Microhematuria Enhances the Risks of Relapse and Renal Progression in Primary Membranous Nephropathy

Objective: To determine whether there is an association between microhematuria and relapse or kidney disease progression in patients with primary membranous nephropathy (PMN).Methods: A cohort of 639 patients with biopsy-proven PMN from two centers was followed for a median of 40 months. The exposures were initial hematuria, time-averaged hematuria, and cumulative duration of hematuria. The outcomes were relapse and renal progression, which were defined by a 40% reduction in renal function or end-stage renal disease. Cox proportional hazards regression and competing risk analyses were performed to yield hazard ratios (HRs) and subdistribution hazard ratios (sHRs) with 95% confidence intervals (CIs). Sensitivity and interaction analyses were also performed.Results: After adjusting for confounders, a higher level of initial hematuria was associated with a 1.43 (95% CI, 1.15–1.78) greater hazard of relapse. Worsening hematuria remarkably increased the risk of short-term relapse (HR, 4.64; 3.29–6.54). Time-averaged hematuria (sHR, 1.35; 1.12–1.63) and cumulative duration of hematuria (sHR, 1.17; 1.02–1.34) were independent predictors of renal progression. Hematuria remission was related to a reduced risk of renal progression over time in patients with positive microhematuria (sHR, 0.63; 0.41–0.96).Conclusions: A higher level of initial hematuria was a remarkable predictor of relapse in patients with PMN, and the magnitude and persistence of microhematuria were independently associated with kidney disease progression.

Prevalence and duration of prescribed opioid use during pregnancy: a cohort study from the Quebec Pregnancy Cohort

Background Recent studies show a rapid growth among pregnant women using high potency opioids for common pain management during their pregnancy. No study has examined the duration of treatment among strong opioid users and weak opioid users during pregnancy. We aimed to investigate the prevalence of prescribed opioid use during pregnancy, in Quebec; and to compare the duration of opioid treatment between strong opioid users and weak opioid users. Methods Using the Quebec Pregnancy Cohort (1998–2015), we included all pregnancies covered by the Quebec Public Prescription Drug Insurance Program. Opioid exposure was defined as filled at least one prescription for any opioid during pregnancy or before pregnancy but with a duration that overlapped the beginning of pregnancy. Prevalence of opioids use was calculated for all pregnancies, according to pregnancy outcome, trimester of exposure, and individual opioids. The duration of opioid use during pregnancy was analyzed according to 8 categories based on cumulative duration (< 90 days vs. ≥90 days), duration of action (short-acting vs. long-acting) and strength of the opioid (weak vs. strong). Results Of 442,079 eligible pregnancies, 20,921 (4.7%) were exposed to opioids. Among pregnancies ending with deliveries (n = 249,234), 5.4% were exposed to opioids; the prevalence increased by 40.3% from 3.9% in 1998 to 5.5% in 2015, more specifically a significant increase in the second and third trimesters of pregnancy. Weak opioid, codeine was the most commonly dispensed opioid (70% of all dispensed opioids), followed by strong opioid, hydromorphone (11%), morphine (10%), and oxycodone (5%). The prevalence of codeine use decreased by 47% from 4.3% in 2005 to 2.3% in 2015, accompanied by an increased use of strong opioid, morphine (0.029 to 1.41%), hydromorphone (0.115 to 1.08%) and oxycodone (0.022 to 0.44%), from 1998 to 2015. The average durations of opioid exposure were significantly longer among pregnancies exposed to strong opioid as compared to weak opioid regardless of the cumulative duration or duration of action (P < 0.05). Conclusions Given the differences in the safety profile between strong opioids and the major weak opioid codeine, the increased use of strong opioids during pregnancy with longer treatment duration raises public health concerns.

