Risk Difference Research Articles

Predictors of early secondary IOL implantation after pediatric cataract surgery

BackgroundPediatric aphakia may be treated conservatively with aphakic contacts or spectacles. Many families and surgeons opt for a secondary intraocular lens (IOL) when the child is older. In certain situations, pediatric aphakic patients must undergo implantation earlier than planned. The purpose of this study was to investigate how often and why early implantation occurs. MethodsWe retrospectively reviewed the medical records of consecutive patients who were left aphakic after cataract surgery in infancy and were seen at our institute at ≥4 years of age. Early implantation was defined as occurring at <4 years of age. ResultsA total of 175 patients fit inclusion criteria. We found that 22 of 90 patients (24%) with unilateral cataracts had undergone early secondary IOL implantation before 4 years of age compared to 10 of 85 patients (12%) with bilateral cataracts, a statistically significant difference in the relative risk of early implantation (OR 2.43 [95% CI 1.07-5.49]). Of our patients undergoing early implantation, 15 of 31 (44%) had Medicaid as the primary insurance provider, which is representative of the practice overall. In patients requiring early implantation, failure with contact lens accounted for 26 of 32 cases (81%), with 7 of 26 (27%) of these failures attributed to nonmedical reasons. ConclusionsOf the factors we analyzed, only the presence of unilateral aphakia was associated with increased risk of early IOL implantation in our study cohort.

Probable antibody-mediated rejection in kidney transplantation is a rare and challenging phenotype to define: Findings from a single-center study

The Banff 2022 consensus introduced probable antibody-mediated rejection (AMR), characterized by mild AMR histologic features and human leukocyte antigen (HLA) donor-specific antibody (DSA) positivity. In a single-center observational cohort study of 1891 kidney transplant recipients transplanted between 2004 and 2021, 566 kidney biopsies were performed in 178 individual HLA-DSA–positive transplants. Evaluated at time of the first HLA-DSA–positive biopsy of each transplant (N = 178), 84 of the 178 (47.2%) of first biopsies were scored as no AMR, 22 of the 178 (12.4%) as probable AMR, and 72 of the 178 (40.4%) as AMR. The majority (77.3%) of probable AMR cases were first diagnosed in indication biopsies. Probable AMR was associated with lower estimated glomerular filtration rate (mL/min/1.73m2) than no AMR (20.2 [8.3-32.3] vs 40.1 [25.4-53.3]; P = .001). The one-year risk of (repeat) AMR was similar for probable AMR and AMR (subdistribution hazard ratio (sHR), 0.99; 0.42-2.31; P = .97) and higher than after no AMR (sHR, 3.05; 1.07-8.73; P = .04). Probable AMR had a higher five-year risk of transplant glomerulopathy vs no AMR (sHR, 4.29; 0.92-19.98; P = 06), similar to AMR (sHR, 1.74; 0.43-7.04; P = .44). No significant differences in five-year risk of graft failure emerged between probable AMR and AMR (sHR, 1.14; 0.36-3.58; P = .82) or no AMR (sHR, 2.46; 0.78-7.74; P = .12). Probable AMR is a rare phenotype, however, sharing significant similarities with AMR in this single-center study. Future studies are needed to validate reproducible diagnostic criteria and associated clinical outcomes to allow for defining best management of this potentially relevant phenotype.

Regional variation in donation after circulatory death heart allograft utilization

ObjectiveRandomized data support transplantation of hearts from donors after circulatory death. This may lead to a sizeable increase in the donor pool. Regional variations in donors after circulatory death heart use were examined to help elucidate barriers to donor pool expansion. MethodsThe United Network for Organ Sharing deceased donor dataset was queried for adult (age ≥ 18 years) donors after circulatory death donors of at least 1 organ between January 2020 and December 2023. Donors were stratified by the extent their respective cardiac allografts progressed through the donation process. United Network for Organ Sharing region-level use rates and annual trends were assessed. ResultsOf 17,239 adult donors after circulatory death donors who donated at least 1 organ for transplant during the study period, 1196 (9.4%) were heart donors. Regional donors after circulatory death heart donor pursuit rates ranged from 97% to 100%, consent attainment rates from 94% to 99%, and heart recovery rates from 5% to 10%. The transplantation rate of recovered organs ranged from 90% to 97%. Multivariable logistic regression demonstrated United Network for Organ Sharing region to be independently associated with donors after circulatory death heart use after controlling for baseline differences in donor risk. ConclusionsTransplantation of donors after circulatory death heart allografts has increased in the United States since 2020, but the overall number of hearts procured and transplanted from donors after circulatory death donors remains low. The operational barriers to transplantation of donors after circulatory death hearts require further investigation. Further, significant regional variation exists regarding rates of progression of donors after circulatory death hearts through the donation process. Sharing of successful practices among Organ Procurement Organizations and transplant centers will facilitate maximal use of this new donor pool.

