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Methods for the early detection of drug-induced pancreatitis: a systematic review of the literature.

ABSTRACT: OBJECTIVES:We systematically reviewed the literature to identify evidence-informed recommendations regarding the detection of drug-induced pancreatitis (DIP) and, secondarily, to describe clinical processes for the diagnosis of DIP. DESIGN:Systematic review. DATA SOURCES:Ovid MEDLINE, including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase Classic+Embase, the Cochrane Library. ELIGIBILITY CRITERIA:We included clinical practice guidelines, systematic reviews, narrative reviews and observational studies with a focus of establishing incidence, prevalence or diagnostic approaches for DIP. Clinical trials that diagnosed DIP as an outcome were also included. DATA EXTRACTION AND SYNTHESIS:Two reviewers screened citations and performed data extraction. A narrative synthesis of the evidence was prepared. RESULTS:Fifty-nine studies were included. Early published evidence suggested serial pancreatic ultrasound could detect subclinical pancreatitis; however, subsequent studies demonstrated no utility of serial ultrasound or serial monitoring of pancreatic enzymes in the early detection of DIP. Two small studies conducted in patients with a high baseline risk of acute pancreatitis concluded serial monitoring of pancreatic enzymes may be useful to guide early discontinuation of medications with known associations with pancreatitis. Early discontinuation of medication was not advised for lower-risk patients because some medications cause transient elevations of pancreatic enzymes that do not progress to acute pancreatitis. Eight of 52 studies (15%) reporting a clinical diagnostic process for DIP reported using currently accepted criteria for the diagnosis of acute pancreatitis. A variety of methods were used to assess drug-related causality. CONCLUSIONS:There is minimal evidence to support the use of serial monitoring by ultrasound or pancreatic enzymes to detect cases of DIP. Serial monitoring may be useful to guide early discontinuation of DIP-associated drugs in high-risk patients, but not in lower-risk patients. Greater uptake of standardised diagnostic and causality criteria for DIP is needed. TRIAL REGISTRATION NUMBER:CRD42017060473.

SUBMITTER: Wolfe D

PROVIDER: S-EPMC6858245 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Methods for the early detection of drug-induced pancreatitis: a systematic review of the literature.

Wolfe Dianna D Kanji Salmaan S Yazdi Fatemeh F Skidmore Becky B Moher David D Hutton Brian B

BMJ open 20191105 11

<h4>Objectives</h4>We systematically reviewed the literature to identify evidence-informed recommendations regarding the detection of drug-induced pancreatitis (DIP) and, secondarily, to describe clinical processes for the diagnosis of DIP.<h4>Design</h4>Systematic review.<h4>Data sources</h4>Ovid MEDLINE, including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase Classic+Embase, the Cochrane Library.<h4>Eligibility criteria</h4>We included clinical practice guidelines, syst ...[more]

PMID: 31694842

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Project description:OBJECTIVE:A current assessment of case reports of possible drug-induced pancreatitis is needed. We systematically reviewed the case report literature to identify drugs with potential associations with acute pancreatitis and the burden of evidence supporting these associations. METHODS:A protocol was developed a priori (PROSPERO CRD42017060473). We searched MEDLINE, Embase, the Cochrane Library, and additional sources to identify cases of drug-induced pancreatitis that met accepted diagnostic criteria of acute pancreatitis. Cases caused by multiple drugs or combination therapy were excluded. Established systematic review methods were used for screening and data extraction. A classification system for associated drugs was developed a priori based upon the number of cases, re-challenge, exclusion of non-drug causes of acute pancreatitis, and consistency of latency. RESULTS:Seven-hundred and thirteen cases of potential drug-induced pancreatitis were identified, implicating 213 unique drugs. The evidence base was poor: exclusion of non-drug causes of acute pancreatitis was incomplete or poorly reported in all cases, 47% had at least one underlying condition predisposing to acute pancreatitis, and causality assessment was not conducted in 81%. Forty-five drugs (21%) were classified as having the highest level of evidence regarding their association with acute pancreatitis; causality was deemed to be probable or definite for 19 of these drugs (42%). Fifty-seven drugs (27%) had the lowest level of evidence regarding an association with acute pancreatitis, being implicated in single case reports, without exclusion of other causes of acute pancreatitis. DISCUSSION:Much of the case report evidence upon which drug-induced pancreatitis associations are based is tenuous. A greater emphasis on exclusion of all non-drug causes of acute pancreatitis and on quality reporting would improve the evidence base. It should be recognized that reviews of case reports, are valuable scoping tools but have limited strength to establish drug-induced pancreatitis associations. REGISTRATION:CRD42017060473.

