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BACKGROUND: Post-endoscopy upper gastrointestinal cancer (PEUGIC) is an important key performance indicator for endoscopy quality. We examined variation in PEUGIC rates among endoscopy providers in England and explored associated factors. METHODS: The was a population-based, retrospective, case-control study, examining data from National Cancer Registration and Analysis Service and Hospital Episode Statistics databases for esophageal and gastric cancers diagnosed between 2009 and 2018 in England. PEUGIC were cancers diagnosed 6 to 36 months after an endoscopy that did not diagnose cancer. Associated factors were identified using multivariable logistic regression analyses. RESULTS: The national PEUGIC rate was 8.5%, varying from 5% to 13% among endoscopy providers. Factors associated with PEUGIC included: female sex (odds ratio [OR] 1.29 [95%CI 1.23-1.36]); younger age (age >80 years, OR 0.52 [0.48-0.56], compared with ≤60 years); increasing comorbidity (Charlson score >4, OR 5.06 [4.45-5.76]); history of esophageal ulcer (OR 3.30 [3.11-3.50]), Barrett's esophagus (OR 3.21 [3.02-3.42]), esophageal stricture (OR 1.28 [1.20-1.37]), or gastric ulcer (OR 1.55 [1.44-1.66]); squamous cell carcinoma (OR 1.50 [1.39-1.61]); and UK national endoscopy accreditation status - providers requiring improvement (OR 1.10 [1.01-1.20]), providers never assessed (OR 1.24 [1.04-1.47]). CONCLUSION: PEUGIC rates varied threefold among endoscopy providers, suggesting unwarranted differences in endoscopy quality. PEUGIC was associated with endoscopy findings known to be associated with upper gastrointestinal cancer and a lack of national endoscopy provider accreditation. PEUGIC variations suggest an opportunity to raise performance standards to detect upper gastrointestinal cancers earlier and improve outcomes.
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BACKGROUND : Missing upper gastrointestinal cancer (UGIC) at endoscopy may prevent curative treatment. We have developed a root cause analysis system for potentially missed UGICs at endoscopy (post-endoscopy UGIC [PEUGIC]) to establish the most plausible explanations. METHODS : The electronic records of patients with UGIC at two National Health Service providers were examined. PEUGICs were defined as UGICs diagnosed 6-36 months after an endoscopy that did not diagnose cancer. An algorithm based on the World Endoscopy Organization post-colonoscopy colorectal cancer algorithm was developed to categorize and identify potentially avoidable PEUGICs. RESULTS : Of 1327 UGICs studied, 89 (6.7â%) were PEUGICs (patient median [IQR] age at endoscopy 73.5 (63.5-81.0); 60.7â% men). Of the PEUGICs, 40â% were diagnosed in patients with Barrett's esophagus. PEUGICs were categorized as: A - lesion detected, adequate assessment and decision-making, but PEUGIC occurred (16.9â%); B - lesion detected, inadequate assessment or decision-making (34.8â%); C - possible missed lesion, endoscopy and decision-making adequate (8.9â%); D - possible missed lesion, endoscopy or decision-making inadequate (33.7â%); E - deviated from management pathway but appropriate (5.6â%); F - deviated inappropriately from management pathway (3.4â%). The majority of PEUGICs (71â%) were potentially avoidable and in 45â% the cancer outcome could have been different if it had been diagnosed on the initial endoscopy. There was a negative correlation between endoscopists' mean annual number of endoscopies and the technically attributable PEUGIC rate (correlation coefficient -0.57; Pâ=â0.004). CONCLUSION : Missed opportunities to avoid PEUGIC were identified in 71â% of cases. Root cause analysis can standardize future investigation of PEUGIC and guide quality improvement efforts.
