Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

Aim: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). Methods: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. Results: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. Conclusion: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

Effects of Primary Metronidazole and Clarithromycin Resistance to Helicobacter pylori on Omeprazole, Metronidazole, and Clarithromycin Triple-Therapy Regimen in a Region with High Rates of Metronidazole Resistance

The aim of this study was to investigate the effect of metronidazole resistance (MtzR) and clarithromycin resistance (CIaR) on the eradication rate for omeprazole, clarithromycin, and metronidazole triple-therapy regimen and on the development of posttherapy drug resistance in a region of high rates of MtzR. One hundred ninety-six Helicobacter pylori isolates were recovered from patients with duodenal ulcer, gastric ulcer, or nonulcer dyspepsia during upper endoscopy. The prevalences of MtzR, ClaR, and dual resistance were 37.8%, 13.8%, and 8.7%, respectively. The intention-to-treat eradication rates for metronidazole-susceptible (87.2% vs. 67.6%; P = .001) and clarithromycin-susceptible (86.4% vs. 40.7%; P < .001 ) strains were significantly higher than the rates for resistant strains. Multiple logistic regression analysis implicated younger age (<40 years old), MtzR, ClaR, and the diagnosis of nonulcer dyspepsia as independent factors that predicted treatment failure. The rates of posttreatment MtzR, ClaR, and dual resistance were 88%, 88%, and 75%, respectively. MtxR and ClaR significantly affected the success of eradication therapy. Posttreatment rates of resistance were high and were related to the presence of pretreatment antibiotic resistance.published_or_final_versio

Effects of cyclooxygenase-1 and -2 gene disruption on Helicobacter pylori-induced gastric inflammation

Background. Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation. Methods. Wild-type (WT), COX-1 and COX-2 heterozygous (COX-1 +/- and COX-2 +/-), and homozygous COX-deficient (COX-1 -/- and COX-2 -/-) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX-deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined. Results. COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX-deficient mice, whereas cell proliferation was increased in WT and COX-1-deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-α and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-α mRNA expression was further increased by COX deficiency. Prostaglandin E 2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B 4 and LTC 4 levels were increased to a similar extent in infected WT and COX-deficient mice. Conclusions. COX deficiency enhances H. pylori-induced gastritis, probably via TNF-α expression. COX-2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation. © 2006 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Association of the labor migration of parents with nonsuicidal self-injury and suicidality among their offspring in China

© 2021 The Authors. Published by American Medical Association. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2785877Importance: The labor migration of parents in China often leaves children behind, which may be adversely associated with children's health. However, few studies have assessed the association of parental migration with nonsuicidal self-injury (NSSI) or with suicidality among their offspring. Objective: To examine the associations of parental labor migration with NSSI and with suicidality as well as potential differential associations by sex among offspring left behind. Design, Setting, and Participants: This nationwide cross-sectional study was conducted from February to October 2015 among individuals aged 11 to 20 years from 45 public middle and high schools across 5 provinces of China. Data analysis was performed from November 1, 2020, to March 1, 2021. Exposures: Parental labor migration, including parental migration status (yes vs no), migration pattern (father, mother, or both), and the child's age at the initial parent-child separation. Main Outcomes and Measures: Less frequent (1-4 episodes) NSSI, more frequent (≥5 episodes) NSSI, suicidal ideation, and suicide attempt in the past year were measured using validated questionnaires. Multinomial or binomial logistic regression analyses were used separately to estimate adjusted odds ratios (aORs) and 95% CIs of the associations between parental migration and NSSI, suicidal ideation, or suicide attempt. Potential covariates (demographic, family-level, and psychological characteristics) were adjusted for in 3 sequential models. Results: A total of 15312 participants (7904 male [51.6%] and 7408 female [48.4%]) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) were included. Of those participants, 5963 (23.3%) experienced parental migration. The 12-month prevalence of less frequent NSSI was 17.2% (2635 of 15312), the 12-month prevalence of more frequent NSSI was 11.6% (1783 of 15312), the 12-month prevalence of suicidal ideation was 15.2% (2335 of 15312), and the 12-month prevalence of suicide attempt was 3.5% (535 of 15312). Parental migration was associated with less frequent NSSI (adjusted odds ratio [aOR], 1.13; 95% CI, 1.03-1.24); no significant association of parental migration with more frequent NSSI (aOR, 1.01; 95% CI, 0.90-1.13), suicidal ideation (aOR, 1.00; 95% CI, 0.90-1.10), or suicide attempt (aOR, 1.09; 95% CI, 0.90-1.33) was identified. Compared with children whose parents did not migrate, the aOR for less frequent NSSI for participants whose father migrated was 1.18 (95% CI, 1.06-1.31), and the aOR for less frequent NSSI for participants having both parents migrate was 1.12 (95% CI, 1.01-1.28). Compared with children whose parents did not migrate, participants who experienced initial separation from 1 or both parents at preschool age had an aOR for less frequent NSSI of 1.16 (95% CI, 1.03-1.31). No sex disparities were found in these associations except for participants who experienced initial separation from 1 or both migrant parents at preschool age, for which the aOR for more frequent NSSI was higher among male (aOR, 1.27; 95% CI, 1.04-1.55) than female (aOR, 0.96; 95% CI, 0.77-1.19) participants. Conclusions and Relevance: This cross-sectional study found that parental migration, mainly of the father or of both parents, or an initial separation of children at preschool age from 1 or both parents who migrated was associated with higher odds of experiencing 1 to 4 NSSI episodes in 1 year among offspring. Overall, the associations of parental migration with NSSI and suicidality were similar between male and female participants..This study was supported by grants 81773457 and 81302445 (to Dr Tang) from the National Natural Science Foundation of China.Published versio

