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BACKGROUND: Previous studies suggest that dietary vitamin C is inversely associated with gastric cancer (GC), but most of them did not consider intake of fruit and vegetables. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project, a consortium of epidemiological studies on GC. METHODS: Fourteen case-control studies were included in the analysis (5362 cases, 11,497 controls). We estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the association between dietary intake of vitamin C and GC, adjusted for relevant confounders and for intake of fruit and vegetables. The dose-response relationship was evaluated using mixed-effects logistic models with second-order fractional polynomials. RESULTS: Individuals in the highest quartile of dietary vitamin C intake had reduced odds of GC compared with those in the lowest quartile (OR: 0.64; 95% CI: 0.58, 0.72). Additional adjustment for fruit and vegetables intake led to an OR of 0.85 (95% CI: 0.73, 0.98). A significant inverse association was observed for noncardia GC, as well as for both intestinal and diffuse types of the disease. The results of the dose-response analysis showed decreasing ORs of GC up to 150-200 mg/day of vitamin C (OR: 0.54; 95% CI: 0.41, 0.71), whereas ORs for higher intakes were close to 1.0. CONCLUSIONS: The findings of our pooled study suggest that vitamin C is inversely associated with GC, with a potentially beneficial effect also for intakes above the currently recommended daily intake (90 mg for men and 75 mg for women).

Introduction We describe the safety of sotorasib monotherapy in patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) and discuss practical recommendations for managing key risks. Methods Incidence rates of treatment-related adverse events (TRAEs) were pooled from 4 clinical trials: CodeBreaK 100 (NCT03600883), CodeBreaK 101 (NCT04185883), CodeBreaK 105 (NCT04380753), and CodeBreaK 200 (NCT04303780) and graded according to CTCAE v5.0. Adverse events were deemed sotorasib-related per investigator causality assessment. Results In the pooled population (n  = 549), TRAEs were reported in 388 (70.7%) patients (grade 1: 124 [22.6%]; grade 2: 117 [21.3%]; grade ≥ 3: 147 [26.8%]). Gastrointestinal and hepatic TRAEs, including diarrhea (171 [31.1%]), nausea (80 [14.6%]), elevated alanine aminotransferase (ALT; 68 [12.4%]), and elevated aspartate aminotransferase (AST; 67 [12.2%]) were the most common (≥10%). Dose interruption and dose reduction of sotorasib resulted in the resolution of >90% of diarrhea events; median time to resolution were 18.0 days and 22.0 days, respectively. Similar trends were observed for elevated ALT and AST events. Patients who stopped immunotherapy <3 months before initiating sotorasib had a higher incidence of treatment-related hepatotoxicity (80/240 [33.3%]) than those who stopped immunotherapy ≥3 months before initiating sotorasib (26/188 [13.8%]). Treatment-related pneumonitis/interstitial lung disease (ILD) and corrected QT (QTc) prolongation were observed in 9 (1.6%) and 4 (0.7%) patients, respectively. Two (0.4%) patients died with TRAEs, 1 with ILD whose ultimate cause of death was disease progression, and the other with an unknown cause. Conclusions Sotorasib has a well-characterized safety profile in patients with KRAS G12C-mutated advanced NSCLC, and key risks are manageable with dose modification. [ABSTRACT FROM AUTHOR]

Background: Current therapies for complex Crohn's perianal fistulas (CPF) have a limited ability to achieve long-term healing. Darvadstrocel (DVS) is an expanded allogeneic adipose-derived mesenchymal stem cell therapy that has demonstrated efficacy in treating complex CPF in clinical trials. There are, however, limited long-term comparative data with standard of care (SoC). The aim of this study was to combine clinical trial data and real-world evidence using statistical methodologies to predict long-term effectiveness of DVS versus SoC in patients with CPF. Methods: Data were pooled from a clinical trial (ADMIRE-CD) and two retrospective chart review studies (INSPECT and PREFACE). Predictive statistical models extrapolated clinical outcomes beyond observed follow-up using parametric curves, which were implemented into a semi-Markov model to obtain the number of patients in remission. The setting was multinational and multicenter. ADMIRE-CD was conducted in 49 hospitals in 7 European countries and Israel. INSPECT used data from the ADMIRE study. PREFACE involved patients from Belgium, France, Germany, Italy, and Spain. The participants were patients with complex CPF treated with DVS or SoC. Times to remission and relapse (clinical, and clinical plus patient-centric remission) were analyzed. Additionally, the proportion of patients in clinical and patient-centric remission was examined. Results: In total, 513 patients were included in the analysis (ADMIRE-CD [N = 200] and PREFACE [N = 313]). Patients in ADMIRE-CD and PREFACE were similar in age (median [interquartile range, IQR], 36 [20.0] versus 36 [22.0] years, respectively) and gender (males, 54% and 52%, respectively). The median (IQR) duration of Crohn's disease was 9.4 [11.3] years for patients in ADMIRE-CD and 6.5 [12.9] years for patients in PREFACE. The estimated time to remission was shorter for patients treated with DVS versus SoC. The estimated time to relapse was longer for patients treated with DVS versus SoC. A higher estimated proportion of patients treated with DVS versus SoC had clinical and patient-centric remission at 24 months (48% and 35%, respectively) and 48 months (49% and 32%, respectively). Conclusion: This novel approach enabled pooled data from a clinical trial and real-world settings to predict long-term effectiveness of DVS versus SoC in patients with complex CPF. [ABSTRACT FROM AUTHOR]

Background: Prucalopride (1 or 2 mg once daily) is approved for treating adults with chronic idiopathic constipation (CIC). Objectives: We determined the effect of age, body mass index (BMI), and renal function on the efficacy and safety of prucalopride in adults with CIC. Design: Data were pooled from six 12-week, phase III–IV clinical studies in adults who received prucalopride (1 or 2 mg once daily) or placebo for CIC. Methods: Adults were stratified by age (<50; 50–64; ⩾65 years), BMI (underweight/healthy weight, <25 kg/m2; overweight, 25 to <30 kg/m2; obese, ⩾30 kg/m2), and renal function (normal renal function, estimated glomerular filtration rate (eGFR) ⩾90 mL/min/1.73 m2; mild renal impairment, eGFR 60 to <90 mL/min/1.73 m2; moderate renal impairment, eGFR 30 to <60 mL/min/1.73 m2). The primary efficacy endpoint was the proportion of patients with a mean of ⩾3 complete spontaneous bowel movements/week over 12 weeks. Safety data were evaluated descriptively. Results: Of 2484 patients stratified by age (prucalopride, n = 1237; placebo, n = 1247), 1402, 708, and 374 were aged <50, 50–64, and ⩾65 years, respectively. Of 2482 patients stratified by BMI (prucalopride, n = 1237; placebo, n = 1245), 1425, 713, and 344 were underweight/healthy weight, overweight, and obese, respectively. Of 2474 patients stratified by renal function (prucalopride, n = 1233; placebo, n = 1241), 1444, 869, and 161 had normal renal function, mild renal impairment, and moderate renal impairment, respectively. More prucalopride-treated than placebo-treated patients achieved the primary efficacy endpoint. The difference was significant for all subgroups, except for the obese and moderate renal impairment subgroups. More prucalopride-treated than placebo-treated patients reported treatment-related adverse events in most subgroups. Conclusion: Prucalopride demonstrated efficacy in adults with CIC, irrespective of age, BMI, and renal function. No unexpected safety concerns were identified. Trial registration: ClinicalTrials.gov identifiers (https://clinicaltrials.gov/): NCT01147926, NCT01424228, NCT01116206, NCT00483886, NCT00485940, NCT00488137. [ABSTRACT FROM AUTHOR]