Subject(s)
Barrett Esophagus , Esophageal Neoplasms , Gastrointestinal Neoplasms , Male , Humans , Female , Root Cause Analysis , State Medicine , Barrett Esophagus/pathology , Endoscopy, Gastrointestinal , Esophageal Neoplasms/diagnosis , Esophageal Neoplasms/etiology , Esophageal Neoplasms/pathology , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/etiologyABSTRACT
BACKGROUND AND AIMS: PEG has been associated with poor case selection and high mortality. We examined indications, 30-day mortality, and 7-day adverse events in a national cohort undergoing PEG tube insertion. METHODS: Adult patients undergoing their first PEG tube insertion from 2007 to 2019 were identified in the Hospital Episode Statistics database. Indications and adverse events were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. Multivariable logistic regression modeling examined factors associated with mortality. RESULTS: Of 87,682 patients identified, 58% were men and median age was 69 years (interquartile range, 57-79). The number of patients with dementia or stroke as the indication for PEG fell from 2007 to 2019 (dementia, from 147 to 28 [P < .001]; stroke, from 2851 to 1781 [P < .001]). The median interval from stroke admission to PEG tube insertion increased from 21 (interquartile range, 12-36) to 28 (interquartile range, 13-45) days (P < .001). Aspiration pneumonia within 7 days of PEG fell from 10.2% to 8.6% (P = .04). Thirty-day mortality fell from 13.2% to 5.3% (P < .001), with associated factors of increasing age (≥82 years quintile odds ratio [OR], 4.44; 95% confidence interval [CI], 4.01-4.92), PEG tube insertion during emergency admission (OR, 2.10; 95% CI, 1.97-2.25), Charlson comorbidity score ≥5 (OR, 1.67; 95% CI, 1.53-1.82), and dementia (OR, 1.46; 95% CI, 1.26-1.71). Female sex (OR, .81; 95% CI, .77-.85), least-deprived quintile (OR, .88; 95% CI, .81-.95), and more recent years of PEG tube insertion (2019; OR, .44; 95% CI, .39-.51) were negatively associated with mortality. CONCLUSIONS: Thirty-day mortality after PEG tube insertion has fallen 60% over 13 years. Dementia or stroke as an indication for PEG fell, and the time interval from stroke to PEG tube insertion increased. These findings may be attributable to improved patient selection and timing for PEG tube insertion.
Subject(s)
Deglutition Disorders , Dementia , Stroke , Humans , Adult , Male , Female , Aged , Aged, 80 and over , Retrospective Studies , Enteral Nutrition , Deglutition Disorders/etiology , Gastrostomy/adverse effects , Stroke/epidemiology , Stroke/complications , Cohort StudiesABSTRACT
BACKGROUND : Data are limited regarding pancreatic cancer diagnosed following a pancreaticobiliary endoscopic ultrasound (EUS) that does not diagnose pancreatic cancer. We have studied the frequency of, and factors associated with, post-EUS pancreatic cancer (PEPC) and 1-year mortality. METHODS : Between 2010 and 2017, patients with pancreatic cancer and a preceding pancreaticobiliary EUS were identified in a national cohort using Hospital Episode Statistics. Patients with a pancreaticobiliary EUS 6-18 months before a later pancreatic cancer diagnosis were the PEPC cases; controls were those with pancreatic cancer diagnosed within 6 months of pancreaticobiliary EUS. Multivariable logistic regression models examined the factors associated with PEPC and a Cox regression model examined factors associated with 1-year cumulative mortality. RESULTS : 9363 pancreatic cancer patients were studied; 93.5â% identified as controls (men 53.2â%; median age 68 [interquartile range (IQR) 61-75]); 6.5â% as PEPC cases (men 58.2â%; median age 69 [IQR 61-77]). PEPC was associated with older age (≥â75 years compared with <â65 years, odds ratio [OR] 1.42, 95â%CI 1.15-1.76), increasing co-morbidity (Charlson co-morbidity score >â5, OR 1.90, 95â%CI 1.49-2.43), chronic pancreatitis (OR 3.13, 95â%CI 2.50-3.92), and diabetes mellitus (OR 1.58, 95â%CI 1.31-1.90). Metal biliary stents (OR 0.57, 95â%CI 0.38-0.86) and EUS-FNA (OR 0.49, 95â%CI 0.41-0.58) were inversely associated with PEPC. PEPC was associated with a higher cumulative mortality at 1 year (hazard ratio 1.12, 95â%CI 1.02-1.24), with only 14â% of PEPC patients (95â%CI 12â%-17â%) having a surgical resection, compared with 21â% (95â%CI 20â%-22â%) of controls. CONCLUSIONS : PEPC occurred in 6.5â% of patients and was associated with chronic pancreatitis, older age, more co-morbidities, and specifically diabetes mellitus. PEPC was associated with a worse prognosis and lower surgical resection rates.
