Category: Statistics

JAMA Netw Open. 2024 Jun 3;7(6):e2418148. doi: 10.1001/jamanetworkopen.2024.18148.

ABSTRACT

IMPORTANCE: Recent evidence suggests that childhood levels of serum lipids, blood pressure, body mass index (BMI), and smoking contribute to adult risk of cardiovascular disease (CVD). Evidence is lacking on whether this is independent of adult risk levels.

OBJECTIVE: To quantify direct and indirect effects of childhood risk factors on adult CVD via adulthood risk factors using mediation analysis, and to quantify their relative importance during different life-course stages using a life-course approach.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study followed participants from the US, Finland, and Australia from childhood (1970s-1990s) until 2019, with data on CVD risk factors in childhood and adulthood. Longitudinal childhood and adulthood risk factors were summarized to describe BMI, lipids, and blood pressure cumulatively. Childhood and adulthood smoking were assessed with questionnaires. Data analysis was performed May 2022 to August 2023.

MAIN OUTCOMES AND MEASURES: The primary outcomes were fatal and nonfatal cardiovascular events in adulthood. Mediation analysis was used to estimate the direct and indirect effects of the childhood risk factors with CVD events, reported as incidence rate ratios (RRs) and 95% CIs.

RESULTS: A total of 10 634 participants (4506 male participants [42.4%]; mean [SD] age at childhood visit, 13.3 [3.0] years; mean [SD] age at adulthood visit, 32.3 [6.0] years) were included in the cohort. The mean (SD) age at CVD event or censoring was 49.2 (7.0) years. The median (IQR) follow-up time was 23.6 (18.7-30.2) years. Childhood risk factors, (low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC], triglycerides, systolic blood pressure [SBP], smoking, BMI, and a combined score of these) were associated with CVD. BMI (direct effect for incidence RR per 1 SD unit, 1.18; 95% CI, 1.05-1.34) and LDL-C (direct effect incidence RR, 1.16; 95% CI, 1.01-1.34) in particular were found to play an important role via direct pathways, whereas the indirect effects were larger for TC, triglycerides, SBP, and the combined score. Childhood smoking only affected CVD via adulthood smoking. Life-course models confirmed that for the risk of CVD, childhood BMI plays nearly as important role as adulthood BMI, whereas for the other risk factors and the combined score, adulthood was the more important period.

CONCLUSIONS AND RELEVANCE: In this cohort study of 10 634 participants, childhood risk factors were found to be associated both directly and indirectly to adult CVD, with the largest direct effect seen for BMI and LDL-C. These findings suggest that intervention for childhood risk factors, in particular BMI, is warranted to reduce incidence of adult CVD as it cannot be fully mitigated by risk factor management in adulthood.

PMID:38913374 | DOI:10.1001/jamanetworkopen.2024.18148

JAMA Netw Open. 2024 Jun 3;7(6):e2418226. doi: 10.1001/jamanetworkopen.2024.18226.

ABSTRACT

IMPORTANCE: Major concerns regarding individuals who adhere to a vegan diet are whether they meet protein and essential amino acid recommendations and how reliant they are on ultraprocessed foods.

OBJECTIVES: To investigate whether individuals who adhere to a vegan diet meet protein and essential amino acid recommendations and, as secondary objectives, to determine ultraprocessed food intake and potential factors associated with inadequate protein intake in this population.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional survey study was conducted between September 2021 and January 2023 in Brazil among male and female adults (aged 18 years or older) who adhered to a vegan diet recruited from social media platforms.

EXPOSURE: Adherence to a vegan diet and unprocessed and minimally processed foods and ultraprocessed food consumption.

MAIN OUTCOMES AND MEASURES: Protein and essential amino acid intake and food consumption by processing level were assessed using a 1-day food diary. Nutrient adequacy ratios were calculated by dividing nutrient intake by its recommendation (using scores truncated at 1) for each participant and then finding the mean across participants for each nutrient. The mean adequacy ratio was the mean of all nutrient adequacy ratios.