Background Chikungunya disease, caused by chikungunya virus (CHIKV), is associated with substantial morbidity, including debilitating CHIKV-related arthralgia. Methods Three clinical trials of a CHIKV vaccine (VLA1553, IXCHIQ®) were conducted in the USA: a Phase 1 dose-finding trial, a pivotal Phase 3 trial and a Phase 3 lot-to-lot consistency trial. Participants were healthy adults (≥18 years) and received a single intramuscular dose of VLA1553 (3520 participants) or placebo (1033 participants). Solicited injection site and systemic adverse events (AEs) (10–14 days post-vaccination), unsolicited AEs (28 and 180 days post-vaccination), AEs of special interest (AESIs) (28 days post-vaccination), medically attended AEs (MAAEs), serious AEs (SAEs) (180 days post-vaccination) and pregnancies were evaluated. Safety data were pooled, and analyses were descriptive. Results Overall, 63.7% of participants receiving VLA1553 experienced AEs (44.7% for placebo) that were generally mild. Solicited injection-site AEs, solicited systemic AEs and unsolicited (Day 29) AEs were reported by 15.5, 50.9 and 22.7% of participants who received VLA1553 and 11.1, 26.9 and 13.4% who received placebo. Arthralgia was reported by 16.7% of participants who received VLA1553 and 4.8% of participants who received placebo; none required medical attention. MAAEs, AESIs and SAEs were reported by 12.4, 0.3 and 1.5% of participants who received VLA1553 and 11.3, 0.1 and 0.8% of participants who received placebo. Protocol-defined AESIs were mild and short-lived, and two VLA1553-related SAEs resolved without sequelae. There were no clinically important differences in AE incidence based on age or medical history and no VLA1553-related adverse pregnancy outcomes. There were three deaths (two in the VLA1553 group and one in the placebo group); none was vaccine-related. Conclusions A single dose of VLA1553 presented with an excellent local tolerability profile and overall safety in line with that expected for a live-attenuated vaccine. The safety profile was comparable in participants aged 18–64 years and ≥65 years. [ABSTRACT FROM AUTHOR]

Abstract Background It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women. Methods Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China. Participants’ height and weight were obtained by measurement or self-reports at cohort baseline. Breast cancer was defined as code C50.0-C50.9 according to the International Classification. Using a Cox proportional hazards model, hazard ratios of breast cancer were estimated for each body mass index category, with the reference group set as the group with a body mass index of 21 to

Abstract Background Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol. Methods All eligible ICU patients who were expected to require sedation for 6–24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05–0.10 mg/kg/h or 0.25–0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol. Results In total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged

Abstract Background Anaemia continues to be a pressing public health concern in India. Despite the high burden of anaemia among lactating adolescents in the country, research addressing this concern among this population remains scarce. Hence, this study attempted to examine the prevalence and determinants of anaemia among lactating adolescents in India. Methods We used data from three latest rounds of the National Family Health Survey (NFHS) carried out in 2005-06, 2015-16, and 2019-21 and analysed a pooled sample of 10,689 lactating adolescents aged 15–19 years from these three rounds. Bivariate statistics was used to analyse the prevalence of anaemia according to the background characteristics of lactating adolescents. Further, binary multivariate logistic regression was carried out to examine the factors associated with anaemia in the study population. Results Three in every five lactating adolescents from the pooled sample were found to have anaemia (66.98% in NFHS-3, 61.08% in NFHS-4 and 66.27% in NFHS-5). Lactating adolescents with a higher education had a 30% lower likelihood [adjusted odds ratio (AOR): 0.70, 95% CI: 0.49–1.01, p = 0.050] of being anaemic compared to those with no education. The likelihood of being anaemic among the poorest quintile was 41% (AOR: 1.41, 1.12-1.77; p = 0.003) higher than those from the richest quintile. Lactating adolescents from the Scheduled Tribe category had higher odds (AOR: 1.29, 95% CI: 1.01–1.46, p = 0.001) of anaemia than those categorised as ‘Others’. Those living in rural areas were 22% more likely to suffer from anaemia (AOR: 1.22, 95% CI: 1.00-1.26, p = 0.050) compared to their urban counterparts. Additionally, underweight lactating adolescents were 15% more likely (AOR: 1.15, 95% CI: 1.05–1.26, p = 0.002) to be anaemic than those with normal BMI. Odds of being anaemic were higher among the ones receiving supplementary nutrition during pregnancy (AOR: 1.18, 95% CI: 1.08–1.29, p < 0.001) in contrast to those not receiving. Conclusion The consistently high prevalence of anemia among lactating adolescents, especially among those with lower education level, rural residence, underweight status, and belonging to ST category and poorest quintile, underscore the urgent need for targeted public health interventions to address and reduce anemia in this population.

Abstract Background The prevalence of low birth weight (LBW) has stagnated at approximately 12% for the past 15 years in Nepal, significantly impacting newborn survival. While antenatal care (ANC) visits and iron-folic acid supplementation are recognised as important interventions to reduce LBW, there is a lack of evidence regarding their combined effect. This study aimed to explore the potential synergistic impact of ANC and iron-folic acid supplementation on LBW in Nepal by analyzing data from two national surveys. Methods The nationally representative Nepal Demographic and Health Surveys of 2016 and 2022 were used, and the pooled dataset was analysed. Birth weight and the prevalence of LBW (i.e. birthweight

