ABSTRACT
The Lyon Consensus provides conclusive criteria for and against the diagnosis of gastro-oesophageal reflux disease (GERD), and adjunctive metrics that consolidate or refute GERD diagnosis when primary criteria are borderline or inconclusive. An international core and working group was assembled to evaluate research since publication of the original Lyon Consensus, and to vote on statements collaboratively developed to update criteria. The Lyon Consensus 2.0 provides a modern definition of actionable GERD, where evidence from oesophageal testing supports revising, escalating or personalising GERD management for the symptomatic patient. Symptoms that have a high versus low likelihood of relationship to reflux episodes are described. Unproven versus proven GERD define diagnostic strategies and testing options. Patients with no prior GERD evidence (unproven GERD) are studied using prolonged wireless pH monitoring or catheter-based pH or pH-monitoring off antisecretory medication, while patients with conclusive GERD evidence (proven GERD) and persisting symptoms are evaluated using pH-impedance monitoring while on optimised antisecretory therapy. The major changes from the original Lyon Consensus criteria include establishment of Los Angeles grade B oesophagitis as conclusive GERD evidence, description of metrics and thresholds to be used with prolonged wireless pH monitoring, and inclusion of parameters useful in diagnosis of refractory GERD when testing is performed on antisecretory therapy in proven GERD. Criteria that have not performed well in the diagnosis of actionable GERD have been retired. Personalisation of investigation and management to each patient's unique presentation will optimise GERD diagnosis and management.
Subject(s)
Esophagitis , Gastroesophageal Reflux , Humans , Esophageal pH Monitoring , Consensus , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/therapy , Esophagitis/drug therapy , Proton Pump Inhibitors/therapeutic useABSTRACT
OBJECTIVE: An international meeting was organised to develop consensus on (1) the landmarks to define the gastro-oesophageal junction (GOJ), (2) the occurrence and pathophysiological significance of the cardiac gland, (3) the definition of the gastro-oesophageal junctional zone (GOJZ) and (4) the causes of inflammation, metaplasia and neoplasia occurring in the GOJZ. DESIGN: Clinical questions relevant to the afore-mentioned major issues were drafted for which expert panels formulated relevant statements and textural explanations.A Delphi method using an anonymous system was employed to develop the consensus, the level of which was predefined as ≥80% of agreement. Two rounds of voting and amendments were completed before the meeting at which clinical questions and consensus were finalised. RESULTS: Twenty eight clinical questions and statements were finalised after extensive amendments. Critical consensus was achieved: (1) definition for the GOJ, (2) definition of the GOJZ spanning 1 cm proximal and distal to the GOJ as defined by the end of palisade vessels was accepted based on the anatomical distribution of cardiac type gland, (3) chemical and bacterial (Helicobacter pylori) factors as the primary causes of inflammation, metaplasia and neoplasia occurring in the GOJZ, (4) a new definition of Barrett's oesophagus (BO). CONCLUSIONS: This international consensus on the new definitions of BO, GOJ and the GOJZ will be instrumental in future studies aiming to resolve many issues on this important anatomic area and hopefully will lead to better classification and management of the diseases surrounding the GOJ.
Subject(s)
Barrett Esophagus , Gastroesophageal Reflux , Barrett Esophagus/diagnosis , Barrett Esophagus/epidemiology , Barrett Esophagus/etiology , Consensus , Esophagogastric Junction , Humans , Inflammation , MetaplasiaABSTRACT
OBJECTIVE: High-resolution manometry (HRM) is the current standard for characterization of esophageal body and esophagogastric junction (EGJ) function. We aimed to examine the prevalence of abnormal esophageal motor patterns in health, and to determine optimal thresholds for software metrics across HRM systems. DESIGN: Manometry studies from asymptomatic adults were solicited from motility centers worldwide, and were manually analyzed using integrated relaxation pressure (IRP), distal latency (DL), and distal contractile integral (DCI) in standardized fashion. Normative thresholds were assessed using fifth and/or 95th percentile values. Chicago Classification v3.0 criteria were applied to determine motor patterns across HRM systems, study positions (upright vs supine), ages, and genders. RESULTS: Of 469 unique HRM studies (median age 28.0, range 18-79 years). 74.6% had a normal HRM pattern; none had achalasia. Ineffective esophageal motility (IEM) was the most frequent motor pattern identified (15.1% overall), followed by EGJ outflow obstruction (5.3%). Proportions with IEM were lower using stringent criteria (10.0%), especially in supine studies (7.1%-8.5%). Other motor patterns were rare (0.2%-4.1% overall) and did not vary by age or gender. DL thresholds were close to current norms across HRM systems, while IRP thresholds varied by HRM system and study position. Both fifth and 95th percentile DCI values were lower than current thresholds, both in upright and supine positions. CONCLUSIONS: Motor abnormalities are infrequent in healthy individuals and consist mainly of IEM, proportions of which are lower when using stringent criteria in the supine position. Thresholds for HRM metrics vary by HRM system and study position.