Long-term cardiovascular risk reduction after gastric cancer surgery: a nationwide cohort study.

Gastrectomy for gastric cancer is associated with postoperative changes in cardiovascular risk factors, however, the impact of gastrectomy on cardiovascular events remains unclear. We assessed the incidence of cardiovascular events between patients undergoing gastrectomy or endoscopic resection for gastric cancer, and the general population. This retrospective nationwide cohort study included patients with gastric cancer undergoing gastrectomy(n=37,698), endoscopic resection(n=2,773), and matched control population(n=161,887) between 2004 and 2013. We included patients without a history of cancer other than gastric cancer, myocardial infarction, or ischemic stroke. The primary outcome was the incidence of major adverse cardiovascular events (MACE) such as acute myocardial infarction, revascularization, or acute ischemic stroke, in patients with gastric cancer. Among patients who underwent gastrectomy for gastric cancer, 2.9% (4.69 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The gastrectomy group demonstrated a significantly decreased risk for MACE than the control population (hazard ratio[HR], 0.65; 95% confidence interval[CI], 0.61-0.69; P <0.001). Among the patients undergoing endoscopic resection for gastric cancer, 5.4% (8.21 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The risk for MACE in the endoscopic resection group was not significantly different from the control population. Patients with gastric cancer who have undergone gastrectomy exhibit a reduced risk of cardiovascular diseases in comparison to the general population. In contrast, the risk for cardiovascular diseases in patients with gastric cancer who underwent endoscopic resection did not demonstrate a significant difference in cardiovascular risk in comparison to the general population.

Revisiting Waist Circumference: A Hypertension Risk Factor that Requires a More In-depth Understanding.

As a major cause of various cardiovascular diseases, the prevalence of hypertension has been increasing in the past 30 years, leading to significant socioeconomic and health burdens. Obesity is one of the major risk factors for hypertension. Body mass index (BMI) is the most used anthropometric index to measure obesity in clinical practice and to assess the risk of obesity-related diseases. However, obesity is a heterogeneous disease, and the accumulation of fat in different body regions leads to differences in cardiovascular and metabolic risks. BMI only reflects the overall obesity but does not consider the distribution of fat and muscle mass. The limitation of BMI makes it insufficient to assess the risk of hypertension attributed to obesity. In addition, waist circumference is an easily obtainable anthropometric index to evaluate abdominal fat distribution. High waist circumference is an independent risk factor for various cardiovascular diseases and all-cause mortality regardless of BMI. Preliminary data indicate that waist circumference is significantly associated with the risk of hypertension at different BMI levels. However, routine measurement of waist circumference is currently not required in current clinical guidelines or is only recommended for obese populations, indicating an insufficient understanding of waist circumference. In this review, we summarize the measurement methods and diagnostic thresholds of waist circumference for abdominal obesity, the trend of central obesity prevalence, the superiority of waist circumference over other anthropometric indices, and recent cross-sectional and longitudinal studies on the association between obesity and hypertension.

Investigating Thoracic Vertebral Fractures in Residential Environments

IntroductionThoracic vertebral fractures within homes are pivotal public health concerns due to their associated morbidity and significant healthcare expenditures. This study aims to dissect the intricate epidemiology of these injuries, integrating comprehensive risk factors beyond conventional demographics and location analyses. MethodsUtilizing a decade of data (2013-2022) from the National Electronic Injury Surveillance System (NEISS), this study examines thoracic vertebral fractures across age and gender in household settings. Inclusion criteria targeted specific thoracic spine-related terms, analyzing fractures by location (e.g., kitchen, stairs) and associated products. Data processing employed R programming, with statistical analysis focusing on descriptive statistics and multivariate logistic regression to identify fracture patterns and assess gender differences in fracture risks through Adjusted Odds Ratios (AORs). ResultsAnalysis of 46,371 thoracic vertebral fractures identified stairs as the primary site (26.81%), with subsequent frequent locations being bedrooms (18.52%), living rooms (17.88%), and kitchens (16.29%). Gender-specific risk analysis revealed females had a higher likelihood of fractures on stairs (AOR = 1.24, 95% CI: 1.16-1.37, p < .001) and in bedrooms (AOR = 1.13, 95% CI: 1.09-1.54, p < .001). The most affected age group was 51-60, showcasing the multifaceted nature of risk factors beyondmere location. DiscussionThis study transcends prior insights by detailing the influence of various factors, including socioeconomic status and lifestyle, on fracture risk. It emphasizes the complexity of household fractures, highlighting gender and age as pivotal but not exclusive risk determinants. ConclusionBy offering a comprehensive analysis that incorporates a wide array of risk factors, this study advances the understanding of thoracic vertebral fractures in residential environments. It underscores the necessity for targeted preventive measures that are cognizant of the multifactorial nature of these injuries, paving the way for improved safety interventions and public health policies.

