Background: Medication-related problems that lead to hospitalization have been the subject of many studies, many of which were limited to 1 hospital or lacked patient follow-up. Furthermore, little information exists on potential risk factors associated with preventable medication-related hospitalizations. Methods: A prospective multicenter study was conducted to determine the frequency and patient outcomes of medication-related hospital admissions. A case-control design was used to determine risk factors for potentially preventable admissions. All unplanned admissions in 21 hospitals were assessed during 40 days. Controls were patients admitted for elective surgery. Cases and controls were followed up until hospital discharge. The frequency of medication-related hospital admissions, potential preventability, and outcomes were assessed. For potentially preventable medication-related admissions, risk factors were identified in the case-control study. Results: Almost 13 000 unplanned admissions were screened, of which 714 (5.6%) were medication related. Almost half (46.5%) of these admissions were potentially preventable, resulting in 332 case patients matched with 332 controls. Outcomes were favorable in most patients. The main determinants of preventable medication-related hospital admissions were impaired cognition (odds ratio, 11.9; 95% confidence interval, 3.9-36.3), 4 or more comorbidities (8.1; 3.1-21.7), dependent living situation (3.0; 1.4-6.5), impaired renal function (2.6; 1.6-4.2), nonadherence to medication regimen (2.3; 1.4-3.8), and polypharmacy (2.7; 1.6-4.4). Conclusions: Adverse drug events are an important cause of hospitalizations, and almost half are potentially preventable. The identified risk factors provide a starting point for preventing medication-related hospital admissions.

https://jamanetwork.com/journals/jamainternalmedicine/articlepdf/414486/ioi80085_1890_1896.pdf

Frequency of and Risk Factors for Preventable Medication-Related Hospital Admissions in the Netherlands

Background The level of anticoagulation in response to a fixed-dose regimen of warfarin is difficult to predict during the initiation of therapy. We prospectively compared the effect of genotype-guided dosing with that of standard dosing on anticoagulation control in patients starting warfarin therapy. Methods We conducted a multicenter, randomized, controlled trial involving patients with atrial fibrillation or venous thromboembolism. Genotyping for CYP2C9*2, CYP2C9*3, and VKORC1 (−1639G→A) was performed with the use of a point-of-care test. For patients assigned to the genotype-guided group, warfarin doses were prescribed according to pharmacogenetic-based algorithms for the first 5 days. Patients in the control (standard dosing) group received a 3-day loading-dose regimen. After the initiation period, the treatment of all patients was managed according to routine clinical practice. The primary outcome measure was the percentage of time in the therapeutic range of 2.0 to 3.0 for the international normalized ratio (INR) during the first 12 weeks after warfarin initiation. Results A total of 455 patients were recruited, with 227 randomly assigned to the genotypeguided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001). Conclusions Pharmacogenetic-based dosing was associated with a higher percentage of time in the therapeutic INR range than was standard dosing during the initiation of warfarin therapy. (Funded by the European Commission Seventh Framework Programme and others; ClinicalTrials.gov number, NCT01119300.)

/pdf/a-randomized-trial-of-genotype-guided-dosing-of-warfarin-3ll2j9cerm.pdf

A Randomized Trial of Genotype-Guided Dosing of Warfarin

One of the most effective ways in which regulatory agencies communicate with sponsors and guide drug development is through the issuance of guidances or guidelines. These can be issued domestically in a given region such as the United States by the Food and Drug Administration (FDA) or internationally through the International Conference on Harmonization. Currently, there are over 400 final or draft guidances that can be found through the FDA website. The development of guidances proceeds through a process known as Good Guidance Practices, which is intended to assure that there is an appropriate level of meaningful public participation in the development of guidance. In the past 10 years, clinical pharmacology guidances covering important areas have been issued, including pharmacokinetic data in patients with renal and hepatic impairment, dose-response studies, and drug-drug interactions.