Subject(s)
Esophageal Achalasia , Esophageal Motility Disorders , Adolescent , Adult , Aged , Esophageal Motility Disorders/diagnosis , Esophageal Motility Disorders/epidemiology , Esophagogastric Junction , Female , Humans , Male , Manometry , Middle Aged , Young AdultABSTRACT
BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.
Subject(s)
Colitis, Ulcerative , Crohn Disease , Inflammatory Bowel Diseases , Aged , Asia, Southeastern , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/therapy , Crohn Disease/diagnosis , Crohn Disease/drug therapy , Crohn Disease/epidemiology , Cross-Sectional Studies , Delayed Diagnosis , Asia, Eastern , Female , Humans , Immunologic Factors , Incidence , Inflammatory Bowel Diseases/diagnosis , Inflammatory Bowel Diseases/epidemiology , Inflammatory Bowel Diseases/therapy , Male , Mesalamine , PhenotypeABSTRACT
Gastroesophageal reflux disease (GERD) is a common problem in the community. The Indian Society of Gastroenterology and Association of Physicians of India have developed this evidence-based practice guideline for management of GERD in adults. A modified Delphi process was used to develop this consensus containing 43 statements, which were generated by electronic voting iteration as well as face-to-face meeting, and review of the supporting literature primarily from India. These statements include 4 on epidemiology, 9 on clinical presentation, 11 on investigations, 18 on treatment (including medical, endoscopic, and surgical modalities), and one on complications of GERD. The statement was regarded as accepted when the proportion of those who voted either to accept completely or with minor reservation was 80% or higher. The prevalence of GERD in large population-based studies in India is approximately 10% and is probably increasing due to lifestyle changes and increase in obesity. The diagnosis of GERD in the community should be mainly based on presence of classical symptoms like heartburn and sour regurgitation, and empiric treatment with a proton pump inhibitor (PPI) or H2 receptor antagonist should be given. All PPIs in equipotent doses are similar in their efficacy in the management of symptoms. Patients in whom symptoms do not respond adequately to PPI are regarded as having PPIrefractory GERD. Invasive investigations should be limited to patients with alarm symptoms and those with refractory GERD.
Subject(s)
Gastroenterology , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/therapy , Adult , Consensus , Humans , India/epidemiology , Proton Pump Inhibitors/therapeutic useABSTRACT
Background & objectives: Prokinetics are extensively prescribed leading to several adverse events (AEs). The aim of this study was to assess the prescription pattern in patients receiving prokinetics, and characteristics of adverse drug reactions (ADRs) in an outpatient department set up in a tertiary care hospital in western India. Methods: Patients attending outpatient departments of a tertiary care hospital and who had received prokinetic agent for at least seven days over the last one month were enrolled. Causality assessment of AEs was done and assessed for severity, preventability, seriousness and predictability. Results: A total of 304 patients [161 males (52.96%); 143 females (47.04%)] were enrolled. Most prescriptions (299/304, 98%) included domperidone, most commonly prescribed as fixed-dose combination (FDC) with pantoprazole (274/304, 90%). Prokinetic dose was not mentioned in 251/304 (83%) prescriptions, and 18/304 (6%) did not mention frequency. Of the 378 AEs reported from 179 patients (47.35%), 306 (81%) were mild, all non-serious; 272 (72%) not preventable and 291 (77%) predictable in nature. Decreased appetite (n=31, 8.2%) and fatigue (n=27,7.14%) were most commonly reported. Causality assessment by the World Health Organization-Uppsala Monitoring Centre scale showed that 180 AEs were related to suspected drug (17 probable and 163 possible ADRs). Significant correlation was observed for AEs with increasing number of drugs per prescription (Spearman's R=+0.8, P =0.05) and with increasing therapy duration (Spearman's R=+1.00, P <0.001). Interpretation & conclusions: Our findings showed that prokinetics were often prescribed as FDCs, with incomplete prescriptions. Domperidone was found to be associated with multiple AEs. It is suggested that regular prescription monitoring should be done in hospitals to encourage rational use of drugs.
