Physician-led in-hospital multidisciplinary team conferences with multiple medical specialities present - A scoping review.

Introduction: Multidisciplinary Team Conferences (MDTs) are complex interventions in the modern healthcare system and they promote a model of coordinated patient care and management. However, MDTs within chronic diseases are poorly defined. Therefore, the aim of this scoping review was to summarise the current literature on physician-led in-hospital MDTs in chronic non-malignant diseases. Method: Following the PRISMA-ScR guideline for scoping reviews, a search on MDT interventions in adult patients, with three or more medical specialties represented, was performed. Results: We identified 2790 studies, from which 8 studies were included. The majority of studies were non-randomised and focused on a single disease entity such as infective endocarditis, atrial fibrillation, IgG4-related disease, or arterial and venous thrombosis. The main reason for referral was confirmation or establishment of a diagnosis, and the MDT members were primarily from medical specialties gathered especially for the MDT. Outcomes of the included studies were grouped into process indicators and outcome indicators. Process indicators included changes in diagnostic confirmation as well as therapeutic strategy and management. All studies reporting process indicators demonstrated significant changes before and after the MDT. Conclusion: MDTs within chronic diseases appeared highly heterogeneous with respect to structure, reasons for referral, and choice of outcomes. While process indicators, such as change in diagnosis, and treatment management/plan seem improved, such have not been demonstrated through outcome indicators.

Postponement of Death by Pharmacological Heart Failure Treatment: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Outcome postponement has been proposed as an effect measure for preventive drug treatment. It describes the average delay of the investigated unwanted clinical event, achieved by taking medication. The objective was to estimate postponement of death for the following heart failure medications compared to placebo: beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), ARB added to ACE inhibitors, aldosterone antagonists, ivabradine, and renin antagonists. METHODS: We searched Medline and Embase from inception of databases until October 2017. Eligibility criteria were randomized placebo-controlled heart failure trials, including at least 1000 participants, with survival as a prespecified outcome and a minimum trial duration of 1 year. We calculated the outcome postponement by modeling the area between survival curves. This area was modeled on the basis of the hazard ratio or relative risk, the rate of mortality in the placebo group, and the trial duration. All results were standardized to a 3-year trial duration to ensure comparability between treatments. RESULTS: We identified 14 eligible trials, with a total of 52,014 patients. The results in terms of postponement of all-cause mortality was: beta-blockers 43.7 days (95% confidence interval [95% CI], 20.8-66.5), ACE inhibitors 41.0 days (95% CI, 18.8-63.3), and aldosterone-antagonists 41.3 days (95% CI, 14.3,68.4). CONCLUSION: The modeled outcome postponement estimates reiterate beta-blockers, ACE inhibitors, and aldosterone antagonists as the mainstay of heart failure treatment. Furthermore, ivabradine or ARBs added to ACE inhibitors results in no statistically significant gain in survival.

Exposure to phthalate-containing prescription drugs and the risk of colorectal adenocarcinoma: A Danish nationwide case-control study.

PURPOSE: Some drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas. METHODS: We used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression. RESULTS: Cumulative exposure to ortho-phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (ORadj  = 0.89; 95% CI, 0.81-0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho-phthalate exposure was positively associated with colorectal cancer (ORadj  = 1.26; 95% CI, 1.05-1.51). CONCLUSION: We found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho-phthalate exposure.

Cumulative exposure to phthalates from phthalate-containing drug products: a Danish population-wide study.

AIMS: Up to 50-fold higher levels of urinary phthalate metabolites have been observed in users of phthalate-containing drug products compared with non-users. This is of concern, as phthalates are suspected endocrine disrupters and have been associated with cancer development. This study aims to quantify annual cumulated phthalate exposure from drug products among users of phthalate-containing oral medications in Denmark throughout the period of 2004-2016. METHODS: We conducted a Danish nationwide cohort study using The Danish National Prescription Registry and an internal database held by The Danish Medicines Agency. These databases hold information on drug products; date of dispensing, and the type and quantity of excipients in drugs with Danish marketing permission. We present the number of users over time and their distribution of exposure to enteric phthalate polymers and ortho-phthalates. RESULTS: The annual number of individuals exposed to phthalate-containing products declined during 2004-2016. The total number of individuals exposed to dibutyl phthalate declined from 21 499 in 2004 to 5400 in 2016. However, among those exposed, the median dibutyl phthalate exposure remained above European regulatory limit of exposure ranging between 380-1710 mg/year throughout the study period. Lithium-products constituted the majority of dibutyl phthalate exposure. Diethyl phthalate exposure, mainly caused by erythromycin, theophylline and diclofenac products, did not exceed the EMA regulatory limit. CONCLUSION: While the number of individuals exposed to phthalates from oral medications during 2004-2016 declined, the use of phthalate-containing drugs is still considerable.