RESULTS: Of 1014 participants who completed the survey, 774 individuals (median [IQR] age, 29 [24-35] years; 637 female [82.3%]) were confirmed as adhering to a vegan diet and provided adequate food recalls, among whom 558 individuals reported body weight and so had relative protein and amino acid intake values available. The median (IQR) body mass index (calculated as weight in kilograms divided by height in meters squared) of participants was 22.6 (20.3-24.8). The nutrient adequacy ratio of protein was 0.93 (95% CI, 0.91-0.94); for essential amino acids, ratios ranged from 0.90 (95% CI, 0.89-0.92) for lysine to 0.98 (95% CI, 0.97-0.99) for phenylalanine and tyrosine. The mean adequacy ratio for protein and all amino acids was 0.95 (95% CI, 0.94-0.96). The median intake level was 66.5% (95% CI, 65.0%-67.9%) of total energy intake for unprocessed and minimally processed food and 13.2% (95% CI, 12.4%-14.4%) of total energy intake for ultraprocessed food. Adjusted logistic regression models showed that consuming protein supplements (odds ratio [OR], 0.06 [95% CI 0.02-0.14]; P < .001) or textured soy protein (OR, 0.32 [95% CI, 0.17-0.59]; P < .001) was associated with decreased odds of inadequate protein intake. Higher ultraprocessed food intake levels were also associated with decreased odds of inadequate protein intake (eg, fourth vs first quartile of intake: OR, 0.16 [95% CI, 0.07-0.33]; P < .001), and higher unprocessed and minimally processed protein intake levels were associated with increased odds of inadequate protein intake (eg, fourth vs first quartile of intake: OR, 12.42 [95% CI, 5.56-29.51]; P < .001).

CONCLUSIONS AND RELEVANCE: In this study, most individuals who adhered to a vegan diet attained protein and essential amino acid intake recommendations, largely based their diet of unprocessed and minimally processed food, and had a significantly lower proportion of ultraprocessed food intake compared with previous reports. Participants consuming less ultraprocessed food were more likely to have inadequate protein intake, suggesting a significant reliance on ultraprocessed proteins for this population.

PMID:38913373 | DOI:10.1001/jamanetworkopen.2024.18226

JAMA Intern Med. 2024 Jun 24. doi: 10.1001/jamainternmed.2024.1640. Online ahead of print.

ABSTRACT

IMPORTANCE: Data describing the early additional protection afforded by the recently recommended BNT162b2 XBB vaccine (Pfizer-BioNTech; 2023-2024 formulation) are limited.

OBJECTIVE: To estimate the association between receipt of the BNT162b2 XBB vaccine and medically attended COVID-19 outcomes among US adults 18 years and older.

DESIGN, SETTING, AND PARTICIPANTS: This test-negative case-control study was performed to estimate the effectiveness of the BNT162b2 XBB vaccine against COVID-19-associated hospitalization and emergency department (ED) or urgent care (UC) encounters among adults in the Kaiser Permanente Southern California health system between October 10, 2023, and December 10, 2023. Cases were those presenting with an acute respiratory illness and who had a positive SARS-CoV-2 polymerase chain reaction test; controls had an acute respiratory illness but tested negative for SARS-CoV-2.

EXPOSURE: The primary exposure was receipt of the BNT162b2 XBB vaccine compared with not receiving an XBB vaccine of any kind, regardless of prior COVID-19 vaccination or SARS-CoV-2 infection history. Receipt of prior (non-XBB) versions of COVID-19 vaccines was also compared with being unvaccinated to estimate remaining protection from older vaccines.

MAIN OUTCOMES AND MEASURES: Analyses for cases and controls were conducted separately for COVID-19 hospital admissions and ED/UC encounters. Adjusted odds ratios and 95% CIs were estimated from multivariable logistic regression models that were adjusted for patient demographic and clinical characteristics. Estimation of vaccine effectiveness was calculated as 1 – odds ratio × 100%.

RESULTS: Among 2854 cases and 15 345 controls (median [IQR] age, 56 [37-72] years; 10 658 [58.6%] female), adjusted estimation of effectiveness of the BNT162b2 XBB vaccine received a median of 34 days prior vs not having received an XBB vaccine of any kind was 62% (95% CI, 32%-79%) against COVID-19 hospitalization and 58% (95% CI, 48%-67%) for ED/UC visits. Compared with being unvaccinated, those who had received only older versions of COVID-19 vaccines did not show statistically significant reduced risk of COVID-19 outcomes, including hospital admission.

CONCLUSIONS AND RELEVANCE: Findings of this case-control study reaffirm current recommendations for broad age-based use of annually updated COVID-19 vaccines given that (1) the BNT162b2 XBB vaccine provided statistically significant additional protection against a range of COVID-19 outcomes and (2) older versions of COVID-19 vaccines offered little, if any, long-term protection, including against hospital admission, regardless of the number or type of prior doses received.