Subject(s)
Domperidone/adverse effects , Drug-Related Side Effects and Adverse Reactions/epidemiology , Pantoprazole/adverse effects , Prescriptions , Adult , Domperidone/therapeutic use , Drug-Related Side Effects and Adverse Reactions/physiopathology , Female , Humans , India/epidemiology , Male , Middle Aged , Pantoprazole/therapeutic use , Prospective Studies , Tertiary Care CentersABSTRACT
BACKGROUND: Proton pump inhibitors (PPIs) are the mainstay of treatment for acid peptic diseases (APDs), but are often irrationally prescribed in clinical practice. Appropriate prescription of PPIs is needed to optimize outcomes, and minimize risks and cost burden on the healthcare system. OBJECTIVE: To review available literature on efficacy and safety of proton pump inhibitors (PPIs) and give recommendations for rational use of PPIs from an Indian perspective. METHODS: Twelve healthcare professionals (9 gastroenterologists, 1 cardiologist, 1 orthopedist, 1 clinical pharmacologist) comprised the expert group; members disclosed conflicts of interest. The creation of the expert review was through a process that included meetings (in-person, online, telephone) where each professional contributed their experiences with regards to efficacy and safety of PPIs. Articles published between the years 2000 and 2017 were reviewed for evaluation of safety and efficacy of PPIs in treatment of various APDs. CONCLUSION: This expert review provides key recommendations for decision making in order to minimize the irrational use of PPIs. Some significant recommendations include: patients with GERD and acid-related complications should take a PPI for minimum 12 weeks for healing of esophagitis, and for maximum up to 48 weeks for symptom control. Patients with Barrett's esophagus should take long-term PPI. Patients at high risk for ulcer-related bleeding from NSAIDs including aspirin should take a PPI if they continue to take NSAIDs. Best practice recommendations are meant to merely assist with decision making in conjunction with patients' clinical history, and are not intended to dictate mandatory rules.
Subject(s)
Proton Pump Inhibitors , Anti-Inflammatory Agents, Non-Steroidal , Aspirin , Humans , IndiaABSTRACT
BACKGROUND & AIMS: Pregnancy is known to have poor outcomes in women with Budd Chiari syndrome. There are no data on fertility and pregnancy outcomes prior to onset of symptoms or the effect of therapy on these parameters. We therefore evaluated reproductive profile of women with Budd Chiari Syndrome before the onset of symptoms and after therapy. PATIENTS AND METHODS: Eighty women with Budd Chiari Syndrome (29 years [20-45]) were enrolled over 8 years. Baseline demographic characteristics, disease severity, thrombophilic disorders and treatment were reviewed. Their obstetric history before symptoms and after therapy was noted and compared. RESULTS: Sixty women conceived at least once (150 pregnancies) before symptom onset and 20 had primary infertility. Eighty-one pregnancies resulted in live births and remaining 69 pregnancies had adverse pregnancy outcomes. Post-intervention, 28 women (15 with primary infertility) attempted conception. Thirteen patients conceived 15 times. More women had live births after successful therapy as compared to presymptomatic period (0/28 vs 5/28 P = .000, Odds ratio5.6; 95% CI: 2.16-14.5). In women with primary infertility, conception (0/15 vs 3/15 P = .007, Odds ratio 5, 95% CI: 1.44-17.27) and proportion of live births (0/15 vs 2/15 P = .002, Odds ratio 7.5, 95% CI: 1.71-32.79) was higher as compared to presymptomatic period. CONCLUSION: Primary infertility is common and pregnancy outcomes are poor before the onset of symptoms in women with Budd-Chiari syndrome. Effective therapy of Budd-Chiari syndrome may improve fertility and pregnancy outcomes.
