Clinical epidemiology and outcomes of emergency department-acute kidney injury: A systematic review.

Background: Over half of all community-acquired acute kidney injury (CA-AKI) initially presented to emergency department (ED), but emergency department acute kidney injury (ED-AKI) is poorly characterised, poorly understood with no systematic review, often under-recognized and under-managed. Objective: To review the incidence, risk factors, and outcomes of ED-AKI, and risk factors of post-ED-AKI mortality globally. Methods: We included published prospective or retrospective observational studies, controlled trials, and systematic reviews reporting AKI in adult ED attendees within 24 h of ED admission. Iatrogenic causes of AKI from medical interventions were excluded. We used PubMed to identify articles from 1996 to August 14, 2021, and adopted the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies to assess risk of bias. We used a Forest plot to present pooled ED-AKI incidence rates and I2 statistics. Other parameters were summarized narratively. Results: Using 24 h from ED admission as the definition for ED-AKI we identified six articles from 2005 to 2018 in high-income settings and one article with a 48-h timeframe. The pooled incidence of ED-AKI was 20 per 1000 adult ED attendances. Risk factors for ED-AKI included increasing age, nursing home residence, previous hospital admission within 30 days, discharge diagnosis of diabetes, obstructive uropathy, sepsis, gastrointestinal medical conditions, high serum creatinine, bilirubin, C-reactive protein, white blood cell, alanine aminotransferase, low serum sodium or albumin on admission, poor premorbid renal function, antibiotic use, active malignancy, lung disease, hyperlipidaemia, and infection. Crude, all-cause 24-h mortality rate was 4.56 % and the one-year mortality rate was 35.04 %. Increasing age and comorbidities including cardiovascular disease and malignancy were associated with higher mortality rates. Conclusion: The review reveals a paucity of relevant literature which calls for further research, increased vigilance, red flag identification, and standardized management protocols for ED-AKI.

Homologous or heterogenous vaccination boosters enhance neutralizing activities against SARS-CoV-2 Omicron BA.1 variant.

The SARS-CoV-2 Omicron BA.1 variant of concern contains more than 30 mutations in the spike protein, with half of these mutations localized in the receptor-binding domain (RBD). Emerging evidence suggests that these large number of mutations impact the neutralizing efficacy of vaccines and monoclonal antibodies. We investigated the relative contributions of spike protein and RBD mutations in Omicron BA.1 variants on infectivity, cell-cell fusion, and their sensitivity to neutralization by monoclonal antibodies or vaccinated sera from individuals who received homologous (CoronaVac, SinoPharm) or heterologous (CoronaVac-BNT162b2, BioNTech) and nonhuman primates that received a recombinant RBD protein vaccine. Our data overall reveal that the mutations in the spike protein reduced infectivity and cell-cell fusion compared to the D614G variant. The impaired infectivity and cell-cell fusion were dependent on non-RBD mutations. We also find reduced sensitivity to neutralization by monoclonal antibodies and vaccinated sera. However, our results also show that nonhuman primates receiving a recombinant RBD protein vaccine show substantial neutralization activity. Our study sheds light on the molecular differences in neutralizing antibody escape by the Omicron BA.1 variant, and highlights the promise of recombinant RBD vaccines in neutralizing the threat posed by the Omicron BA.1 variant.

Risks of post-colonoscopic polypectomy bleeding and thromboembolism with warfarin and direct oral anticoagulants: a population-based analysis.

BACKGROUND: There were limited data on the risk of post-polypectomy bleeding (PPB) in patients on direct oral anticoagulants (DOAC). We aimed to evaluate the PPB and thromboembolic risks among DOAC and warfarin users in a population-based cohort. METHODS: We performed a territory-wide retrospective cohort study involving patients in Hong Kong from 2012 to 2020. Patients who received an oral anticoagulant and had undergone colonoscopy with polypectomy were identified. Propensity-score models with inverse probability of treatment weighting were developed for the warfarin-DOAC and between-DOAC comparisons. The primary outcome was clinically significant delayed PPB, defined as repeat colonoscopy requiring haemostasis within 30 days. The secondary outcomes were 30-day blood transfusion requirement and new thromboembolic event. RESULTS: Apixaban was associated with lower PPB risk than warfarin (adjusted HR (aHR) 0.39, 95% CI 0.24 to 0.63, p<0.001). Dabigatran (aHR 2.23, 95% CI 1.04 to 4.77, adjusted p (ap)=0.035) and rivaroxaban (aHR 2.72, 95% CI 1.35 to 5.48, ap=0.002) were associated with higher PPB risk than apixaban. In subgroup analysis, apixaban was associated with lower PPB risk in patients aged ≥70 years and patients with right-sided colonic polyps.For thromboembolic events, apixaban was associated with lower risk than warfarin (aHR 0.22, 95% CI 0.11 to 0.45, p<0.001). Dabigatran (aHR 2.60, 95% CI 1.06 to 6.41, ap=0.033) and rivaroxaban (aHR 2.96, 95% CI 1.19 to 7.37, ap =0.013) were associated with higher thromboembolic risk than apixaban. CONCLUSIONS: Apixaban was associated with a significantly lower risk of PPB and thromboembolism than warfarin, dabigatran and rivaroxaban, particularly in older patients with right-sided polyps.