Population Exposure to Phthalate-containing Drugs.

Phthalates are known endocrine disruptors. Not commonly recognized, phthalates are used as excipients in a number of drug formulations. We aimed to describe the sale of phthalate-containing drugs in Denmark from 2004 to 2015. National data on annual sale of medications (tablets only) were accessed from medstat.dk. Data from the Danish Medicines Agency on phthalate content per tablet were merged with data on total sale for each active substance and drug formulation. We used the 'defined daily dose' (DDD) as the unit of sale and calculated the total amount of phthalate (mg) dispensed per 1000 inhabitants. Specific tablet content was compared with the maximum daily exposure limits defined by regulatory agencies for diethyl phthalate (DEP) and dibutyl phthalate (DBP) of 4.0 and 0.01 mg/kg/day, respectively. Use of phthalate-containing drugs in Denmark was common. We found 154 drug products containing five different phthalates. Two low-molecular-weight phthalates and three high-molecular-weight phthalates were identified, with a total sale of 59.4 and 112 DDD per 1000 inhabitants per day during the study period, respectively. The highest amount of DBP was found in multi-enzymes (24.6-32.8 mg per DDD) and mesalazine (12.5-26.4 mg per DDD). Budesonide, lithium and bisacodyl also exceeded the DBP exposure limit of 0.01 mg/kg/day. Other drugs had high levels of DEP, although not exceeding the exposure limit. Sales of phthalate-containing drugs in Denmark from 2004 to 2015 were substantial, and phthalate exposure from several products exceeded the regulatory exposure limit introduced in 2014.

Perception of drug teratogenicity among general practitioners and specialists in obstetrics/gynecology: a regional and national questionnaire-based survey.

BACKGROUND: Estimating the true risk of fetal malformations attributable to the use of medications is difficult and perception of risk by health professionals will impact their counseling and treatment of patients who need medication during pregnancy. The objective of this study was to assess the perception of the teratogenic risk of 9 commonly and 3 rarely prescribed drugs among general practitioners and specialists in obstetrics/gynecology. METHODS: All 811 general practitioners in the Region of Southern Denmark and all 502 specialist obstetricians/gynecologists in Denmark as a whole were invited to participate in the study based on an online questionnaire. Medians and interpercentile ranges of the perceived background risk and perceived risks for each of the drugs were included in the questionnaire. RESULTS: One hundred forty three (18 %) general practitioners and 138 (27 %) obstetricians/gynecologists participated. Estimates provided by the participants were generally in accordance with current knowledge of drugs with established safety during pregnancy. Perceptions of risks associated with warfarin and retinoid exposure were severely underestimated. CONCLUSIONS: Understanding of teratogenic background risk and specific risks associated with in utero exposure to 12 different drugs generally approached the established knowledge. The risk associated with warfarin and retinoid exposure was severely underestimated by both groups of health care professionals, while general practitioners specifically overestimated the risk of sertraline and citalopram to some extent. In Denmark, general practitioners can prescribe antidepressants, and even minor misconceptions of the teratogenic potential of citalopram and sertraline may be of clinical relevance. In Denmark, systemic retinoids can only be prescribed by a dermatologist, and warfarin treatment is only rarely initiated in women of the fertile age without involvement of specialists in internal medicine. Hence, the active knowledge on the teratogenic potential of these drugs is likely to be less accurate among general practitioners and obstetricians/gynecologists; although still of clinical importance since these specialists are largely involved in the counselling of pregnant women.

Long-term use of lithium and risk of colorectal adenocarcinoma: a nationwide case-control study.

