Anti-tuberculosis drug resistance in Bangladesh: reflections from the first nationwide survey.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) drug resistance in Bangladesh. DESIGN: Weighted cluster sampling among smear-positive cases, and standard culture and drug susceptibility testing on solid medium were used. RESULTS: Of 1480 patients enrolled during 2011, 12 falsified multidrug-resistant TB (MDR-TB) patients were excluded. Analysis included 1340 cases (90.5% of those enrolled) with valid results and known treatment antecedents. Of 1049 new cases, 12.3% (95%CI 9.3-16.1) had strains resistant to any of the first-line drugs tested, and 1.4% (95%CI 0.7-2.5) were MDR-TB. Among the 291 previously treated cases, this was respectively 43.2% (95%CI 37.1-49.5) and 28.5% (95%CI 23.5-34.1). History of previous anti-tuberculosis treatment was the only predictive factor for first-line drug resistance (OR 34.9). Among the MDR-TB patients, 19.2% (95%CI 11.3-30.5; exclusively previously treated) also showed resistance to ofloxacin. Resistance to kanamycin was not detected. CONCLUSION: Although MDR-TB prevalence was relatively low, transmission of MDR-TB may be increasing in Bangladesh. MDR-TB with fluoroquinolone resistance is rapidly rising. Integrating the private sector should be made high priority given the excessive proportion of MDR-TB retreatment cases in large cities. TB control programmes and donors should avoid applying undue pressure towards meeting global targets, which can lead to corruption of data even in national surveys.

Review article: towards a considered and ethical approach to organ support in critically-ill patients with cirrhosis.

BACKGROUND: Increasing numbers of patients are being admitted to hospital with decompensated chronic liver disease in the UK. A significant proportion will develop complicating extra-hepatic organ dysfunction, but the selection of those who should be admitted to intensive care is complex and challenging. Alcohol-related liver disease also presents complex ethical dilemmas. AIM: To review recent survival analyses and explore differences in secondary and tertiary care; to highlight strengths and weaknesses of prognostic models, therapeutic advances and shifts in prognostic expectation. We also aim to explore the ethical challenges presented by addiction and self-injury in an area of limited resource. METHODS: We searched PubMed for articles discussing 'cirrhosis', 'prognosis', 'critical illness', 'organ failure', 'renal failure', 'alcohol', 'ethics' and 'addiction'. We also explored particular ethical dilemmas encountered by the authors and colleagues. RESULTS: Prognosis has improved in many cirrhotic complications and historically poor outcomes in tertiary care may reflect a more complex patient cohort. Previously 'untreatable' complications are now being managed successfully. Estimates of survival are more accurate after a 48-h period of supportive care. Physicians are not best placed to make judgments with regard to deservingness, moral responsibility, rationing and access to organ support in cases of acute deterioration related to alcoholism, and the case for denying support must be made on purely medical grounds. CONCLUSIONS: An early, aggressive approach to organ support is justified. Further discussions between hepatologists and critical care physicians are required to determine acceptable burden-to-benefit ratios for prolonged intensive care support in young alcoholic patients.

Upper gastrointestinal haemorrhage in the acute cardiac care setting: antiplatelets and endoscopy.

Upper gastrointestinal haemorrhage (UGIH) in cardiac patients receiving antiplatelets presents a difficult management problem. The aim of this study was to describe a series of cardiac inpatients receiving antiplatelets who underwent endoscopy for an acute UGIH. Cardiac inpatients receiving antiplatelets and requiring endoscopy for UGIH over an 18-month period were followed up. Forty-one patients were studied. Most patients (25 [61%]) presented with melaena. Antiplatelets were withheld in 34 (83%) patients; predominantly in those with higher pre-endoscopy Rockall scores (median, 4; interquartile range [IQR], 3-5 versus median, 3; IQR, 2-4; P < 0.05). Positive findings were identified at endoscopy in 80%. Duodenal ulcers were the most common lesion and adrenaline the most common method of haemostasis. Median time to first endoscopy was 0 (IQR, 0-1) days. Seven (17%) patients re-bled, median Rockall score was six (IQR, 4-8). Three (7%) patients experienced procedural complications, two patients became hypoxic and one patient died. Following endoscopy, antiplatelets were restarted after a median of three (IQR, 3-5) days. On discharge, 27/28 (96%) patients continued with antiplatelet and proton-pump inhibitor therapy. Thirty-day inpatient mortality was 7% (3 patients). One patient re-bled within six months of discharge. Endoscopy helped assess the risk of re-bleeding and timing of antiplatelet re-introduction in cardiac inpatients experiencing UGIH.