Prevalence/Incidence of Low Back Pain and Associated Risk Factors Among Nursing and Medical Students: A Systematic Review and Meta-Analysis.

OBJECTIVE: To summarize evidence regarding the prevalence and incidence of low back pain and associated risk factors in nursing and medical students. TYPE: Systematic review and meta-analysis. LITERATURE SURVEY: The protocol was registered with PROSPERO (CRD42015029729). Its reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seven databases were searched until August 2020 to identify relevant studies. METHODOLOGY: Two independent reviewers screened, extracted, and evaluated the risk of bias of the selected studies. Meta-analyses were used to estimate 12-month prevalence/incidence rates of low back pain and associated risk factors in these students. Levels of evidence for risk factors were determined by the updated Guidelines for Systematic Reviews in the Cochrane Collaboration Back Review Group. SYNTHESIS: Sixteen studies involving 7072 students were included. The pooled 12-month prevalence rates of low back pain for nursing and medical students were 44% (95% confidence interval [95% CI]: 27%-61%) and 53% (95% CI: 44%-62%), respectively. The 12-month incidence of low back pain in nursing students ranged from 29% to 67%. No incidence rate was reported in medical students. Strong/moderate-quality evidence supported that final year of study (pooled odds ratio [OR] from five studies, 1.96, 95% CI: 1.13-3.40), anxiety (OR ranging from 3.12 to 4.61), or high mental pressure or psychological distress (OR ranging from 1.37 to 4.52) was associated with a higher 12-month low back pain prevalence in both student groups. Moderate-quality evidence suggested that prior history of low back pain (pooled OR from two studies: 3.46, 95% CI: 1.88-6.36) was associated with a higher 12-month low back pain incidence in nursing students. Similarly, moderate-quality evidence suggested that female medical students (pooled OR from two studies: 1.77, 95% CI: 1.09-2.86) demonstrated a higher 12-month low back pain prevalence than male counterparts. CONCLUSIONS: Although it is impossible to alter nonmodifiable risk factors for low back pain, universities may develop and implement proper strategies to mitigate modifiable risk factors in these students.

Needle in a haystack: Looking for tuberculosis in a low-incidence setting.

Background: Canada is a low-incidence country for tuberculosis (TB). The BC Public Health Laboratory diagnostic algorithm for pulmonary TB includes acid fast bacilli (AFB) smear and mycobacterial culture of all submitted sputa. TB nucleic acid amplification testing (NAT) is routinely performed on AFB-smear-positive (AFB+) sputa only. We assessed the laboratory-associated costs of implementing the international recommendations for TB NAT on AFB-smear-negative (AFB-) sputa. Methods: Two data sets were obtained: (1) all AFB- samples for a 3-year period (October 1, 2014-September 30, 2017) and (2) all AFB-, TB-culture-positive samples for the same period. One AFB- sample/patient from each defined diagnostic set of sputa was deemed eligible for TB NAT. To stratify patients by ordering location, a 1-year subset of data (October 1, 2016-September 30, 2017) was examined. Results: In the 3-year period, 0.7% of all diagnostic sets were AFB- and culture-positive. In the 1-year period, the provincial TB Services clinics submitted 26% of all AFB- samples received, but these constituted 78% of AFB-, culture-positive samples. Conclusions: The annual cost of TB NAT on one AFB- sputum sample from each eligible diagnostic set would total approximately $247,000. Targeting only TB Services clinic patients would reduce this cost to approximately $64,000/year while capturing more than 75% of AFB-, culture-positive patients. On the basis of our provincial positivity rate, it would cost approximately $6,000 to provide an early TB diagnosis for an AFB-, culture-positive patient. The cost-effectiveness to public health of this approach in a TB low-incidence setting needs to be carefully evaluated.

