Category: Statistics

JAMA Netw Open. 2024 Jun 3;7(6):e2418620. doi: 10.1001/jamanetworkopen.2024.18620.

ABSTRACT

IMPORTANCE: The US Supreme Court Dobbs v Jackson Women’s Health Organization decision allowed states to strengthen restrictions on abortion access, triggering the closure of family planning clinics and leading to confusion about the legality of emergency contraceptives (ECs).

OBJECTIVES: To evaluate the association between the Dobbs decision and fills for oral and emergency contraceptives in states that enacted the most restrictive abortion policies after Dobbs.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data on contraceptive fills for women of reproductive age (15-49 years) in the US from IQVIA’s National Prescription Audit PayerTrak and data from the Guttmacher Institute were used to categorize changes in abortion restrictions in each state. A difference-in-differences analysis compared changes in monthly fill rates for daily oral contraceptive pills (OCPs) and ECs in states that became most restrictive (implemented a full abortion ban after Dobbs) and comparison states (kept a medium level of abortion restrictions after Dobbs) before (March 2021 to November 2021) and after (July 2022 to October 2023) the Dobbs decision.

EXPOSURE: State-level abortion restrictions.

MAIN OUTCOMES AND MEASURES: Monthly fills of OCPs and ECs per 100 000 women of reproductive age.

RESULTS: Between March 2021 and October 2023, 142.8 million prescriptions for OCPs and 904 269 prescriptions for ECs were dispensed at US retail pharmacies. Before Dobbs, trends in monthly fill rates were similar for OCPs and ECs between the most restrictive and comparison states. After the Dobbs decision, states that became the most restrictive experienced an additional 4.1% decline in OCP fills with 285.9 fewer fills per 100 000 (95% CI, -495.8 to -6.8; P = .04). In contrast to OCPs, fills for ECs increased during the first year after Dobbs (July 2022 to June 2023) in both groups of states. However, 1 year after Dobbs (July 2023 to October 2023), the most restrictive states experienced an additional 65% decrease in emergency contraceptive fills with 13.2 fewer fills per 100 000 (95% CI, -27.2 to -4.1; P = .01).

CONCLUSIONS AND RELEVANCE: In this cohort study of prescriptions filled at US pharmacies, the Dobbs decision was associated with declines in oral contraceptives, particularly ECs, in states enacting the most restrictive abortion policies. Given the important role of OCPs and ECs in preventing pregnancy and the need for abortion, efforts to improve access may be needed, especially in states where legal abortion is no longer an option.

PMID:38922616 | DOI:10.1001/jamanetworkopen.2024.18620

JAMA Netw Open. 2024 Jun 3;7(6):e2418800. doi: 10.1001/jamanetworkopen.2024.18800.

ABSTRACT

IMPORTANCE: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear.

OBJECTIVE: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation’s cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024.

INTERVENTIONS: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate.

MAIN OUTCOMES AND MEASURES: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort.

RESULTS: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively.

CONCLUSIONS AND RELEVANCE: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

PMID:38922614 | DOI:10.1001/jamanetworkopen.2024.18800

JAMA Netw Open. 2024 Jun 3;7(6):e2418808. doi: 10.1001/jamanetworkopen.2024.18808.

ABSTRACT

IMPORTANCE: Chronic kidney disease (CKD) is an often-asymptomatic complication of type 2 diabetes (T2D) that requires annual screening to diagnose. Patient-level factors linked to inadequate screening and treatment can inform implementation strategies to facilitate guideline-recommended CKD care.

OBJECTIVE: To identify risk factors for nonconcordance with guideline-recommended CKD screening and treatment in patients with T2D.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was performed at 20 health care systems contributing data to the US National Patient-Centered Clinical Research Network. To evaluate concordance with CKD screening guidelines, adults with an outpatient clinician visit linked to T2D diagnosis between January 1, 2015, and December 31, 2020, and without known CKD were included. A separate analysis reviewed prescription of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in adults with CKD (estimated glomerular filtration rate [eGFR] of 30-90 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio [UACR] of 200-5000 mg/g) and an outpatient clinician visit for T2D between October 1, 2019, and December 31, 2020. Data were analyzed from July 8, 2022, through June 22, 2023.

EXPOSURES: Demographics, lifestyle factors, comorbidities, medications, and laboratory results.

MAIN OUTCOMES AND MEASURES: Screening required measurement of creatinine levels and UACR within 15 months of the index visit. Treatment reflected prescription of ACEIs or ARBs and SGLT2 inhibitors within 12 months before or 6 months following the index visit.