Population-scale variability of the human UDP-glycosyltransferase gene family

Human UDP-glycosyltransferases (UGTs) are responsible for the glucuronidation of a wide variety of endogenous substrates and multiple commonly prescribed drugs. Different genetic polymorphisms in UGT genes are implicated in interindividual differences in drug response and cancer risk. However, the genetic complexity beyond these variants has not been comprehensively assessed. We here leveraged whole-exome and whole-genome sequencing data from 141,456 unrelated individuals across seven major human populations to provide a comprehensive profile of genetic variability across the human UGT gene family. Overall, 9666 exonic variants were observed of which 98.9% were rare. To interpret the functional impact of UGT missense variants, we developed a gene family-specific variant effect predictor. This algorithm identified a total of 1208 deleterious variants, most of which were found in African and South Asian populations. Structural analysis corroborated the predicted effects for multiple variations in substrate binding sites. Combined, our analyses provide a systematic overview of UGT variability, which can yield insights into interindividual differences in phase 2 metabolism and facilitate the translation of sequencing data into personalized predictions of UGT substrate disposition.

Left ventricular mass as a modulator of ventricular arrhythmia risk and sex differences after CRT for nonischemic cardiomyopathy and LBBB

BackgroundThe risk of ventricular arrhythmias (VAs) after cardiac resynchronization therapy (CRT) has been associated with ischemic disease/scar, sex, and possibly left ventricular mass (LVM). ObjectiveThe purpose of this study was to evaluate sex differences and baseline/postimplant change in LVM on VA risk after CRT implantation in patients with nonischemic cardiomyopathy and left bundle branch block. MethodsIn patients meeting the criteria, baseline and follow-up echocardiographic images were obtained for LVM assessment. VA events were reported from device diagnostics and therapies. VA risk was stratified by receiver operating characteristic (Youden index cutoff point) for baseline LVM and baseline/postimplant change in LVM, and baseline patient characteristics by using a multivariable Cox regression model. ResultsOne hundred eighteen patients (71 female [60.2%]; mean age 60.5 ± 11.3 years; left ventricular ejection fraction 19.2% ± 7.0%; QRS duration 165.6 ± 20 ms; LVM 313.9 ± 108.8 g) were enrolled and followed up for a median of 90 months (interquartile range 44–158 months). Thirty-five patients (29.6%) received appropriate shocks or antitachycardia pacing at a median of 73.5 months (interquartile range 25–130 months) postimplantation. Males had a higher VA incidence (male 18 of 47 [38.3%] vs female 17 of 71 [23.9%]; P = .02). Baseline LVM > 308.9 g separated patients with higher VA risk (P = .001). Less than a 20% decrease in LVM increased VA risk (P < .001). Baseline LVM was the only baseline characteristic predicting VA events in the Cox regression model (hazard ratio 1.01; 95% confidence interval 1.001–1.009; log-rank, P = .003). Sex differences in VA risk were eliminated by the baseline LVM parameters. ConclusionVA risk after CRT in nonischemic cardiomyopathy was associated with baseline LV > 308.9 g and a decrease in LVM ≤ 20%, without sex differences.

Lifestyle modifies the associations of early-life smoking behaviors and genetic susceptibility with type 2 diabetes: A prospective cohort study involving 433,872 individuals from UK Biobank

BackgroundTo investigate whether and what lifestyle factors in later life modify the associations of early-life smoking behaviors and genetic susceptibility with type 2 diabetes (T2D). MethodsIn the UK Biobank, in utero tobacco exposure (n=354,493) and age of smoking initiation (n=353,557) were self-reported. A composite lifestyle score was calculated based on diet, physical activity, nicotine exposure, sleep duration, and BMI. Hazard ratio (HR) and absolute risk difference (ARD) were used to estimate the associations of early-life smoking behaviors and genetic risk with incident T2D, as well as the effect modification of the lifestyle score. ResultsDuring a median follow-up of 14.6 years, the HRs (95% CIs) of T2D for in utero tobacco exposure, and smoking initiation in adulthood, adolescence, and childhood, compared with no smoking behavior, were 1.19 (1.16-1.23), 1.34 (1.29-1.39), 1.58 (1.53-1.64), 2.22 (2.11-2.32), respectively (P for trend<0.001). Early-life smoking behaviors and high genetic risk (vs no smoking behavior and low genetic risk) were associated with a 302%-593% higher T2D risk (P for additive interaction<0.05). Compared to participants with early-life smoking behaviors, high genetic risk, and an unfavorable lifestyle, those who adhered to a favorable lifestyle had a lower T2D risk in all subgroups (HRs from 0.05 to 0.36 and ARD from -14.97% to -9.51%), with the highest ARD attributable to lifestyle in participants with early-life smoking behaviors and high genetic risk. ConclusionsThe T2D risk associated with early-life smoking behaviors and genetic risk was modified by a favorable lifestyle.

