Fatal hepatotoxicity secondary to nimesulide MERLANI, Giorgio; FOX, Mark; OEHEN, Hans-Peter ...
European journal of clinical pharmacology,
07/2001, Letnik:
57, Številka:
4
Journal Article
Recenzirano
This report describes a 57-year-old female patient with chronic lumbago, who died from the sequelae of acute liver failure induced by nimesulide medication. Nimesulide is a non-steroidal ...anti-inflammatory drug (NSAID) which preferentially inhibits cyclo-oxygenase 2 and has been associated with a total of 13 reported cases of severe liver injury including our case. On the basis of the literature reports, the following features of nimesulide-associated hepatotoxicity were identified: female sex (84% of cases), age (mean age 62 years), jaundice as a primary manifestation (90%) and the absence of peripheral blood eosinophilia. The average duration of therapy of the published cases was 62 days (range 7-180 days). Based on spontaneous reports to the World Health Organization, nimesulide induces a high proportion of severe adverse hepatic reactions compared with other NSAIDs registered in Switzerland. Hepatotoxicity thus represents an important risk factor of nimesulide usage.PUBLICATION ABSTRACT
We present the case of a 74-years old man with subtotal gastrectomy for adenocarcinoma, whose postoperative course is complicated by a prolonged fever. Despite extensive diagnostics, the origin of ...the postoperative fever remains unexplained for 47 days, when the patient is transferred to the ICU because of lethargy, hemodynamic instability, lung edema and abdominal symptoms. The diagnosis of Addison crisis is established and under substitution with hydrocortisone all the symptoms rapidly resolve. Postoperative fever is relatively frequent and infectious causes account for about half of the cases only. An infectious origin has imperatively to be excluded when the fever arises later than 48 hrs after surgery. In case of prolonged fever we suggest to extend the differential diagnosis to other than infectious causes by means of special lists (e.g fever of unknown origin).
This report describes a 57-year-old female patient with chronic lumbago, who died from the sequelae of acute liver failure induced by nimesulide medication. Nimesulide is a non-steroidal ...anti-inflammatory drug (NSAID) which preferentially inhibits cyclo-oxygenase 2 and has been associated with a total of 13 reported cases of severe liver injury including our case. On the basis of the literature reports, the following features of nimesulide-associated hepatotoxicity were identified: female sex (84% of cases), age (mean age 62 years), jaundice as a primary manifestation (90%) and the absence of peripheral blood eosinophilia. The average duration of therapy of the published cases was 62 days (range 7-180 days). Based on spontaneous reports to the World Health Organization, nimesulide induces a high proportion of severe adverse hepatic reactions compared with other NSAIDs registered in Switzerland. Hepatotoxicity thus represents an important risk factor of nimesulide usage.
Background
There is evidence that water‐loss dehydration is common in older people and associated with many causes of morbidity and mortality. However, it is unclear what clinical symptoms, signs and ...tests may be used to identify early dehydration in older people, so that support can be mobilised to improve hydration before health and well‐being are compromised.
Objectives
To determine the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs and tests to be used as screening tests for detecting water‐loss dehydration in older people by systematically reviewing studies that have measured a reference standard and at least one index test in people aged 65 years and over. Water‐loss dehydration was defined primarily as including everyone with either impending or current water‐loss dehydration (including all those with serum osmolality ≥ 295 mOsm/kg as being dehydrated).
Search methods
Structured search strategies were developed for MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, LILACS, DARE and HTA databases (The Cochrane Library), and the International Clinical Trials Registry Platform (ICTRP). Reference lists of included studies and identified relevant reviews were checked. Authors of included studies were contacted for details of further studies.
Selection criteria
Titles and s were scanned and all potentially relevant studies obtained in full text. Inclusion of full text studies was assessed independently in duplicate, and disagreements resolved by a third author. We wrote to authors of all studies that appeared to have collected data on at least one reference standard and at least one index test, and in at least 10 people aged ≥ 65 years, even where no comparative analysis has been published, requesting original dataset so we could create 2 x 2 tables.