Clostridium difficile-associated disease acquired in the neurocritical care unit.

BACKGROUND: Clostridium difficile is an important cause of nosocomial infection on the intensive care unit. Little is known about infection rates on the neurocritical care unit (NICU). The purpose of this study was to determine the prevalence, severity, and outcome associated with Clostridium difficile-associated disease (CDAD) acquired on the NICU. METHODS: Patients on NICU with a positive stool Clostridium difficile toxin assay, from August 2004 to February 2008, were identified by the Department of Microbiology. Each patient's medical notes and charts were reviewed in turn. Patients with a positive assay within 48 h of NICU admission were excluded. RESULTS: Twenty-one (0.6%) NICU patients developed CDAD. All were emergency admissions, 18 (86.0%) were neurosurgical. Subarachnoid hemorrhage was the most common diagnosis, 5 (23.8%) patients. Median age and APACHE II score on admission were 55 (IQR 40-66) and 21 (IQR 16-24), respectively. Thirteen (61.9%) patients were female. Median interval between NICU admission and diarrhea onset and CDAD diagnosis were 5 (3-8) days and 7 (4-12) days, respectively. At the time of diagnosis most, 11 (52.4%) patients, had moderate CDAD. Previously identified risk factors for ICU-acquired CDAD comprised: age > 65 (6), antibiotics (21), and medical device requirements (21). Five (23.8%) patients deteriorated clinically as a result of CDAD. The overall in-hospital mortality for those with NICU acquired CDAD was 19%. CONCLUSIONS: Although CDAD is rarely acquired on the NICU, up to one quarter of affected patients may experience complications. Prospective validation of severity definitions and treatment guidelines may help to reduce the complication rates.

Outcomes of critically ill patients with cirrhosis admitted to intensive care: an important perspective from the non-transplant setting.

BACKGROUND: Hospital admissions for cirrhosis have been increasing in the United Kingdom, leading to increased pressure on intensive care (ICU) services. Outcome data for patients admitted to ICU are currently limited to transplant centre reports, with mortality rates exceeding 70%. These tertiary reports could fuel a negative bias when patients with cirrhosis are reviewed for ICU admission in secondary care. AIMS: To determine whether disease severity and mortality rates in non-transplant general ICU are less severe than those reported by tertiary datasets. METHODS: A prospective dual-centre non-transplant ICU study. Admissions were screened for cirrhosis and physiological and biochemical data were collected. Disease-specific and critical illness scoring systems were evaluated. RESULTS: Cirrhosis was present in 137/4198 (3.3%) of ICU admissions. ICU and hospital mortality were 38% and 47%, respectively; median age 50 [43-59] years, 68% men, 72% alcoholic cirrhosis, median Child Pugh Score (CPS) 10 [8-11], Model for End-Stage Liver Disease (MELD) 18 [12-24], Acute Physiology and Chronic Health Evaluation II score (APACHE II) 16 [13-22]. CONCLUSIONS: Mortality rates and disease staging were notably lower than in the published literature, suggesting that patients have a more favourable outlook than previously considered. Transplant centre data should therefore be interpreted with caution when evaluating the merits of intensive care admission for patients in general secondary care ICUs.

The increasing hospital disease burden of haemochromatosis in England.

BACKGROUND: Hereditary haemochromatosis is a preventable cause of liver disease with an increasing disease burden. AIMS: To investigate time trends for hospital admission ascribed to haemochromatosis in England during the period from 1989/1990 to 2002/2003 and mortality from 1979 to 2005. METHODS: Hospital admission data, relating to both in-patients and day-cases, were obtained from the Hospital Episodes Statistics service. Mortality rates for England and Wales were provided by the Office for National Statistics. RESULTS: Haemochromatosis is an uncommon cause for hospital admission. Age-standardized in-patient admission rates increased over the study period by 269% in men and by 290% in women: (from 0.64 to 2.36 and from 0.21 to 0.81 per year per 100 000). The increase in age-standardized day-case admission rates was even higher (men: from 2.78 to 34.9 per year per 100 000, 1155%; women: from 0.58 to 11.67 per year per 100 000, 1924%). Haemochromatosis was recorded as an uncommon cause of death. CONCLUSIONS: Hospital in-patient and day case admissions for haemochromatosis increased markedly over the study period while mortality remained low. Both admission rates and mortality were higher in men than in women. The increase in admission rate may reflect improved recognition and diagnosis of iron overload disorders following identification of the HFE gene.

