Economic Evaluation of Elective Cesarean Section on Maternal Request Compared With Planned Vaginal Birth-Application to Swedish Setting Using National Registry Data.

Objectives: There is a lack of consensus around the definition of delivery by cesarean section (CS) on maternal request, and clinical practice varies across and within countries. Previous economic evaluations have focused on specific populations and selected complications. Our aim was to evaluate the cost-effectiveness of CS on maternal request compared with planned vaginal birth in a Swedish context, based on a systematic review of benefits and drawbacks and national registry data on costs.

Prevalence and initiation of statin therapy in the oldest old-a longitudinal population-based study.

Purpose: To investigate the prevalence and initiation of statins as well as treatment intensity in the oldest old, with younger olds as a reference.

Methods: A population-based cohort was used, including record-linked data from the Total Population Register, the Swedish Prescribed Drug Register, and the Swedish Patient Register. In each year over the study period (2009-2015), statin use was described in individuals 85 years or older and 65-84 years of age, and initiation rates were calculated among individuals with no statin treatment during a preceding 3-year period.

Use of statins in the elderly according to age and indication-a cross-sectional population-based register study.

Purpose: To investigate statin use in the elderly by age (≥ 80 vs. 65-79 years) in relation to established indications.

Methods: A population-based cohort, including data from four registers, encompassing inhabitants in Region Västra Götaland, Sweden, was used.

Acute Myelogenous Leukemia Cells Secrete Factors that Stimulate Cellular LDL Uptake via Autocrine and Paracrine Mechanisms.

Leukemic cells isolated from most patients with acute myelogenous leukemia (AML) have higher low density lipoprotein (LDL) uptake than normal mononuclear blood cells. Little is known, however, about the mechanism behind the elevated LDL uptake. We investigated if AML cells secrete factors that stimulate cellular LDL uptake.

GRADE equity guidelines 1: considering health equity in GRADE guideline development: introduction and rationale.

Objectives: This article introduces the rationale and methods for explicitly considering health equity in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology for development of clinical, public health, and health system guidelines.

Study Design And Setting: We searched for guideline methodology articles, conceptual articles about health equity, and examples of guidelines that considered health equity explicitly. We held three meetings with GRADE Working Group members and invited comments from the GRADE Working Group listserve.

GRADE equity guidelines 3: considering health equity in GRADE guideline development: rating the certainty of synthesized evidence.

Objectives: The aim of this paper is to describe a conceptual framework for how to consider health equity in the Grading Recommendations Assessment and Development Evidence (GRADE) guideline development process.

Study Design And Setting: Consensus-based guidance developed by the GRADE working group members and other methodologists.

Results: We developed consensus-based guidance to help address health equity when rating the certainty of synthesized evidence (i.

Long-term use of proton pump inhibitors and prevalence of disease- and drug-related reasons for gastroprotection-a cross-sectional population-based study.

Purpose: To analyse the prevalence of long-term use of proton pump inhibitors (PPI) with respect to underlying diseases and drugs, and to find predictors for such treatment when an evident rationale for the PPI treatment is lacking.

Methods: The study cohort consisted of individuals, ≥65 years in 2010, residing in the Region Västra Götaland during 2005-2010. For individuals with and without long-term use of PPI in 2010, we investigated the prevalence of an underlying diagnosis, that is, an acid-related disease during the five preceding years, as well as concomitant long-term use of antiplatelet agents or cyclooxygenase inhibitors.

Biosimilar erythropoiesis-stimulating agents and the risk of developing anti-drug antibodies-a systematic review.

Purpose: We systematically reviewed published observational studies and randomized controlled trials (RCT) reports of clinical trials on erythropoiesis-stimulating agents (ESA's). Only studies evaluating the risk of developing anti-drug antibodies (ADA) of both original and biosimilar drugs were chosen.

Methods: Databases including PubMed, EMBASE and Cochrane Library were searched up to 17 March 2015.

Aromatase inhibitors alone or sequentially combined with tamoxifen in postmenopausal early breast cancer compared with tamoxifen or placebo - Meta-analyses on efficacy and adverse events based on randomized clinical trials.

Tamoxifen (TAM) and aromatase inhibitors (AI) are adjuvant therapy options for postmenopausal women with estrogen receptor positive (ER+) breast cancer. This systematic review of seven randomized controlled studies comparing TAM and AI, and one study comparing extended therapy with an AI with placebo after about 5 years of tamoxifen, aims to assess long-term clinical efficacy and adverse events. The literature review was performed according to the principles of the Cochrane Collaboration.

Pronounced Interindividual But Not Intraindividual Variation in Tamoxifen and Metabolite Levels in Plasma During Adjuvant Treatment of Women With Early Breast Cancer.

Background: Tamoxifen is still an important antihormonal treatment option for patients with breast cancer and estrogen receptor-positive tumors. More than 20% of patients relapse despite treatment. The drug is usually dosed 20 mg/d irrespective of interindividual variation in drug clearance.

Differential role of thiopurine methyltransferase in the cytotoxic effects of 6-mercaptopurine and 6-thioguanine on human leukemia cells.