Data collection and analysis
Diagnostic accuracy of each test was assessed against the best available reference standard for water‐loss dehydration (serum or plasma osmolality cut‐off ≥ 295 mOsm/kg, serum osmolarity or weight change) within each study. For each index test study data were presented in forest plots of sensitivity and specificity. The primary target condition was water‐loss dehydration (including either impending or current water‐loss dehydration). Secondary target conditions were intended as current (> 300 mOsm/kg) and impending (295 to 300 mOsm/kg) water‐loss dehydration, but restricted to current dehydration in the final review.
We conducted bivariate random‐effects meta‐analyses (Stata/IC, StataCorp) for index tests where there were at least four studies and study datasets could be pooled to construct sensitivity and specificity summary estimates. We assigned the same approach for index tests with continuous outcome data for each of three pre‐specified cut‐off points investigated.
Pre‐set minimum sensitivity of a useful test was 60%, minimum specificity 75%. As pre‐specifying three cut‐offs for each continuous test may have led to missing a cut‐off with useful sensitivity and specificity, we conducted post‐hoc exploratory analyses to create receiver operating characteristic (ROC) curves where there appeared some possibility of a useful cut‐off missed by the original three. These analyses enabled assessment of which tests may be worth assessing in further research. A further exploratory analysis assessed the value of combining the best two index tests where each had some individual predictive ability.
Main results
There were few published studies of the diagnostic accuracy of state (one time), minimally invasive clinical symptoms, signs or tests to be used as screening tests for detecting water‐loss dehydration in older people. Therefore, to complete this review we sought, analysed and included raw datasets that included a reference standard and an index test in people aged ≥ 65 years.
We included three studies with published diagnostic accuracy data and a further 21 studies provided datasets that we analysed. We assessed 67 tests (at three cut‐offs for each continuous outcome) for diagnostic accuracy of water‐loss dehydration (primary target condition) and of current dehydration (secondary target condition).
Only three tests showed any ability to diagnose water‐loss dehydration (including both impending and current water‐loss dehydration) as stand‐alone tests: expressing fatigue (sensitivity 0.71 (95% CI 0.29 to 0.96), specificity 0.75 (95% CI 0.63 to 0.85), in one study with 71 participants, but two additional studies had lower sensitivity); missing drinks between meals (sensitivity 1.00 (95% CI 0.59 to 1.00), specificity 0.77 (95% CI 0.64 to 0.86), in one study with 71 participants) and BIA resistance at 50 kHz (sensitivities 1.00 (95% CI 0.48 to 1.00) and 0.71 (95% CI 0.44 to 0.90) and specificities of 1.00 (95% CI 0.69 to 1.00) and 0.80 (95% CI 0.28 to 0.99) in 15 and 22 people respectively for two studies, but with sensitivities of 0.54 (95% CI 0.25 to 0.81) and 0.69 (95% CI 0.56 to 0.79) and specificities of 0.50 (95% CI 0.16 to 0.84) and 0.19 (95% CI 0.17 to 0.21) in 21 and 1947 people respectively in two other studies). In post‐hoc ROC plots drinks intake, urine osmolality and axillial moisture also showed limited diagnostic accuracy. No test was consistently useful in more than one study.
Combining two tests so that an individual both missed some drinks between meals and expressed fatigue was sensitive at 0.71 (95% CI 0.29 to 0.96) and specific at 0.92 (95% CI 0.83 to 0.97).
There was sufficient evidence to suggest that several stand‐alone tests often used to assess dehydration in older people (including fluid intake, urine specific gravity, urine colour, urine volume, heart rate, dry mouth, feeling thirsty and BIA assessment of intracellular water or extracellular water) are not useful, and should not be relied on individually as ways of assessing presence or absence of dehydration in older people.
No tests were found consistently useful in diagnosing current water‐loss dehydration.