Background: It has been suggested that the association between body mass index and breast cancer risk differs between Asian women and Western women. We aimed to assess the associations between body mass index and breast cancer incidence in East Asian women. Methods: Pooled analyses were performed using individual participant data of 319,189 women from 13 cohort studies in Japan, Korea, and China. Participants' height and weight were obtained by measurement or self-reports at cohort baseline. Breast cancer was defined as code C50.0-C50.9 according to the International Classification. Using a Cox proportional hazards model, hazard ratios of breast cancer were estimated for each body mass index category, with the reference group set as the group with a body mass index of 21 to < 23 kg/m2. The hazard ratio for a 5 kg/m2 increase in body mass index was also calculated. Results: During a mean 16.6 years of follow-up, 4819 women developed breast cancer. Similar to Westerners, a steady increase in breast cancer risk with increasing body mass index was observed in postmenopausal women, but the slope of the risk increase appeared to slow at a body mass index of 26–28 kg/m2. In premenopausal women, the inverse association seen in Westerners was not observed. The risk of developing breast cancer after 50 years of age increased slightly with increasing body mass index, which was more pronounced in the older birth cohort. There was no significant association between body mass index and the risk of developing breast cancer before 50 years of age, but the risk estimates changed from positive to negative as the birth cohort got younger. Conclusions: In East Asia, the role of body mass index in breast cancer in premenopausal women may be changing along with the increase in obesity and breast cancer. The increased risk of postmenopausal breast cancer with a higher body mass index was as robust as that of Western women. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to evaluate the effect of baseline body mass index (BMI) and glycated hemoglobin (HbA1c) on the effectiveness and safety of initiating iGlarLixi (insulin glargine 100 U/ml and lixisenatide) in people with type 2 diabetes (T2D) in routine clinical practice. Methods: We pooled patient-level data from 1406 people with inadequately controlled T2D, initiating a 24-week iGlarLixi treatment. Analysis sets were based on baseline BMI and HbA1c. In the BMI set, 894 (64%) people had a BMI ≥ 30 kg/m2 and 510 (36%) a BMI < 30 kg/m2; in the HbA1c set, 615 (44%) people had an HbA1c >9%, 491 (35%) between 8 and 9%, and 298 (21%) < 8%. Results: After initiating iGlarLixi, HbA1c decreased in all participants, with the greatest least-squares mean reduction at 2.15% from baseline to week 24 in those with baseline HbA1c > 9% (using a mixed model for repeated measures). Overall, mean ± standard deviation body weight decreased by 1.9 ± 4.8 kg, with the most prominent loss of 2.6 ± 4.9 kg recorded in people presenting with obesity. Reported hypoglycemia rates were low across all groups. Conclusions: Initiation of iGlarLixi in people with uncontrolled T2D is effective and safe in clinical practice, across different baseline HbA1c and BMI categories. [ABSTRACT FROM AUTHOR]

Background: Anaemia continues to be a pressing public health concern in India. Despite the high burden of anaemia among lactating adolescents in the country, research addressing this concern among this population remains scarce. Hence, this study attempted to examine the prevalence and determinants of anaemia among lactating adolescents in India. Methods: We used data from three latest rounds of the National Family Health Survey (NFHS) carried out in 2005-06, 2015-16, and 2019-21 and analysed a pooled sample of 10,689 lactating adolescents aged 15–19 years from these three rounds. Bivariate statistics was used to analyse the prevalence of anaemia according to the background characteristics of lactating adolescents. Further, binary multivariate logistic regression was carried out to examine the factors associated with anaemia in the study population. Results: Three in every five lactating adolescents from the pooled sample were found to have anaemia (66.98% in NFHS-3, 61.08% in NFHS-4 and 66.27% in NFHS-5). Lactating adolescents with a higher education had a 30% lower likelihood [adjusted odds ratio (AOR): 0.70, 95% CI: 0.49–1.01, p = 0.050] of being anaemic compared to those with no education. The likelihood of being anaemic among the poorest quintile was 41% (AOR: 1.41, 1.12-1.77; p = 0.003) higher than those from the richest quintile. Lactating adolescents from the Scheduled Tribe category had higher odds (AOR: 1.29, 95% CI: 1.01–1.46, p = 0.001) of anaemia than those categorised as ‘Others’. Those living in rural areas were 22% more likely to suffer from anaemia (AOR: 1.22, 95% CI: 1.00-1.26, p = 0.050) compared to their urban counterparts. Additionally, underweight lactating adolescents were 15% more likely (AOR: 1.15, 95% CI: 1.05–1.26, p = 0.002) to be anaemic than those with normal BMI. Odds of being anaemic were higher among the ones receiving supplementary nutrition during pregnancy (AOR: 1.18, 95% CI: 1.08–1.29, p < 0.001) in contrast to those not receiving. Conclusion: The consistently high prevalence of anemia among lactating adolescents, especially among those with lower education level, rural residence, underweight status, and belonging to ST category and poorest quintile, underscore the urgent need for targeted public health interventions to address and reduce anemia in this population. [ABSTRACT FROM AUTHOR]

Background: Ciprofol was approved for use in intensive care unit (ICU) patients requiring sedation during mechanical ventilation in July 2022. A pooled post-hoc analysis of phase 2 and phase 3 trials was conducted primarily to explore hypotension-free outcome in ICU patients who required mechanical ventilation and achieved the target light sedation goal at an early stage after being sedated with ciprofol or propofol. Methods: All eligible ICU patients who were expected to require sedation for 6–24 h were randomly assigned in a 2:1 ratio to either a ciprofol or propofol group. Ciprofol or propofol was initially infused at loading doses of 0.5 or 1.0 mg/kg followed by maintenance doses of 0.3 or 1.5 mg/kg/h. Ciprofol or propofol dosages were adjusted up or down at rates of 0.05–0.10 mg/kg/h or 0.25–0.50 mg/kg/h, respectively, to achieve the target light sedation (a Richmond Agitation-Sedation Scale of -2 to + 1). The primary post-hoc outcome was the hypotension-free rate in patients who had achieved the target sedation goal after 30-min administration of ciprofol or propofol. Results: In total, 174 patients were enrolled for pooled post-hoc analysis, of whom 116 and 58 were assigned to the ciprofol and propofol groups, respectively. The hypotension-free rate was significantly higher in patients who achieved the target sedation goal after 30-min administration of ciprofol (93.0% vs. 81.0%, P = 0.018), and especially in the subgroups of males and patients aged < 65 years. Multivariable analysis revealed that ciprofol treatment, a younger age and lower baseline body mass index were independent favorable predictors for a higher hypotension-free rate in patients who achieved the target sedation goal after 30-min of drug administration. Moreover, hypotension-free patients who reached the target sedation level after 30 min had a more favorable short-term prognosis including a lower incidence of drug-related treatment-emergent adverse events, shorter time to extubation and fewer dose adjustments of ciprofol or propofol (all P < 0.05). Conclusion: ICU patients undergoing mechanical ventilation and sedated with ciprofol had significantly lower rate of hypotension during the early phase of achieving light sedation during a 6–24 h period, leading to a more favorable short-term prognosis (within 24 h). Trial registration: Phase 2 trial (clinicaltrials.gov, NCT04147416. Registered November 1, 2019, https://classic.clinicaltrials.gov/ct2/show/NCT04147416) and phase 3 trial (clinicaltrials.gov, NCT04620031. Registered November 6, 2020, https://classic.clinicaltrials.gov/ct2/show/NCT04620031). [ABSTRACT FROM AUTHOR]