307. Predictors of Respiratory Bacterial Co-Infection in Hospitalized COVID-19 Patients

Background COVID-19 pneumonia can be indistinguishable from other infectious respiratory etiologies, so providers are challenged with deciding whether empiric antibiotics should be prescribed to hospitalized patients with SARS-CoV-2. This study aimed to evaluate predictors of respiratory bacterial co-infections (RBCI) in hospitalized patients with COVID-19. Methods Retrospective study evaluating COVID-19 inpatients from Feb 1, 2020 to Sept 30, 2020 at a tertiary academic medical center. Patients with RBCI were matched with three COVID-19 inpatients lacking RBCI admitted within 7 days of each other. The primary objectives of this study were to determine the prevalence of and identify variables associated with RBCI in COVID-19 inpatients. Secondary outcomes included length of stay and mortality. Data collected included demographics; inflammatory markers; bacterial culture/antigen results; antibiotic exposure; and COVID-19 severity. Wilcoxon rank sum, Chi Square tests, or Fisher’s exact tests were utilized as appropriate. A multivariable logistic regression (MLR) model was conducted to identify covariates associated with RBCI. Results Seven hundred thirty-five patients were hospitalized with COVID-19 during the study period. Of these, 82 (11.2%) had RBCI. Fifty-seven of these patients met inclusion criteria and were matched to three patients lacking RBCI (N = 228 patients). Patients with RBCI were more likely to receive antibiotics [57 (100%) vs. 130 (76%), p &lt; 0.0001] and for a longer cumulative duration [19 (13-33) vs. 8 (4-13) days, p &lt; 0.0001] compared to patients lacking RBCI. The MLR model revealed risk factors of RBCI to be admission from SNF/LTAC/NH (AOR 6.8, 95% CI 2.6-18.2), severe COVID-19 (AOR 3.03, 95% CI 0.78-11.9), and leukocytosis (AOR 3.03, 95% CI 0.99-1.16). Conclusion Although RBCI is rare in COVID-19 inpatients, antibiotic use is common. COVID-19 inpatients may be more likely to have RBCI if they are admitted from a SNF/LTAC/NH, have severe COVID-19, or present with leukocytosis. Early and prompt recognition of RBCI predictors in COVID-19 inpatients may facilitate timely antimicrobial therapy while improving antimicrobial stewardship among patients at low risk for co-infection. Disclosures All Authors: No reported disclosures

Comparative Study of the Feeding Characteristics and Digestion Physiology of Haliotis discus hannai and Haliotis gigantea

Abalone (Haliotis spp.) are typical nocturnal creatures but Haliotis discus hannai is bold and active in the nighttime whereas H. gigantea tends to be timid and inactive. In this study, we quantified and compared differences in movement, feeding, and digestive physiology between H. discus hannai and H. gigantea as well as the potential molecular mechanisms on the basis of video observations and expression levels of genes related to feeding regulation. The feeding behaviors of both species were characterized by significant circadian rhythms (P &lt; 0.05). However, the distance moved and the cumulative duration of movement were 2.61 and 1.94 times higher, respectively, in H. discus hannai than in H. gigantea over the 24-h cycle. The cumulative duration of feeding by H. discus hannai was only 1.15 times that by H. gigantea, but the feeding time as a percentage of the cumulative duration of movement (FTP) was up to 94.6% for H. gigantea and only 56.0% for H. discus hannai. The peaks for α-amylase activity and NPF expression levels in both species as well as the peak OX2R expression level in H. gigantea occurred during 20:00–00:00 h. By contrast, the peaks for alginate lyase activity and NPYR expression levels in H. discus hannai occurred at 16:00 h, when the FTP was significantly higher for H. discus hannai than for H. gigantea. These initial findings quantify specific behavior parameters and thus provide a reference for the selection of appropriate feeding strategies and the proliferation of abalone via bottom sowing.

Metformin Reduces the Risk of Diverticula of Intestine in Taiwanese Patients with Type 2 Diabetes Mellitus

Aim: To investigate the risk of diverticula of intestine associated with metformin use.Methods: This retrospective cohort study used the Taiwan’s National Health Insurance database to enroll 307,548 ever users and 18,839 never users of metformin. The patients were followed up starting on January 1, 2006 and ending on a date up to December 31, 2011. To address confounding by indication, hazard ratios were derived from Cox regression based on the inverse probability of treatment weighting using propensity score.Results: During follow-up, newly diagnosed cases of diverticula were identified in 1,828 ever users (incidence rate: 125.59 per 100,000 person-years) and 223 never users (incidence rate: 268.17 per 100,000 person-years). Ever users had an approximately 54% lower risk, as shown by the overall hazard ratio of 0.464 (95% confidence interval 0.404–0.534). While patients categorized in each tertile of cumulative duration of metformin therapy were compared to never users, a dose-response pattern was observed with hazard ratios of 0.847 (0.730–0.983), 0.455 (0.391–0.531) and 0.216 (0.183–0.255) for the first (&lt;27.37 months), second (27.37–59.70 months) and third (&gt;59.70 months) tertiles, respectively. The findings were similar when the diagnosis of diverticula was restricted to the small intestine or to the colon. Subgroup analyses suggested that the lower risk of diverticula of intestine associated with metformin use was significant in all age groups of &lt;50, 50–64 and ≥65 years, but the magnitude of risk reduction attenuated with increasing age.Conclusion: Metformin treatment is associated with a significantly reduced risk of diverticula of intestine.

