Effectiveness and safety of lactulose retention enema in cirrhotic patients with grade 3 or grade 4 hepatic encephalopathy

Background: Hepatic encephalopathy (HE) is a complex, reversible neuropsychiatric syndrome. The present study evaluated the clinical effectiveness and safety of lactulose retention enema for the treatment of Grade 3 or 4 HE (West Haven Criteria, WHC) in Indian patients.Methods: This retrospective, open-label, uncontrolled cohort study was conducted at three study centers in India. Patients of either gender (18-65 years) admitted to the hospital with liver cirrhosis having Grade 3 or 4 HE were included. The primary endpoint was to evaluate complete reversal of Grade 3 and 4 HE after 24 h and 48h. The secondary endpoints were grade shift at 24 and 48 h before and after administration of lactulose enema, time to complete reversal of Grade 3 or 4 HE, and mortality. Safety was also evaluated.Results: Overall, retrospective records of 50 patients were evaluated. Complete reversal of Grade 3 or 4 HE was observed in a statistically significant (p<0.0001) proportion (95% confidence interval) of patients at 24 h (n=40, 80% [66. 3%-90.0%]) and 48 h (n=45, 90% [78. 2%-96.7%]) after treatment. After 24 h of treatment, majority of the patients were noted with Grade 2 (78%) HE. Further improvement was noted after 48 h of treatment with majority of the patients having Grade 2 (40%) and Grade 1 (48%) HE. Mean (SD) time for complete reversal of Grade 3 or 4 HE was 25.39±8.85 h after treatment. All death cases observed (n=6, 12.0%) were assessed as unrelated to the treatment by the investigator, but rather related to the underlying disease and/or precipitating factors. Four non-serious adverse drug reactions in two patients and one rectal device-associated complication in one patient were noted during the patient record reviews.Conclusions: Lactulose retention enema was clinically effective and resulted in complete reversal of Grade 3 or 4 HE in the majority of patients. It was overall well-tolerated

Developing Standard Treatment Workflows—way to universal healthcare in India

Primary healthcare caters to nearly 70% of the population in India and provides treatment for approximately 80–90% of common conditions. To achieve universal health coverage (UHC), the Indian healthcare system is gearing up by initiating several schemes such as National Health Protection Scheme, Ayushman Bharat, Nutrition Supplementation Schemes, and Inderdhanush Schemes. The healthcare delivery system is facing challenges such as irrational use of medicines, over- and under-diagnosis, high out-of-pocket expenditure, lack of targeted attention to preventive and promotive health services, and poor referral mechanisms. Healthcare providers are unable to keep pace with the volume of growing new scientific evidence and rising healthcare costs as the literature is not published at the same pace. In addition, there is a lack of common standard treatment guidelines, workflows, and reference manuals from the Government of India. Indian Council of Medical Research in collaboration with the National Health Authority, Govt. of India, and the WHO India country office has developed Standard Treatment Workflows (STWs) with the objective to be utilized at various levels of healthcare starting from primary to tertiary level care. A systematic approach was adopted to formulate the STWs. An advisory committee was constituted for planning and oversight of the process. Specialty experts' group for each specialty comprised of clinicians working at government and private medical colleges and hospitals. The expert groups prioritized the topics through extensive literature searches and meeting with different stakeholders. Then, the contents of each STW were finalized in the form of single-pager infographics. These STWs were further reviewed by an editorial committee before publication. Presently, 125 STWs pertaining to 23 specialties have been developed. It needs to be ensured that STWs are implemented effectively at all levels and ensure quality healthcare at an affordable cost as part of UHC

Blackbox polynomial identity testing for depth 3 circuits

We study EIIE(k) circuits, i.e., depth three arithmetic circuits with top fanin k. We give the first deterministic polynomial time blackbox identity test for EIIE(k) circuits over the field Q of rational numbers, thus resolving a question posed by Klivans and Spielman (STOC 2001).National Science Foundation (U.S.) (Award CCF 0829672

Tubercular lymphadenopathy with duodenal fistula

Tuberculosis, both pulmonary and extrapulmonary, is one of the leading causes of significant morbidity and mortality in developing countries. A 29-year-old chronic alcoholic patient presented to gastroenterology outpatient department with complaints of decreased appetite, weight loss, and generalized weakness. On endoscopy, the second part of duodenum appeared edematous with some luminal compromise. There was also presence of an opening in the inferolateral wall of the second part of duodenum, through which milky white caseous material was coming out. Computed tomography demonstrated large conglomerate of paraduodenal, celiac, para-aortic, peripancreatic, and retrocaval nodes with central necrosis. Endoscopic ultrasound showed hypoechoic lymph nodes in paraduodenal, parapancreatic, and celiac axis. Fine needle aspiration cytology showed epithelioid granuloma with Langerhans giant cells suggestive of granulomatous lymphadenitis of tubercular etiology. Tubercular lymphadenopathy eroding into duodenum has been very rarely reported in literature. This case reports the rare possibility of extrinsic tubercular lymphadenopathy eroding into duodenum

Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific association for the study of the liver (APASL): an update Authors Authors and affiliations

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the APASL ACLF Research Consortium (AARC) was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the \u27Golden Therapeutic Window\u27, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here