Maternal implications of fetal anomalies: a population-based cross-sectional study

BackgroundAlthough it is well-known that the presence of fetal anomalies is associated with maternal morbidity, granular information on these risks by type of anomaly is not available. ObjectiveTo examine adverse maternal outcomes according to the type of fetal anomaly. Study DesignThis was a repeated cross-sectional analysis of US vital statistics Live Birth/Infant Death linked data from 2011 to 2020. All pregnancies at 20 weeks or greater were included. Our primary outcome was severe maternal morbidity (SMM), defined as any maternal intensive care unit admission, transfusion, uterine rupture, or hysterectomy. Outcomes were compared between pregnancies with a specific type of fetal anomaly and pregnancies without any fetal anomaly. Fetal anomalies that were available in the dataset included anencephaly, meningomyelocele/spina bifida, cyanotic congenital heart disease, congenital diaphragmatic hernia, omphalocele, gastroschisis, cleft lip and/or palate, hypospadias, limb anomaly, and chromosomal disorders. If a fetus had more than one anomaly, it was classified as multiple anomalies. Adjusted relative risks (aRR) with 99% confidence intervals (99% CI) were calculated using modified Poisson regression. Adjusted risk differences (aRDs) were calculated using the marginal standardization form of predictive margins. ResultsOf 35,760,626 pregnancies included in the analysis, 35,655,624 pregnancies had no fetal anomaly and 105,002 had isolated or multiple fetal anomalies. Compared to pregnancies without fetal anomaly, all fetal anomalies were associated with an increased risk of SMM except for gastroschisis and limb anomaly in order of aRRs (99% CI): 1.58 (1.29–1.92) with cleft lip and/or palate; 1.75 (1.35–2.27) with multiple anomalies; 1.76 (1.18–2.63) with a chromosomal disorder; 2.19 (1.82–2.63) with hypospadias; 2.20 (1.51–3.21) with spina bifida; 2.39 (1.62–3.53) with congenital diaphragmatic hernia; 2.66 (2.27–3.13) with congenital heart disease; 3.15 (2.08–4.76) with omphalocele; and 3.27 (2.22–4.80) with anencephaly. Compared to pregnancies without fetal anomaly, all fetal anomalies were associated with an increased absolute risk of SMM except for gastroschisis and limb anomaly in order of aRDs (99% CI): 0.26 (0.12–0.40) with cleft lip and/or palate, 0.34 (0.13–0.55) with multiple anomalies, 0.34 (0.02–0.66) with a chromosomal disorder, 0.54 (0.36–0.72) with hypospadias, 0.54 (0.17–0.92) with spina bifida, 0.63 (0.21–1.05) with congenital diaphragmatic hernia, 0.75 (0.56–0.95) with congenital heart disease, 0.97 (0.38–1.56) with omphalocele, and 1.03 (0.46–1.59) with anencephaly. ConclusionThe presence of fetal anomalies is associated with adverse maternal health outcomes. The risk of SMM varies according to the type of fetal anomaly. Counseling mothers about the maternal implications of fetal anomalies is paramount to help them make informed decisions regarding their pregnancy outcome.

Medical abortion in Ghana: A non-randomized, non-inferiority study of access through pharmacies compared with clinics