Subject(s)
Pancreatic Neoplasms , Pancreatitis, Chronic , Aged , Humans , Male , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Endosonography , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/complications , Pancreatitis, Chronic/complications , Retrospective Studies , Female , Middle Aged , Pancreatic NeoplasmsABSTRACT
OBJECTIVE: We conducted this study to review deaths due to dengue fever (DF) during a large outbreak of DF in Lahore, Pakistan. METHODS: We reviewed deaths due to DF at Jinnah Hospital Lahore between August and November 2011. Clinical and laboratory data were abstracted. The 2011 World Health Organization Regional Office for South-East Asia (WHO SEARO) guidelines were used to classify the disease. RESULTS: Out of 128,634 probable DF patients who visited the outpatient department, 2313 patients were hospitalized; 1699 (73.3%) were male. RT-PCR was positive in 92 of 114 hospitalized patients (DENV-2 in 91 patients and DENV-3 in 1 patient). Sixty dengue-related deaths were reported; 41 (68.3%) were male. The mean age (± standard deviation) was 44 (± 20.5) y. The diagnosis at the time of presentation was DF in 5 (8.3%), dengue haemorrhagic fever without shock in 16 (26.6%), dengue shock syndrome in 20 (33%), and expanded dengue syndrome in 19 (31.7%) patients. Expanded dengue syndrome included encephalopathy in 12 (20%) patients, intracerebral bleed in 3 (5%), multiorgan failure in 3 (5%), and Guillain-Barré syndrome in 1 (1.6%). Twenty-nine (48.3%) patients had at least 1 comorbidity. CONCLUSION: Dengue shock syndrome and expanded dengue syndrome were the most common causes of death.
Subject(s)
Dengue/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Dengue/physiopathology , Female , Hospital Mortality , Humans , Infant , Male , Middle Aged , Pakistan/epidemiology , Severe Dengue/mortality , Severe Dengue/physiopathology , Tertiary Care Centers/statistics & numerical data , Young AdultABSTRACT
BACKGROUND: Scientific data regarding effects of platelet transfusion on platelet count in dengue-related thrombocytopenia is scanty. METHODS: A single center, randomized non-blinded trial was conducted on adult patients with dengue fever and platelet counts less than 30,000/µl. Patients were randomized to treatment and control group. Treatment group received single donor platelets. Patients with post-transfusion platelet increment (PPI) ≥10,000/µl and/or corrected count increment (CCI) ≥5,000/µl 1 h post-transfusion were considered responders. Primary outcome was platelet count increments at 24 and 72 h. RESULTS: 87 patients were enrolled, and 43 (48.2%) received platelet transfusion. Mean PPI and CCI at 1 h post-transfusion in the treatment group were 18,800/µl and 7,000/µl respectively. 22 (53.6%) patients in the treatment group were non-responders. Mean platelet increments at 24 and 72 h were higher in the treatment group as compared to the control group. Responders showed significantly higher increments when compared to non-responders and the control group at 24 h (p = 0.004 and p ≤ 0.001, respectively) and 72 h (p = 0.001 and p ≤ 0.001, respectively). Significant differences were found between non-responders and the control group at 24 h (p ≤ 0.001), but not at 72 h (p = 0.104). Patients with lower baseline platelet count were more likely to be non-responders. Platelet transfusion neither prevented development of severe bleeding nor shortened time to cessation of bleeding. Three severe transfusion reactions and two deaths occurred in treatment group. CONCLUSION: In this trial, almost half the patients showed no response to a high-dose platelet transfusion. Platelet transfusion did not prevent development of severe bleeding or shorten time to cessation of bleeding and was associated with significant side effects. Therefore, platelet transfusion should not be routinely done in the management of dengue fever.
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Background and study aims Upper gastrointestinal (UGI) endoscopy lacks established quality indicators. We conducted an umbrella systematic review of potential quality indicators for the detection of UGI cancer and dysplasia. Methods Bibliographic databases were searched up to December 2021 for systematic reviews and primary studies. Studies reporting diagnostic accuracy, detection rates or the association of endoscopy or endoscopist-related factors with UGI cancer or dysplasia detection were included. AMSTAR2 and JBI checklists were used to assess systematic review and primary study quality. Clinical heterogeneity precluded meta-analysis and findings are summarized narratively. Results Eight systematic reviews and nine primary studies were included. Image enhancement, especially narrow band imaging, had high diagnostic accuracy for dysplasia and early gastric cancer (pooled sensitivity 0.87 (95% CI 0.84-0.89) and specificity 0.97 (0.97-0.98)). Higher detection rates with longer endoscopy examination times were reported in three studies, but no difference was observed in one study. Endoscopist biopsy rate was associated with increased gastric cancer detection (odds ratio 2.5; 95% confidence interval [CI] 2.1-2.9). Early esophageal cancer (0.17% vs 0.14%, P =0.04) and gastric cancer (0.16% vs 0.12%, P =0.02) detection rates were higher with propofol sedation compared to no sedation. Endoscopies performed by trained endoscopists on dedicated Barrett's surveillance lists had higher detection rates (8% vs 3%, P <0.001). The neoplasia detection rate during diagnostic endoscopies for Barrett's esophagus was 7% (95% CI 4%-10%). Conclusions Image enhancement use, longer examination times, biopsy rate and propofol sedation are potential quality indicators for UGI endoscopy. Neoplasia detection rate and dedicated endoscopy lists are additional potential quality indicators for Barrett's esophagus.