Global, regional, and national estimates of the population at increased risk of severe COVID-19 due to underlying health conditions in 2020: a modelling study

Background: The risk of severe COVID-19 if an individual becomes infected is known to be higher in older individuals and those with underlying health conditions. Understanding the number of individuals at increased risk of severe COVID-19 and how this varies between countries should inform the design of possible strategies to shield or vaccinate those at highest risk. / Methods: We estimated the number of individuals at increased risk of severe disease (defined as those with at least one condition listed as “at increased risk of severe COVID-19” in current guidelines) by age (5-year age groups), sex, and country for 188 countries using prevalence data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 and UN population estimates for 2020. The list of underlying conditions relevant to COVID-19 was determined by mapping the conditions listed in GBD 2017 to those listed in guidelines published by WHO and public health agencies in the UK and the USA. We analysed data from two large multimorbidity studies to determine appropriate adjustment factors for clustering and multimorbidity. To help interpretation of the degree of risk among those at increased risk, we also estimated the number of individuals at high risk (defined as those that would require hospital admission if infected) using age-specific infection–hospitalisation ratios for COVID-19 estimated for mainland China and making adjustments to reflect country-specific differences in the prevalence of underlying conditions and frailty. We assumed males were twice at likely as females to be at high risk. We also calculated the number of individuals without an underlying condition that could be considered at increased risk because of their age, using minimum ages from 50 to 70 years. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 95% confidence limits for country population size, disease prevalences, multimorbidity fractions, and infection–hospitalisation ratios, and plausible low and high estimates for the degree of clustering, informed by multimorbidity studies. / Findings: We estimated that 1·7 billion (UI 1·0–2·4) people, comprising 22% (UI 15–28) of the global population, have at least one underlying condition that puts them at increased risk of severe COVID-19 if infected (ranging from 66% of those aged 70 years or older). We estimated that 349 million (186–787) people (4% [3–9] of the global population) are at high risk of severe COVID-19 and would require hospital admission if infected (ranging from <1% of those younger than 20 years to approximately 20% of those aged 70 years or older). We estimated 6% (3–12) of males to be at high risk compared with 3% (2–7) of females. The share of the population at increased risk was highest in countries with older populations, African countries with high HIV/AIDS prevalence, and small island nations with high diabetes prevalence. Estimates of the number of individuals at increased risk were most sensitive to the prevalence of chronic kidney disease, diabetes, cardiovascular disease, and chronic respiratory disease. / Interpretation: About one in five individuals worldwide could be at increased risk of severe COVID-19, should they become infected, due to underlying health conditions, but this risk varies considerably by age. Our estimates are uncertain, and focus on underlying conditions rather than other risk factors such as ethnicity, socioeconomic deprivation, and obesity, but provide a starting point for considering the number of individuals that might need to be shielded or vaccinated as the global pandemic unfolds

Expression of Mir-21 and Mir-143 in Cervical Specimens Ranging from Histologically Normal through to Invasive Cervical Cancer

MicroRNA expression is severely disrupted in carcinogenesis, however limited evidence is available validating results from cell-line models in human clinical cancer specimens. MicroRNA-21 (mir-21) and microRNA-143 (mir-143) have previously been identified as significantly deregulated in a range of cancers including cervical cancer. Our goal was to investigate the expression patterns of several well-studied microRNA species in cervical samples and compare the results to cell line samples.We measured the expression of mir-21 and mir-143 in 142 formalin-fixed, paraffin embedded (FFPE) cervical biopsy tissue blocks, collected from Dantec Oncology Clinic, Dakar, Senegal. MicroRNA expression analysis was performed using Taqman-based real-time PCR assays. Protein immunohistochemical staining was also performed to investigate target protein expression on 72 samples. We found that mir-21 expression increased with worsening clinical diagnosis but that mir-143 was not correlated with histology. These observations were in stark contrast to previous reports involving cervical cancer cell lines in which mir-143 was consistently down-regulated but mir-21 largely unaffected. We also identified, for the first time, that cytoplasmic expression of Programmed Cell Death Protein 4 PDCD4; a known target of mir-21) was significantly lower in women with invasive cervical carcinoma (ICC) in comparison to those with cervical intraepithelial neoplasia (2-3) or carcinoma in situ (CIN2-3/CIS), although there was no significant correlation between mir-21 and PDCD4 expression, despite previous studies identifying PDCD4 transcript as a known mir-21 target.Whilst microRNA biomarkers have a number of promising features, more studies on expression levels in histologically defined clinical specimens are required to investigate clinical relevance of discovery-based studies. Mir-21 may be of some utility in predictive screening, given that we observed a significant correlation between mir-21 expression level and worsening histological diagnosis of cervical cancer

