Number of drugs most frequently found to be independent risk factors for serious adverse reactions: a systematic literature review.

In order to reduce the numbers of medication errors (MEs) that cause adverse reactions (ARs) many authors have tried to identify patient-related risk factors. However, the evidence remains controversial. The aim was to review systematically the evidence on the relationship between patient-related risk factors and the risk of serious ARs. A systematic search in Pubmed, Embase, Cochrane Systematic Reviews, Psychinfo and SweMed+ was performed. Included full text articles were hand searched for further references. Peer reviewed papers including adults from primary and secondary healthcare were included if they clearly defined seriousness of the ARs and described correlations to risk factors by statistical analysis. A total of 28 studies were identified including 85,212 patients with 3385 serious ARs, resulting in an overall frequency of serious ARs in 4% of patients. Age, gender and number of drugs were by far the most frequently investigated risk factors. The total number of drugs was the most consistent correlated risk factor found in both univariate and multivariate analyses. The number of drugs is the most frequently documented independent patient-related risk factor for serious ARs in both the general adult population as well as in the elderly. The existing evidence is however conflicting due to heterogeneity of populations and study methods. The knowledge of patient-related risk factors for experiencing ARs could be used for electronic risk stratification of patients and thereby allocation of healthcare resources to high risk patients.

Identifying high-risk medication: a systematic literature review.

PURPOSE: A medication error (ME) is an error that causes damage or poses a threat of harm to a patient. Several studies have shown that only a minority of MEs actually causes harm, and this might explain why medication reviews at hospital admission reduce the number of MEs without showing an effect on length of hospital stay, readmissions, or death. The purpose of this study was to define drugs that actually cause serious MEs. We conducted a literature search of medication reviews and other preventive efforts. METHODS: A systematic search in PubMed, Embase, Cochrane Reviews, Psycinfo, and SweMed+ was performed. Danish databases containing published patient complaints, patient compensation, and reported medication errors were also searched. Articles and case reports were included if they contained information of an ME causing a serious adverse reaction (AR) in a patient. Information concerning AR seriousness, causality, and preventability was required for inclusion. RESULTS: This systematic literature review revealed that 47 % of all serious MEs were caused by seven drugs or drug classes: methotrexate, warfarin, nonsteroidal anti-inflammatory drugs (NSAIDS), digoxin, opioids, acetylic salicylic acid, and beta-blockers; 30 drugs or drug classes caused 82 % of all serious MEs. The top ten drugs involved in fatal events accounted for 73 % of all drugs identified. CONCLUSION: Increasing focus on seven drugs/drug classes can potentially reduce hospitalizations, extended hospitalizations, disability, life-threatening conditions, and death by almost 50 %.

Toxic use of baclofen causing cramps during tapering.

The spasmolytic agent baclofen is regarded as having a low dependence potential. This is a case report of a 46-year-old woman with an escalating use of baclofen to four times the highest recommended dose. She was initially admitted to hospital due to decreased consciousness. Later, during tapering, she was readmitted unresponsive with myoclonus. Baclofen was discontinued abruptly during sedation with propofol and remifentanil infusion as well as midazolam in refract doses. Eight days later she was discharged without sequelae.

Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial.

BACKGROUND: The trans-membrane protease serine 2 (TMPRSS2) is essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cell entry and infection. Efficacy and safety of TMPRSS2 inhibitors in patients with coronavirus disease 2019 (Covid-19) have not been evaluated in randomized trials. METHODS: We conducted an investigator-initiated, double-blind, randomized, placebo-controlled multicenter trial in patients hospitalized with confirmed SARS-CoV-2 infection from April 4, to December 31, 2020. Within 48 h of admission, participants were randomly assigned in a 2:1 ratio to receive the TMPRSS2 inhibitor camostat mesilate 200 mg three times daily for 5 days or placebo. The primary outcome was time to discharge or clinical improvement measured as ≥2 points improvement on a 7-point ordinal scale. Other outcomes included 30-day mortality, safety and change in oropharyngeal viral load. FINDINGS: 137 patients were assigned to receive camostat mesilate and 68 to placebo. Median time to clinical improvement was 5 days (interquartile range [IQR], 3 to 7) in the camostat group and 5 days (IQR, 2 to 10) in the placebo group (P = 0·31). The hazard ratio for 30-day mortality in the camostat compared with the placebo group was 0·82 (95% confidence interval [CI], 0·24 to 2·79; P = 0·75). The frequency of adverse events was similar in the two groups. Median change in viral load from baseline to day 5 in the camostat group was -0·22 log10 copies/mL (p <0·05) and -0·82 log10 in the placebo group (P <0·05). INTERPRETATION: Under this protocol, camostat mesilate treatment was not associated with increased adverse events during hospitalization for Covid-19 and did not affect time to clinical improvement, progression to ICU admission or mortality. ClinicalTrials.gov Identifier: NCT04321096. EudraCT Number: 2020-001200-42.