Drug interaction studies: study design, data analysis, and implications for dosing and labeling.

Adverse drug reactions (ADRs) are a major cause of hospital admissions, but recent data on the incidence and clinical characteristics of ADRs which occur following hospital admission, are lacking. Patients admitted to twelve wards over a six-month period in 2005 were assessed for ADRs throughout their admission. Suspected ADRs were recorded and analysed for causality, severity and avoidability and whether they increased the length of stay. Multivariable analysis was undertaken to identify the risk factors for ADRs. The 5% significance level was used when assessing factors for inclusion in multivariable models. Out of the 3695 patient episodes assessed for ADRs, 545 (14.7%, 95% CI 13.6–15.9%) experienced one or more ADRs. Half of ADRs were definitely or possibly avoidable. The patients experiencing ADRs were more likely to be older, female, taking a larger number of medicines, and had a longer length of stay than those without ADRs. However, the only significant predictor of ADRs, from the multivariable analysis of a representative sample of patients, was the number of medicines taken by the patient with each additional medication multiplying the hazard of an ADR episode by 1.14 (95% CI 1.09, 1.20). ADRs directly increased length of stay in 147 (26.8%) patients. The drugs most frequently associated with ADRs were diuretics, opioid analgesics, and anticoagulants. In conclusion, approximately one in seven hospital in-patients experience an ADR, which is a significant cause of morbidity, increasing the length of stay of patients by an average of 0.25 days/patient admission episode. The overall burden of ADRs on hospitals is high, and effective intervention strategies are urgently needed to reduce this burden.

/pdf/adverse-drug-reactions-in-hospital-in-patients-a-prospective-4ycbf6otx0.pdf

Adverse Drug Reactions in Hospital In-Patients: A Prospective Analysis of 3695 Patient-Episodes

Aim: Previous systematic reviews have found that drug-related morbidity accounts for 4.3% of preventable hospital admissions. None, however, has identified the drugs most commonly responsible for preventable hospital admissions. The aims of this study were to estimate the percentage of preventable drug-related hospital admissions, the most common drug causes of preventable hospital admissions and the most common underlying causes of preventable drug-related admissions. Methods: Bibliographic databases and reference lists from eligible articles and study authors were the sources for data. Seventeen prospective observational studies reporting the proportion of preventable drug-related hospital admissions, causative drugs and/or the underlying causes of hospital admissions were selected. Included studies used multiple reviewers and/or explicit criteria to assess causality and preventability of hospital admissions. Two investigators abstracted data from all included studies using a purpose-made data extraction form. Results: From 13 papers the median percentage of preventable drug-related admissions to hospital was 3.7% (range 1.4-15.4). From nine papers the majority (51%) of preventable drug-related admissions involved either antiplatelets (16%), diuretics (16%), nonsteroidal anti-inflammatory drugs (11%) or anticoagulants (8%). From five studies the median proportion of preventable drug-related admissions associated with prescribing problems was 30.6% (range 11.1-41.8), with adherence problems 33.3% (range 20.9-41.7) and with monitoring problems 22.2% (range 0-31.3). Conclusions: Four groups of drugs account for more than 50% of the drug groups associated with preventable drug-related hospital admissions. Concentrating interventions on these drug groups could reduce appreciably the number of preventable drug-related admissions to hospital from primary care.

