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Association between birth weight and risk of nonneurological childhood cancers: a systematic review and meta-analysis

Eur J Cancer Prev. 2024 May 20. doi: 10.1097/CEJ.0000000000000894. Online ahead of print.

ABSTRACT

OBJECTIVES: This systematic review aims to synthesize the available literature to determine the association between birthweight and the risk of nonneurological childhood cancers.

METHODS: We conducted a systematic search of PubMed, Web of Science, and Scopus databases up to May 2023 to identify observational studies. Heterogeneity between studies was evaluated using the I2 statistics. Publication bias was assessed using Begg and Egger tests. We calculated the odds ratio (OR) or risk ratio (RR) with a 95% confidence interval (CI) using a random-effects model.

RESULTS: Of 11 034 studies retrieved from the search, 56 studies (including 10 568 091 participants) were eligible. The ORs (95% CI) of low (<2500 g) versus normal birthweight (2500-4000 g) and childhood cancers were as follows: leukemia, 0.92 (0.77-1.11); acute lymphoblastic leukemia, 0.82 (0.72-0.94); acute myeloid leukemia, 0.98 (0.77-1.24); lymphoma, 0.99 (0.47-2.10); Hodgkin, 0.79 (0.61-1.03); non-Hodgkin, 0.85 (0.60-1.20); neuroblastoma, 1.34 (1.14-1.58); retinoblastoma, 0.95 (0.68-1.32); rhabdomyosarcoma, 0.86 (0.61-1.20); embryonal, 0.97 (0.66-1.43); alveolar, 1.92 (0.43-8.51); and Wilms tumor, 1.01 (0.83-1.24). The ORs (95% CI) of high (>4000 g) versus normal birthweight and childhood cancers were as follows: leukemia, 1.30 (1.18-1.42); acute lymphoblastic leukemia, 1.27 (1.16-1.39); acute myeloid leukemia, 1.13 (0.98-1.30); lymphoma, 1.69 (0.72-3.94); Hodgkin, 1.22 (1.02-1.46); non-Hodgkin, 1.22 (0.80-1.86); neuroblastoma, 1.20 (1.02-1.41); retinoblastoma, 1.17 (0.93-1.48); rhabdomyosarcoma, 1.07 (0.90-1.27); embryonal, 1.22 (1.00-1.49); alveolar, 1.02 (0.46-2.27); and Wilms tumor, 1.49 (1.34-1.67).

CONCLUSION: This meta-analysis identified high birth weight as a potential risk factor for some childhood cancers, while low birth weight might be protective against a few.

PMID:38837193 | DOI:10.1097/CEJ.0000000000000894

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Access to general obstetrics and gynecology care among Medicaid beneficiaries and the privately insured: a nationwide mystery caller study in the USA

Minerva Obstet Gynecol. 2024 Jun 4. doi: 10.23736/S2724-606X.24.05497-6. Online ahead of print.

ABSTRACT

BACKGROUND: The mean wait time for new patient appointments has been growing across specialties, including obstetrics and gynecology, in recent years. This study aimed to assess the impact of insurance type (Medicaid versus commercial insurance) on new patient appointment wait times in general obstetrics and gynecology practices.

METHODS: A cross-sectional study used covert mystery calls to general obstetrician gynecologists. Physicians were selected from the American College of Obstetricians and Gynecologists directory and stratified by districts to ensure nationwide representation. Wait times for new patient appointments were collected and analyzed.

RESULTS: Regardless of insurance type, the mean wait time for all obstetrician gynecologists was 29.9 business days. Medicaid patients experienced a marginally longer wait time of 4.8% (Ratio: 1.048). While no statistically significant difference in wait times based on insurance type was observed (P=0.39), the data revealed other impactful factors. Younger physicians and those in university-based practices had longer wait times. The gender of the physician also influenced wait times, with female physicians having a mean wait time of 34.7 days compared to 22.7 days for male physicians (P=0.03). Additionally, geographical variations were noted, with physicians in American College of Obstetricians and Gynecologists District I (Atlantic Provinces, CT, ME, MA, NH, RI, VT) having the longest mean wait times and those in District III (DE, NJ, PA) the shortest.

CONCLUSIONS: While the type of insurance did not significantly influence the wait times for general obstetrics and gynecology appointments, physician demographic and geographic factors did.