Heart insufficiency after combination of verapamil and metoprolol: A fatal case report and literature review.

The combination of verapamil or diltiazem with beta-blockers should be avoided because of potentially profound adverse effects on AV (atrioventricular) nodal conduction, heart rate, or cardiac contractility. This effect is unpredictable but may be enhanced due to CYP2D6 poor metabolizer status which could be a special vulnerability factor.

Levothyroxine Poisoning - Symptoms and Clinical Outcome.

Levothyroxine (LT), T4, poisoning is rarely associated with a severe outcome. However, cases with significant complications have been reported. The aim of this study was to identify factors associated with symptoms of poisoning including late-onset symptoms. All enquiries to the Danish Poison Information Centre (DPIC) concerning LT poisoning between March 2007 and September 2012 were reviewed and the following parameters were recorded: age, dose, time from ingestion, multiple drug intake and symptoms. To evaluate the frequency of late-onset symptoms, a subgroup of patients without initial symptoms were contacted. A total of 181 patients were registered (112 children). Ingested LT dose ranged from 10 to 9000 mcg (median 275 mcg). A total of 29 of 181 (16%) patients were symptomatic at the time of enquiry, and there was no difference in ingested LT dose between asymptomatic and symptomatic patients, neither in children nor in adults (age 16-92 years) (p < 0.68 and p < 0.47, respectively). In total, 153 of 181 (85%) patients did not have symptoms of poisoning at the time of enquiry; however, in 9 of 21 (43%) patients, we were able to contact, late-onset symptoms existed. In none of the cases, hospital contact was needed and there were no reports of long-term sequelae. Acute LT poisoning often follows a benign course. The occurrence of symptoms appears not to be dose dependent. Late-onset symptoms seem to be common. However, all symptoms resolved spontaneously without need of medical care.

A randomized, open, parallel group, multicenter trial to investigate analgesic efficacy and safety of a new transdermal fentanyl patch compared to standard opioid treatment in cancer pain.

A new 72-hour transdermal fentanyl matrix patch has been designed, which has a 35%-50% reduction of the absolute fentanyl content compared with other currently available transdermal fentanyl patches that are using the matrix technology. The new patch has previously been shown to be pharmacokinetically bioequivalent to the marketed fentanyl patch. To determine noninferiority in efficacy in cancer patients and to compare safety, a clinical trial comparing the new fentanyl patch with standard oral or transdermal opioid treatment was planned. The design was an open, parallel group, multicenter trial, in which 220 patients were randomized to receive either the fentanyl patch or standard opioid treatment for 30 days. The primary efficacy variable, pain intensity (PI) on a 0-10-point numerical rating scale, was recorded once daily. The primary endpoint was the relative area under the curve of PI expressed as a percentage of the maximum possible PI area under the curve. Any adverse events were recorded; four tolerability endpoints, constipation, nausea, daytime drowsiness, and sleeping disturbances, were assessed daily. Noninferiority was shown; the upper 95% confidence interval limits of the mean difference in relative PI area under the curve between the fentanyl patch and standard opioid treatment were less than 10% for both the intention-to-treat and per-protocol populations. Scores for the tolerability endpoints were similar in the treatment groups. The new fentanyl matrix patch with a lower drug load was found noninferior and as safe as established standard oral and transdermal opioid treatment.