PMID:38913355 | DOI:10.1001/jamainternmed.2024.1640

JAMA Pediatr. 2024 Jun 24. doi: 10.1001/jamapediatrics.2024.0885. Online ahead of print.

ABSTRACT

IMPORTANCE: Prior observational research has shown that infants born in states with more abortion restrictions are more likely to die during infancy. It is unclear how recent and more severe abortion bans in the US have impacted infant mortality.

OBJECTIVE: To examine whether Texas Senate Bill 8 (SB8), which banned abortions after embryonic cardiac activity and did not allow exemptions for congenital anomalies, is associated with infant mortality in the state of Texas.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study of all recorded infant deaths from the state of Texas and 28 comparison states used a comparative interrupted time series analysis with an augmented synthetic control approach and national birth certificate data from January 1, 2018, to December 31, 2022, to estimate the difference between the number of observed and expected infant and neonatal deaths and death rates among monthly cohorts exposed to Texas’ SB8.

EXPOSURE: Deaths in March 2022 were treated as the first cohort exposed to the Texas’ SB8 abortion policy because these infants (if born full term) were approximately 10 to 14 weeks’ gestation when SB8 went into effect on September 1, 2021. The exposure period was thus March through December 2022.

MAIN OUTCOMES AND MEASURES: Our outcomes were monthly counts and rates of infant (aged <1 year) and neonatal (aged <28 days) deaths in the exposure period in Texas. In secondary analyses, annual changes in cause-specific infant deaths between 2021 and 2022 in Texas and the rest of the US were examined.

RESULTS: Between 2018 and 2022, there were 102 391 infant deaths in the US, with 10 351 of these deaths occurring in the state of Texas. Between 2021 and 2022, infant deaths in Texas increased from 1985 to 2240, or 255 additional deaths. This corresponds to a 12.9% increase, whereas the rest of the US experienced a comparatively lower 1.8% increase. On the basis of the counterfactual analysis that used data from Texas and eligible comparison states, an excess of 216 infant deaths (95% CI, -122 to 554) was observed from March to December 2022, or a 12.7% increase above expectation. At the monthly level, significantly greater-than-expected counts were observed for 4 months between March and December 2022: April, July, September, and October. An analysis of neonatal deaths found somewhat similar patterns, with significantly greater-than-expected neonatal deaths in April and October 2022. Descriptive statistics by cause of death showed that infant deaths attributable to congenital anomalies in 2022 increased more for Texas (22.9% increase) but not the rest of the US (3.1% decrease).

CONCLUSIONS AND RELEVANCE: This study found that Texas’ 2021 ban on abortion in early pregnancy was associated with unexpected increases in infant and neonatal deaths in Texas between 2021 and 2022. Congenital anomalies, which are the leading cause of infant death, also increased in Texas but not the rest of the US. Although replication and further analyses are needed to understand the mechanisms behind these findings, the results suggest that restrictive abortion policies may have important unintended consequences in terms of trauma to families and medical cost as a result of increases in infant mortality. These findings are particularly relevant given the recent Dobbs v Jackson Women’s Health Organization US Supreme Court decision and subsequent rollbacks of reproductive rights in many US states.

PMID:38913344 | DOI:10.1001/jamapediatrics.2024.0885

J Clin Sleep Med. 2024 Jun 24. doi: 10.5664/jcsm.11238. Online ahead of print.

ABSTRACT

STUDY OBJECTIVES: Pediatric obstructive sleep apnea (OSA) is common, however, inclusion of adolescents and especially those of ethnic/racial minorities in research is scarce. We hypothesized that ethnic/racial minority adolescents undergoing polysomnography (PSG) have higher prevalence and more severe OSA compared to those who are non-Hispanic (NH) White.

METHODS: Retrospective review of 1,745 adolescents undergoing diagnostic PSG. Demographic characteristics, age, body mass index percentile (BMIp), and PSG parameters were obtained. Descriptive statistics comparing race/ethnicity were analyzed. Linear regression of log-transformed obstructive apnea-hypopnea index (OAHI), and logistic regression of moderate-severe OSA (OAHI ≥ 5 events/h) adjusting for covariates were analyzed.