Historique: Le Canada est un pays à faible incidence de tuberculose. L'algorithme diagnostique de tuberculose pulmonaire du BC Public Health Laboratory inclut la recherche des bacilles acido-alcoolo-résistants (BAAR) par frottis et la culture mycobactérienne de toutes les expectorations soumises. Le test d'amplification de l'acide nucléique (TAN) pour dépister la tuberculose (TAN TB) est effectué systématiquement, mais seulement sur les expectorations positives au BAAR par frottis (BAAR+). Les chercheurs ont évalué quelle somme le laboratoire devrait investir pour mettre en œuvre les recommandations internationales visant l'utilisation du TAN TB sur des expectorations négatives BAAR par frottis (BAAR-). Méthodologie: Les chercheurs ont obtenu deux groupes de données : 1) tous les échantillons BAAR­ sur une période de trois ans (du 1er octobre 2014 au 30 septembre 2017) et 2) tous les échantillons BAAR­ dont la culture était positive à la tuberculose pendant la même période. Un échantillon de BAAR­ par patient de chaque groupe diagnostique d'expectoration était considéré comme admissible au TAN TB. Pour stratifier les patients selon la provenance du test, les chercheurs ont examiné un sous-groupe de données sur un an (du 1er octobre 2016 au 30 septembre 2017). Résultats: Pendant la période de trois ans, 0,7 % de tous les groupes diagnostiques étaient BAAR­ et positifs à la culture. Pendant la période d'un an, les cliniques provinciales de services pour la tuberculose ont soumis 26 % de tous les échantillons BAAR­ reçus, mais ils représentaient 78 % des échantillons BAAR­ positifs aux cultures. Conclusions: Le coût annuel du TAN TB sur un échantillon d'expectoration BAAR­ de chaque groupe diagnostique admissible totaliserait environ 247 000 $. Si on ciblait seulement les patients ayant consulté des services pour la tuberculose, ce coût fléchirait à environ 64 000 $ par année, mais saisirait plus de 75 % des patients BAAR­ dont la culture est positive. D'après le taux de positivité provinciale, un diagnostic précoce de tuberculose chez un patient BAAR­ positif à la culture coûterait environ 6 000 $. Le rapport coût-efficacité de cette approche pour la santé publique dans les milieux à faible incidence de tuberculose devra faire l'objet d'une évaluation attentive.

Estimating surge in COVID-19 cases, hospital resources and PPE demand with the interactive and locally-informed COVID-19 Health System Capacity Planning Tool.

Introduction: The COVID-19 pandemic revealed an urgent need for analytic tools to help health system leaders plan for surges in hospital capacity. Our objective was to develop a practical and locally informed Tool to help explore the effects of public health interventions on SARS-CoV-2 transmission and create scenarios to project potential surges in hospital admissions and resource demand. Methods: Our Excel-based Tool uses a modified S(usceptible)-E(xposed)-I(nfected)-R(emoved) model with vaccination to simulate the potential spread of COVID-19 cases in the community and subsequent demand for hospitalizations, intensive care unit beds, ventilators, health care workers, and personal protective equipment. With over 40+ customizable parameters, planners can adapt the Tool to their jurisdiction and changes in the pandemic. Results: We showcase the Tool using data for Ontario, Canada. Using healthcare utilization data to fit hospitalizations and ICU cases, we illustrate how public health interventions influenced the COVID-19 reproduction number and case counts. We also demonstrate the Tool's ability to project a potential epidemic trajectory and subsequent demand for hospital resources. Using local data, we built three planning scenarios for Ontario for a 3-month period. Our worst-case scenario accurately projected the surge in critical care demand that overwhelmed hospital capacity in Ontario during Spring 2021. Conclusions: Our Tool can help different levels of health authorities plan their response to the pandemic. The main differentiators between this Tool and other existing tools include its ease of use, ability to build scenarios, and that it provides immediate outcomes that are ready to share with executive decision makers. The Tool is used by provincial health ministries, public health departments, and hospitals to make operational decisions and communicate possible scenarios to the public. The Tool provides educational value for the healthcare community and can be adapted for existing and emerging diseases.

An audit of propofol administration in the intensive care unit: Infusion pump-recorded versus electronically documented amounts.