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A clear understanding of the potential complications or adverse events (AEs) of diagnostic endoscopy is an essential component of being an endoscopist. Creating a culture of safety and prevention of AEs should be part of routine endoscopy practice. Appropriate patient selection for procedures, informed consent, periprocedure risk assessments and a team approach, all contribute to reducing AEs. Early recognition, prompt management and transparent communication with patients are essential for the holistic and optimal management of AEs. In this review, we discuss the complications of diagnostic upper gastrointestinal endoscopy, including their recognition, treatment and prevention.
Subject(s)
Endoscopy, Gastrointestinal , Humans , Endoscopy, Gastrointestinal/adverse effects , Endoscopy, Gastrointestinal/methods , Risk AssessmentABSTRACT
BACKGROUND: The British Society of Gastroenterology has recommended the Edinburgh Dysphagia Score (EDS) to risk-stratify dysphagia referrals during the endoscopy COVID recovery phase. AIMS: External validation of the diagnostic accuracy of EDS and exploration of potential changes to improve its diagnostic performance. METHODS: A prospective multicentre study of consecutive patients referred with dysphagia on an urgent suspected upper gastrointestinal (UGI) cancer pathway between May 2020 and February 2021. The sensitivity and negative predictive value (NPV) of EDS were calculated. Variables associated with UGI cancer were identified by forward stepwise logistic regression and a modified Cancer Dysphagia Score (CDS) developed. RESULTS: 1301 patients were included from 19 endoscopy providers; 43% male; median age 62 (IQR 51-73) years. 91 (7%) UGI cancers were diagnosed, including 80 oesophageal, 10 gastric and one duodenal cancer. An EDS ≥3.5 had a sensitivity of 96.7 (95% CI 90.7-99.3)% and an NPV of 99.3 (97.8-99.8)%. Age, male sex, progressive dysphagia and unintentional weight loss >3 kg were positively associated and acid reflux and localisation to the neck were negatively associated with UGI cancer. Dysphagia duration <6 months utilised in EDS was replaced with progressive dysphagia in CDS. CDS ≥5.5 had a sensitivity of 97.8 (92.3-99.7)% and NPV of 99.5 (98.1-99.9)%. Area under receiver operating curve was 0.83 for CDS, compared to 0.81 for EDS. CONCLUSIONS: In a national cohort, the EDS has high sensitivity and NPV as a triage tool for UGI cancer. The CDS offers even higher diagnostic accuracy. The EDS or CDS should be incorporated into the urgent suspected UGI cancer pathway.