ObjectivesTo compare self-reported clinical outcomes following medical abortion with mifepristone and misoprostol sourced from either a pharmacy or health clinic. Study designWe conducted a prospective, non-randomized, non-inferiority cohort study across four regions in Ghana, from high-volume pharmacies and health clinics. Participants seeking medical abortion (less than nine weeks’ gestation) who met usual medical abortion eligibility criteria were recruited. Data collection included baseline surveys, follow-up phone interviews, and self-reported assessments of medical abortion outcomes. The study aimed to enroll 2000 medical abortion users (1000 from each source). ResultsComplete outcome data was available and analyzed from 1958 participants (of 2208 enrolled), with the adjusted risk difference of need for additional treatment to complete the abortion indicating non-inferiority of the pharmacy group compared to the clinic group [−2.3% (95% CI −5.3% to 0.7%)]. Both groups reported low rates of additional treatment (4.9%) and adhered similarly to the abortion regimen. Secondary outcomes showed no significant differences, with moderate acceptability in both groups (65.4% pharmacy, 52.3% facility). Adverse outcomes were rare: one ectopic pregnancy, one blood transfusion and no deaths or other major complications were reported. ConclusionsAccessing medical abortion pills directly from pharmacies without prior consultation from a provider demonstrated non-inferior self-reported clinical outcomes compared to seeking care from health clinics. The findings align with the growing global evidence supporting the safety and effectiveness of medical abortion self-care. ImplicationsThis study contributes data which support future registration of over-the-counter use of medical abortion drugs up to nine weeks’ gestation. Such measures could expand options for safe abortion care, especially in regions where unsafe abortion poses a substantial maternal health risk. Trial registrationClinicalTrials.gov (NCT03727308).

Tenofovir Is Associated With a Better Prognosis Than Entecavir for Hepatitis B Virus–Related Hepatocellular Carcinoma

Whether tenofovir or entecavir has different effects on the prevention of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in secondary and tertiary preventive settings is still a matter of debate. This study aimed to compare the long-term prognosis of HCC between tenofovir and entecavir in patients with chronic hepatitis B. Chronic hepatitis B patients diagnosed with HCC between November 2008 and December 2018 and treated with either entecavir or tenofovir at a tertiary center in Korea were included. The effect of tenofovir compared with entecavir on the prognosis of HBV-related HCC was assessed using multivariable-adjusted Cox and propensity score (PS)-matched analyses. Various predefined subgroup analyses were conducted. During a median follow-up period of 3.0 years, the mortality rate for entecavir-treated patients (n= 3469) was 41.2%, while tenofovir-treated patients (n= 3056) had a mortality rate of 34.6%. Overall survival (OS) was better in the tenofovir group (adjusted hazard ratio [aHR], 0.79; P < .001), which were consistently observed in the PS-matched analysis. The magnitude of the risk difference in OS was more prominent 2 years after the diagnosis of HCC (aHR, 0.50; P < .001) than 2 years before (aHR, 0.88; P= .005), and it was more pronounced in patients with earlier HCC stages. In all subgroups, except for those with shorter life expectancy, such as those with compromised liver function, tenofovir was associated with better OS compared with entecavir. Among patients with HBV-related HCC, those treated with tenofovir had a better prognosis than those treated with entecavir, particularly among those with prolonged survival.

Additive interaction of disability with chronic conditions on mortality risk in middle-aged and older adults in Spain

BackgroundDisability and chronic diseases are prevalent conditions associated with mortality, but little information is available on their potential synergistic effects. ObjectiveThis study aimed to describe additive interactions between disability and chronic diseases on mortality risk in middle-aged and older adults. MethodsA representative cohort of 22,800 community-dwelling Spanish people aged 50 years or older were interviewed for disability with the Global Activity Limitation Indicator and specific chronic diseases in the 2011–12 and 2014 National Health Surveys and subsequently followed up for mortality. Five-year all-cause mortality risks were standardized in each disability-by-comorbidity category through inverse probability weighting. We computed interaction contrasts as the departure of the standardized risk difference for people with both conditions from the sum of the standardized risk differences for those with any single condition. ResultsThe baseline prevalence of disability was 35.1 % (95 % confidence interval [CI] 34.4 %, 35.9 %). There was compelling evidence of synergistic effects of disability with chronic liver disease, heart diseases other than myocardial infarction, cancer, and cerebrovascular disease, with large positive interaction contrasts (95 % CIs) of 106.7 (−16.4, 229.9), 45.7 (6.9, 84.5), 45.1 (−15.0, 105.2), and 42.9 (−41.0, 126.9) excess deaths per 1000 persons. Less clear synergistic responses were observed for other comorbidities. We found some evidence of antagonism for osteoporosis, with a negative interaction contrast of −18.0 (95 % CI −82.2, 46.2) deaths per 1000 persons. ConclusionGiven the high mortality risk in people with disability, the study of its synergistic effects with target comorbidities can provide relevant information regarding preventive measures.

Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial

HIV-associated lipohypertrophy, which is characterised by an abnormal accumulation of abdominal visceral adipose tissue, remains problematic in people with HIV. Effective interventions are lacking, despite HIV-associated lipohypertrophy carrying a substantial risk of cardiometabolic comorbidity. The primary aim of this trial was to investigate effects of the GLP-1 receptor agonist, semaglutide, on adipose tissue in HIV-associated lipohypertrophy. This randomised, double-blind, placebo-controlled phase 2b clinical trial was conducted at a single US site. Key inclusion criteria included people with HIV aged 18 years or older with controlled HIV-1, a BMI of 25 kg/m2 or more, and lipohypertrophy but without type 1 or type 2 diabetes. Participants were randomly assigned 1:1 to receive 32 weeks of once-weekly subcutaneous semaglutide (8-week dose titration and 24 weeks at 1·0 mg) or placebo; all research personnel and participants remained masked to treatment assignment. Primary outcomes were changes at 32 weeks in adipose tissue quantity by body compartment. Analyses, including safety, were performed using intention-to-treat principles. This trial was registered ClinicalTrials.gov (NCT04019197) and is complete. Between June 10, 2019, and July 28, 2022, 108 participants were randomly assigned to receive semaglutide (n=54) or placebo (n=54). Eight (15%) in each group withdrew prematurely. Significant effects of semaglutide were seen over the 32-week study period in sex-adjusted multiplicative regression analyses for the primary outcome, abdominal visceral adipose tissue (β -30·82 cm2, 95% CI -50·13 to -11·51; % change -30·6%). Decreases were also seen in other key measures, including abdominal subcutaneous adipose tissue (β -42·01 cm2, 95% CI -75·49 to -8·52; % change -11·2%) and total body fat (natural logarithmic -0·21 kg, 95% CI -0·33 to -0·08; % change -18·9%). There were no statistically significant differences in possibly related or related adverse events (absolute risk difference 0·1111, 95% CI -0·0727 to 0·2869); however, one semaglutide-related grade 4 elevated lipase and two possibly related cases of cholelithiasis (grades 1 and 2) were observed. Semaglutide holds promise as an effective treatment for HIV-associated lipohypertrophy. The potential risk of serious adverse events deserves further scrutiny in large trials in people with HIV. National Institutes of Health.

Treatment options for patients with pilonidal sinus disease: PITSTOP, a mixed-methods evaluation.

There is no consensus on optimal management of pilonidal disease. Surgical practice is varied, and existing literature is mainly single-centre cohort studies of varied disease severity, interventions and outcome assessments. A prospective cohort study to determine: • disease severity and intervention relationship • most valued outcomes and treatment preference by patients • recommendations for policy and future research. Observational cohort study with nested mixed-methods case study. Discrete choice experiment. Clinician survey. Three-stage Delphi survey for patients and clinicians. Inter-rater reliability of classification system. Thirty-one National Health Service trusts. Patients aged > 16 years referred for elective surgical treatment of pilonidal disease. Surgery. Pain postoperative days 1 and 7, time to healing and return to normal activities, complications, recurrence. Outcomes compared between major and minor procedures using regression modelling, propensity score-based approaches and augmented inverse probability weighting to account for measured potential confounding features. Clinician survey: There was significant heterogeneity in surgeon practice preference. Limited training opportunities may impede efforts to improve practice. Cohort study: Over half of patients (60%; N = 667) had a major procedure. For these procedures, pain was greater on day 1 and day 7 (mean difference day 1 pain 1.58 points, 95% confidence interval 1.14 to 2.01 points, n = 536; mean difference day 7 pain 1.53 points, 95% confidence interval 1.12 to 1.95 points, n = 512). There were higher complication rates (adjusted risk difference 17.5%, 95% confidence interval 9.1 to 25.9%, n = 579), lower recurrence (adjusted risk difference -10.1%, 95% confidence interval -18.1 to -2.1%, n = 575), and longer time to healing (>34 days estimated difference) and time to return to normal activities (difference 25.9 days, 95% confidence interval 18.4 to 33.4 days). Mixed-methods analysis: Patient decision-making was influenced by prior experience of disease and anticipated recovery time. The burden involved in wound care and the gap between expected and actual time for recovery were the principal reasons given for decision regret. Discrete choice experiment: The strongest predictors of patient treatment choice were risk of infection/persistence (attribute importance 70%), and shorter recovery time (attribute importance 30%). Patients were willing to trade off these attributes. Those aged over 30 years had a higher risk tolerance (22.35-34.67%) for treatment failure if they could experience rapid recovery. There was no strong evidence that younger patients were willing to accept higher risk of treatment failure in exchange for a faster recovery. Patients were uniform in rejecting excision-and-leave-open because of the protracted nursing care it entailed. Wysocki classification analysis: There was acceptable inter-rater agreement (κ = 0.52, 95% confidence interval 0.42 to 0.61). Consensus exercise: Five research and practice priorities were identified. The top research priority was that a comparative trial should broadly group interventions. The top practice priority was that any interventions should be less disruptive than the disease itself. Incomplete recruitment and follow-up data were an issue, particularly given the multiple interventions. Assumptions were made regarding risk adjustment. Results suggest the burden of pilonidal surgery is greater than reported previously. This can be mitigated with better selection of intervention according to disease type and patient desired goals. Results indicate a framework for future higher-quality trials that stratify disease and utilise broad groupings of common interventions with development of a patient-centred core outcome set. This trial is registered as ISRCTN95551898. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/17/02) and is published in full in Health Technology Assessment; Vol. 28, No. 33. See the NIHR Funding and Awards website for further award information.