RESULTS: 58.2% adolescents were Hispanic, 24.1% NH-White, 4.3% NH-Asian/Pacific Islander (PI), 4.2% NH-Black/African American (AA), and 6.6% NH-other. Compared to the NH-White group, the Hispanic group had higher OAHI and any level of OSA severity; the Black/AA group had higher moderate-severe and severe OSA, and the NH-Asian group had higher moderate-severe OSA. Multiple linear regression of log-OAHI identified an association with Hispanic ethnicity (β: 0.25, P-value < .05). Compared to the NH-White group, the Hispanic and the Asian/PI groups were 1.45 (95% CI: 1.10, 1.93) and 1.81 (95% CI: 1.05, 3.10) times more likely to have moderate-severe OSA, respectively, after adjusting for relevant covariates. Stratified analysis by sex identified an association only among males between Hispanic ethnicity (OR: 1.85, 95% CI: 1.27, 2.70) and Asian/PI ethnicity (OR: 2.62, 95% CI: 1.35, 5.11) and moderate-severe OSA, compared to the NH-White group.

CONCLUSIONS: Among adolescents undergoing PSG evaluation, we identified OSA racial/ethnic and sex disparities in Hispanic and NH-Asian adolescents. Community level studies with adequate representation of these minority groups are needed to identify factors associated with the reported increased susceptibility.

PMID:38913342 | DOI:10.5664/jcsm.11238

Methods Mol Biol. 2024;2825:309-331. doi: 10.1007/978-1-0716-3946-7_18.

ABSTRACT

Across eukaryotes, genome stability is essential for normal cell function, physiology, and species survival. Aberrant expression of key genes or exposure to genotoxic agents can have detrimental effects on genome stability and contribute to the development of various diseases, including cancer. Chromosome instability (CIN), or ongoing changes in chromosome complements, is a frequent form of genome instability observed in cancer and is a driver of genetic and cell-to-cell heterogeneity that can be rapidly detected and quantitatively assessed using surrogate markers of CIN. For example, single cell quantitative imaging microscopy (QuantIM) can be used to simultaneously identify changes in nuclear areas and micronucleus formation. While changes in nuclear areas are often associated with large-scale changes in chromosome complements (i.e., ploidy), micronuclei are small extra-nuclear bodies found outside the primary nucleus that have previously been employed as a measure of genotoxicity of test compounds. Here, we present a facile QuantIM approach that allows for the rapid assessment and quantification of CIN associated phenotypes and genotoxicity. First, we provide protocols to optimize and execute CIN and genotoxicity assays. Secondly, we present the critical imaging settings, optimization steps, downstream statistical analyses, and data visualization strategies employed to obtain high quality and robust data. These approaches can be easily applied to assess the prevalence of CIN associated phenotypes and genotoxic stress for a myriad of experimental and clinical contexts ranging from direct tests to large-scale screens of various genetic contexts (i.e., aberrant gene expression) or chemical compounds. In summary, this QuantIM approach facilitates the identification of novel CIN genes and/or genotoxic agents that will provide greater insight into the aberrant genes and pathways underlying CIN and genotoxicity.

PMID:38913318 | DOI:10.1007/978-1-0716-3946-7_18

Updates Surg. 2024 Jun 24. doi: 10.1007/s13304-024-01923-2. Online ahead of print.

ABSTRACT

This study aims to explore the safety and efficacy of 3D laparoscopy in elderly patients undergoing transabdominal preperitoneal (TAPP) surgery for inguinal hernia. Patients were divided into two groups based on the laparoscopic equipment used during surgery. Clinical data preoperatively, intraoperatively, and postoperatively were collected and subjected to statistical analysis. From January 2020 to August 2023, a total of 127 patients with primary unilateral inguinal hernia were evaluated in this study, 61 in the 3D TAPP group and 66 in the 2D TAPP group. There were no statistically significant differences in baseline data, including average age, gender distribution, BMI index, hernia type, hernia defect size and location, comorbidities, and usage of anticoagulant drugs between the two groups (P > 0.05). In terms of operative indicators, the 3D group showed shorter mean operation time (51.61 ± 7.16 min vs. 78.59 ± 13.51 min, P < 0.001), mean mesh placement time (6.07 ± 1.40 min vs. 9.77 ± 1.21 min, P < 0.001), and mean peritoneal suture time (7.34 ± 1.85 min vs. 9.73 ± 1.32 min, P < 0.001) compared to the 2D group. However, there were no statistically significant differences in mean blood loss, postoperative pain scores, postoperative hospital stay, and total hospital costs between the two groups (P > 0.05). The incidence of postoperative complications did not differ significantly between the two groups (P > 0.05). No adverse reactions such as dizziness or nausea were reported by surgeons during the procedures in either group. Three-dimensional laparoscopy in TAPP surgery provides high-definition, three-dimensional surgical images, reducing the difficulty of operations and effectively shortening the operation time.

