Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

What is the impact of zinc deficiency for pancreatectomies in patients with pancreatic ductal adenocarcinoma?

Backgroundand purpose: Zinc is an essential element for human health and plays an important role in metabolic, immunological and other biological processes. The present study was conducted to investigate the association between zinc deficiency (ZD) and the perioperative clinical course in patients with pancreatic ductal adenocarcinoma (PDAC).MethodsOf 216 patients with PDAC who underwent elective pancreatectomy between 2013 and 2017 at our institution, 206 patients with sufficient clinical data were retrospectively reviewed. The perioperative variables were compared and the risk factors associated with infectious complications were identified.ResultsZD was preoperatively present in 36 (17.5%) of 206 patients with PDAC. In the patients of the ZD group, a higher proportion of males, higher preoperative modified Glasgow prognostic scores, a higher neutrophil-to-lymphocyte ratio, and a higher occurrence of postoperative infectious complications after pancreatectomy were observed, compared to the non-ZD group. By a univariate analysis, three risk factors were significantly associated with infectious complications after pancreatectomy: ZD (vs non-ZD: p = 0.002), serum albumin <3.5 g/dl (vs ≥ 3.5 g/dl: p = 0.005), and the procedure of pancreaticoduodenectomy (vs others: p = 0.013). By multivariate logistic regression analysis, the occurrence of infectious complications was significantly associated with ZD (OR 3.430, 95%CI 1.570 to 7.490, p = 0.002) and the procedure of pancreaticoduodenectomy (OR 2.030, 95%CI 1.090 to 3.770, p = 0.025).ConclusionsThe current study newly demonstrated that ZD could serve as a preoperative predictor of infectious complications after pancreatectomies in the patients with PDAC.     

Sex and smoking differences in the association between gastroesophageal reflux and risk of esophageal squamous cell carcinoma in a high-incidence area: Golestan Cohort Study

Prior studies have conflicting findings regarding the association between gastroesophageal reflux disease (GERD) and esophageal squamous cell carcinoma (ESCC). We examined this relationship in a prospective cohort in a region of high ESCC incidence. Baseline exposure data were collected from 50 045 individuals using in-person interviews at the time of cohort entry. Participants were followed until they developed cancer, died, or were lost to follow up. Participants with GERD symptoms were categorized into any GERD (heartburn or regurgitation), mixed symptoms, or heartburn alone. Multivariable Cox regression was used to assess the relationship between GERD symptom group and histologically confirmed ESCC. The model was adjusted for known risk factors for GERD and ESCC. 49 559 individuals were included in this study, of which 9005 had GERD symptoms. Over 13.0 years of median follow up, 290 individuals were diagnosed with ESCC. We found no association between any GERD and risk of ESCC (aHR 0.90, 95% CI: 0.66-1.24, P = .54). Similar findings were observed for the GERD symptom subtypes. Significant interactions between any GERD and sex (P = .013) as well as tobacco smoking (P = .028) were observed. In post-hoc analyses, GERD was associated with a decreased risk of ESCC in men (aHR 0.51, 95% CI: 0.27-0.98 P = .04) and in smokers (aHR 0.26, 95% CI: 0.08-0.83 P = .02). While there was little evidence for an overall association between GERD symptoms and ESCC risk, significant interactions with sex and smoking were observed. Men and smokers with GERD symptoms had a lower risk of ESCC development.     

Adherence to a Mediterranean Lifestyle and Changes in Frequency,Severity, and Localization of Pain in Older Adults

ObjectiveTo assess the association between adherence to a Mediterranean lifestyle and changes in pain, and its characteristics over time in older adults.Patients and MethodsWe analyzed data from 864 and 862 community-dwelling individuals aged 65+ years from the Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain (Seniors-ENRICA) Seniors-ENRICA-1 (2008–2010 to 2012) and Seniors-ENRICA-2 (2015–2017 to 2019) cohorts, with a median follow-up of 2.8 and 2.4 years, respectively. Adherence to a Mediterranean lifestyle was assessed at baseline with the 27-item Mediterranean lifestyle (MEDLIFE) index. Pain changes over time were calculated with a pain scale that assessed the frequency, severity, and the number of pain locations both at baseline and follow-up. Multivariable-adjusted relative risk ratios (RRRs) were obtained using multinomial logistic regression.ResultsIn the pooled cohorts, after a median follow-up of 2.6 years, pain worsened for 697 participants, improved for 734, and did not change for 295. Compared with the lowest category of MEDLIFE adherence, those in the highest category showed an RRR of improvement vs worsening of overall pain of 1.85 (95% CI, 1.28 to 2.67; P-trend<.001). MEDLIFE adherence was also linked to improvement in pain frequency (RRR, 1.98; 95% CI, 1.31 to 3.01; P-trend=.001), pain severity (RRR, 2.00; 95% CI, 1.33 to 3.00; P-trend=.001), and a reduction in the number of pain locations (RRR, 1.68; 95% CI, 1.13 to 2.50; P-trend=.004). Limitations of this study are the use of self-reported lifestyle data.ConclusionA Mediterranean lifestyle was associated with improvement of pain characteristics in older adults. Experimental studies should assess the efficacy of an integral lifestyle approach for the management of pain in older adults.     

Do social support and community engagement act as mechanisms in the association between neighbourhood income inequality and the mental health of mothers in Calgary,Canada? A mediation analysis

PurposeAccording to the social determinants of health framework, income inequality is a potential risk factor for adverse mental health. However, few studies have explored the mechanisms suspected to mediate this relationship. The current study addresses this gap through a mediation analysis to determine if social support and community engagement act as mediators linking neighbourhood income inequality to maternal anxiety and depressive symptoms within a cohort of new mothers living in the City of Calgary, Canada.MethodsData collected at three years postpartum from mothers belonging to the All Our Families (AOF) cohort were used in the current study. Maternal data were collected between 2012 and 2015 and linked to neighbourhood socioeconomic data from the 2006 Canadian Census. Income inequality was measured using Gini coefficients derived from 2006 after-tax census data. Generalized structural equation models were used to quantify the associations between income inequality and mental health symptoms, and to assess the potential direct and indirect mediating effects of maternal social support and community engagement.ResultsIncome inequality was not significantly associated with higher depressive symptoms (β = 0.32, 95%CI = −0.067, 0.70), anxiety symptoms (β = 0.11, 95%CI = −0.39, 0.60), or lower social support. Income inequality was not associated with community engagement. For the depression models, higher social support was significantly associated with lower depressive symptoms (β = −0.13, 95%CI = −0.15, −0.097), while community engagement was not significantly associated with depressive symptoms (β = 0.059, 95%CI = −0.15, 0.27). Similarly, for the anxiety models, lower anxiety symptoms were significantly associated with higher levels of social support (β = −0.17, 95%CI = −0.20, −0.13) but not with higher levels of community engagement (β = 0.14, 95%CI = −0.14, 0.41).ConclusionThe current study did not find clear evidence for social support or community engagement mediating the relationship between neighbourhood income inequality and maternal mental health. Future investigations should employ a broader longitudinal approach to capture changes in income inequality, potential mediators, and mental health symptomatology over time.