Emollient application from birth to prevent eczema in high-risk children: the BEEP RCT.

Atopic eczema is a common childhood skin problem linked with asthma, food allergy and allergic rhinitis that impairs quality of life. To determine whether advising parents to apply daily emollients in the first year can prevent eczema and/or other atopic diseases in high-risk children. A United Kingdom, multicentre, pragmatic, two-arm, parallel-group randomised controlled prevention trial with follow-up to 5 years. Twelve secondary and four primary care centres. Healthy infants (at least 37 weeks' gestation) at high risk of developing eczema, screened and consented during the third trimester or post delivery. Infants were randomised (1 : 1) within 21 days of birth to apply emollient (Doublebase Gel®; Dermal Laboratories Ltd, Hitchin, UK or Diprobase Cream®) daily to the whole body (excluding scalp) for the first year, plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). Families were not blinded to allocation. Primary outcome was eczema diagnosis in the last year at age 2 years, as defined by the UK Working Party refinement of the Hanifin and Rajka diagnostic criteria, assessed by research nurses blinded to allocation. Secondary outcomes up to age 2 years included other eczema definitions, time to onset and severity of eczema, allergic rhinitis, wheezing, allergic sensitisation, food allergy, safety (skin infections and slippages) and cost-effectiveness. One thousand three hundred and ninety-four newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in the emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months. At 2 years, eczema was present in 139/598 (23%) in the emollient group and 150/612 (25%) in controls (adjusted relative risk 0.95, 95% confidence interval 0.78 to 1.16; p = 0.61 and adjusted risk difference -1.2%, 95% confidence interval -5.9% to 3.6%). Other eczema definitions supported the primary analysis. Food allergy (milk, egg, peanut) was present in 41/547 (7.5%) in the emollient group versus 29/568 (5.1%) in controls (adjusted relative risk 1.47, 95% confidence interval 0.93 to 2.33). Mean number of skin infections per child in the first year was 0.23 (standard deviation 0.68) in the emollient group versus 0.15 (standard deviation 0.46) in controls; adjusted incidence rate ratio 1.55, 95% confidence interval 1.15 to 2.09. The adjusted incremental cost per percentage decrease in risk of eczema at 2 years was £5337 (£7281 unadjusted). No difference between the groups in eczema or other atopic diseases was observed during follow-up to age 5 years via parental questionnaires. Two emollient types were used which could have had different effects. The median time for starting emollients was 11 days after birth. Some contamination occurred in the control group (< 20%). Participating families were unblinded and reported on some outcomes. We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children. Emollient use was associated with a higher risk of skin infections and a possible increase in food allergy. Emollient use is unlikely to be considered cost-effective in this context. To pool similar studies in an individual patient data meta-analysis. This trial is registered as ISRCTN21528841. This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/67/12) and is published in full in Health Technology Assessment; Vol. 28, No. 29. See the NIHR Funding and Awards website for further award information.

Healthcare-seeking behaviour preceding diagnosis of Lyme neuroborreliosis: population-based nationwide matched nested case-control study

ObjectivesTo identify diagnostic opportunities, we investigated healthcare-seeking behaviour among patients with Lyme neuroborreliosis (LNB) within 28 weeks before diagnosis. MethodsWe conducted a population-based, nationwide matched nested case-control study (Denmark, 2009–2021). As cases, we included all Danish residents with LNB (positive Borrelia burgdorferi intrathecal antibody index test and cerebrospinal fluid pleocytosis). We randomly selected controls from the general population and matched 10:1 on date of birth and sex. Exposures were assignment of diagnostic codes for symptoms, contact to medical specialties, medical wandering, and undergoing diagnostic procedures. We calculated the weekly and 3-month proportions of individuals with exposures and calculated absolute risk differences with corresponding 95% CI. ResultsWe included 1056 cases with LNB and 10 560 controls.Within 3 months before diagnosis, the most frequent assigned symptoms were pain (difference: 13.0%, 95% CI: 10.9–15.1). Cases with LNB exhibited increased contact with most specialties, particularly general practitioners (difference: 48.7%, 95% CI: 46.0–51.4), neurology (difference: 14.3%, 95% CI: 11.7–16.8), and internal medicine (difference: 11.1%, 95% CI: 8.7–13.5), and medical wandering (difference: 17.1%, 95% CI: 14.3–20.0). Common diagnostic procedures included imaging of the brain (difference: 10.2, 95% CI: 8.3–12.1), the spine (difference: 8.8%, 85% CI: 7.0–10.6), and the abdomen (difference: 7.2%, 95% CI: 5.4–9.1). The increase in healthcare-seeking behaviour was observed ≤12 weeks preceding diagnosis. DiscussionPain appears to be an ambiguous symptom of LNB, potentially contributing to delays in establishing the correct diagnosis. It would be difficult to identify patients with LNB more effectively as the increased healthcare-seeking behaviour preceding diagnosis is distributed across many medical specialties.