Background Chikungunya is a serious and debilitating viral infection with a significant disease burden. VLA1553 (IXCHIQ®) is a live-attenuated vaccine licensed for active immunization for prevention of disease caused by chikungunya virus (CHIKV). Methods Immunogenicity following a single dose of VLA1553 was evaluated in healthy adults aged ≥18 years in two Phase 3 trials [ N  = 656 participants (per protocol analysis set)]. Immunogenicity data to 180 days post-vaccination [geometric mean titres (GMTs), seroresponse rate, seroconversion rate] were pooled for the two trials. A comparison of subgroups based on age, sex, body mass index (BMI), race and baseline seropositivity was included. All analyses were descriptive. Results Most participants were aged 18–64 years (N  = 569/656 [86.7%]), there were slightly more females (N  = 372/656 [56.7%]), most were not Hispanic/Latino (N  = 579/656 [88.3%]), and most were White (N  = 517/656 [78.8%]). In baseline seronegative participants, GMT peaked at Day 29 post-vaccination, and subsequently declined slightly but remained elevated until Day 180. At Days 29, 85 and 180, seroresponse rate was 98.3, 97.7 and 96.4% and seroconversion rate was 98.5, 98.4 and 98.2%. There were no differences in seroresponse rate in participants aged 18–64 years or ≥65 years at Day 29 (98.1 vs 100%), Day 85 (97.4 vs 100%) and Day 180 (96.3 vs 96.5%) nor based on sex, BMI, ethnicity or race. An immune response was shown in a small heterogenous population of baseline seropositive participants, with GMTs showing the same trend as baseline seronegative participants. Conclusions A single dose of VLA1553 elicited a very strong immune response by Day 29 that remained elevated at Day 180 in both baseline seronegative and seropositive participants in a combined evaluation of two Phase 3 trials. The vaccine was similarly immunogenic in participants aged ≥65 years and 18–64 years, and there were no differences based on subgroup analyses for sex, BMI, ethnicity or race. [ABSTRACT FROM AUTHOR]

Background: The prevalence of low birth weight (LBW) has stagnated at approximately 12% for the past 15 years in Nepal, significantly impacting newborn survival. While antenatal care (ANC) visits and iron-folic acid supplementation are recognised as important interventions to reduce LBW, there is a lack of evidence regarding their combined effect. This study aimed to explore the potential synergistic impact of ANC and iron-folic acid supplementation on LBW in Nepal by analyzing data from two national surveys. Methods: The nationally representative Nepal Demographic and Health Surveys of 2016 and 2022 were used, and the pooled dataset was analysed. Birth weight and the prevalence of LBW (i.e. birthweight < 2500 g) were reported using descriptive statistics. The associations among LBW, ANC visits, and iron-folic acid supplementation were examined using logistic regression analyses. Results: The mean birth weight was 3011 g, with an LBW prevalence of 11.2%. Not attending ANC (Adjusted Odds Ratio (AOR): 1.49; 95% Confidence Interval (CI): 1.14, 1.95) and not consuming iron-folic acid supplements (AOR: 1.43; 95% CI: 1.11, 1.84) were independently associated with a higher likelihood of having LBW. Furthermore, when considering both factors together, mothers who attended less than four ANC visits and consumed iron-folic acid for ≤ 90 days had the higher likelihood of having LBW (AOR: 1.99; 95% CI: 1.35, 2.60) compared to those who did not. Conclusions: This study highlights that the individual and joint influence of ANC visits and iron-folic acid supplementation on having LBW. These findings underscore the significance of ANC attendance and iron-folic acid supplementation in preventing LBW. Traditionally, these two interventions were primarily considered as maternal survival strategies. However, our findings indicate that these existing interventions could be utilised further for both maternal and newborn survival. Given that these services are offered free of cost and are available near people's homes through the National Safe Motherhood Programme in Nepal, efforts to increase the uptake of these services should be strengthened while emphasising their role in preventing LBW. [ABSTRACT FROM AUTHOR]

Background: Probiotics could decrease irinotecan-induced diarrhea due to the reduction of intestinal beta-d-glucuronidase activity. This study included a combined analysis of two clinical trials aimed to determine the effectiveness of the probiotics in the prophylaxis of irinotecan-induced diarrhea in metastatic colorectal cancer (CRC) patients. Methods: This combined analysis included 46 patients with CRC enrolled in the Probio-SK-003 (NCT01410955) and 233 patients from Probio-SK-005 (NCT02819960) starting a new line of irinotecan-based therapy with identical eligibility criteria. Patients were randomized in a ratio 1:1 to probiotic formulas vs. placebo administered for 12 and 6 weeks, respectively. Due to the different durations of study treatments, only the first 6 weeks of therapy were used for analysis. Results: In total, 279 patients were randomized, including 142 patients in the placebo and 137 participants in the probiotic arm. Administration of probiotics did not significantly reduce the incidence of grade 3/4 diarrhea compared to placebo (placebo 12.7% vs. probiotics 6.6%, p = 0.11). Neither the overall incidence of diarrhea (placebo 48.6% vs. probiotics 41.6%, p = 0.28) nor the incidence of enterocolitis (placebo 4.2% vs. probiotics 0.7%, p = 0.12) was different in the placebo vs. probiotic arm. However, subgroup analysis revealed that patients with a colostomy who received a placebo had a significantly higher incidence of any diarrhea (placebo 51.2% vs. probiotics 25.7%, p = 0.028) and grade 3/4 diarrhea (placebo 14.6% vs. probiotics 0.0%, p = 0.03) compared to the probiotic arm. Conclusions: This combined analysis suggests that probiotics could be beneficial in the prevention of irinotecan-induced diarrhea in colorectal cancer patients with colostomy. [ABSTRACT FROM AUTHOR]

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 (MET ex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, MET ex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1–56.3%], the DCR was 81.3% (95% CI: 63.6–92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6–9.7) and 17.0 month (95% CI: 10.3–not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591. [ABSTRACT FROM AUTHOR]

The female predominance of gallbladder cancer (GBC) has led to a hypothesis regarding the hormone‐related aetiology of GBC. We aimed to investigate the association between female reproductive factors and GBC risk, considering birth cohorts of Asian women. We conducted a pooled analysis of 331,323 women from 12 cohorts across 4 countries (China, Japan, Korea, and Singapore) in the Asia Cohort Consortium. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) to assess the association between reproductive factors (age at menarche, parity, age at first delivery, breastfeeding, and age at menopause) and GBC risk. We observed that a later age at menarche was associated with an increased risk of GBC (HR 1.4, 95% CI 1.16–1.70 for 17 years and older vs. 13–14 years), especially among the cohort born in 1940 and later (HR 2.5, 95% CI 1.50–4.35). Among the cohort born before 1940, women with a later age at first delivery showed an increased risk of GBC (HR 1.56, 95% CI 1.08–2.24 for 31 years of age and older vs. 20 years of age and younger). Other reproductive factors did not show a clear association with GBC risk. Later ages at menarche and at first delivery were associated with a higher risk of GBC, and these associations varied by birth cohort. [ABSTRACT FROM AUTHOR]

Purpose: Hepatic veno-occlusive disease (HVOD) after liver transplantation (LT) is almost always a fatal complication. We assessed the outcomes of HVOD in a single institute and analyzed a literature-based cohort. Methods: We reviewed the medical records of recipients of LT performed between 1995 and 2020 at our institute and the literature on HVOD after LT. We then analyzed the clinical features based on a "pooled" cohort of cases identified in our institute and reported in the literature. Results: HVOD was diagnosed in 3 of 331 LT recipients, all of whom died in hospital, on days 164, 12, and 13, respectively. Our comprehensive review of the literature, as well as our cases, identified eight cases of HVOD that developed within 14 days after LT (early-onset type). Early-onset HVOD had a significantly worse prognosis than HVOD that developed beyond 2 weeks after LT (non-early-onset type), which was identified in 22 cases (25.0% vs. 86.1% of the 3-month graft survival rate). The most common causes of early-onset and non-early-onset types were acute cellular rejection (50%) and drug-induced disease (50%), respectively. Conclusion: Early-onset HVOD developing within 14 days after LT has a poor prognosis. [ABSTRACT FROM AUTHOR]