Subject(s)
Budd-Chiari Syndrome/therapy , Pregnancy Outcome , Adult , Anticoagulants/therapeutic use , Budd-Chiari Syndrome/physiopathology , Female , Humans , India , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic , Pregnancy , Prospective Studies , Quality of Life , Young AdultABSTRACT
Achalasia cardia (AC) is a frequently encountered motility disorder of the esophagus resulting from an irreversible degeneration of neurons. Treatment modalities are palliative in nature, and there is no curative treatment available for AC as of now. Significant advancements have been made in the management of AC over last decade. The introduction of high resolution manometry and per-oral endoscopic myotomy (POEM) has strengthened the diagnostic and therapeutic armamentarium of AC. High resolution manometry allows for the characterization of the type of achalasia, which in turn has important therapeutic implications. The endoscopic management of AC has been reinforced with the introduction of POEM that has been found to be highly effective and safe in palliating the symptoms in short-term to mid-term follow-up studies. POEM is less invasive than Heller's myotomy and provides the endoscopist with the opportunity of adjusting the length and orientation of esophageal myotomy according to the type of AC. The management of achalasia needs to be tailored for each patient, and the role of pneumatic balloon dilatation, POEM, or Heller's myotomy needs to be revisited. In this review, we discuss the important aspects of diagnosis as well as management of AC. The statements presented in the manuscript reflect the cumulative efforts of an expert consensus group.
Subject(s)
Consensus , Esophageal Achalasia/diagnosis , Esophageal Achalasia/therapy , Manometry/methods , Myotomy/methods , Dilatation/methods , Esophagoscopy , Fundoplication/methods , Heller Myotomy/methods , Humans , Palliative Care , Treatment OutcomeABSTRACT
BACKGROUND AND AIM: Percutaneous radiologic interventions are increasingly being used in management of Budd-Chiari syndrome (BCS). Minimal invasive approach has resulted in excellent long-term outcomes. We evaluated the treatment efficacy and safety of radiological intervention in patients with BCS. METHODS: Between January 2008 and June 2014, 190 patients with BCS underwent endovascular procedures (hepatic vein, collateral vein or inferior vena cava [IVC] plasty with or without stenting, or transjugular intrahepatic portosystemic shunting [TIPSS]). Clinical features, biochemical profile, and stent patency were monitored pre-procedure and post-procedure, and for a median duration of 42 (12-88) months. RESULTS: Of 190 patients (mean [SD] age = 26.9 [11.5] years; 102 men), imaging revealed hepatic vein obstruction in 147 patients, IVC obstruction in 40 patients, and concomitant hepatic vein and IVC obstruction in three patients. At presentation, the radiological interventions included hepatic vein plasty/stenting in 38 patients, collateral vein stenting in three patients, IVC plasty/stenting in 40 patients, both IVC and hepatic vein stenting in three patients, and TIPSS in 106 patients. Response was seen in 153 patients (80.5%). Repeat interventions were required in 19 patients (10.0%). Complications were noted in nine patients (4.7%). CONCLUSION: Our study demonstrates that venous recanalization and TIPSS for BCS are safe and efficacious.