Inhaled Corticosteroids Increase Risk of Nontuberculous Mycobacterial Lung Disease: A Nested Case-Control Study and Meta-analysis

Studies on use of inhaled corticosteroids (ICS) and the risk of nontuberculous mycobacterial lung disease (NTM-LD) are limited and have some conflicting results. We recruited 1235 NTM-LD patients and found that ICS use within 1 year was associated with increased NTM-LD, and the risk increased with elevated ICS dose and cumulative duration. Discontinuation of ICS use for more than 120 days could reduce the risk of NTM-LD to an insignificant level. For NTM species, the development of NTM-LD by ICS was highest for Mycobacterium kansasii lung disease. The pooled results of the meta-analysis showed that ICS use might increase the risk of NTM-LD with dose response in medium and high dose of daily ICS. In addition, budesonide had a smaller impact on the risk of NTM-LD than other ICS medications. The present study and meta-analysis provide evidence for ICS adjustment, including dose, discontinuation effect, and medications to possibly reduce the risk of NTM-LD.

Evaluation of coercive measures in different psychiatric hospitals: the impact of institutional characteristics

Background Epidemiological studies have demonstrated considerable differences in the use of coercive measures among psychiatric hospitals; however, the underlying reasons for these differences are largely unclear. We investigated to what extent these differences could be explained by institutional factors. Methods Four psychiatric hospitals with identical responsibilities within the mental health care system, but with different inpatient care organizations, participated in this prospective observational study. We included all patients admitted over a period of 24 months who were affected by mechanical restraint, seclusion, or compulsory medication. In addition to the patterns of coercive measures, we investigated the effect of each hospital on the frequency of compulsory medication and the cumulative duration of mechanical restraint and seclusion, using multivariate binary logistic regression. To compare the two outcomes between hospitals, odds ratios (OR) with corresponding 95% confidence intervals (CI) were calculated. Results Altogether, coercive measures were applied in 1542 cases, corresponding to an overall prevalence of 8%. The frequency and patterns of the modalities of coercive measures were different between hospitals, and the differences could be at least partially related to institutional characteristics. For the two hospitals that had no permanently locked wards, certain findings were particularly noticeable. In one of these hospitals, the probability of receiving compulsory medication was significantly higher compared with the other institutions (OR 1.9, CI 1.1–3.0 for patients < 65 years; OR 8.0, CI 3.1–20.7 for patients ≥65 years); in the other hospital, in patients younger than 65 years, the cumulative duration of restraint and seclusion was significantly longer compared with the other institutions (OR 2.6, CI 1.7–3.9). Conclusions The findings are compatible with the hypothesis that more open settings are associated with a more extensive use of coercion. However, due to numerous influencing factors, these results should be interpreted with caution. In view of the relevance of this issue, further research is needed for a deeper understanding of the reasons underlying the differences among hospitals.

Metformin and Risk of Malignant Brain Tumors in Patients with Type 2 Diabetes Mellitus