BACKGROUND: Although propofol is widely used for sedation in intensive care units around Australia, evaluation of bedside nursing practices of the administration of propofol have been limited. We investigated whether there was a discrepancy between the amount of propofol delivered by the infusion pump and that recorded electronically and consequently patient exposure to avoidable harms. AIMS: The aim of this research was to compare the total amount of propofol administered to intensive care patients via a programmable infusion pump with that documented in the electronic medical record (EMR). Secondary objectives were to ascertain the percentage of 1) patients exposed to a propofol dose greater than recommended and 2) daily energy requirements administered as propofol infusion. METHODS: This was a prospective, observational study of total propofol delivered to 50 patients in a 14-bed metropolitan, Australian intensive care unit. Infusion pump data and entries from the EMR were collated. RESULTS: Propofol sedation was administered for a median 18 (interquartile range: 14-47) hours with median total propofol 3025 mg (interquartile range: 1840-7755 mg) by pump and 3250 mg (interquartile range: 1915-6960 mg) by EMR, i.e. 1.9 (interquartile range: 1.3-2.3) mg/kg/hour by pump (correlation coefficient = 0.99). The total bolus propofol documented in the EMR was a median 330 mg (interquartile range: -838 to -124) less than the pump amount. Nineteen (38%) patients had no EMR-documented propofol boluses yet had received at least one bolus via the pump. In two of 50 (4%) patients, the pump propofol infusion dose was above the recommended maximum safe dose of 4 mg/kg/h. CONCLUSION: In this cohort of patients, the bolus administration of propofol was frequently not documented, potentially placing some patients at risk of drug-related toxicity. Further research to develop and implement strategies to improve the documentation of propofol administration is indicated.

Impact of dose and duration of corticosteroid on the risk of hepatitis flare in patients with chronic hepatitis B.

BACKGROUND: Systemic corticosteroid is used for different medical conditions and may cause hepatitis B virus (HBV) reactivation. AIMS: To study the impact of duration and peak dose of corticosteroid on the risk of hepatitis flare in patients with chronic hepatitis B (CHB). METHODS: All patients who received corticosteroid from January 2001 to December 2004 were retrieved from the Hospital Authority, Hong Kong. We stratified patients by daily dose prednisolone equivalents (<20 mg, 20-40 mg, >40 mg) and durations (<7; 7-28; >28 days). The primary endpoint was hepatitis flare (alanine aminotransferase >2×upper limit of normal, ie 80 IU/L) at 1 year. RESULTS: A total of 85 763 patients fulfilled the inclusion criteria (5254 CHB, 80 509 non-CHB). CHB patients had higher risk of hepatitis flare (388/5254 [7.8%]) than those without CHB (2728/80 509 [4.2%]; P < 0.001 by log-rank test). Among CHB patients, peak daily dose >40 mg compared to <20 mg prednisolone equivalents (adjusted hazard ratio [aHR] 1.64, 95% CI 1.26-2.14; P < 0.001) was an independent risk factor of hepatitis flare. Risk of hepatitis flare started to increase in those receiving corticosteroid of peak daily dose >40 mg prednisolone equivalents even for <7 days (aHR 1.55, P = 0.026), which was also increased for 7-28 days and >28 days (aHR 1.90 and 1.64 respectively, both P < 0.001). CONCLUSION: Even short courses of high-dose corticosteroid increase the risk of hepatitis flare in CHB patients. Patients receiving high-dose corticosteroid should be considered for antiviral prophylaxis regardless of the duration of treatment.

Risk of Postpolypectomy Bleeding With Uninterrupted Clopidogrel Therapy in an Industry-Independent, Double-Blind, Randomized Trial.