PMID:38837187 | DOI:10.23736/S2724-606X.24.05497-6

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Access to Dietary Treatment for Inborn Errors of Metabolism: You Do Not Get What You Do Not Pay For

JAMA Netw Open. 2024 Jun 3;7(6):e2412784. doi: 10.1001/jamanetworkopen.2024.12784.

NO ABSTRACT

PMID:38837165 | DOI:10.1001/jamanetworkopen.2024.12784

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The Quest for Evidence on Time to Antibiotics in Children With Sepsis-Finding the Sweet Spot

JAMA Netw Open. 2024 Jun 3;7(6):e2413926. doi: 10.1001/jamanetworkopen.2024.13926.

NO ABSTRACT

PMID:38837164 | DOI:10.1001/jamanetworkopen.2024.13926

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Insurance Reimbursement for Special Foods and Phenylalanine Levels in Patients With PKU in China

JAMA Netw Open. 2024 Jun 3;7(6):e2412886. doi: 10.1001/jamanetworkopen.2024.12886.

ABSTRACT

IMPORTANCE: Recent changes in China’s social medical insurance reimbursement policy have impacted the financial burden of patients with phenylketonuria (PKU) for special foods. However, whether this policy change is associated with their blood phenylalanine (PHE) concentration is unclear.

OBJECTIVE: To investigate the association between the reimbursement policy and blood PHE concentration in patients with PKU.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study measured the blood PHE concentrations of 167 patients with PKU across 4 newborn screening centers in China from January 2018 to December 2021. The reimbursement policy for special foods for patients with PKU at 2 centers was canceled in 2019 and restored from 2020 onwards. In contrast, the other 2 centers consistently implemented the policy. Data were analyzed from September 10 to December 6, 2023.

EXPOSURES: The implementation and cancelation of the reimbursement policy for special foods of patients with PKU.

MAIN OUTCOMES AND MEASURES: The blood PHE concentration was regularly measured from 2018 to 2021. A 1-sided Z test was used to compare the mean of the blood PHE concentration between different years.

RESULTS: Among 167 patients with PKU (mean [SD] age, 84.4 [48.3] months; 87 males [52.1%]), a total of 4285 measurements of their blood PHE concentration were collected from 2018 to 2021. For patients at the center that canceled the reimbursement policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (5.73) mg/dL, significantly higher than 4.84 (4.11) mg/dL in 2018 (P < .001), 5.06 (5.21) mg/dL in 2020 (P = .006), and 4.77 (4.04) mg/dL in 2021 (P < .001). Similarly, for patients at the other center that canceled the policy in 2019, the mean (SD) of the blood PHE concentrations in 2019 was 5.95 (3.43) mg/dL, significantly higher than 5.34 (3.45) mg/dL in 2018 (P = .03), 5.13 (3.15) mg/dL in 2020 (P = .003), and 5.39 (3.46) mg/dL in 2021 (P = .03). On the contrary, no significant difference was observed between any of the years for patients at the 2 centers that consistently implemented the policy.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with PKU from multiple centers, the implementation of the reimbursement policy for special foods was associated with controlling the blood PHE concentration. Special foods expenditure for patients with PKU should be included in the scope of long-term social medical insurance reimbursement.

PMID:38837161 | DOI:10.1001/jamanetworkopen.2024.12886

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Delays to Antibiotics in the Emergency Department and Risk of Mortality in Children With Sepsis

JAMA Netw Open. 2024 Jun 3;7(6):e2413955. doi: 10.1001/jamanetworkopen.2024.13955.

ABSTRACT

IMPORTANCE: Pediatric consensus guidelines recommend antibiotic administration within 1 hour for septic shock and within 3 hours for sepsis without shock. Limited studies exist identifying a specific time past which delays in antibiotic administration are associated with worse outcomes.

OBJECTIVE: To determine a time point for antibiotic administration that is associated with increased risk of mortality among pediatric patients with sepsis.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used data from 51 US children’s hospitals in the Improving Pediatric Sepsis Outcomes collaborative. Participants included patients aged 29 days to less than 18 years with sepsis recognized within 1 hour of emergency department arrival, from January 1, 2017, through December 31, 2021. Piecewise regression was used to identify the inflection point for sepsis-attributable 3-day mortality, and logistic regression was used to evaluate odds of sepsis-attributable mortality after adjustment for potential confounders. Data analysis was performed from March 2022 to February 2024.

EXPOSURE: The number of minutes from emergency department arrival to antibiotic administration.

MAIN OUTCOMES AND MEASURES: The primary outcome was sepsis-attributable 3-day mortality. Sepsis-attributable 30-day mortality was a secondary outcome.