Urgency adjusted outcomes of emergency abdominal surgery for inflammatory bowel disease.

Patients undergoing emergency abdominal surgery for inflammatory bowel disease (IBD) are a complex cohort who are relatively poorly represented in published literature. This is partly due to the lack of consensus of the definition of the term emergency in IBD surgery. There is ongoing and recent work defining clinical urgency for unplanned surgical procedures and categorizing the high-risk surgical patient. This paper aims to report the difference in patient metrics and risks as recorded by the National Emergency Laparotomy Audit (NELA). Complete patient data, including histology, were available in the NELA database between 2013 and 2016. Urgency categories recorded by NELA are <2h, 2-6h, 6-18h, and >18h. Patient characteristics, physiology, biochemistry, and outcomes are reported according to these urgency categories with regression analysis used to compare differences between them. Mortality in Crohn's disease (CD) ranged from 1.4% in the >18h urgency to 14.6% in the most urgent. In ulcerative colitis (UC), this range was from 3.1% to 14.8%. In both CD and UC, there were significant trends in hemodynamic instability, serum white cell count, serum electrolytes and creatinine, and outcome measures length of stay and unplanned return to theater. Patients having emergency surgery for IBD are not a single cohort when considering physiology, blood biochemistry, or most importantly, outcomes. Risk counseling and management should reflect this. Hemodynamic changes are subtle and may be missed in this cohort.

Cryptocurrency Investment in Indonesia

Objective - Different countries have different policies towards cryptocurrencies. In Indonesia, cryptocurrency is prohibited as a means of payment or transaction. The prohibition is stated in Bank Indonesia Regulation (PBI) Number 18/40/PBI/2016 concerning the Implementation of Payment Transaction Processing. However, cryptocurrencies are recognized as long-term commodities or investment assets, so their supervision is carried out by the Commodity Futures Trading Supervisory Agency (bappepti) and regulated in Bappebti Regulation No. 7 of 2020 concerning the Determination of the List of Crypto Assets that Can be Traded on the Crypto Asset Physical Market. This study aims to analyze the differences in return and risk on the 5 cryptocurrencies with the largest market capitalization in Indonesia. Methodology/Technique - This research uses quantitative methods with a descriptive approach, and secondary data is used. The population in this study consisted of 383 cryptocurrencies that were legal and registered with Bappepti from 2020 to 2022. The sample was determined using purposive sampling to determine the top 5 cryptocurrencies with the largest market capitalization during the observation period from January 2020 to September 2022. The data analysis technique used the Kruskal-Wallis test. Findings - The results showed no significant differences in return and risk between Bitcoin, Ethereum, Tether, BNB, and USD coins. Empirically, this study proves that each cryptocurrency has the same risk and return. Novelty - This research was conducted in Indonesia with regulations that may differ from other countries towards cryptocurrencies. As a long-term commodity investment asset, this study finds empirical evidence that each cryptocurrency has the same risk and return. Type of Paper: Empirical JEL Classification: G11; G18; G28 Keywords: Cryptocurrency; Investment; Return; Risk; Bappepti Reference to this paper should be referred to as follows: Dewi, D.M; Faizal, I; Sambe, T.A. (2024). Cryptocurrency Investment in Indonesia, Acc. Fin. Review, 9(1), 32 – 41. https://doi.org/10.35609/afr.2024.9.1(1)

Use of digital patient decision-support tools for atrial fibrillation treatments: a systematic review and meta-analysis

ObjectivesTo assess the effects of digital patient decision-support tools for atrial fibrillation (AF) treatment decisions in adults with AF.Study designSystematic review and meta-analysis.Eligibility criteriaEligible randomised controlled trials (RCTs) evaluated digital...