BACKGROUND: Lithium accumulates in the colon and inhibits the enzyme GSK-3ß that possesses anti-carcinogenic effects. We therefore examined the association between lithium use and colorectal cancer risk in a nationwide study. METHODS: We used the Danish Cancer Registry to identify all patients diagnosed with incident colorectal adenocarcinoma during 2000-2012 (n=36 248). Using a matched case-control approach, we estimated the association between long-term use (⩾5 years) of lithium and risk of colorectal adenocarcinoma using conditional logistic regression. RESULTS: Long-term use of lithium was similar among cases (0.22%) and controls (0.20%), yielding an odds ratio of 1.13 (95% confidence interval (CI), 0.89-1.43) for colorectal adenocarcinoma. Dose-response, subgroup and other subanalyses returned neutral associations. However, ORs differed for colorectal subsites (proximal colon: 1.01 (95% CI, 0.66-1.55; distal colon: 1.52 (95% CI, 1.05-2.20); and rectum: 0.80 (95% CI, 0.50-1.30). CONCLUSIONS: Lithium use was not associated with an overall increased risk of colorectal adenocarcinoma. The variation by subsite warrants further investigation.

First-Trimester Pregnancy Exposure to Venlafaxine or Duloxetine and Risk of Major Congenital Malformations: A Systematic Review.

Major depressive disorder is common among women in child-bearing age, and medical treatment is subject to substantial discussions and controversies. For Selective Serotonin reuptake inhibitors, SSRIs, a vast amount of data are available. For the newer antidepressant group of serotonin and noradrenaline reuptake inhibitors, SNRIs, significantly less data are available. Following the PRISMA guideline for systematic reviews, we performed a systematic search on the risk of major congenital malformations after first trimester in utero exposure to venlafaxine or duloxetine. We identified eight cohort studies reporting on the outcome upon in utero exposure to venlafaxine or duloxetine during the first trimester. The cumulated data for venlafaxine were 3186 exposed infants and 107 major malformations, resulting in a relative risk estimate and 95% confidence interval of 1.12 (0.92-1.35). The corresponding data for duloxetine were 668 infants and 16 major malformations, resulting in a relative risk estimate and 95% confidence interval of 0.80 (0.46-1.29). First-trimester in utero exposure to venlafaxine is not associated with an increased risk of major congenital malformations. The amount of data for duloxetine are significantly smaller but does not suggest a clinically important increased risk.

Acetaminophen for Chronic Pain: A Systematic Review on Efficacy.

Acetaminophen (paracetamol) is the most commonly used analgesic worldwide and recommended as first-line treatment in all pain conditions by WHO. We performed a systematic literature review to evaluate the efficacy of acetaminophen when used for chronic pain conditions. Applying three broad search strategies for acetaminophen use in chronic pain in both Embase and PubMed, 1551 hits were obtained. After cross-reference searches of both trials and 38 reviews, seven studies comparing acetaminophen in continuous dosing regimens of more than 2 weeks with placebo were included. The review was conducted according to the PRISMA guidelines. All studies were conducted in patients with hip- or knee osteoarthritis and six of seven studies had observation periods of less than 3 months. All included studies showed no or little efficacy with dubious clinical relevance. In conclusion, there is little evidence to support the efficacy of acetaminophen treatment in patients with chronic pain conditions. Assessment of continuous efficacy in the many patients using acetaminophen worldwide is recommended.

Pregnancy exposure to olanzapine, quetiapine, risperidone, aripiprazole and risk of congenital malformations. A systematic review.

To review available data on first-trimester exposure to olanzapine, quetiapine, risperidone and aripiprazole and risk of congenital malformations. We performed a systematic literature search in accordance with PRISMA guidelines identifying studies containing original data on first-trimester exposure and pregnancy outcome with respect to congenital malformations. Cumulated data for olanzapine were 1090 first-trimester-exposed pregnancies with 38 malformations resulting in a malformation rate of 3.5%. The corresponding numbers for quetiapine, risperidone and aripiprazole were 443/16 (3.6%), 432/22 (5.1%) and 100/5 (5.0%), respectively. Relative risk estimates and 95% confidence intervals were 1.0 (0.7-1.4) (olanzapine), 1.0 (0.6-1.7) (quetiapine), 1.5 (0.9-2.2) (risperidone) and 1.4 (0.5-3.1) (aripiprazole). First-trimester exposure to olanzapine is not associated with an increased risk of congenital malformation. Data for quetiapine and risperidone do not suggest a substantially increased risk, while the risk estimate for aripiprazole remains imprecise owing to a low amount of data.