/pdf/which-drugs-cause-preventable-admissions-to-hospital-a-45s677n2lc.pdf

Which drugs cause preventable admissions to hospital? A systematic review

Objective To ascertain the current burden of adverse drug reactions (ADRs) through a prospective analysis of all admissions to hospital. Design Prospective observational study. Setting Two large general hospitals in Merseyside, England. Participants 18 820 patients aged > 16 years admitted over six months and assessed for cause of admission. Main outcome measures Prevalence of admissions due to an ADR, length of stay, avoidability, and outcome. Results There were 1225 admissions related to an ADR, giving a prevalence of 6.5%, with the ADR directly leading to the admission in 80% of cases. The median bed stay was eight days, accounting for 4% of the hospital bed capacity. The projected annual cost of such admissions to the NHS is £466m (€706m, $847m). The overall fatality was 0.15%. Most reactions were either definitely or possibly avoidable. Drugs most commonly implicated in causing these admissions included low dose aspirin, diuretics, warfarin, and non-steroidal anti-inflammatory drugs other than aspirin, the most common reaction being gastrointestinal bleeding. Conclusion The burden of ADRs on the NHS is high, accounting for considerable morbidity, mortality, and extra costs. Although many of the implicated drugs have proved benefit, measures need to be put into place to reduce the burden of ADRs and thereby further improve the benefit:harm ratio of the drugs.

https://www.bmj.com/content/bmj/329/7456/15.full.pdf

Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients

### What you need to know

A 46 year old ophthalmologist presents with a two week history of loss of sense of smell and taste. He believes he may have been exposed to covid-19 but, at the time, did not meet the criteria for testing. 

With the discovery of covid-19 and as the clinical syndromes associated with this virus have been defined, many areas of practice require updating. This article is a guide to assessment and management of patients with loss of smell based on review of the current literature and guidelines from the British Rhinology Society and ENT UK, the professional membership body representing ear, nose, and throat surgery in the UK.1

Olfactory dysfunction is common: estimates of point prevalence in the general population before the covid-19 pandemic suggest that 19.1% of adults (80% in people over 75) suffer from complete or partial loss of smell.2

Causes can be broadly subdivided into conductive (physical barriers to odorants reaching the olfactory system) and sensorineural (failure of the olfactory system to detect odorants). Causes are outlined in table 1, with the more common causes in the top half of the table and less common causes in the bottom half. A comprehensive history is invaluable, especially if consultations are performed remotely.

View this table:

Table 1 
Causes of loss of smell



Points to …

https://www.bmj.com/content/bmj/370/bmj.m2808.full.pdf

Anosmia and loss of smell in the era of covid-19.

Introduction Malignant bowel obstruction (MBO) is a recognized complication of advanced pelvic or abdominal malignancy frequently occurring in advanced stages of illness. Suggested incidences in ovarian carcinoma range from 5.5 to 42% and in colorectal cancer 4.4 to 24%. Where surgery for MBO is inappropriate medical management may help bring about resolution of the unpleasant symptoms. Aim(s) and method(s) The aim of this review was to evaluate current evidence and opinion on treatment of symptoms associated with MBO. A comprehensive systematic review of the literature was undertaken to evaluate the evidence for the medical management of MBO. A questionnaire-based survey was used to establish professional attitudes, opinions and to review current practice. Results Following exclusions 44 relevant papers were systematically appraised. There is good evidence for the use of octreotide to reduce secretions and corticosteroids may help bring about resolution of MBO. Ranitidine may also reduce secretions. Venting gastrostomies can alleviate nausea and vomiting with low complication rates and may be considered where prognosis is greater than 2 weeks. No evidence was found for any specific medication to treat vomiting or pain associated with MBO. In local current practice hyoscine buytlbromide is used first line to treat colic; cyclizine and/or haloperidol to treat vomiting with levomepromazine second line. Corticosteroids and octreotide are routinely prescribed. In practice consideration for referral for venting gastrostomies is guided by local surgical practice. Conclusion(s) There is a paucity of evidence with regards to medical management of MBO, much more is required. Subsequent to this review, new local guidelines have been developed.

https://spcare.bmj.com/content/bmjspcare/5/1/119.1.full.pdf

A Scott

Papers

Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients

Anosmia and loss of smell in the era of covid-19.

Malignant bowel obstruction—a systematic literature review and evaluation of current practice

ratsmetabolism, and histone acetylation in IUGR Uteroplacental insufficiency alters DNA methylation,