RESULTS: Concordance with CKD screening guidelines was assessed in 316 234 adults (median age, 59 [IQR, 50-67] years), of whom 51.5% were women; 21.7%, Black; 10.3%, Hispanic; and 67.6%, White. Only 24.9% received creatinine and UACR screening, 56.5% received 1 screening measurement, and 18.6% received neither. Hispanic ethnicity was associated with lack of screening (relative risk [RR], 1.16 [95% CI, 1.14-1.18]). In contrast, heart failure, peripheral arterial disease, and hypertension were associated with a lower risk of nonconcordance. In 4215 patients with CKD and albuminuria, 3288 (78.0%) received an ACEI or ARB; 194 (4.6%), an SGLT2 inhibitor; and 885 (21.0%), neither therapy. Peripheral arterial disease and lower eGFR were associated with lack of CKD treatment, while diuretic or statin prescription and hypertension were associated with treatment.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with T2D, fewer than one-quarter received recommended CKD screening. In patients with CKD and albuminuria, 21.0% did not receive an SGLT2 inhibitor or an ACEI or an ARB, despite compelling indications. Patient-level factors may inform implementation strategies to improve CKD screening and treatment in people with T2D.

PMID:38922613 | DOI:10.1001/jamanetworkopen.2024.18808

Phys Chem Chem Phys. 2024 Jun 26. doi: 10.1039/d4cp01580k. Online ahead of print.

ABSTRACT

Many fundamental biophysical processes involving gene regulation and gene editing rely, at the molecular level, on an intricate methodology of searching and locating the precise target base pair sequence on the genome by specific binding proteins. A unique mechanism, known as ‘facilitated diffusion’, which is a combination of 1D sliding along with 3D movement, is considered to be the key step for such events. This also explains the relatively much shorter timescale of the target searching process, compared to other diffusion-controlled biophysical processes. In this work, we aim to probe the modulation of target search dynamics of a protein moiety by estimating the rate of the target search process, and the statistics of the search rounds and timescales accomplished by the 1D and 3D motions, based on first passage time (FPT) calculations. This is studied with its characteristics getting influenced by various given conditions such as, when the DNA is rigid or flexible, and when the target is placed at different locations on the DNA. The current theoretical framework includes a Brownian dynamics simulation setup adopting a straightforward coarse-grained model for a diffusing protein on DNA. Moreover, this theoretical analysis provides insights into the complex target search dynamics by highlighting the significance of the chain dynamics in the mechanistic details of the facilitated diffusion process.

PMID:38922594 | DOI:10.1039/d4cp01580k

J Toxicol Environ Health A. 2024 Jun 26:1-10. doi: 10.1080/15287394.2024.2369255. Online ahead of print.

ABSTRACT

Sarcoidosis is a chronic granulomatous disease predominantly affecting the lungs and inducing significant morbidity and elevated mortality rate. The etiology of the disease is unknown but may involve exposure to an antigenic agent and subsequent inflammatory response resulting in granuloma formation. Various environmental and occupational risk factors have been suggested by previous observations, such as moldy environments, insecticides, and bird breeding. Our study investigated the association of air pollution with diagnosis of sarcoidosis using a case-control design. Penn State Health electronic medical records from 2005 to 2018 were examined for adult patients with (cases) and without (controls) an International Classification of Disease (ICD)-9 or -10 code for sarcoidosis. Patient addresses were geocoded and 24-hr residential-level air pollution concentrations were estimated using spatio-temporal models of particulate matter <2.5 μm (PM_2.5), ozone, and PM_2.5 elemental carbon (EC) and moving averages calculated. In total, 877 cases and 34,510 controls were identified. Logistic regression analysis did not identify significant associations between sarcoidosis incidence and air pollution exposure estimates. However, the odds ratio (OR) for EC for exposures occurring 7-10 years prior did approach statistical significance, and ORs exhibited an increasing trend for longer averaging periods. Data suggested a latency period of more than 6 years for PM_2.5 and EC for reasons that are unclear. Overall, results for PM_2.5 and EC suggest that long-term exposure to traffic-related air pollution may contribute to the development of sarcoidosis and emphasize the need for additional research and, if the present findings are substantiated, for public health interventions addressing air quality as well as increasing disease surveillance in areas with a large burden of PM_2.5 and EC.

PMID:38922578 | DOI:10.1080/15287394.2024.2369255

Clin Rheumatol. 2024 Jun 26. doi: 10.1007/s10067-024-07043-x. Online ahead of print.