Subject(s)
Budd-Chiari Syndrome/surgery , Endovascular Procedures/methods , Adult , Budd-Chiari Syndrome/diagnostic imaging , Constriction, Pathologic , Female , Hepatic Veins/diagnostic imaging , Hepatic Veins/pathology , Humans , Male , Portasystemic Shunt, Transjugular Intrahepatic , Stents , Treatment Outcome , Vena Cava, Inferior/diagnostic imaging , Vena Cava, Inferior/pathology , Young AdultABSTRACT
OBJECTIVE: Since the publication of the Asia-Pacific consensus on gastro-oesophageal reflux disease in 2008, there has been further scientific advancement in this field. This updated consensus focuses on proton pump inhibitor-refractory reflux disease and Barrett's oesophagus. METHODS: A steering committee identified three areas to address: (1) burden of disease and diagnosis of reflux disease; (2) proton pump inhibitor-refractory reflux disease; (3) Barrett's oesophagus. Three working groups formulated draft statements with supporting evidence. Discussions were done via email before a final face-to-face discussion. We used a Delphi consensus process, with a 70% agreement threshold, using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria to categorise the quality of evidence and strength of recommendations. RESULTS: A total of 32 statements were proposed and 31 were accepted by consensus. A rise in the prevalence rates of gastro-oesophageal reflux disease in Asia was noted, with the majority being non-erosive reflux disease. Overweight and obesity contributed to the rise. Proton pump inhibitor-refractory reflux disease was recognised to be common. A distinction was made between refractory symptoms and refractory reflux disease, with clarification of the roles of endoscopy and functional testing summarised in two algorithms. The definition of Barrett's oesophagus was revised such that a minimum length of 1â cm was required and the presence of intestinal metaplasia no longer necessary. We recommended the use of standardised endoscopic reporting and advocated endoscopic therapy for confirmed dysplasia and early cancer. CONCLUSIONS: These guidelines standardise the management of patients with refractory gastro-oesophageal reflux disease and Barrett's oesophagus in the Asia-Pacific region.
Subject(s)
Barrett Esophagus , Endoscopy, Digestive System/methods , Gastroesophageal Reflux , Proton Pump Inhibitors , Asia/epidemiology , Barrett Esophagus/diagnosis , Barrett Esophagus/epidemiology , Barrett Esophagus/therapy , Consensus , Delphi Technique , Disease Management , Drug Resistance , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/epidemiology , Gastroesophageal Reflux/therapy , Humans , Pacific Islands/epidemiology , Prevalence , Proton Pump Inhibitors/pharmacology , Proton Pump Inhibitors/therapeutic useSubject(s)
Fistula , Pleural Diseases , Septal Occluder Device , Humans , Pleural Diseases/etiology , Treatment OutcomeABSTRACT
BACKGROUND AND AIM: The aim of this study was to analyze etiologies and frequency of hepatic and extrahepatic organ failures (OFs) and outcome of acute-on-chronic liver failure (ACLF) at 10 tertiary centers in India. METHODS: In this retrospective study (2011-2014), patients satisfying Asian Pacific Association for the Study of the Liver definition of ACLF were included. Etiology of acute precipitating insult and chronic liver disease and outcomes were assessed. Occurrence and severity of OF were assessed by chronic liver failure-sequential organ failure assessment score. RESULTS: The mean (±SD) age of 1049 consecutive ACLF patients was 44.7 ± 12.2 years; Eighty-two percent were men. Etiology of acute precipitants included alcohol 35.7%, hepatitis viruses (hepatitis A, hepatitis B, and hepatitis E) 21.4%, sepsis 16.6%, variceal bleeding 8.4%, drugs 5.7%, and cryptogenic 9.9%. Among causes of chronic liver disease, alcohol was commonest 56.7%, followed by cryptogenic and hepatitis viruses. Predictors of survival were analyzed for a subset of 381 ACLF patients; OF's liver, renal, coagulation, cerebral, respiratory, and failure were seen in 68%, 32%, 31.5%, 22.6%, 14.5%, and 15%, respectively. Fifty-seven patients had no OF, whereas 1, 2, 3, 4, and 5 OFs were recorded in 126, 86, 72, 28, and 12 patients, respectively. The mortality increased progressively with increasing number of OFs (12.3% with no OF, 83.3% with five OFs). During a median hospital stay of 8 days, 42.6% (447/1049) of patients died. On multivariate analysis by Cox proportional hazard model, elevated serum creatinine (hazard ratio [HR] 1.176), advanced hepatic encephalopathy (HR 2.698), and requirement of ventilator support (HR 2.484) were independent predictors of mortality. CONCLUSIONS: Alcohol was the commonest etiology of ACLF. Within a mean hospital stay of 8 days, 42% patients died. OFs independently predicted survival.