Authors' conclusions
There is limited evidence of the diagnostic utility of any individual clinical symptom, sign or test or combination of tests to indicate water‐loss dehydration in older people. Individual tests should not be used in this population to indicate dehydration; they miss a high proportion of people with dehydration, and wrongly label those who are adequately hydrated.
Promising tests identified by this review need to be further assessed, as do new methods in development. Combining several tests may improve diagnostic accuracy.
Summary
Background
Nearly 10% of all cases of cutaneous melanoma (CM) occur in patients with a personal or family history of the disease.
Objectives
To obtain information about genetic predisposition ...to CM in Ticino, the southern region of Switzerland, a zone with moderate‐to‐high CM incidence.
Methods
We identified germline mutations in highly CM‐associated genes (CDKN2A and CDK4) and low/medium‐penetrance variants (MC1R and MITF) in patients with multiple primary CMs or individuals with one or more CM and a positive family history for CM or pancreatic cancer among first‐ or second‐degree relatives. Healthy blood donors (n = 146) were included as a control group.
Results
From July 2010 to July 2012, 57 patients (41 pedigrees) were included. Twenty‐six were melanoma‐prone families (with at least two cases) and 15 had multiple CMs. Pancreatic cancer was found in six families. The CDKN2A mutation p.V126D was identified in seven patients (four families) with a founder effect, whereas CDKN2A A148T was detected in seven cases (five families) and seven healthy donors (odds ratio 2·76, 95% confidence interval 0·83–9·20). At least one MC1R melanoma‐associated polymorphism was detected in 32 patients (78%) and 97 healthy donors (66%), with more than one polymorphism in 12 patients (29%) and 25 healthy donors (17%). The MITF variant p.E318K was identified in four patients from three additional pedigrees (7%) and one healthy control (0·7%).
Conclusions
Inclusion criteria for the Ticino population for genetic assessment should follow the rule of two (two affected individuals in a family or a patient with multiple CMs), as we detected a CDKN2A mutation in almost 10% of our pedigrees (four of 41), MITF p.E318K in 7% (three of 41) and a higher number of MC1R variants than in the control population.
What's already known about this topic?
CDKN2A as a high‐penetrance risk factor and MITF and MCR1, with low‐to‐intermediate penetrance, are the most important genes involved in melanoma susceptibility.
Mutation detection rates in these genes are highly variable across regions.
CDKN2A mutation detection increases with the number of melanomas, young age at diagnosis and concomitant pancreatic cancer in the family.
What does this study add?
The genetic predisposition to melanoma in southern Switzerland is analysed for the first time.
A CDKN2A high‐risk mutation is detected in almost 10% of pedigrees and MITF p.E318K mutation in 7%.
It is difficult to establish a rule for recommending genetic testing based on only the number of melanomas in the family or the individual.
The stressful work environment of ICUs can lead to burnout. Burnout can impact on the welfare and performance of caregivers, and may lead them to resign their job. The shortage of ICU caregivers is ...becoming a real threat for health care leaders.
To investigate the factors associated with burnout on a national level in order to determine potential important factors.
Prospective, multicenter, observational survey of all caregivers from 74 of the 92 Swiss ICUs, measuring the prevalence of burnout among the caregivers and the pre-specified center-, patient- and caregiver-related factors influencing its prevalence.
Out of the 4322 questionnaires distributed from March 2006 to April 2007, 3052 (71%) were returned, with a response rate of 72% by center, 69% from nurse-assistants, 73% from nurses and 69% from physicians. A high proportion of female nurses among the team was associated with a decreased individual risk of high burnout (OR 0.98, 95% CI:0.97-0.99 for every %). The caregiver-related factors associated with a high risk of burnout were being a nurse-assistant, being a male, having no children and being under 40 years old.
The findings of this study seem to open a new frontier concerning burnout in ICUs, highlighting the importance of team composition. Our results should be confirmed in a prospective multicenter, multinational study. Whether our results can be exported to other medical settings where team-working is pivotal remains to be investigated.
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