The risk of malignant brain tumors associated with metformin use has rarely been investigated in humans. This retrospective cohort study investigated such an association. Patients with new-onset type 2 diabetes mellitus diagnosed from 1999 to 2005 in the nationwide database of Taiwan’s national health insurance were used to enroll study subjects. We first identified an unmatched cohort of 153,429 ever users and 16,222 never users of metformin. A cohort of 16,222 ever users and 16,222 never users matched on propensity score was then created from this unmatched cohort. All patients were followed up from 1 January 2006 until 31 December 2011. The incidence density was calculated and hazard ratios were derived from Cox regression incorporated with the inverse probability of treatment weighting using a propensity score. The results showed that 27 never users and 155 ever users developed malignant brain tumors in the unmatched cohort. The incidence rate was 37.11 per 100,000 person-years in never users and 21.39 per 100,000 person-years in ever users. The overall hazard ratio comparing ever users versus never users was 0.574 (95% confidence interval: 0.381–0.863). The respective hazard ratios comparing the first (<27.13 months), second (27.13–58.33 months), and third (>58.33 months) tertiles of cumulative duration of metformin therapy versus never users were 0.897 (0.567–1.421), 0.623 (0.395–0.984), and 0.316 (0.192–0.518). In the matched cohort, the overall hazard ratio was 0.317 (0.149–0.673) and the respective hazard ratios were 0.427 (0.129–1.412), 0.509 (0.196–1.322), and 0.087 (0.012–0.639) for the first, second, and third tertile of cumulative duration of metformin therapy. In conclusion, this study shows a risk reduction of malignant brain tumors associated with metformin use in a dose–response pattern. The risk reduction is more remarkable when metformin has been used for approximately 2–5 years.

Proton pump inhibitors and risk of colorectal cancer

ObjectiveTo determine whether proton pump inhibitors (PPIs) are associated with an increased risk of colorectal cancer, compared with histamine-2 receptor antagonists (H2RAs).DesignThe United Kingdom Clinical Practice Research Datalink was used to identify initiators of PPIs and H2RA from 1990 to 2018, with follow-up until 2019. Cox proportional hazards models were fit to estimate marginal HRs and 95% CIs of colorectal cancer. The models were weighted using standardised mortality ratio weights using calendar time-specific propensity scores. Prespecified secondary analyses assessed associations with cumulative duration, cumulative dose and time since treatment initiation. The number needed to harm was calculated at five and 10 years of follow-up.ResultsThe cohort included 1 293 749 and 292 387 initiators of PPIs and H2RAs, respectively, followed for a median duration of 4.9 years. While the use of PPIs was not associated with an overall increased risk of colorectal cancer (HR: 1.02, 95% CI 0.92 to 1.14), HRs increased with cumulative duration of PPI use (<2 years, HR: 0.93, 95% CI 0.83 to 1.04; 2–4 years, HR: 1.45, 95% CI 1.28 to 1.60; ≥4 years, HR: 1.60, 95% CI 1.42 to 1.80). Similar patterns were observed with cumulative dose and time since treatment initiation. The number needed to harm was 5343 and 792 for five and 10 years of follow-up, respectively.ConclusionWhile any use of PPIs was not associated with an increased risk of colorectal cancer compared with H2RAs, prolonged use may be associated with a modest increased risk of this malignancy.

Vildagliptin Has a Neutral Association With Dementia Risk in Type 2 Diabetes Patients

Background and aimsAnimal studies suggested that vildagliptin might exert a beneficial effect on cognitive function. The present study evaluated whether the use of vildagliptin in patients with type 2 diabetes mellitus might affect dementia risk.MethodsThe database of Taiwan’s National Health Insurance was used to enroll an unmatched cohort and a propensity score-matched-pair cohort of ever and never users of vildagliptin from patients with newly diagnosed diabetes mellitus during 2002-2014. The patients should be alive on January 1, 2015 and were followed up for dementia diagnosis until December 31, 2016. Unadjusted and multivariate-adjusted hazard ratios (HR) and their 95% confidence intervals (CI) were estimated for vildagliptin ever versus never users, for cumulative duration and cumulative dose of vildagliptin therapy categorized into tertiles versus never users, and for cumulative duration and cumulative dose treated as continuous variables.ResultsThere were 355610 never users and 43196 ever users in the unmatched cohort and 40489 never users and 40489 ever users in the matched cohort. In the unmatched cohort, unadjusted HR (95% CI) was 0.929 (0.683-1.264) and the multivariate-adjusted HR (95% CI) was 0.922 (0.620-1.372). In the matched cohort, the unadjusted HR (95% CI) was 0.930 (0.616-1.402) and the multivariate-adjusted HR (95% CI) was 0.825 (0.498-1.367). None of the analyses conducted for cumulative duration and cumulative dose was significant, either being treated as tertile cutoffs or as continuous variables, in either the unmatched cohort or the matched cohort.ConclusionsThis study showed a neutral effect of vildagliptin on dementia risk.