and TKA in different perioperative environments can increase the reliability of surgical duration predictions and optimize scheduling. Future studies with study populations at multiple community hospitals and academic medical centers are needed before extrapolating these findings.

Effectiveness of preconception weight loss interventions on fertility in women: a systematic review and meta-analysis.

IMPORTANCE: Weight loss before conception is recommended for women with overweight or obesity to improve fertility outcomes, but evidence supporting this recommendation is mixed. OBJECTIVE: To examine the effectiveness of weight loss interventions using lifestyle modification and/or medication in women with overweight or obesity on pregnancy, live birth, and miscarriage. DATA SOURCES: An electronic search of MEDLINE, Embase, Cochrane Library, including Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature was conducted through July 6, 2022, via Wiley. STUDY SELECTION AND SYNTHESIS: Randomized controlled trials examining weight loss interventions through lifestyle and/or medication in women with overweight or obesity planning pregnancy were included. Random-effects meta-analysis was conducted, reporting the risk ratio (RR) for each outcome. Subgroup analyses were conducted by intervention type, type of control group, fertility treatment, intervention length, and body mass index (BMI). MAIN OUTCOME(S): Clinical pregnancy, live birth, and miscarriage events. RESULT(S): A narrative review and meta-analysis were possible for 16 studies for pregnancy (n = 3,588), 13 for live birth (n = 3,329), and 11 for miscarriage (n = 3,248). Women randomized and exposed to a weight loss intervention were more likely to become pregnant (RR = 1.24, 95% CI 1.07-1.44; I2 = 59%) but not to have live birth (RR = 1.19, 95% CI 0.97-1.45; I2 = 69%) or miscarriage (RR = 1.17, 95% CI 0.79-1.74; I2 = 31%) compared with women in control groups. Subgroup analyses revealed women randomized to weight loss interventions lasting 12 weeks or fewer (n = 9, RR = 1.43; 95% CI 1.13-1.83) and women with a BMI ≥ 35 kg/m2 (n = 7, RR = 1.54; 95% CI, 1.18-2.02) were more likely to become pregnant compared with women in the control groups. Miscarriage was higher in intervention groups who underwent fertility treatment (n = 8, RR 1.45; 95% CI 1.07-1.96). CONCLUSION(S): Pregnancy rates were higher in women undergoing preconception weight loss interventions with no impact on live birth or miscarriage rates. Findings do not support one-size-fits-all recommendation for weight loss through lifestyle modification and/or medication in women with overweight or obesity immediately before conception to improve live birth or miscarriage outcomes.

Apple CRISPR-Cas9-A Recipe for Successful Targeting of AGAMOUS-like Genes in Domestic Apple.

Fruit trees and other fruiting hardwood perennials are economically valuable, and there is interest in developing improved varieties. Both conventional breeding and biotechnology approaches are being utilized towards the goal of developing advanced cultivars. Increased knowledge of the effectiveness and efficiency of biotechnology approaches can help guide use of the CRISPR gene-editing technology. Here, we examined CRISPR-Cas9-directed genome editing in the valuable commodity fruit tree Malus x domestica (domestic apple). We transformed two cultivars with dual CRISPR-Cas9 constructs designed to target two AGAMOUS-like genes simultaneously. The main goal was to determine the effectiveness of this approach for achieving target gene changes. We obtained 6 Cas9 control and 38 independent CRISPR-Cas9 events. Of the 38 CRISPR-Cas9 events, 34 (89%) had gene edits and 14 (37%) showed changes to all alleles of both target genes. The most common change was large deletions, which were present in 59% of all changed alleles, followed by small deletions (21%), small insertions (12%), and a combination of small insertions and deletions (8%). Overall, a high rate of successful gene alterations was found. Many of these changes are predicted to cause frameshifts and alterations to the predicted peptides. Future work will include monitoring the floral development and floral form.

Quantitative proteomic analysis of bronchoalveolar lavage fluids from patients with small cell lung cancers.

PURPOSE: Small cell lung cancer (SCLC) is one of the malignant cancers with aggressive progression and poor prognosis. Bronchoalveolar lavage fluid (BALF) has been arising recently as a potential source of biomarkers for lung cancers. In this study, we performed quantitative BALF proteomic analysis to identify potential biomarkers for SCLC. EXPERIMENTAL DESIGN: BALF were collected from tumor-bearing lungs and non-tumor lungs of five SCLC patients. Then, BALF proteomes were prepared for a TMT-based quantitative mass spectrometry analysis. Differentially expressed proteins (DEP) were identified when considering individual variation. Potential SCLC biomarker candidates were validated by immunohistochemistry (IHC). A public database of multiple SCLC cell lines was used to evaluate the correlation of these markers with SCLC subtypes and chemo-drug responses. RESULTS: We identified 460 BALF proteins in SCLC patients and observed considerable individual variation among the patients. Immunohistochemical analysis and bioinformatics resulted in the identification of CNDP2 and RNPEP as potential subtype markers for ASCL1 and NEUROD1, respectively. In addition, CNDP2 was found to be positively correlated with responses to etoposide, carboplatin, and irinotecan. CONCLUSIONS AND CLINICAL RELEVANCE: BALF is an emerging source of biomarkers, making it useful for the diagnosis and prognosis of lung cancers. We characterized the proteomes of paired BALF samples collected from tumor-bearing and non-tumor lungs of SCLC patients. Several proteins were found elevated in tumor-bearing BALF, and especially CNDP2 and RNPEP appeared to be potential indicators for ASLC1-high and NEUROD1-high subtypes of SCLC, respectively. The positive correlation of CNDP2 with chemo-drug responses would help to make decisions for treatment of SCLC patients. These putative biomarkers could be comprehensively investigated for a clinical use towards precision medicine.