PMID:38913298 | DOI:10.1007/s13304-024-01923-2

Updates Surg. 2024 Jun 24. doi: 10.1007/s13304-024-01918-z. Online ahead of print.

ABSTRACT

The recommended treatment for early stage thymoma without myasthenia gravis is complete thymectomy (CT). Limited thymectomy (LT) (simply resecting the thymoma with safe surgical margins) is gaining popularity. In this study, we compared the surgical and oncological results of complete and limited thymectomy in non-myasthenic patients with early stage thymoma. Non-myasthenic, Masaoka stage I-II, 86 patients who underwent surgical resection for thymoma were included in the study. Complete thymectomy (n:44) included patients who had resection of the thymoma together with the entire thymus and limited thymectomy (n:42) included patients who had resection of the thymoma without remaining thymus. The surgical approach, tumor size, histological type, pathological stage, adjuvant therapy, complications, postop myasthenia gravis, recurrence and death were recorded and compared between groups. Complete thymectomy group had more WHO type B1-3 tumors, more complications and more deaths than patients in the limited thymectomy group (p = 0.03, 0.018 and 0.023 respectively). Although statistically not significant CT group had more recurrences than LT group (11.4%/4.8%, p = 0.43). The 10-year freedom from recurrence (FFR) rate in the CT group was 84.8% and in the LT group ıt was 97.6%, the difference was not statistically significant (p = 0.15). None of the factors including surgical extent analysed with univariate and multivariate analysis had a significant effect on FFR. Limited thymectomy may be a good treatment option for non-myasthenic early stage thymoma patients but randomized controlled trials with long follow-up periods, ideally comparing patients operated with minimally invasive surgery are necessary.

PMID:38913297 | DOI:10.1007/s13304-024-01918-z

Am J Cardiovasc Drugs. 2024 Jun 24. doi: 10.1007/s40256-024-00654-4. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels.

METHODS: A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I² index. The risk of bias was assessed using Cochrane’s RoB 2 tool. This review has been registered with PROSPERO (CRD42023471020).

RESULTS: A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = – 63.78, 95% CI – 65.88 to – 61.68, p value < 0.00001, I² = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, p value < 0.00001, I² = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, p value < 0.00001, I² = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB 2 tool.

CONCLUSIONS: Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations.

REGISTRATION: PROSPERO identifier number CRD42023471020.

PMID:38913274 | DOI:10.1007/s40256-024-00654-4

J Nephrol. 2024 Jun 24. doi: 10.1007/s40620-024-01983-y. Online ahead of print.

ABSTRACT

BACKGROUND: Itching is an annoying symptom which afflicts patients with chronic renal failure. We aimed to assess the impact and patient’s perception and experience of itching in the dialysis population in Italy.

METHODS: A questionnaire was developed by the National Hemodialysis and Dialysis Association of Italy (ANED) and administered to 996 hemodialysis recipients across 153 Italian dialysis centers. The main outcomes investigated by the questionnaire were patients’ satisfaction on answers regarding the nature of itching; continuing to talk about itching with the nephrologist; beliefs about resolution of itching.

RESULTS: A total of 1903 patients from 153 centers responded to the questionnaire. Patients who responded had a mean age of 67.9 ± 13.8 years (63.9% male) and were stratified by itch discomfort graded as mild (35.9%), moderate (29.6%), and severe (34.4%). Severe itching disrupted patients’ daily lives, strained their relationships, caused anxiety, and diminished their quality of life. Patients with severe itch were more likely to talk about it with dialysis staff and to undertake dermatological visits. However, only 18.0% of patients reporting severe itching found the clinicians’ responses satisfactory, compared to 49.1% of mild itch patients. Those who continued talking to nephrologists about itching received more satisfactory response. However, 40.8% believed itching could not be alleviated and were less likely to discuss it with nephrologists.

CONCLUSIONS: There is an intricate relationship between the severity of itching, patient perceptions, and healthcare communication among hemodialysis patients. A substantial proportion of patients experiencing severe itching expressed feelings of resignation, highlighting the pressing need for enhanced clinician-patient communication.

PMID:38913267 | DOI:10.1007/s40620-024-01983-y