RESULTS: A total of 19 515 cases (median [IQR] age, 6 [2-12] years) were included. The median (IQR) time to antibiotic administration was 69 (47-116) minutes. The estimated time to antibiotic administration at which 3-day sepsis-attributable mortality increased was 330 minutes. Patients who received an antibiotic in less than 330 minutes (19 164 patients) had sepsis-attributable 3-day mortality of 0.5% (93 patients) and 30-day mortality of 0.9% (163 patients). Patients who received antibiotics at 330 minutes or later (351 patients) had 3-day sepsis-attributable mortality of 1.2% (4 patients), 30-day mortality of 2.0% (7 patients), and increased adjusted odds of mortality at both 3 days (odds ratio, 3.44; 95% CI, 1.20-9.93; P = .02) and 30 days (odds ratio, 3.63; 95% CI, 1.59-8.30; P = .002) compared with those who received antibiotics within 330 minutes.

CONCLUSIONS AND RELEVANCE: In this cohort of pediatric patients with sepsis, 3-day and 30-day sepsis-attributable mortality increased with delays in antibiotic administration 330 minutes or longer from emergency department arrival. These findings are consistent with the literature demonstrating increased pediatric sepsis mortality associated with antibiotic administration delay. To guide the balance of appropriate resource allocation with time for adequate diagnostic evaluation, further research is needed into whether there are subpopulations, such as those with shock or bacteremia, that may benefit from earlier antibiotics.

PMID:38837160 | DOI:10.1001/jamanetworkopen.2024.13955

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Cannabis Use Reported by Patients Receiving Primary Care in a Large Health System

JAMA Netw Open. 2024 Jun 3;7(6):e2414809. doi: 10.1001/jamanetworkopen.2024.14809.

ABSTRACT

IMPORTANCE: Despite the changing legal status of cannabis and the potential impact on health, few health systems routinely screen for cannabis use, and data on the epidemiology of cannabis use, and especially medical cannabis use among primary care patients, are limited.

OBJECTIVE: To describe the prevalence of, factors associated with, and reasons for past-3 month cannabis use reported by primary care patients.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used electronic health record data from patients aged 18 years and older who had an annual wellness visit between January 2021 and May 2023 from a primary care clinic within a university-based health system in Los Angeles, California.

EXPOSURES: Factors of interest included age, race and ethnicity, sex, employment status, and neighborhood Area Deprivation Index (ADI).

MAIN OUTCOMES AND MEASURES: Cannabis use was assessed using the Alcohol Substance Involvement Screening Test (ASSIST). Patients were also asked about reasons for use, symptoms for which they used cannabis, and mode of use.

RESULTS: Among the 175 734 patients screened, the median (range) age was 47 (18-102) years; 101 657 (58.0%) were female; 25 278 (15.7%) were Asian, 21 971 (13.7%) were Hispanic, and 51 063 (31.7%) were White. Cannabis use was reported by 29 898 (17.0%), with 10 360 (34.7%) having ASSIST scores indicative of moderate to high risk for cannabis use disorder (CUD). Prevalence of cannabis use was higher among male patients than female patients (14 939 [20.0%] vs 14 916 [14.7%]) and younger patients (18-29 years, 7592 [31.0%]; ≥60 years, 4200 [8.5%]), and lower among those who lived in the most disadvantaged neighborhoods (ADI decile 9-10, 189 [13.8%]; ADI decile 1-2, 12 431 [17.4%]). The most common modes of use included edibles (18 201 [61.6%]), smoking (15 256 [51.7%]), and vaporizing (8555 [29.0%]). While 4375 patients who reported using cannabis (15.6%) did so for medical reasons only, 21 986 patients (75.7%) reported using cannabis to manage symptoms including pain (9196 [31.7%]), stress (14 542 [50.2%]), and sleep (16 221 [56.0%]). The median (IQR) number of symptoms managed was 2 (1-4), which was higher among patients who were at moderate to high risk for CUD (4 [2-6] symptoms).

CONCLUSIONS AND RELEVANCE: In this study, cannabis use and risk of CUD were common, and more than three-quarters of patients who reported any cannabis use reported doing so to manage a health-related symptom. These findings suggest that integration of information regarding cannabis use for symptom management could help provide a crucial point-of-care opportunity for clinicians to understand their patients’ risk for CUD.