Project description:IntroductionAcute pancreatitis (AP) is the most common cause of gastroenterological hospitalization in the USA, with a mortality ranging from 5 to 20%. Up to 80% of cases are caused by cholelithiasis and alcohol abuse. Less common etiologies that need to be explored include hypertriglyceridemia, trauma, ERCP, infections, and drugs. A number of medications are known to cause acute pancreatitis, with 0.3-1.4% of all cases of pancreatitis being drug induced (DIP). Here, we present a case of metronidazole-induced acute pancreatitis.Case summaryA 60-year-old female presented with constant severe epigastric pain associated with nausea, vomiting, and anorexia for one day. She had no past medical history of alcohol use or hypertriglyceridemia and was s/p cholecystectomy in the distant past. Symptoms had begun three days after starting metronidazole for Clostridium difficile colitis. Lipase was > 396, and CT abdomen revealed peripancreatic fat stranding. She was diagnosed with AP, metronidazole was suspected to be responsible and hence stopped, and supportive management initiated. Her symptoms improved rapidly, and pancreatic enzymes normalized within 2 days. Of note, she had had an episode of acute pancreatitis 3 years ago, also following metronidazole use, with resolution at discontinuation of the drug. She had concurrently been on omeprazole during both episodes.DiscussionMetronidazole is a commonly used antibiotic and is infrequently reported as a cause of DIP. Our review suggests the possibility of a dose-response and duration-response effect between metronidazole use and occurrence of pancreatitis. The most common presenting symptom and sign was moderate to severe epigastric pain and tenderness, accompanied by nausea/vomiting. Symptoms usually start within 2-7 days of starting the medication and usually resolve 2-5 days after discontinuation of therapy and pancreatitis treatment. The most common causative dose was 1-1.5 g/day. Our review also supports findings by Norgaard et al. suggesting that concurrent use of omeprazole potentiates the risk of metronidazole-induced pancreatitis.ConclusionMetronidazole is a commonly used antibiotic that may cause metronidazole-induced pancreatitis, especially if patients are concurrently taking PPIs. Awareness needs to be raised amongst clinicians regarding this association, in order to correctly identify etiology of pancreatitis and discontinue metronidazole promptly when suspected as the causative factor.

Project description:Since the 1960s, drugs have been known to cause teratogenic effects in humans. Such teratogenicity has been postulated to be influenced by genetics. The aim of this review was to provide an overview of the current knowledge on genetic susceptibility to drug teratogenicity in humans and reflect on future directions within the field of genetic teratology. We focused on 12 drugs and drug classes with evidence of teratogenic action, as well as 29 drugs and drug classes with conflicting evidence of fetal safety in humans. An extensive literature search was performed in the PubMed and EMBASE databases using terms related to the drugs of interest, congenital anomalies and fetal development abnormalities, and genetic variation and susceptibility. A total of 29 studies were included in the final data extraction. The eligible studies were published between 1999 and 2020 in 10 different countries, and comprised 28 candidate gene and 1 whole-exome sequencing studies. The sample sizes ranged from 20 to 9,774 individuals. Several drugs were investigated, including antidepressants (nine studies), thalidomide (seven studies), antiepileptic drugs (five studies), glucocorticoids (four studies), acetaminophen (two studies), and sex hormones (estrogens, one study; 17-alpha hydroxyprogesterone caproate, one study). The main neonatal phenotypic outcomes included perinatal complications, cardiovascular congenital anomalies, and neurodevelopmental outcomes. The review demonstrated that studies on genetic teratology are generally small, heterogeneous, and exhibit inconsistent results. The most convincing findings were genetic variants in SLC6A4, MTHFR, and NR3C1, which were associated with drug teratogenicity by antidepressants, antiepileptics, and glucocorticoids, respectively. Notably, this review demonstrated the large knowledge gap regarding genetic susceptibility to drug teratogenicity, emphasizing the need for further efforts in the field. Future studies may be improved by increasing the sample size and applying genome-wide approaches to promote the interpretation of results. Such studies could support the clinical implementation of genetic screening to provide safer drug use in pregnant women in need of drugs.

Project description:IntroductionSeveral versions of Early Warning Systems (EWS) are used in obstetrics to detect and treat early clinical deterioration to avert morbidity and mortality. EWS can potentially be useful to improve the quality of care and reduce the risk of maternal mortality in resource-limited settings. We conducted a systematic literature review of published obstetric early warning systems, define their predictive accuracy for morbidity and mortality, and their effectiveness in triggering corrective actions and improving health outcomes.MethodsWe systematically searched for primary research articles on obstetric EWS published in peer-reviewed journals between January 1997 and March 2018 in Medline, CINAHL, SCOPUS, Science Direct, and Science Citation Index. We also searched reference lists of relevant articles and websites of professional societies. We included studies that assessed the predictive accuracy of EWS to detect clinical deterioration, or/and their effectiveness in improving clinical outcomes in obstetric inpatients. We excluded studies with a paediatric or non-obstetric adult population. Cross-sectional and qualitative studies were also excluded. We performed a narrative synthesis since the outcomes reported were heterogeneous.ResultsA total of 381 papers were identified, 17 of which met the inclusion criteria. Eleven of the included studies evaluated the predictive accuracy of EWS for obstetric morbidity and mortality, 5 studies assessed the effectiveness of EWS in improving clinical outcomes, while one study addressed both. Sixteen published EWS versions were reviewed, 14 of which included five basic clinical observations (pulse rate, respiratory rate, temperature, blood pressure, and consciousness level). The obstetric EWS identified had very high median (inter-quartile range) sensitivity-89% (72% to 97%) and specificity-85% (67% to 98%) but low median (inter-quartile range) positive predictive values-41% (25% to 74%) for predicting morbidity or ICU admission. Obstetric EWS had a very high accuracy in predicting death (AUROC >0.80) among critically ill obstetric patients. Obstetric EWS improves the frequency of routine vital sign observation, reduces the interval between the recording of specifically defined abnormal clinical observations and corrective clinical actions, and can potentially reduce the severity of obstetric morbidity.ConclusionObstetric EWS are effective in predicting severe morbidity (in general obstetric population) and mortality (in critically ill obstetric patients). EWS can contribute to improved quality of care, prevent progressive obstetric morbidity and improve health outcomes. There is limited evidence of the effectiveness of EWS in reducing maternal death across all settings. Clinical parameters in most obstetric EWS versions are routinely collected in resource-limited settings, therefore implementing EWS may be feasible in such settings.

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Methods for the early detection of drug-induced pancreatitis: a systematic review of the literature.

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Methods for the early detection of drug-induced pancreatitis: a systematic review of the literature.

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