ABSTRACT

INTRODUCTION/OBJECTIVES: The heterodimer exostosin-1/exostosin-2 (EXO-1/2) is a novel antigen observed in membranous nephropathy associated with systemic lupus erythematosus. This study aimed to evaluate the association between EXO-1/2 positivity in kidney biopsy and kidney outcomes.

METHODS: The kidney biopsy tissue from 50 class 5 lupus nephritis (LN) and 55 mixed class 3/4 + 5 LN patients was stained for EXO-1/2. Baseline clinical and histological characteristics were compared between EXO-1/2 positive and EXO-1/2 negative patients. Time-to-event analyses were performed to compare rates of response to therapy, kidney flares, and progression to a 40% decline of the glomerular filtration rate (eGFR), doubling of serum creatinine, and kidney failure.

RESULTS: Fourteen out of 50 (28%) of class 5 and 5 out of 55 (9%) of mixed class 3/4 + 5 LN stained positive for EXO-1/2. Patients with class 5 LN and EXO-1/2 positive stain were younger, with better kidney function at presentation, and lower scarring in the kidney biopsy analysis. Over a median follow-up of 100 months, patients with positive EXO-1/2 staining had significantly lower rates of progression in the full cohort. When analyzed separately in class 5 and mixed class LN subgroups, there were significantly lower rates of progression to a 40% decline of the eGFR and non-statistically significant trends for doubling of serum creatinine and kidney failure.

CONCLUSION: EXO-1/2 is a novel antigen detected in class 5 LN and associated with a good prognosis of kidney function. The incorporation of EXO-1/2 staining in clinical practice can potentially modify the management of LN due to its prognostic implications. Key Points • Exostosin-1/exostosin-2 antigen has been found in cases of membranous nephropathy associated with autoimmune diseases such as systemic lupus erythematosus. • Exostosin-1/exostosin-2 staining in the kidney biopsy of class 5 or mixed class 3/4 + 5 lupus nephritis is associated with a good long-term prognosis of kidney function. • The incorporation of exostosin-1/exostosin-2 staining into clinical practice can potentially modify management due to its prognostic implications.

PMID:38922553 | DOI:10.1007/s10067-024-07043-x

Clin Rheumatol. 2024 Jun 26. doi: 10.1007/s10067-024-07040-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Omega-3 possesses anti-inflammatory and lipid metabolism modifying effects in rheumatoid arthritis (RA), but inconsistency exists among previous studies. This meta-analysis intended to explore the effects of omega-3 supplementation on fatty acid distribution, blood lipid profiles, inflammation, and disease activity in RA patients.

METHODS: This meta-analysis followed the Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA) protocol. PubMed, Web of Science, and Embase databases were searched until August 31, 2023.

RESULTS: Eighteen randomized controlled trials with 1018 RA patients were included. Regarding fatty acid distribution, omega-3 supplementation increased eicosapentaenoic acid (EPA) [standardized mean difference (SMD): 0.74; 95% confidence interval (CI): 0.46, 1.01; P < 0.001] and docosahexanoic acid (DHA) (SMD: 0.62; 95% CI: 0.35, 0.89; P < 0.001), but reduced omega-6:omega-3 ratio (SMD: -1.06; 95% CI: -1.39, -0.73; P < 0.001) in RA patients. Regarding blood lipid, omega-3 supplementation decreased triglyceride (TG) in RA patients (SMD: -0.47; 95% CI: -0.78, -0.16; P = 0.003). Regarding clinical symptoms, omega-3 supplementation reduced tender joint count (TJC) in RA patients (SMD: -0.59; 95% CI: -0.79, -0.39; P < 0.001). Notably, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and disease activity score on 28 joints (DAS28) score were slightly decreased by omega-3 supplementation but without statistical significance (all P > 0.05). Publication bias was low, and stability assessed by sensitivity analysis was good.

CONCLUSION: Omega-3 supplementation increases EPA and DHA, but reduces the omega-6:omega-3 ratio, TG, and TJC in RA patients.

PMID:38922552 | DOI:10.1007/s10067-024-07040-0

Clin Rheumatol. 2024 Jun 26. doi: 10.1007/s10067-024-07035-x. Online ahead of print.