Subject(s)
Acute-On-Chronic Liver Failure/epidemiology , Acute-On-Chronic Liver Failure/etiology , Acute-On-Chronic Liver Failure/therapy , Adult , Aged , Esophageal and Gastric Varices/complications , Esophageal and Gastric Varices/epidemiology , Female , Hepatitis, Viral, Human/complications , Hepatitis, Viral, Human/epidemiology , Humans , India/epidemiology , Liver Diseases, Alcoholic/epidemiology , Male , Middle Aged , Prognosis , Retrospective Studies , Severity of Illness Index , Survival Analysis , Young AdultABSTRACT
The reference intervals (RIs) of serum aminotransferases and Gamma-glutamyl transferase (GGT) have been established many years ago. Recent RIs are not available. The prospective study was conducted to re-evaluate the RIs of liver enzymes and the effect of demographic and anthropometric variables on them in western Indian population. A total of 1059 blood donors comprised the study population. Anthropometry and serum liver enzymes levels were measured. Subjects were categorized into normal weight and overweight by using body mass index (BMI) and waist circumference (WC). For RI determination, non-parametric methodology recommended by IFCC/CLSI was adopted. Mann-Whitney test and Spearman's rank correlation were used for statistical analysis. Upper limit of normal reference value of liver enzymes were lower in female compared to male. (ALT-23.55 F vs 36.00 M, GGT-34.58 F vs 36.20 M) When RI of liver enzymes were calculated according to body mass index, the upper limit of normal of ALT and GGT were higher in overweight group compared to normal weight group. (ALT-38.00 vs 27.00 IU/L and GGT-37.59 vs 35.26 IU/L). In both male and female, liver enzymes correlated significantly with age. WC and BMI were positively correlated with AST, ALT and GGT in both subgroups and the correlation was stronger in male. Demographic factors should be considered for making liver enzyme tests more clinically relevant. Gender based partitioning should be adopted for serum alanine aminotransferase (ALT) and GGT reference values for Western Indian population.
ABSTRACT
Acute severe exacerbation of ulcerative colitis is a potentially life threatening medical emergency. The management of acute severe ulcerative colitis depends on early recognition and prompt initiation of intensive intravenous treatment along with continuous objective monitoring for possible medical failure. The intensive regime is the accepted standard of care. This includes primarily a) intravenous corticosteroids, b) intravenous supportive management, and d) intravenous antibiotics in instances. This review discusses the timing, duration and dosage of the intensive intravenous treatment including the evidence based protocol for effective monitoring to enable timely escalation to second line therapy & colectomy.
Subject(s)
Adrenal Cortex Hormones/therapeutic use , Anti-Bacterial Agents/therapeutic use , Colitis, Ulcerative/drug therapy , Acute Disease , Adrenal Cortex Hormones/administration & dosage , Anti-Bacterial Agents/administration & dosage , Colectomy , Fluid Therapy , Humans , Infusions, Intravenous , Nutritional Support , Salvage TherapyABSTRACT
Rising number of inflammatory bowel disease (IBD) cases in developing countries necessitate clear guidance for clinicians for the appropriate use of advanced therapies. An expert consensus document was generated to guide the usage of tofacitinib, a Janus kinase inhibitor, in ulcerative colitis. Tofacitinib is a useful agent for the induction and maintenance of remission in ulcerative colitis. It can be used in the setting of biological failure or even steroid-dependent and thiopurine refractory disease. Typically, the induction dose is 10 mg BD orally. Usually, clinical response is evident within eight weeks of therapy. In those with clinical response, the dose can be reduced from 10 mg BD to 5 mg BD. Tofacitinib should be avoided or used cautiously in the elderly, patients with cardiovascular co-morbidity, uncontrolled cardiac risk factors, previous thrombotic episodes and those at high risk for venous thrombosis or previous malignancy. Baseline evaluation should include testing for and management of hepatitis B infection and latent tuberculosis. Where feasible, it is prudent to ensure complete adult vaccination, including Herpes zoster, before starting tofacitinib. The use of tofacitinib may be associated with an increased risk of infections such as herpes zoster and tuberculosis reactivation. Maternal exposure to tofacitinib should be avoided during pre-conception, pregnancy, and lactation. There is emerging evidence of tofacitinib in acute severe colitis, although the exact positioning (first-line with steroids or second-line) is uncertain.