This article presents a study that examines the effectiveness and safety of iGlarLixi, a treatment for type 2 diabetes, in both individuals who have not previously used insulin and those who have. The study found that iGlarLixi improved glycemic control, with a greater reduction in HbA1c levels seen in insulin-naïve participants. The treatment was well-tolerated, with few instances of hypoglycemia and gastrointestinal adverse events. The study concludes that iGlarLixi is a safe and effective option for managing type 2 diabetes. [Extracted from the article]

Background: The authors aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). Methods: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR Results: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR =0.4, and sLNR >0.4. Patients in the D2+No. 10 group were randomly divided into the training (n=302) and validation (n=130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate, and high SHLN metastasis burden groups (LMB, MMB, and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) (P<0.001). Conclusions: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL. [ABSTRACT FROM AUTHOR]

Localized exercises are employed to activate, train, or restore the function of particular muscles and they are usually considered as part of treating individuals suffering low back pain. So, this systematic review and meta-analysis aimed to assess the efficacy of specific exercises in general population with non-specific low back pain (LBP). We conducted electronic searches in MEDLINE/PubMed, Scopus, Web of Science (WoS), and Google scholar from January 1990 to June 2021. Initially, 47,740 records were identified. Following the removal of duplicates, 32,138 records were left. After reviewing titles and abstracts, 262 papers were chosen for thorough assessment. Among these, 208 studies were excluded, resulting in 54 trials meeting the inclusion criteria for this study. Additionally, 46 of these trials were randomized controlled trials and were further evaluated for the meta-analysis. We included trials investigating the effectiveness of exercise therapy, including isometric activation of deep trunk muscles, strengthening exercises, stabilization exercises, stretching exercises, and proprioceptive neuromuscular facilitation exercises (PNF) in LBP patients. The primary outcome was pain intensity, measured using tools such as the visual analogue scale (VAS) and numeric pain rating scale (NPRS). The secondary outcome was disability, assessed through instruments such as the Roland Morris Disability Questionnaire (RMDQ) and Oswestry Disability Index (ODI). The quality of the eligible studies was assessed using the Verhagen tool, and the level of evidence was evaluated using the GRADE approach. Based on the Verhagen tool, 46 trials (85.2%) were categorized as having low methodological quality, while 8 studies (14.8%) were considered to have medium methodological quality. The meta-analysis indicated a small efficacy in favor of isometric activation of deep trunk muscles (−0.37, 95% CI: −0.88 to 0.13), a moderate efficacy in favor of stabilization exercises (−0.53, 95% CI: −1.13 to 0.08), and a large efficacy in favor of PNF exercises (−0.91, 95% CI: −1.62 to −0.2) for reducing pain intensity as assessed by VAS or NPRS tools. Moreover, the meta-analysis revealed a moderate efficacy for isometric activation of deep trunk muscles (−0.61, CI: −1.02 to −0.19), and a large efficacy for PNF exercises (−1.26, 95% CI: −1.81 to −0.72) in improving disability, assessed using RMDQ or ODI questionnaires. The level of certainty in the evidence, as determined by the GRADE approach, was very low to low. These findings emphasize the importance of incorporating localized therapeutic exercises as a fundamental aspect of managing non-specific LBP. Clinicians should consider utilizing localized therapeutic exercise tailored to individual patient needs. Furthermore, further research investigating optimal exercise therapy, optimal dose of the exercises, durations, and long-term adherence is warranted to enhance the precision and efficacy of exercise-based interventions for non-specific LBP. • This study aimed to investigate the effectiveness of localized exercises among individuals suffering from LBP. • The evidence level for localized exercise interventions ranged from very low to low. • Among these exercises, PNF exercises demonstrated the most effectiveness in improving pain and disability. [ABSTRACT FROM AUTHOR]

An investigation was carried out in maize to estimate General Combining ability (GCA), Specific Combining Ability (SCA) and their interaction with three environments. Nine maize inbred lines were crossed in all possible combinations including reciprocals in 9 × 9 diallel fashion. The resultant single cross hybrids along with parents were evaluated for their combining ability over environments. The combining ability analysis of diallel crosses across three environments showed high significance of GCA and SCA variances for all the traits viz., days to physiological maturity, plant height, cob length, cob girth, cob weight, 100 grain weight and grain yield per plant indicating the importance of both additive and non-additive gene action for the expression of these traits. The ratio of additive to non-additive variance was greater than one for all the traits except for cob length, cob girth, cob weight and grain yield across the environments, indicating the additive type of gene effects were more important in the expression days to physiological maturity, plant height and 100 grain weight and thus simple selection would confer rapid improvement of these characters. The hybrid combination UMI79 × UMI176 was the best for grain yield, cob weight, cob girth and early maturity. For reduced plant height UMI176 × UMI467 was the best across environments. The hybrid UMI176 × UMI13 was identified as the best for cob weight and cob girth. The crosses UMI79 × UMI57, UMI79 × UMI285 and UMI432 × UMI936(W) were the best for cob length. [ABSTRACT FROM AUTHOR]

Background Evidence on the potential association between dietary copper intake and gastric cancer (GC) is lacking. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project—an international consortium of epidemiological studies on GC. Methods Data from five case–control studies within the StoP Project were included (2448 cases, 4350 controls). We estimated adjusted odds ratios (ORs) and 95% CIs for the association between dietary copper intake and GC using multivariable mixed-effects logistic regression models. We also modelled the dose–response relationship between copper intake and GC using a logistic mixed-effects model with fractional polynomial. Results The OR for the highest quartile of copper intake compared with the lowest one was 0.78 (95% CI: 0.63–0.95; P for trend = 0.013). Results were similar for non-cardia-type (OR: 0.72; 95% CI: 0.57–0.91), intestinal-type (OR: 0.75; 95% CI: 0.56–0.99) and other histological-type GC (OR: 0.65; 95% CI: 0.44–0.96). The dose–response analysis showed a steep decrease in ORs for modest intakes (<1 mg/day), which were subsequently steady for ≤3 mg/day (OR: 0.09; 95% CI: 0.02–0.41) and slowly increased for higher intakes. Conclusions The findings of our large study suggest that copper intake might be inversely associated with GC, although their confirmation by prospective studies is required. [ABSTRACT FROM AUTHOR]

Objective: To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high‐risk HPV‐positive women, focusing on the trade‐off between cervical precancer detections and colposcopy referrals. Methods: A bivariate random‐effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy. Results: A total of 16,982 women (mean age 46.1 years, range 17–69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1‐year return decision threshold according to internal benchmarks. Conclusions: Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV‐based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification. [ABSTRACT FROM AUTHOR]