ABSTRACT

Tofacitinib is the first oral JAK inhibitor approved for treating rheumatoid arthritis (RA). To enhance our understanding of tofacitinib drug response, we used hierarchical clustering to analyse the profiles of patient who responded to the treatment in a real-world setting. Patients who commenced on tofacitinib treatment were selected from 12 major rheumatology centres in Malaysia. The aim was to assess their response to tofacitinib defined as achieving DAS28-CRP/ESR ≤ 3.2 and DAS28 improvement > 1.2 at 12 weeks. A hierarchical clustering analysis was performed using sociodemographic and clinical parameters at baseline. All 163 RA patients were divided into three clusters (Clusters 1, 2 and 3) based on specific clinical factors at baseline including bone erosion, antibody positivity, disease activity and anaemia status. Cluster 1 consisted of RA patients without bone erosion, antibody negative, low baseline disease activity measure and absence of anaemia. Cluster 2 comprised of patients without bone erosion, RF positivity, anti-CCP negativity, moderate to high baseline disease activity score and absence of anaemia. Cluster 3 patients had bone erosion, antibody positivity, high baseline disease activity and anaemia. The response rates to tofacitinib varied among the clusters: Cluster 1 had a 79% response rate, Cluster 2 had a 66% response rate, and Cluster 3 had a 36% response rate. The differences in response rates between the three clusters were found to be statistically significant. This cluster analysis study indicates that patients who are seronegative and have low disease activity, absence of bone erosion and no signs of anaemia may have a higher likelihood of benefiting from tofacitinib therapy. By identifying clinical profiles that respond to tofacitinib treatment, we can improve treatment stratification yielding significant benefits and better health outcomes for individuals with RA.

PMID:38922551 | DOI:10.1007/s10067-024-07035-x

Int Urol Nephrol. 2024 Jun 26. doi: 10.1007/s11255-024-04121-6. Online ahead of print.

ABSTRACT

PURPOSE: Mohs micrographic surgery (MMS) is a low-risk penile cancer management option. However, contemporary patients’ short-term oncologic control and preoperative characteristics predicting reconstruction needs are undefined. This study assesses MMS’s oncologic efficacy for low-risk penile cancer and identifies baseline predictors of post-resection reconstruction referral.

METHODS: We retrospectively reviewed 73 adult males with 78 penile cutaneous malignancies treated with MMS from 2005 to 2019. Patients underwent MMS with or without surgical reconstruction. Demographic information, MMS operative details, lesion pathology, and short-term outcomes were recorded. Descriptive statistics for all variables were calculated, and logistic regression identified predictive factors for urologic referral for complex reconstruction.

RESULTS: Seventy-three men with 78 lesions, all staged ≤ cT1a prior to MMS, were identified. Twenty-one men were found to have invasive SCC. Median follow-up was 2.0 years (IQR 0.8-5.2 years). MMS was able to clear the disease in 90.4% of cases. One patient had disease related death following progression. Dermatology closed primarily in 68% of patients. Twenty percent of patients had a complication, most commonly poor wound healing. On univariate and multivariate linear regression analysis, lesion size > 3 cm and involvement of the glans independently predicted the need for referral to a reconstructive surgeon.

CONCLUSIONS: MMS for penile cancer appears to provide sound oncologic control in the properly selected patient. Involvement of a reconstructive surgeon may be needed for glandular and large lesions, necessitating early referral to a comprehensive multidisciplinary care team.

PMID:38922534 | DOI:10.1007/s11255-024-04121-6

Daru. 2024 Jun 26. doi: 10.1007/s40199-024-00523-0. Online ahead of print.

ABSTRACT

BACKGROUND: The focus on repurposing readily available, well-known drugs for new, creative uses has grown recently. One such medication is metformin, a drug commonly used to manage diabetes, which shows a favorable correlation between its use and lower cancer morbidity and death. Numerous investigations and clinical trials have been conducted to evaluate the possible application of metformin as an anticancer medication in light of this conclusion.

OBJECTIVE: This study used ‘pathway/gene-set analysis’ Gene2drug, a resource for Gene Ontology (GO), and DepMap to determine whether metformin would be potentially advantageous for treating cancer.

METHODS: A total of 1826 tumor cell lines were analyzed using the Drug Sensitivity (Primary Purposing Primary Screening) 19Q4 Tool.

RESULTS: 9 genes from 402 genes, SGPL1, CXCR6, ATXN2L, LAMP3, RTN3, BTN2A1, FOXM1, NQO1, and L1TD1 in 1826 cancer cell line showed statistical sensitivity to metformin.

CONCLUSION: This in-silico study showed the sensitivity of specific cancer cell lines to metformin. Therefore, holding promises for metformin and tumor-targeted treatment strategies. It is recommended, however, to conduct further research into its potential effectiveness and mechanism of action.

PMID:38922530 | DOI:10.1007/s40199-024-00523-0