Subject(s)
COVID-19 , Deglutition Disorders , Gastrointestinal Neoplasms , Aged , Deglutition Disorders/diagnosis , Deglutition Disorders/etiology , Endoscopy, Gastrointestinal , Female , Gastrointestinal Neoplasms/complications , Gastrointestinal Neoplasms/diagnosis , Humans , Male , Middle Aged , Prospective Studies , Referral and Consultation , TriageABSTRACT
Background and study aims Population-level data on the outcomes of pancreaticobiliary endoscopic ultrasound (PB-EUS) are limited. We examined national PB-EUS and fine-needle aspiration (FNA) activity, its relation to pancreatic cancer therapy, associated mortality and adverse events. Patients and methods Adults undergoing PB-EUS in England from 2007-2016 were identified in Hospital Episode Statistics. A pancreatic cancer cohort diagnosed within 6 months of PB-EUS were studied separately. Multivariable logistic regression models examined associations with 30-day mortality and therapies for pancreatic cancer. Results 79,269 PB-EUS in 68,908 subjects were identified. Annual numbers increased from 2,874 (28â% FNA) to 12,752 (35â% FNA) from 2007 to 2016. 8,840 subjects (13â%) were diagnosed with pancreatic cancer. Sedation related adverse events were coded in 0.5â% and emergency admission with acute pancreatitis in 0.2â% within 48 hours of PB-EUS.â1.5â% of subjects died within 30 days of PB-EUS.âFactors associated with 30-day mortality included increasing age (odds ratio 1.03 [95â% CI 1.03-1.04]); male sex (1.38 [1.24-1.56]); increasing comorbidity (1.49 [1.27-1.74]); EUS-FNA (2.26 [1.98-2.57]); pancreatic cancer (1.39 [1.19-1.62]); increasing deprivation (least deprived quintile 0.76 [0.62-0.93]) and lower provider PB-EUS volume (2.83 [2.15-3.73]). Factors associated with surgical resection in the pancreatic cancer cohort included lower provider PB-EUS volume (0.44 [0.26-0.74]) and the least deprived subjects (1.33 [1.12-1.57]). 33â% of pancreatic cancer subjects who underwent EUS, did not subsequently receive active cancer treatment. Conclusions Lower provider PB-EUS volume was associated with higher 30-day mortality and reduced rates of both pancreatic cancer surgery and chemotherapy. These results suggest potential issues with case selection in lower-volume EUS providers.
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BACKGROUND AND AIMS: Cirrhosis increases perioperative and postoperative mortality in nonhepatic surgery. Transjugular intrahepatic portosystemic shunt (TIPSS), by reducing portal pressure, may reduce intraoperative bleeding and postoperative decompensation. We report our experience of prophylactic TIPSS in nonhepatic surgery. METHODS: Patients who underwent prophylactic TIPSS before nonhepatic surgery were identified from database with retrospective data collection via an e-patient record system. Primary outcome was discharged without hepatic decompensation after a planned surgery. RESULTS: Twenty-one patients [age (median, range): 55, 33-76 years, Child's score: 6, 5-9] who underwent prophylactic TIPSS before nonhepatic surgery over a period of 9 years were included. All patients underwent successful TIPSS with a reduction in portal pressure gradient from 21.5 (11-35) to 16 (7-25) mmHg (P < 0.001). Immediate post-TIPSS complications were seen in 7 (33%) patients including hepatic encephalopathy in four. Eighteen patients (86%) underwent planned surgical intervention. Significant postoperative complications included hepatic encephalopathy (3), sepsis (2) and bleed (1). Two patients died postoperatively with multi-organ failure. The primary outcome was achieved in 12 (57%) patients. Post-TIPSS portal pressure gradient was significantly higher in patients with the adverse primary outcome. Over a follow-up period of 11 (1-78) months; 1-, 6- and 12-months' survival was 90, 80 and 76%, respectively. CONCLUSION: Prophylactic TIPSS is associated with complications in up to one-third of patients, with 57% achieving the primary outcome. Careful patient selection in a multidisciplinary team setting is essential. Multicentre studies are necessary before the universal recommendation of prophylactic TIPSS.
Subject(s)
Hepatic Encephalopathy , Portasystemic Shunt, Transjugular Intrahepatic , Adult , Aged , Child , Child, Preschool , Decompression , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/prevention & control , Humans , Middle Aged , Portasystemic Shunt, Transjugular Intrahepatic/adverse effects , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Bowel preparation for colonoscopy is often poorly tolerated due to poor palatability and adverse effects. This can negatively impact on the patient experience and on the quality of bowel preparation. This systematic review and meta-analysis was carried out to assess whether adjuncts to bowel preparation affected palatability, tolerability and quality of bowel preparation (bowel cleanliness). METHODS: A systematic search strategy was conducted on PubMed, MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews to identify studies evaluating adjunct use for colonoscopic bowel preparation. Studies comparing different regimens and volumes were excluded. Specific outcomes studied included palatability (taste), willingness to repeat bowel preparation, gastrointestinal adverse events and the quality of bowel preparation. Data across studies were pooled using a random-effects model and heterogeneity assessed using I2-statistics. RESULTS: Of 467 studies screened, six were included for analysis (all single-blind randomised trials; n = 1187 patients). Adjuncts comprised citrus reticulata peel, orange juice, menthol candy drops, simethicone, Coke Zero and sugar-free chewing gum. Overall, adjunct use was associated with improved palatability (mean difference 0.62, 95% confidence interval 0.29-0.96, p < 0.001) on a scale of 0-5, acceptability of taste (odds ratio 2.75, 95% confidence interval: 1.52-4.95, p < 0.001) and willingness to repeat bowel preparation (odds ratio 2.92, 95% confidence interval: 1.97-4.35, p < 0.001). Patients in the adjunct group reported lower rates of bloating (odds ratio 0.48, 95% confidence interval: 0.29-0.77, p = 0.003) and vomiting (odds ratio 0.47, 95% confidence interval 0.27-0.81, p = 0.007), but no difference in nausea (p = 0.10) or abdominal pain (p = 0.62). Adjunct use resulted in superior bowel cleanliness (odds ratio 2.52, 95% confidence interval: 1.31-4.85, p = 0.006). Heterogeneity varied across outcomes, ranging from 0% (vomiting) to 81% (palatability), without evidence of publication bias. The overall quality of evidence was rated moderate. CONCLUSION: In this meta-analysis, the use of adjuncts was associated with better palatability, less vomiting and bloating, willingness to repeat bowel preparation and superior quality of bowel preparation. The addition of adjuncts to bowel preparation may improve outcomes of colonoscopy and the overall patient experience.