BACKGROUND & AIMS: Guidelines recommend withholding clopidogrel 7 days before polypectomy to decrease bleeding risk, but these were written based on limited evidence. We investigated whether uninterrupted clopidogrel therapy increases the risk of delayed postpolypectomy bleeding in patients undergoing colonoscopy. METHODS: We identified patients receiving clopidogrel for cardiovascular disease undergoing elective colonoscopies in Hong Kong from February 28, 2012 through April 11, 2018. Eligible patients were instructed to stop taking clopidogrel 7 days before colonoscopy. Then, they were randomly assigned to groups given clopidogrel (75 mg) or placebo daily until the morning of colonoscopy. All patients resumed their usual prescriptions of clopidogrel after colonoscopy. The primary end point was delayed postpolypectomy bleeding that required hospitalization or intervention up to 30 days after colonoscopy. Secondary end points were immediate postpolypectomy bleeding and serious cardio-thrombotic events for as long as 6 months after colonoscopy, according to Antithrombotic Trialists' criteria. All events were adjudicated by an independent masked committee. RESULTS: In total, 387 patients underwent colonoscopy and 216 required polypectomies (106 patients in the clopidogrel group and 110 patients in the placebo group). The cumulative incidence of delayed postpolypectomy bleeding was 3.8% (95% confidence interval 1.4-9.7) in the clopidogrel group and 3.6% (95% confidence interval 1.4-9.4) in the placebo group (P = .945 by log-rank test). There were no significant differences in immediate postpolypectomy bleeding (8.5% vs 5.5%; P = .380) and cardio-thrombotic events (1.5% vs 2%; P = .713). CONCLUSIONS: In a randomized controlled trial of clopidogrel users undergoing colonoscopy, a slightly larger proportion of patients continuing clopidogrel developed delayed and immediate postpolypectomy bleeding, although this difference was not statistically significant. ClinicalTrials.gov, number NCT01806090.

HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues.

BACKGROUND & AIMS: In treated patients with chronic hepatitis B (CHB) who have achieved complete viral suppression, it is unclear if functional cure as indicated by hepatitis B surface antigen (HBsAg) seroclearance confers additional clinical benefit. We compared the risk of hepatocellular carcinoma (HCC) and hepatic events in nucleos(t)ide analogue (NA)-treated patients with and without HBsAg seroclearance. METHODS: We performed a territory-wide retrospective cohort study on all patients with CHB who had received entecavir and/or tenofovir disoproxil fumarate (TDF) for at least 6 months between 2005 and 2016 from Hospital Authority, Hong Kong. Patients' demographics, comorbidities, and laboratory parameters were analyzed. The primary outcome was HCC. The secondary outcomes were hepatic events including cirrhotic complications, liver transplantation, and liver-related mortality. RESULTS: A total of 20,263 entecavir/TDF-treated patients with CHB were identified; 17,499 (86.4%) patients had complete viral suppression; 376 (2.1%) achieved HBsAg seroclearance. At a median (interquartile range) follow-up of 4.8 (2.8-7.0) years, 603 (3.5%) and 121 (4.4%) patients with and without complete viral suppression developed HCC; 2 (0.5%) patients with HBsAg seroclearance developed HCC. Compared to complete viral suppression, lack of complete viral suppression was associated with a higher risk of HCC (7.8% vs. 5.6% at 8 years, Gray's test, p <0.001) (adjusted hazard ratio [aHR] 1.69; 95% CI 1.36-2.09; p <0.001); patients who achieved functional cure had a lower risk of HCC (0.6% vs. 5.6% at 8 years, Gray's test, p <0.001) (aHR 0.24; 95% CI 0.06-0.97; p = 0.045) but not hepatic events (aHR 0.99; 95% CI 0.30-3.26; p = 0.991). CONCLUSIONS: Patients who achieved HBsAg seroclearance on top of complete viral suppression with entecavir/TDF treatment may have a lower risk of HCC but not hepatic events. LAY SUMMARY: We investigated 20,263 nucleos(t)ide analogue (NA)-treated patients with chronic hepatitis B. Patients with NA-induced hepatitis B surface antigen seroclearance on top of complete viral suppression have a lower risk of hepatocellular carcinoma but not hepatic events than those only achieving complete viral suppression under prolonged NA treatment.

On-Treatment Improvement of MELD Score Reduces Death and Hepatic Events in Patients With Hepatitis B-Related Cirrhosis.