The impact of multimorbidity on adult physical and mental health in low- and middle-income countries: what does the study on global ageing and adult health (SAGE) reveal?

BACKGROUND: Chronic diseases contribute a large share of disease burden in low- and middle-income countries (LMICs). Chronic diseases have a tendency to occur simultaneously and where there are two or more such conditions, this is termed as 'multimorbidity'. Multimorbidity is associated with adverse health outcomes, but limited research has been undertaken in LMICs. Therefore, this study examines the prevalence and correlates of multimorbidity as well as the associations between multimorbidity and self-rated health, activities of daily living (ADLs), quality of life, and depression across six LMICs. METHODS: Data was obtained from the WHO's Study on global AGEing and adult health (SAGE) Wave-1 (2007/10). This was a cross-sectional population based survey performed in LMICs, namely China, Ghana, India, Mexico, Russia, and South Africa, including 42,236 adults aged 18 years and older. Multimorbidity was measured as the simultaneous presence of two or more of eight chronic conditions including angina pectoris, arthritis, asthma, chronic lung disease, diabetes mellitus, hypertension, stroke, and vision impairment. Associations with four health outcomes were examined, namely ADL limitation, self-rated health, depression, and a quality of life index. Random-intercept multilevel regression models were used on pooled data from the six countries. RESULTS: The prevalence of morbidity and multimorbidity was 54.2 % and 21.9 %, respectively, in the pooled sample of six countries. Russia had the highest prevalence of multimorbidity (34.7 %) whereas China had the lowest (20.3 %). The likelihood of multimorbidity was higher in older age groups and was lower in those with higher socioeconomic status. In the pooled sample, the prevalence of 1+ ADL limitation was 14 %, depression 5.7 %, self-rated poor health 11.6 %, and mean quality of life score was 54.4. Substantial cross-country variations were seen in the four health outcome measures. The prevalence of 1+ ADL limitation, poor self-rated health, and depression increased whereas quality of life declined markedly with an increase in number of diseases. CONCLUSIONS: Findings highlight the challenge of multimorbidity in LMICs, particularly among the lower socioeconomic groups, and the pressing need for reorientation of health care resources considering the distribution of multimorbidity and its adverse effect on health outcomes

Effects of octreotide on expression of L-type voltage-operated calcium channels and on intracellular Ca2+ in activated hepatic stellate cells

Background. The contractility of hepatic stellate cells (HSCs) may play an important role in the pathogenesis of cirrhosis with portal hypertension. The aim of this study was to research the effects of octreotide, an analogue of somatostatin, on intracellular Ca2+ and on the expression of L-type voltage-operated calcium channels (L-VOCCs) in activated HSCs, and to try to survey the use of octreotide in treatment and prevention of cirrhosis with portal hypertension complications. Methods. HSC-T6, an activated HSCs line, was plated on small glass coverslips in 35-mm culture dishes at a density of 1 × 105/ml, and incubated in DMEM media for 24 hours. After the cells were loaded with Fluo-3/AM, intracellular Ca2+ was measured by Laser Scanning Confocal Microscopy (LSCM). The dynamic changes in activated HSCs of intracellular Ca2+, stimulated by octreotide, endothelin-1, and KCI, respectively, were also determined by LSCM. Each experiment was repeated six times. L-VOCC expression in HSCs was estimated by immunocytochemistry. Results. After octreotide stimulation, a signifcant decrease in the intracellular Ca2+ of activated HSCs was observed. However, octreotide did not inhibit the increases in intracellular Ca2+ after stimulation by KCI and endothelin-1. Moreover, octreotide did not significantly affect L-VOCC expression. These results suggest that neither L-VOCC nor endothelin-1 receptors in activated HSCs are inhibited by octreotide. Conclusions. Octreotide may decrease portal hypertension and intrahepatic vascular tension by inhibiting activated HSCs contractility through decreases in intracellular Ca2+. The somatostatin receptors in activated HSCs may be inhibited by octreotide.link_to_OA_fulltex