PMID:38837159 | DOI:10.1001/jamanetworkopen.2024.14809

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New Supplemental Benefits and Plan Ratings Among Medicare Advantage Enrollees

JAMA Netw Open. 2024 Jun 3;7(6):e2415058. doi: 10.1001/jamanetworkopen.2024.15058.

ABSTRACT

IMPORTANCE: In 2018, the US Congress gave Medicare Advantage (MA) historic flexibility to address members’ social needs with a set of Special Supplemental Benefits for the Chronically Ill (SSBCIs). In response, the Centers for Medicare & Medicaid Services expanded the definition of primarily health-related benefits (PHRBs) to include nonmedical services in 2019. Uptake has been modest; MA plans cited a lack of evidence as a limiting factor.

OBJECTIVE: To evaluate the association between adopting the expanded supplemental benefits designed to address MA enrollees’ nonmedical and social needs and enrollees’ plan ratings.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study compared the plan ratings of MA enrollees in plans that adopted an expanded PHRB, SSBCI, or both using difference-in-differences estimators with MA Consumer Assessment of Health Care Providers and Systems survey data from March to June 2017, 2018, 2019, and 2021 linked to Medicare administrative claims and publicly available benefits and enrollment data. Data analysis was performed between April 2023 and March 2024.

EXPOSURE: Enrollees in MA plans that adopted a PHRB and/or SSBCI in 2021.

MAIN OUTCOMES AND MEASURES: Enrollee plan rating on a 0- to 10-point scale, with 0 indicating the worst health plan possible and 10 indicating the best health plan possible.

RESULTS: The study sample included 388 356 responses representing 467 MA contracts and 2558 plans in 2021. Within the weighted population of responders, the mean (SD) age was 74.6 (8.7) years, 57.2% were female, 8.9% were fully Medicare-Medicaid dual eligible, 74.6% had at least 1 chronic medical condition, 13.7% had not graduated high school, 9.7% were helped by a proxy, 45.1% reported fair or poor physical health, and 15.6% were entitled to Medicare due to disability. Adopting both a new PHRB and SSBCI benefit in 2021 was associated with an increase of 0.22 out of 10 points (95% CI, 0.4-4.0 points) in mean enrollee plan ratings. There was no association between adoption of only a PHRB (adjusted difference, -0.12 points; 95% CI, -0.26 to 0.02 points) or SSBCI (adjusted difference, 0.09 points; 95% CI, -0.03 to 0.21 points) and plan rating.

CONCLUSIONS AND RELEVANCE: Medicare Advantage plans that adopted both benefits saw modest increases in mean enrollee plan ratings. This evidence suggests that more investments in supplemental benefits were associated with improved plan experiences, which could contribute to improved plan quality ratings.

PMID:38837157 | DOI:10.1001/jamanetworkopen.2024.15058

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Genetic Testing for Global Developmental Delay in Early Childhood

JAMA Netw Open. 2024 Jun 3;7(6):e2415084. doi: 10.1001/jamanetworkopen.2024.15084.

ABSTRACT

IMPORTANCE: Global developmental delay (GDD) is characterized by a complex etiology, diverse phenotypes, and high individual heterogeneity, presenting challenges for early clinical etiologic diagnosis. Cognitive impairment is the core symptom, and despite the pivotal role of genetic factors in GDD development, the understanding of them remains limited.

OBJECTIVES: To assess the utility of genetic detection in patients with GDD and to examine the potential molecular pathogenesis of GDD to identify targets for early intervention.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter, prospective cohort study enrolled patients aged 12 to 60 months with GDD from 6 centers in China from July 4, 2020, to August 31, 2023. Participants underwent trio whole exome sequencing (trio-WES) coupled with copy number variation sequencing (CNV-seq). Bioinformatics analysis was used to unravel pathogenesis and identify therapeutic targets.

MAIN OUTCOMES AND MEASURES: The main outcomes of this study involved enhancing the rate of positive genetic diagnosis for GDD, broadening the scope of genetic testing indications, and investigating the underlying pathogenesis. The classification of children into levels of cognitive impairment was based on the developmental quotient assessed using the Gesell scale.