OBJECTIVES: Antiviral treatment modifies the natural history of chronic hepatitis B (CHB)-related cirrhosis as reflected by improving Model for End-Stage Liver Disease (MELD) score over time. We evaluated the impact of on-treatment change of MELD score on clinical outcomes in patients with CHB-related cirrhosis. METHODS: Cirrhotic CHB patients who received entecavir and/or tenofovir disoproxil fumarate for at least 6 months in Hong Kong between 2005 and 2016 were identified. The primary outcome was all-cause mortality; secondary outcomes were hepatocellular carcinoma (HCC), and hepatic events including ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatorenal syndrome, hepatic encephalopathy, and liver transplantation. RESULTS: We identified 1743 cirrhotic CHB patients. Their mean MELD score decreased from 12.3 ± 5.5 at baseline to 11.0 ± 4.7 at month 6. At a median (interquartile range) follow-up of 3.9 (1.9-6.0) years, 290 (16.6%) patients died; 201 (11.5%) developed HCC. Among 1140 patients without prior hepatic events, 150 (13.2%) developed hepatic events. Among 464 patients with baseline MELD score ≥15, the 6-year cumulative mortality was 72.8, 36.7, and 23.1% for unchanged or increased MELD score, 1-5 point improvement in MELD score, and >5 point improvement in MELD score at month 6, respectively (log-rank test, P < 0.001); the corresponding 6-year cumulative incidence of hepatic events was 52.7, 30.5, and 23.9% in the three subgroups (Gray's test, P = 0.004). Patients with MELD score <15 at month 6 had lower risk of mortality and hepatic events (all P < 0.001). CONCLUSIONS: On-treatment improvement of MELD score correlates with reduced risk of mortality and hepatic events in cirrhotic CHB patients.

Chronic Hepatitis B Increases Liver-Related Mortality of Patients With Acute Hepatitis E: A Territorywide Cohort Study From 2000 to 2016.

Background: The epidemiology of acute hepatitis A and E has been changing over the last 2 decades. The impact of concomitant chronic hepatitis B (CHB) on clinical outcomes remains unclear. We aimed to evaluate the morbidity and mortality of patients with acute hepatitis A or E with and without underlying CHB. Methods: We identified consecutive patients with acute hepatitis A or E based on hepatitis serology from the electronic medical records of the Hospital Authority of Hong Kong from January 2000 to December 2016. Hepatic events, all-cause mortality, and liver-related mortality within 30 days of the diagnosis of acute hepatitis were evaluated. Results: The cohort included 1068 cases of acute hepatitis A and 846 cases of acute hepatitis E. More patients with acute hepatitis E than those with acute hepatitis A had underlying CHB (13.5% vs 8.0%; P < .001). Patients with hepatitis E had more all-cause mortality (3.9% vs 0.6%; P < .001), liver-related mortality (2.0% vs 0.3%; P < .001), and hepatic events (2.8% vs 0.3%; P < .001) within 30 days from diagnosis. In patients with acute hepatitis E, underlying renal failure (adjusted hazard ratio [aHR], 3.90; P < .001) and age ≥50 years (aHR, 3.25; P = .036) were associated with 30-day all-cause mortality, whereas CHB (aHR, 3.34; P = .02) was associated with 30-day liver-related mortality. Conclusions: The mortality is higher in patients with acute hepatitis E than in those with hepatitis A. Coexisting CHB is the independent risk factor for liver-related mortality in patients with acute hepatitis E.

Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection.

Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT ("responders") display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas "nonresponders" and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.

Chronic kidney disease progression in patients with chronic hepatitis B on tenofovir, entecavir, or no treatment.

BACKGROUND: In clinical trials involving patients with preserved renal function, tenofovir disoproxil fumarate (TDF) use was associated with mild renal impairment in 1% of patients. AIM: To compare serial renal function of entecavir (ETV)-treated, TDF-treated, and untreated patients with chronic hepatitis B. METHODS: We studied the risk of chronic kidney disease (CKD) progression in a territory-wide cohort of patients with chronic hepatitis B without treatment and of those on ETV or TDF treatment. Estimated glomerular filtration rate (eGFR) was determined by the CKD Epidemiology Collaboration equation and was classified into five CKD stages. CKD progression, defined as an increase of at least one CKD stage, was compared among treated and untreated patients. RESULTS: After propensity score matching, 2254 ETV-treated, 2254 TDF-treated, and 2254 untreated patients were included in the analysis. Their mean baseline eGFR was 90.3 ± 19.6, 91.3 ± 20.6, and 92.2 ± 20.0 mL/min/1.73 m2 , respectively. During a mean follow-up of 2.4 ± 1.5 years, 639 ETV-treated, 706 TDF-treated, and 564 untreated patients exhibited CKD progression ≥1 stage. The 5-year cumulative incidence (95% confidence interval) of CKD progression was 43% (40%-46%) in ETV-treated, 48% (45%-51%) in TDF-treated, and 43% (39%-47%) in untreated patients (reference group), respectively (P = 0.267 and <0.001, respectively). The number of patients who exhibited CKD progression ≥2 stages was 92 (4.1%) in the untreated cohort, 95 (4.2%) in the ETV-treated cohort, and 51 (2.3%) in the TDF-treated cohort. CONCLUSIONS: The use of TDF was associated with mild renal impairment in a minority of patients; those treated with ETV had a similar risk compared to untreated patients.

Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding.

BACKGROUND & AIMS: There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy. METHODS: We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 µg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline. RESULTS: Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%-42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005). CONCLUSIONS: In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776.

Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reveal that the rate of normal on-treatment alanine aminotransferase (ALT) appears different for different nucleos(t)ide analogues (NAs); yet its clinical significance is unclear. We aimed to evaluate the impact of normal on-treatment ALT during antiviral treatment with entecavir (ETV) or tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB). METHODS: A territory-wide cohort of patients with CHB who received ETV and/or TDF in 2005-2016 was identified. Serial on-treatment ALT levels were collected and analyzed. Normal on-treatment ALT (ALT-N) was defined as ALT <30 U/L in males and <19 U/L in females. The primary and secondary outcomes were composite hepatic events (including hepatocellular carcinoma) based on diagnostic codes. Patients with hepatic events before or during the first year of antiviral treatment or follow-up <1 year were excluded. RESULTS: A total of 21,182 patients with CHB (10,437 with and 10,745 without ALT-N at 12 months after antiviral treatment) were identified and followed for 4.0 ±â€¯1.7 years. Patients with and without ALT-N differed in baseline ALT (58 vs. 61 U/L), hepatitis B virus DNA (4.9 vs. 5.1 log10 IU/ml) and cirrhosis status (8.8% vs. 10.5%). A total of 627 (3.0%) patients developed composite hepatic events. Compared to no ALT-N, ALT-N at 3, 6, 9 and 12 months reduced the risk of hepatic events, after adjustment for baseline ALT and other important covariates, with adjusted hazard ratios (95% CI) of 0.61 (0.49-0.77), 0.55 (0.45-0.67), 0.54 (0.44-0.65) and 0.51 (0.42-0.61) respectively (all p <0.001). The cumulative incidence (95% CI) of composite hepatic events at six years was 3.51% (3.06%-4.02%) in ALT-N and 5.70% (5.15%-6.32%) in the no ALT-N group (p <0.001). CONCLUSIONS: Normal on-treatment ALT is associated with a lower risk of hepatic events in patients with CHB receiving NA treatment, translating into improved clinical outcomes in these patients. LAY SUMMARY: We investigated 21,182 patients with chronic hepatitis B receiving antiviral treatment. Alanine aminotransferase is a laboratory marker of liver function, with raised levels indicating liver dysfunction and in severe cases hepatitis. Normal on-treatment alanine aminotransferase during the first year of treatment in patients with CHB is associated with a lower risk of hepatic events.

A new screening strategy for varices by liver and spleen stiffness measurement (LSSM) in cirrhotic patients: A randomized trial.

BACKGROUND: Variceal bleeding is a common and life-threatening complication in patients with cirrhosis. Screening with upper endoscopy is recommended but is uncomfortable to patients. Non-invasive assessment with transient elastography for liver/spleen stiffness measurement (LSM and SSM) is accurate in detecting varices. AIMS: To test the hypothesis that a new screening strategy for varices guided by LSM/SSM results (LSSM-guided) is non-inferior to universal endoscopic screening in detecting clinically significant varices in patients with cirrhosis. METHODS: This was a non-inferiority, open-label, randomized controlled trial. Adult patients with known chronic liver diseases, radiological evidence of cirrhosis and compensated liver function. The primary outcome was clinically significant varix diagnosed with upper endoscopy. RESULTS: Between October 2013 and June 2016, 548 patients were randomized to LSSM arm (n = 274) and conventional arm (n = 274) which formed the intention-to-test (ITT) population. Patients in both study arms were predominantly middle-aged men with viral hepatitis-related cirrhosis in 85% of the cases. In the ITT analysis, 11/274 participants in the LSSM arm (4.0%) and 16/274 in the conventional arm (5.8%) were found to have clinically significant varices. The difference between two groups was -1.8% (90% CI, -4.9% to -1.2%, P < .001). The absolute difference in the number of patients with clinically significant varices detected was 5/16 (31.3%) fewer in the LSSM arm. CONCLUSIONS: Non-inferiority of the LSSM-guided screening strategy to the convention approach cannot be excluded by this RCT. This approach should be further evaluated in a cohort of larger sample size with more clinically significant varices.

Effects of Diabetes and Glycemic Control on Risk of Hepatocellular Carcinoma After Seroclearance of Hepatitis B Surface Antigen.