Purpose: Deficiencies in methionine sulfoxide reductase (MSR) enzymes, which function as a defense system against oxidative stress, have been linked to age-related diseases, including cancer and neurodegenerative diseases. This study aimed to assess the association between genetic variants in MSR genes and susceptibility to renal cell carcinoma (RCC). Materials and methods: We systematically evaluated the effects of 89 common MSR gene polymorphisms on the risk of developing RCC in a cohort of 630 patients and controls. Furthermore, publicly available gene expression datasets were used to analyze gene expression and patient prognosis. Results: After adjusting for covariates and multiple testing corrections, MSRA rs56198596 and rs11782000 showed significant associations with the risk of RCC. Analysis of expression quantitative trait loci indicated that the risk alleles of these 2 variants tended to correlate with reduced MSRA expression. Pooled analyses of 19 kidney cancer gene expression datasets revealed that RCC exhibited lower MSRA expression than did normal tissues (P < 0.001) and that higher MSRA expression was associated with improved patient prognosis (P < 0.001). Conclusion: These findings suggest that MSRA gene variants may affect the risk of RCC, highlighting the potential protective role of MSRA and its contribution to a favorable RCC prognosis. [ABSTRACT FROM AUTHOR]

IntroductionThough consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear.MethodsWe harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults.ResultsUsing no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week).DiscussionThis cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

Abstract Background The prevalence of low birth weight (LBW) has remained high (24.9%) in the South Asian region with a significant impact on newborn survival. This region bears nearly 40% of global burden of LBW. While antenatal care (ANC) and iron-folic acid supplementation independently have been considered effective for improving maternal and newborn outcomes, the evidence on the combined effect of these two supplements on LBW is lacking. This study aimed to examine the synergistic association of ANC and iron-folic acid supplementation on LBW in the South Asian region using pooled data from six South Asian countries. Methods Nationally representative surveys from Nepal, India, Bangladesh, Pakistan, Maldives, and Afghanistan were included in the study. Birth weight and the prevalence of LBW for singleton last-born children were reported using descriptive statistics. The association between LBW and ANC visits and the interaction between iron-folic acid consumption and ANC were examined using multiple logistic regression. Results The mean birth weight in the region was 2841.8 g with an LBW prevalence of 17.1%. Country-specific prevalence ranged from 11.4% in Nepal to 22.4% in Pakistan. Not attending ANC visits (adjusted odds ratio (AOR): 1.24; 95% confidence interval (CI): 1.16, 1.34) and not consuming iron-folic acid (AOR: 1.14; 95% CI: 1.08, 1.21) were significantly associated with a higher likelihood of LBW. Furthermore, jointly, having

Gisèle Pickering,1 Sylvia Engelen,2 Maria Stupar,2 Hervé Ganry,3 Mariëlle Eerdekens2 1Faculty of Medicine Inserm 1107, Clinical Pharmacology Centre, CPC/CIC Inserm 1405 University Hospital, Clermont-Ferrand, France; 2Grünenthal GmbH, Aachen, Germany; 3Hergan Consulting 4U, Amiens, 80000, FranceCorrespondence: Mariëlle Eerdekens, Grünenthal GmbH, Zieglerstrasse 6, Aachen, 52078, Germany, Tel +492415 691090, Email Marielle.Eerdekens@grunenthal.comIntroduction: Capsaicin 179 mg (8% weight per weight) cutaneous patch (“capsaicin patch”) is a recommended topical treatment for peripheral neuropathic pain (PNP). In older patients, topical treatments may be preferred over systemic treatments, but data specific to the older population are scarce.Methods: We conducted pooled analyses of multiple clinical trials to evaluate efficacy and safety of capsaicin patch in older patients. The analysis of efficacy included four randomized, double-blind, 12-week studies with similar trial design comparing a single treatment of capsaicin 179 mg cutaneous patch vs low-dose control patch in post-herpetic neuralgia. For the safety evaluation, data were pooled from 18 interventional studies in which capsaicin patch was used in PNP with varying etiologies.Results: Capsaicin patch had similar analgesic efficacy in elderly (n=582) and non-elderly patients (n=545) in terms of change from baseline to 2– 12 weeks in the 11-point numeric pain rating scale (NPRS) score for average pain over the previous 24 hours. In both age groups, decrease in NPRS score was significantly greater with capsaicin patch vs control. Older patients treated with capsaicin patch were significantly more likely than those in the control group to achieve responder status (ie mean decrease in NPRS score from baseline to week 2– 12 of at least 30% or ≥ 2 points): 36.1% vs 27.1% (odds ratio [OR] [95% CI] 1.52 [1.06, 2.18]; P=0.0231) and 33.1% vs 20.9% (OR [95% CI] 1.90 [1.30, 2.78]; P=0.0009) for active treatment vs control group, respectively. Similar proportions of non-elderly patients (n=2,311) and elderly patients (n=537) treated with capsaicin patch experienced treatment-emergent adverse events (TEAEs) (81.6% and 78.1%, respectively) and serious TEAEs (8.2% and 7.2%), with application-site reactions the most common TEAEs in both groups.Conclusion: The capsaicin patch was equally efficacious and well tolerated in older patients as in younger patients.Plain language summary: Peripheral neuropathic pain is a common challenge among the elderly, yet effective treatments for this age group remain underexplored. This research focuses on the use of a high-concentration capsaicin patch, a specialized treatment for this type of pain. The patch, which is applied directly to the affected skin area, has been shown to reduce pain significantly for up to 12 weeks. This analysis of multiple clinical trials showed that the high-concentration capsaicin patch significantly reduced pain intensity and was well tolerated in older patients with peripheral neuropathic pain.Keywords: capsaicin patch, elderly, peripheral neuropathic pain, pooled analysis, topical treatment

INTRODUCTION: Perfluorooctanoic acid (PFOA) has been associated with kidney cancer in human studies. METHODS: We conducted a pooled analysis of two large studies of PFOA and renal cell carcinoma (RCC, the most common type of kidney cancer); one from the National Cancer Institute (NCI) (324 cases and controls), and a second from the C8 Science Panel (103 cases and 511 controls). Serum PFOA levels were estimated a median of 8 years before diagnosis. Analyses were conducted via conditional logistic regression. Lifetime risk of kidney cancer per unit serum PFOA concentration and per unit dose were calculated. RESULTS: The 25th, 50th and 75th percentiles of serum PFOA levels were 4.8, 7.3, and 23.9 ng/ml for the pooled analysis. The preferred model for the pooled datawas a two-piece linear spline model (knot at 12.5 ng/ml serum PFOA); the log odds of RCC increased 0.1349 per 1 ng/ml increase in serum PFOA up to the knot (eg, an OR of 2.02 (1.45-2.80) from the median to the knot), and was flat thereafter. The estimated lifetime excess risk (cancer slope factor) with an exposure of 1 ng/ml was 0.0018, similar to the excess risk of 0.0026 recently reported by CalEPA based on different methods. Assuming a serum half-life of 2.3 years and a distribution volume of 170 ml/kg for PFOA, our results are equivalent to 0.0128 per ng/kg/d of PFOA intake. To limit excess lifetime kidney cancer risk to 1/1,000,000, our data suggest a limit of 0.0015 ng/L (0.0015 ppt) for PFOA in drinking water, similar to CalEPAs proposed Public Health Goal and the new US EPA Drinking Water Health Advisory. CONCLUSIONS: Our results correspond reasonably well with cancer slope factors developed by other investigators using published summary data, and suggest drinking water limits similar to new recommendations by the US EPA.