'Liver function tests' on the intensive care unit: a prospective, observational study.

AIMS: To evaluate the prevalence, patterns and significance of deranged liver function tests (LFT) in critically ill patients. METHODS: A prospective, observational data collection of the LFT [bilirubin, alanine aminotransferase (ALT), alkaline phosphatase (AKP), gamma glutaryl transferase (gammaGT)] and critical care parameters in all admissions to the general intensive care unit (ICU) of our institution. Prevalence of abnormal LFT on the day of ITU admission is described and the relationship of abnormal LFT to clinical events and 30-day mortality analysed. RESULTS: Of 263 first admissions without hepatobiliary disease, 61% demonstrated an abnormal LFT at the point of admission. The majority of abnormalities were less than twice the upper limit of normal. Episodes of ventilation, haemofiltration and hypotension during the first 48 h were associated with an abnormal ALT on day 3. The presence of an abnormal ALT [odds ratio 2.7 (1.2-6.0)], AKP [OR 2.8 (1.1-7.3)] or gammaGT [OR 3.9 (1.9-8.3)] was associated with an increased risk of death within 30 days of admission. When adjusted for APACHE II score, LFTs were not independent predictors of mortality. DISCUSSION: Low-grade abnormalities of LFT are a significant entity in critically ill patients and show an association with mortality outcomes and clinical events on ICU. They are likely to represent part of a spectrum of liver injury associated with critical illness and should not be disregarded.

Severe hepatic dysfunction in pregnancy.

Acute liver disease in pregnancy may have fatal consequences. Pre-eclampsia, HELLP syndrome and acute fatty liver of pregnancy form a spectrum of disease that range from mild symptoms to severe life-threatening multi-organ dysfunction. Early recognition of signs and prognostic indicators may enable prompt referral to specialist centres providing the multidisciplinary support required to reduce maternal and perinatal morbidity and mortality. We review the common causes of acute hepatic failure associated with pregnancy, and current management practices.

Animal models of acute hepatic failure.

The understanding and treatment of acute hepatic failure has developed rapidly over the last 40 years reducing morbidity and mortality from this syndrome. Progress has been made by the study of animal models that reflect the clinical, biochemical and histological pattern of the syndrome seen in man. This is of increasing importance with the use of therapeutic intervention, liver transplantation and the use of extra-corporeal liver support devices. This review examines and critically appraises the various approaches to the study of acute hepatic failure in animal models, including both surgical and pharmacological approaches.

Review article: liver support systems in acute hepatic failure.

The treatment of acute hepatic failure has developed rapidly over the last 40 years, reducing morbidity and mortality from this syndrome. Whilst this has been partly attributed to significant improvements in the specialist medical management of these patients, advances in surgical techniques and pharmaceutical developments have led to the establishment of successful liver transplantation programmes, which have improved mortality significantly. This review will examine the clinical impact of alternative methods that have been used to provide extra-corporeal hepatic support. Non-biological, bio- logical and hybrid hepatic extra-corporeal support will be explored, offering a comprehensive historical overview and an appraisal of present and future advances.

Synthesis of some new biologically active 2,3-disubstituted quinazolin-4-ones.

The facile synthesis of 2-(2'-4-anisoylvinyl)-3-arylquinazolin-4-ones (2a, b) involves the condensation of 2-toluidine or 4-phenylenediamine with the corresponding 2-[2'-(4-anisoylvinyl)]-4H-3,1-benzoxazine-4-one (1). Reaction of compound 2 with aldehydes, bromine, alcohols, hydrazine hydrate, urea and thiourea are discussed. The former structure of the products have been characterized by elemental analysis and spectral data. Preliminary screening of some selected compounds for antimicrobial activity is reported.