BACKGROUND & AIMS: Diabetes is associated with a 2-fold increase in risk of hepatocellular carcinoma (HCC) among patients with chronic hepatitis B virus (HBV) infection. However, we know little about the effect of diabetes on HCC risk after seroclearance of hepatitis B surface antigen (HBsAg). We evaluated the effect of diabetes and glycemic control on HCC development after HBsAg seroclearance in a population-wide study in Hong Kong. METHODS: We performed a retrospective study of 4568 patients with chronic HBV infection who cleared HBsAg from January 2000 through August 2016, using the Clinical Data Analysis and Reporting System of the Hospital Authority, Hong Kong. We collected and analyzed data on patient demographics, comorbidities, medications, laboratory test results, and subsequent development of HCC. The presence of diabetes was defined by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis code, with level of hemoglobin A1c (HbA1c) above 6.5%, fasting glucose level of 7 mmol/L or more, or treatment with any antidiabetic agent. RESULTS: We identified 1560 patients with diabetes; 29 patients (1.9%) developed HCC after a median follow-up time of 3.4 years (interquartile range, 1.5-5.0 years). Diabetes was associated with increased risk of HCC after adjustment of age, sex, presence of cirrhosis, and the use of medications (adjusted hazard ratio, 1.85; 95% CI, 1.04-3.28; P = .036). Among patients with diabetes, time-weighted average level of HbA1c was an independent risk factor for HCC, after adjustment for age at clearance, use of statins, and other important covariates (adjusted hazard ratio: 1.51; 95% CI, 1.20-1.91; P < .001). A time-weighted average level of HbA1c of 7% or more was associated with a higher 5-year cumulative incidence of HCC (4.0%) than a time-weighted average HbA1c level below 7% (1.8%; log-rank test P = .035). CONCLUSIONS: In a population-based analysis of patients with chronic HBV infection in Hong Kong, we found diabetes to be an independent risk factor for HCC after HBsAg seroclearance. However, glycemia control appears to reduce the risk of HCC.

Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.

OBJECTIVE: Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI. DESIGN: Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response. RESULTS: Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone. CONCLUSIONS: In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI. TRIAL REGISTRATION NUMBER: NCT02570477.

Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients.

BACKGROUND & AIMS: It is uncertain if nucleos(t)ide analogue (NA)-induced hepatitis B surface antigen (HBsAg) seroclearance is durable. We investigated the impact of hepatitis B surface antibody (anti-HBs) and duration of consolidation antiviral therapy on the durability of HBsAg seroclearance. METHODS: A territory-wide cohort study was conducted using data from the Hospital Authority, Hong Kong. We identified all subjects with positive HBsAg between January 1, 2000 and August 31, 2016. NA use, liver biochemistries, serial HBsAg and anti-HBs results were retrieved. The primary endpoint was confirmed HBsAg seroclearance, defined least two negative HBsAg test results, with the last HBsAg test being negative in patients with chronic hepatitis B (CHB). RESULTS: A total of 4,080 CHB patients were included for analysis. In patients with spontaneous HBsAg seroclearance (n=3,563), 1,771 patients (49.7%) had confirmed HBsAg seroclearance and 75 patients (2.1%) had HBsAg seroreversion. In patients with NA-induced HBsAg seroclearance (n=475), 320 patients (67.4%) had confirmed HBsAg seroclearance and 14 patients (2.9%) had HBsAg seroreversion. The five-year cumulative probability of confirmed HBsAg seroclearance was comparable in patients with spontaneous and NA-induced HBsAg seroclearance (88.1% vs. 92.2%; Log-rank test, p=0.964); it was also similar in patients with or without anti-HBs in NA-treated patients (95.4% vs. 95.5%, Log-rank test, p=0.602). HBsAg seroreversion was only observed in 3 (2.0%) patients who had received consolidation therapy for 6-12months and none of those who had received it for ≥12months. CONCLUSIONS: NA-induced HBsAg seroclearance is as durable as spontaneous HBsAg seroclearance. NA-treated patients may not need to have positive anti-HBs before stopping treatment. Longer consolidation NA treatment may result in more durable HBsAg seroclearance. LAY SUMMARY: We investigated 4,080 patients with hepatitis B surface antigen (HBsAg) seroclearance. HBsAg seroreversion occurred in 2.1% of patients with spontaneous and 2.9% of those with nucleos(t)ide analogues-induced HBsAg seroclearance.