Aim: We pooled data from three observational studies (INSIGHT MM, UVEA-IXA and REMIX) to investigate the real-world effectiveness of ixazomib-lenalidomide-dexamethasone (IRd) in relapsed/refractory myeloma. Materials & methods: INSIGHT MM was a prospective study conducted in countries across Europe, Asia and North/Latin America while UVEA-IXA and REMIX were multicenter, retrospective/prospective studies conducted in Europe. Patients who had received IRd as ≥2nd line of therapy were analyzed. Primary outcomes were time-to-next treatment (TTNT) and progression-free survival (PFS). Results: Overall, 564 patients were included (median follow-up: 18.5 months). Median TTNT and PFS were 18.4 and 19.9 months; both outcomes were numerically longer for earlier versus later lines. Median treatment duration was 14.0 months. Overall response rate was 64.6%. No new safety concerns were noted. Conclusion: The effectiveness of IRd in routine practice appears similar to the efficacy observed in TOURMALINE-MM1. IRd benefit in earlier versus later lines was consistent with previous reports. [ABSTRACT FROM AUTHOR]

Statins are a group of medications that lower lipid and are used for primary and secondary prevention of cardiovascular diseases (CVD). Patients can either be partially (15%) or completely (5%) intolerant to statins. Symptoms of statin intolerance can include muscle aches (myalgia), weakness, cramps, myopathy, diabetes mellitus, and elevated creatine kinase levels. Decreasing statin intolerance also improves statin adherence, which in turn results in lower number of CVD events among patients. Studies on statin intolerance is often embedded within studies of statin adherence. However, relevant data can be obtained from digital health systems. This preliminary literature review looks at studies from the past 10 years to identify and determine the effectiveness of strategies to address statin intolerance. The NLA definition for statin intolerance was used in this review. The initial search results on EMBASE, PubMed, SCOPUS, and CINAHL showed 91 articles and applying the inclusion and exclusion criteria, four articles were used in this review and pooled analysis. The study patients were identified through electronic health records. The pooled analysis was done using the Metafor package in R, applying a random-effect model to estimate pooled effect size. The findings suggest that using fixed dose combination therapy and switching from a lipophilic statin to a hydrophilic statin, while correcting metabolic abnormalities, or initiating evolocumab alongside statin can address statin intolerance. The overall relative risk (RR) was 0.40 (95% CI, 0.09 to 1.70) with I² 90%, and the overall odds ratio (OR) was 0.11 (95% CI, 0.01 to 1.59) with I² 94%, suggesting that the interventions work well in addressing statin intolerance. Since statin intolerance is has a vast range of effects, further research works may be done on exploring the possibility of using digital health systems to identify and provide targeted interventions to patients. [ABSTRACT FROM AUTHOR]

Background: Isolated radial nerve palsy is a debilitating injury that may potentially be reconstructed with either tendon transfers, nerve grafts, or nerve transfers. Currently, there is no consensus on the optimal technique for reconstruction. We performed a systematic review and analysis to determine which surgical intervention provides the best clinical outcomes. Methods: A systematic review was conducted according to PRISMA guidelines. Twenty-nine papers met inclusion criteria. Grading scales of function and strength were converted into a tripartite scoring system to compare outcomes between techniques. χ2 analyses were performed with a P value <.05. Results: Seven hundred fifty-four patients were analyzed. Tendon transfers resulted in the highest percentage of good outcomes (82%) and the lowest percentage of poor outcomes (9%). Tendon transfers were superior to nerve grafts and nerve transfers for restoration of wrist extension. Nerve transfers for wrist extension were superior to nerve transfers for finger extension. Nerve grafts and nerve transfers had equivalent rates of good and poor clinical outcomes. Conclusions: This study analyzed reported outcomes of tendon transfers, nerve grafts, and nerve transfers for reconstruction of isolated radial nerve palsy. On pooled analysis, tendon transfers had higher rates of superior clinical outcomes as compared with nerve transfers and nerve grafts. Tendon transfers should be considered first-line reconstruction for isolated radial nerve palsy as nerve-based reconstruction is less predictable and reproducible. [ABSTRACT FROM AUTHOR]

Mounting evidence suggests that body mass index (BMI) is inversely associated with the risk of lung cancer. However, relatively few studies have explored this association in Asian people, who have a much lower prevalence of obesity than Caucasians. We pooled data from 10 prospective cohort studies involving 444,143 Japanese men and women to address the association between BMI and the risk of lung cancer. Study‐specific hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated in each cohort using the Cox proportional hazards model. A meta‐analysis was undertaken by combining the results from each cohort. Heterogeneity across studies was evaluated using Cochran's Q and I2statistics. During 5,730,013 person‐years of follow‐up, 6454 incident lung cancer cases (4727 men and 1727 women) were identified. Baseline BMI was inversely associated with lung cancer risk in men and women combined. While leanness (BMI <18.5) was associated with a higher risk of lung cancer (HR 1.35; 95% CI, 1.16–1.57), overweight and obesity were associated with a lower risk, with HRs of 0.77 (95% CI, 0.71–0.84) and 0.69 (95% CI, 0.45–1.07), respectively. Every 5 kg/m2 increase in BMI was associated with a 21% lower risk of lung cancer (HR 0.79; 95% CI, 0.75–0.83; p < 0.0001). Our pooled analysis indicated that BMI is inversely associated with the risk of lung cancer in the Japanese population. This inverse association could be partly attributed to residual confounding by smoking, as it was more pronounced among male smokers. [ABSTRACT FROM AUTHOR]

Body fatness is considered a probable risk factor for biliary tract cancer (BTC), whereas cholelithiasis is an established factor. Nevertheless, although obesity is an established risk factor for cholelithiasis, previous studies of the association of body mass index (BMI) and BTC did not take the effect of cholelithiasis fully into account. To better understand the effect of BMI on BTC, we conducted a pooled analysis using population‐based cohort studies in Asians. In total, 905 530 subjects from 21 cohort studies participating in the Asia Cohort Consortium were included. BMI was categorized into four groups: underweight (<18.5 kg/m2); normal (18.5‐22.9 kg/m2); overweight (23‐24.9 kg/m2); and obese (25+ kg/m2). The association between BMI and BTC incidence and mortality was assessed using hazard ratios (HR) and 95% confidence intervals (CIs) by Cox regression models with shared frailty. Mediation analysis was used to decompose the association into a direct and an indirect (mediated) effect. Compared to normal BMI, high BMI was associated with BTC mortality (HR 1.19 [CI 1.02‐1.38] for males, HR 1.30 [1.14‐1.49] for females). Cholelithiasis had significant interaction with BMI on BTC risk. BMI was associated with BTC risk directly and through cholelithiasis in females, whereas the association was unclear in males. When cholelithiasis was present, BMI was not associated with BTC death in either males or females. BMI was associated with BTC death among females without cholelithiasis. This study suggests BMI is associated with BTC mortality in Asians. Cholelithiasis appears to contribute to the association; and moreover, obesity appears to increase BTC risk without cholelithiasis. [ABSTRACT FROM AUTHOR]