The thiopurine antimetabolites, 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are inactive pro-drugs that require intracellular metabolism for activation to cytotoxic metabolites. Thiopurine methyltransferase (TPMT) is one of the most important enzymes in this process metabolizing both 6-MP and 6-TG to different methylated metabolites including methylthioinosine monophosphate (meTIMP) and methylthioguanosine monophosphate (meTGMP), respectively, with different suggested pharmacological and cytotoxic properties. While meTIMP is a potent inhibitor of de novo purine synthesis (DNPS) and significantly contributes to the cytotoxic effects of 6-MP, meTGMP, does not add much to the effects of 6-TG, and the cytotoxicity of 6-TG seems to be more dependent on incorporation of thioguanine nucleotides (TGNs) into DNA rather than inhibition of DNPS.

Comparison of uptake mechanisms for anthracyclines in human leukemic cells.

Aims: The mechanisms behind cellular anthracycline uptake are not completely understood. Knowledge about uptake mechanisms could be used to increase the selectivity of the drugs. We compared the uptake patterns of, daunorubicin (DNR), doxorubicin (DOX), epirubicin (EPI), idarubicin (IDA), and pirarubicin (PIRA) by cultured leukemic cells and investigated possible involvement of specific carriers.

The 'wise list'- a comprehensive concept to select, communicate and achieve adherence to recommendations of essential drugs in ambulatory care in Stockholm.

The aim was to present and evaluate the impact of a comprehensive strategy over 10 years to select, communicate and achieve adherence to essential drug recommendations (EDR) in ambulatory care in a metropolitan healthcare region. EDRs were issued and launched as a 'Wise List' by the regional Drug and Therapeutics Committee in Stockholm. This study presents the concept by: (i) documenting the process for selecting, communicating and monitoring the impact of the 'Wise List'; (ii) analysing the variation in the number of drug substances recommended between 2000 and 2010; (iii) assessing the attitudes to the 'Wise List' among prescribers and the public; (iv) evaluating the adherence to recommendations between 2003 and 2009.

Inverse relationship between leukaemic cell burden and plasma concentrations of daunorubicin in patients with acute myeloid leukaemia.

Aims: It has been shown that the cellular uptake and cytotoxicity of anthracyclines decrease with increasing cell density in vitro, an event termed 'the inocculum effect'. It is not known whether such an effect occurs in vivo. In this study the relationships between white blood cell (WBC) count, plasma and cellular concentrations of daunorubicin (DNR) in patients with acute myeloid leukaemia were investigated.

Daunorubicin metabolism in leukemic cells isolated from patients with acute myeloid leukemia.

Background: Anthracyclines like daunorubicin (DNR) are important drugs in the treatment of acute myeloid leukaemia (AML). In vitro studies have shown that cellular metabolism of anthracyclines could play a role in drug resistance. Currently, it is not known what enzyme is responsible for anthracycline metabolism in leukemic cells.

Uptake of anthracyclines in vitro and in vivo in acute myeloid leukemia cells in relation to apoptosis and clinical response.

Aims: To study anthracycline-induced apoptosis in leukemic cells isolated from patients with acute myelogenous leukemia (AML) in vitro and to compare intracellular anthracycline concentrations causing apoptosis in vitro with those obtained in vivo during anthracycline treatment.

Methods: Mononuclear blood cells from AML patients were isolated before (n = 20) and after anthracycline infusion (n = 24). The pre-treated cells were incubated in vitro with daunorubicin (DNR) and/or idarubicin (IDA).

ApoB100-LDL acts as a metabolic signal from liver to peripheral fat causing inhibition of lipolysis in adipocytes.

Background: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown.

Methods And Findings: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells.

Plasma concentrations of lamotrigine and its 2-N-glucuronide metabolite during pregnancy in women with epilepsy.

Objective: To further characterize pregnancy-induced alterations in the pharmacokinetics of lamotrigine (LTG).

Methods: Fifteen women treated with LTG were studied during 17 pregnancies. Complete trough blood samples from all trimesters and baseline > 1 month after delivery were available for 12 pregnancies (Group A), whereas, five contributed with samples only from the third trimester and baseline (Group B).

Pharmacokinetics of gabapentin during delivery, in the neonatal period, and lactation: does a fetal accumulation occur during pregnancy?

Purpose: To study the pharmacokinetics of gabapentin (GBP) during delivery, lactation, and in the neonatal period.

Methods: GBP concentrations in plasma and breast milk were determined with high-performance liquid chromatography in samples from six women treated with GBP and in their offspring. Blood samples were obtained at delivery from mothers, from the umbilical cord, and from the newborns on three occasions during 2 days after delivery.

Cytotoxic effect of a lipophilic alkylating agent after incorporation into low density lipoprotein or emulsions: studies in human leukemic cells.

The use of low density lipoprotein (LDL) as drug carrier in acute myeloblastic leukemia chemotherapy is attractive due to high LDL uptake by leukemic cells. Lipid-based formulations, such as liposomes or microemulsions are promising alternatives. In the current study, we incorporated N-trifluoroacetyl-adriamycin-14-valerate (AD32), a lipophilic derivative of daunorubicin (DNR), and WB4291, a lipophilic alkylating agent, into LDL or lipid microemulsions and evaluated their cytotoxic activities towards leukemic cell lines using as references DNR and melphalan.

[It's possible to influence prescriptions patterns by producer-independent information].

Following the publication of a metaanalysis over effectiveness and tolerability of triptanes for acute treatment of migraine we investigated whether a short oral information by clinical pharmacologists, describing the rationale for prescribing a certain triptane, combined with memory cards could influence the prescription by general practitioners. The primary care units, which had received the information, showed a significantly better adherence to prescription of the recommended triptane than units that had not received such information. The desired influence on prescription was, however, transient and not statistically significant for more than three months following the prescription.