RESULTS: The study encompassed 434 patients with GDD (262 [60%] male; mean [SD] age, 25.75 [13.24] months) with diverse degrees of cognitive impairment: mild (98 [23%]), moderate (141 [32%]), severe (122 [28%]), and profound (73 [17%]). The combined use of trio-WES and CNV-seq resulted in a 61% positive detection rate. Craniofacial abnormalities (odds ratio [OR], 2.27; 95% CI, 1.45-3.56), moderate or severe cognitive impairment (OR, 1.69; 95% CI, 1.05-2.70), and age between 12 and 24 months (OR, 1.57; 95% CI, 1.05-2.35) were associated with a higher risk of carrying genetic variants. Additionally, bioinformatics analysis suggested that genetic variants may induce alterations in brain development and function, which may give rise to cognitive impairment. Moreover, an association was found between the dopaminergic pathway and cognitive impairment.

CONCLUSIONS AND RELEVANCE: In this cohort study of patients with GDD, combining trio-WES with CNV-seq was a demonstrable, instrumental strategy for advancing the diagnosis of GDD. The close association among genetic variations, brain development, and clinical phenotypes contributed valuable insights into the pathogenesis of GDD. Notably, the dopaminergic pathway emerged as a promising focal point for potential targets in future precision medical interventions for GDD.

PMID:38837156 | DOI:10.1001/jamanetworkopen.2024.15084

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Adjuvant Psychotherapies to Prevent Relapse in Bipolar Disorder: A Randomized Clinical Trial

JAMA Psychiatry. 2024 Jun 5. doi: 10.1001/jamapsychiatry.2024.1310. Online ahead of print.

ABSTRACT

IMPORTANCE: Several psychotherapy protocols have been evaluated as adjuncts to pharmacotherapy for patients with bipolar disorder (BD). Little is known about their comparative effectiveness.

OBJECTIVE: To compare the effectiveness of 2 types of group psychotherapy, skill-oriented, material-based cognitive behavioral therapy (SEKT) and supportive, patient-centered, emotion-focused therapy (FEST), to prevent relapse in patients with euthymic BD.

DESIGN, SETTING, AND PARTICIPANTS: This was a large, observer-blind, randomized clinical trial conducted over 18 months (posttreatment after 6 months; follow-up at 12 and 18 months). In addition to psychiatric care as usual (including mood-stabilizing medication), each participant at 9 clinical outpatient units in Germany received 24 hours of group psychotherapy over 4, full-day sessions spread over 5 months. Patients with euthymic BD type 1 (BD 1) or BD type 2 (BD 2) between the ages of 18 and 50 years were randomly assigned to 1 of 2 forms of psychotherapy, SEKT or FEST. Independent clinicians blinded to patient grouping performed assessments using structured interviews (Structured Clinical Interview for DSM Disorders and Longitudinal Interval Follow-Up Evaluation) and self-rating and clinician rating for inclusion criteria and outcome. Kaplan-Meier survival curves were calculated for time to relapse. Cox proportional hazards statistics and propensity score matching were calculated for the multivariate analysis. Study data were analyzed from March 2020 to September 2022.

INTERVENTIONS: SEKT intervention is a structured cognitive behavioral therapy integrating elements of interpersonal social rhythm therapy, and of mindfulness-based cognitive therapy. FEST psychotherapy has its roots in emotion-focused, supportive, and nondirective therapy.

MAIN OUTCOMES AND MEASURES: Recurrence of a new affective episode assessed by blinded interviewer with the LIFE interview. In addition, self-rating and clinician rating of depressive and mania symptoms as well as level of social functioning were assessed.

RESULTS: Of 348 screened referrals, 305 patients (median [IQR] age, 34 [18-50] years; 162 male [53%]) with euthymic BD 1 or BD 2 were included in the study. A total of 207 patients (68%) had BD 1, 98 (32%) had BD 2, and 278 (91%) received psychiatric care. Both therapies were equally effective in preventing recurrence of a new episode. Outcome (higher rate of new episodes) was not predicted by kind of treatment (SEKT: 69 [49%] relapse; FEST: 63 [46%] relapse) but was predicted by BD 2, comorbidity, attending all sessions, and the interaction of type of treatment by BD 1 or 2. Patients with BD 2 had the highest rate of relapse (60 [61%] relapse), in particular, when treated by SEKT (39 [70%] relapse).

CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial revealed that a structured, skill-oriented, material-based cognitive behavioral therapy (SEKT) and a supportive, patient-centered, emotion-focused therapy (FEST) were equally effective in preventing relapse of affective episodes when delivered in a new, intensive group format. Additionally, there were baseline factors, in particular BD 2, that influenced outcomes.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02506322.

PMID:38837133 | DOI:10.1001/jamapsychiatry.2024.1310