Subject(s)
Colonoscopy/methods , Laxatives/administration & dosage , Pharmaceutic Aids/administration & dosage , Preoperative Care/methods , Colonoscopy/statistics & numerical data , Humans , Laxatives/adverse effects , Laxatives/chemistry , Patient Outcome Assessment , Patient Satisfaction , Pharmaceutic Aids/chemistry , Randomized Controlled Trials as Topic , Taste , Treatment OutcomeABSTRACT
Malnutrition encompassing both macro- and micro-nutrient deficiency, remains one of the most frequent complications of alcohol-related liver disease (ArLD). Protein-energy malnutrition can cause significant complications including sarcopenia, frailty and immunodepression in cirrhotic patients. Malnutrition reduces patient's survival and negatively affects the quality of life of individuals with ArLD. Moreover, nutritional deficit increases the likelihood of hepatic decompensation in cirrhosis. Prompt recognition of at-risk individuals, early diagnosis and treatment of malnutrition remains a key component of ArLD management. In this review, we describe the pathophysiology of malnutrition in ArLD, review the screening tools available for nutritional assessment and discuss nutritional management strategies relevant to the different stages of ArLD, ranging from acute alcoholic hepatitis through to decompensated end stage liver disease.
Subject(s)
Malnutrition , Quality of Life , Humans , Liver Cirrhosis , Malnutrition/etiology , Malnutrition/therapy , Nutrition Assessment , Nutritional StatusABSTRACT
We investigated an outbreak of darkening of skin, bleeding from multiple sites, leucopenia and thrombocytopenia in ischaemic heart disease patients. Case patients were defined as patients who had received medicines from the pharmacy of Punjab Institute of Cardiology between 1 December 2011 and 12 January 2012 and who developed any one of the following: darkening of skin, bleeding from any site, thrombocytopenia and leucopenia. Clinical and drug-related data were abstracted. All 664 case patients had received iso-sorbide-mono-nitrate contaminated with about 50 mg of pyrimethamine, and 151 (23%) died. The median age of 117 patients admitted at Jinnah Hospital Lahore was 57 years (range, 37-100) and 92 (79%) were male. The median time from intake of medicine to presentation was 37 days (range 13-72). Symptoms and signs included bleeding (in 95% of the patients), skin hyperpigmentation (in 61%), diarrhoea (in 53%) and abdominal pain (in 48%). At presentation, the median white cell count was 2.3 × 10(9) /L (range, 0.1 × 10(9) -16.0 × 10(9) ), the median hemoglobin concentration was 109 g/L (range 58-169) and the median platelet count was 18 × 10(9) /L (range, 0 × 10(9) -318 × 10(9) ). Bone marrow examination revealed trileneage dysplasia and severe megaloblastosis. The predictors of mortality included presentation prior to 15 January 2012, age more than 57 years, hypotension and leukocyte count less than 1.5 × 10(9) /L. None of the patients who died received Calcium folinate because all deaths occurred prior to contaminant identification. We describe an outbreak of pyrimethamine toxicity in ischaemic heart disease patients receiving medicines from a single pharmacy due to accidental contamination of iso-sorbide mono-nitrate tablets at industrial level. Late recognition of illness resulted in high mortality.