Subject(s)
Colitis, Ulcerative , Colitis , Herpes Zoster , Pyrimidines , Adult , Female , Humans , Aged , Colitis, Ulcerative/drug therapy , Consensus , Piperidines/adverse effects , Herpes Zoster/chemically induced , Herpes Zoster/drug therapyABSTRACT
BACKGROUND/OBJECTIVES: To assess the efficacy and safety of pancreatin (pancrelipase) enteric-coated minimicrospheres (MMS) over a one-year period in patients with pancreatic exocrine insufficiency (PEI) due to chronic pancreatitis (CP). METHODS: This was a 51-week, open-label extension (OLE) of a one-week, multicenter, double-blind, randomized, placebo-controlled trial in India that enrolled patients ≥18 years of age with confirmed PEI due to CP. Patients received pancreatin (Creon(®) 40000 MMS™) at a dose of 80,000 Ph. Eur. lipase units with each of three main meals/day and 40,000 with each of up to three snacks/day. RESULTS: Of 61 patients entering the OLE, 48 completed treatment (nine were lost to follow up, two withdrew consent, one discontinued due to adverse event [acute exacerbation of CP], one protocol violation). There were significant improvements from baseline to end of OLE in mean ± SD coefficient of fat absorption (CFA: 22.7 ± 12.2%), coefficient of nitrogen absorption (CNA: 6.5 ± 7.9%), body weight (4.9 ± 4.9 kg), BMI (1.9 ± 1.9 kg/m(2)), and most nutritional laboratory parameters tested (p ≤ 0.001). Mean daily stool frequency was reduced from 2.8 to 1.6 (p < 0.001). Improvements in clinical symptoms, clinical global impression of disease symptoms, and quality of life were also observed. Treatment-emergent adverse events (TEAEs) were observed in 64% of patients overall. Only 13% of patients experienced TEAEs judged treatment related. CONCLUSIONS: In patients with PEI due to CP, treatment with pancreatin for one year was associated with significant improvements in fat absorption, nitrogen absorption, and nutritional parameters, improvements in clinical symptoms, and a favorable safety and tolerability profile.
Subject(s)
Microspheres , Pancreatin/adverse effects , Pancreatin/therapeutic use , Pancreatitis, Chronic/drug therapy , Adolescent , Adult , Drug Delivery Systems , Female , Humans , India , Male , Middle Aged , Pancreatin/administration & dosage , Young AdultABSTRACT
BACKGROUND AND AIM: Patients with alcoholic hepatitis and alcoholic cirrhosis have significant morbidity and mortality. The model for end-stage liver disease (MELD) score is used to predict mortality in patients with liver disease. Our study aimed to validate the utility of MELD score versus Child Pugh Turcotte (CPT) and modified CPT (CPT+creatinine; CPTC) scores in predicting mortality among alcoholic liver disease (ALD) patients. METHODS: We examineda retrospective (n=110; mean age 44.5years; 109 men) and a prospective (n=96; mean age 45 years; 92 men) cohort of patients suffering from ALD, with varying disease severity, and compared the ability of MELD, CTP and CPTC scores to predict the 1-, 3- and 6-month mortality using concordance (c-) statistics. RESULTS: The median MELD, CPT and CPTC scores were 21, 10 and 11 in the retrospective group and 21, 10 and 10 in prospective groups, respectively. The 1-month, 3-month and 6-month mortality was 41 (37.3%), 59 (53.6%) and 81 (73.6%) in the retrospective group and 27 (28.1%), 41 (42.7%) and 65 (67.7%) in the prospective group. The predictive ability of MELD, CPT and CPTC was 0.72, 0.67, 0.68 for 1-month mortality, 0.73, 0.70, 0.68 for 3-month mortality and 0.83, 0.75, 0.73 for 6-month mortality in retrospective group and 0.86, 0.56, 0.63 for 1-month mortality, 0.80, 0.57, and 0.60 for 3-month mortality, and 0.88, 0.51, and 0.64 for 6-month mortality in the prospective cohort, respectively. The predictive accuracy of MELD was significantly better than CPT and CPTC scores in the prospective group. CONCLUSIONS: MELD is a valid prognostic score compared to CPT and CPTC scores for predicting short-term mortality in patients of alcoholic liver disease.