Background The prevalence of low birth weight (LBW) has remained high (24.9%) in the South Asian region with a significant impact on newborn survival. This region bears nearly 40% of global burden of LBW. While antenatal care (ANC) and iron-folic acid supplementation independently have been considered effective for improving maternal and newborn outcomes, the evidence on the combined effect of these two supplements on LBW is lacking. This study aimed to examine the synergistic association of ANC and iron-folic acid supplementation on LBW in the South Asian region using pooled data from six South Asian countries. Methods Nationally representative surveys from Nepal, India, Bangladesh, Pakistan, Maldives, and Afghanistan were included in the study. Birth weight and the prevalence of LBW for singleton last-born children were reported using descriptive statistics. The association between LBW and ANC visits and the interaction between iron-folic acid consumption and ANC were examined using multiple logistic regression. Results The mean birth weight in the region was 2841.8 g with an LBW prevalence of 17.1%. Country-specific prevalence ranged from 11.4% in Nepal to 22.4% in Pakistan. Not attending ANC visits (adjusted odds ratio (AOR): 1.24; 95% confidence interval (CI): 1.16, 1.34) and not consuming iron-folic acid (AOR: 1.14; 95% CI: 1.08, 1.21) were significantly associated with a higher likelihood of LBW. Furthermore, jointly, having<4 ANC visits and <180 days of iron-folic acid supplementation was associated with a higher likelihood (AOR: 1.29; 95% CI: 1.22, 1.36) of having LBW compared to those who had ≥4 ANC visits and ≥180 days of iron-folic acid consumption after controlling for key confounding factors. Conclusions The current study provides important evidence on the synergy between ANC visits and iron-folic acid consumption during pregnancy to capitalize on the existing national maternal health programs in the South Asian region, including low-and middle-income countries for positive foetal outcomes. [ABSTRACT FROM AUTHOR]

BackgroundProbiotics could decrease irinotecan-induced diarrhea due to the reduction of intestinal beta-d-glucuronidase activity. This study included a combined analysis of two clinical trials aimed to determine the effectiveness of the probiotics in the prophylaxis of irinotecan-induced diarrhea in metastatic colorectal cancer (CRC) patients.MethodsThis combined analysis included 46 patients with CRC enrolled in the Probio-SK-003 (NCT01410955) and 233 patients from Probio-SK-005 (NCT02819960) starting a new line of irinotecan-based therapy with identical eligibility criteria. Patients were randomized in a ratio 1:1 to probiotic formulas vs. placebo administered for 12 and 6 weeks, respectively. Due to the different durations of study treatments, only the first 6 weeks of therapy were used for analysis.ResultsIn total, 279 patients were randomized, including 142 patients in the placebo and 137 participants in the probiotic arm. Administration of probiotics did not significantly reduce the incidence of grade 3/4 diarrhea compared to placebo (placebo 12.7% vs. probiotics 6.6%, p = 0.11). Neither the overall incidence of diarrhea (placebo 48.6% vs. probiotics 41.6%, p = 0.28) nor the incidence of enterocolitis (placebo 4.2% vs. probiotics 0.7%, p = 0.12) was different in the placebo vs. probiotic arm. However, subgroup analysis revealed that patients with a colostomy who received a placebo had a significantly higher incidence of any diarrhea (placebo 51.2% vs. probiotics 25.7%, p = 0.028) and grade 3/4 diarrhea (placebo 14.6% vs. probiotics 0.0%, p = 0.03) compared to the probiotic arm.ConclusionsThis combined analysis suggests that probiotics could be beneficial in the prevention of irinotecan-induced diarrhea in colorectal cancer patients with colostomy.

Background A limited number of studies investigated the association between blood pressure variability (BPV) and cognitive impairment in patients with hypertension. This study aimed to identify the longitudinal association between BPV and cognitive decline and the role of blood pressure (BP) control in this association. Methods and Results Participants with hypertension from the HRS (Health and Retirement Study), the ELSA (English Longitudinal Study of Ageing), and the CHARLS (China Health and Retirement Longitudinal Study) were included. Variation independent of the mean (VIM) was adopted to measure BPV. Cognitive function was measured by standard questionnaires, and a standardized Z score was calculated. Linear mixed‐model and restricted cubic splines were adopted to explore the association between BPV and cognitive decline. The study included 4853, 1616, and 1432 eligible patients with hypertension from the HRS, ELSA, and CHARLS, respectively. After adjusting for covariates, per‐SD increment of VIM of BP was significantly associated with global cognitive function decline in Z scores in both systolic BP (pooled β, −0.045 [95% CI, −0.065 to −0.029]) and diastolic BP (pooled β, −0.022 [95% CI, −0.040 to −0.004]) among hypertensive patients. Similar inverse associations were observed in patients with hypertension taking antihypertensive drugs and in patients with hypertension with well‐controlled BP. Conclusions High BPV was independently associated with a faster cognitive decline among patients with hypertension, even those with antihypertensive medications or well‐controlled BP. Further studies are needed to confirm our results and determine whether reducing BPV can prevent or delay cognitive decline.

BackgroundHelicobacter pylori is the most important risk factor for non-cardia gastric cancer (NCGC); however, the magnitude of the association varies across epidemiological studies. This study aimed to quantify the association between H. pylori infection and NCGC, using different criteria to define infection status.MethodsA pooled analysis of individual-level H. pylori serology data from eight international studies (1325 NCGC and 3121 controls) from the Stomach Cancer Pooling (StoP) Consortium was performed. Cases and controls with a negative H. pylori infection status were reclassified as positive considering the presence of anti-Cag A antibodies, gastric atrophy, or advanced stage at diagnosis, as available and applicable. A two-stage approach was used to pool study-specific adjusted odds ratios (OR), and 95% confidence intervals (95% CI). A meta-analysis of published prospective studies assessing H. pylori seropositivity in NCGCs was conducted.ResultsThe OR for the association between serology-defined H. pylori and NCGC was 1.45 (95% CI: 0.87-2.42), which increased to 4.79 (95% CI: 2.39-9.60) following the reclassification of negative H. pylori infection. The results were consistent across strata of sociodemographic characteristics, clinical features and lifestyle factors, though significant differences were observed according to geographic region-a stronger association in Asian studies. The pooled risk estimates from the literature were 3.01 (95% CI: 2.22-4.07) for ELISA or EIA and 9.22 (95% CI: 3.12-27.21) for immunoblot or multiplex serology.ConclusionThe NCGC risk estimate from StoP based on the reclassification of H. pylori seronegative individuals is consistent with the risk estimates obtained from the literature. Our classification algorithm may be useful for future studies.

Background: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians. Methods: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models. Results: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07–1.40), 1.22 (95% CI, 1.09–1.36), and 1.27 (95% CI, 1.08–1.49), respectively, in men and 1.21 (95% CI, 1.09–1.35), 1.23 (95% CI, 1.08–1.40), and 1.35 (95% CI, 1.003–1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes. Conclusion: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Background: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan. Methods: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated. Results: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18–1.82) and current smokers (HR 1.96; 95% CI, 1.62–2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67–3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97–1.63). Conclusion: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.