Prevalence of untreated and uncontrolled cardiovascular risk factors in survivors of allogeneic cell transplantation.

Cardiovascular risk factors (CVRF) are frequent among long-term survivors after allogeneic hematopoietic cell transplantation (HCT) but prospective data on CVRF are sparse. We conducted a cross-sectional single center study including patients who underwent a first HCT mostly for hematologic malignancies at our center between 2000 and 2016, surviving at least 1 year. 260 patients (median age 54 years [range 19-78], 40% female) who were median 6 years (range 1-16) after transplantation were included. Most patients (232, 89%) had peripheral blood stem cell transplantation. cGVHD was present in 41% at the time of study inclusion. Prevalence of hypertension, dyslipidemia, and diabetes was 58%, 63% and 9%, respectively. Untreated hypertension, dyslipidemia and diabetes was found in 15%, 35% and 2%. Among patients with treated hypertension, 38% did not have blood pressure controlled to levels ≤140/90 mmHg. 36% patients under lipid-lowering therapy did not reach their LDL target. Multivariable logistic regression analyses showed that age and diabetes increased the likelihood for hypertension and dyslipidemia, whereas body mass index, cGVHD and male sex predicted hypertension only. In summary, CVRF in long-term survivors are frequent and persisting after cessation of immunosuppression. A large proportion of CVRF are either untreated or uncontrolled.

Acute calcineurin inhibitor overdose: analysis of cases reported to a national poison center between 1995 and 2011.

Transplant recipients and other patients requiring immunosuppression with calcineurin inhibitors or their household contacts may be exposed to overdose. This study investigated the circumstances, pharmacokinetics and outcomes of overdose with cyclosporine and tacrolimus reported to the Swiss Toxicological Information Centre between 1995 and 2011. Of 145,396 reports by healthcare professionals, 28 (0.02%) concerned enteral or parenteral overdose with these calcineurin inhibitors. Thirteen (46%) were iatrogenic errors, 12 (43%) were with suicidal intent and 3 (11%) were accidental. Iatrogenic overdoses usually involved noncapsule drug formulations. Acute enteral overdoses caused symptoms in a dose-dependent fashion but were generally well tolerated; the mean multiple of patient's usual dose was 20.8 ± 28.8 for symptomatic versus 4.4 ± 3.4 for asymptomatic cases (p = 0.037). The most common symptoms were nausea, headache, somnolence, confusion, hypertension and renal impairment. In contrast, acute intravenous overdoses were often poorly tolerated and resulted in one fatality due to cerebral edema after a cyclosporine overdose. Enteral decontamination measures were performed in six cases involving oral ingestion and appeared to reduce drug absorption, as shown by pharmacokinetic calculations. In the one case where it was used, pharmacoenhancement appeared to accelerate tacrolimus clearance after intravenous overdose.

Clinical usefulness of electronic drug-drug interaction checking in the care of cardiovascular surgery inpatients.

OBJECTIVES: Drug-related problems (DRPs) are events or circumstances involving drug therapy that actually or potentially interfere with desired health outcomes. This study tested the applicability of clinical decision support software in identifying and managing DRPs among cardiovascular surgery inpatients. METHODS: Two clinical pharmacologists attended ward rounds on a low-dependency cardiovascular surgery ward every 2 weeks over a 7-month period. Three hundred and three patients were assessed. On average, patients received 17 scheduled and 'as required' medicines. DRPs were identified 'manually' via assessment of electronic prescription charts and patient records and 'electronically' using clinical decision support software (Pharmavista). The numbers of alerts for optimizing medication safety generated by the two methods were compared. RESULTS: Manual checking identified 346 DRPs leading to 346 alerts in 201 patients (overall 1.1 alerts/patient). Relevant interactions accounted for 44% of DRPs detected by clinical pharmacologists. Clinical decision support software, which could only report interactions, however, generated 1,370 alerts (average 4.5 alerts/patient). Only 147 (11%) drug-drug interaction alerts were identical to those identified by manual checking; the remaining 89% were considered not clinically relevant. CONCLUSIONS: Compared to identification of DRPs by clinical pharmacologists, the clinical decision support software performed poorly due to over-alerting and inability to assess for problems not caused by drug-drug interactions.

[Clinically important food-drug interactions: what the practitioner needs to know]. / Alle Medikamente zum Frühstück?--Einfluss der Nahrung auf die Medikamentenwirkung.

Most medicines are taken with breakfast which is usually unproblematic and has the advantage of improving adherence through establishment of a daily routine. However, due to alterations in absorption from the gastrointestinal tract, there are a number of medicines that either lose (such as bisphosphonates) or gain (such as albendazole) efficacy if taken together with food. Food components can also affect drug-metabolising enzymes and even cause drug toxicity (alcohol and grapefruit juice are notable examples). Conversely, drugs such as monoamine oxidase inhibitors can inhibit the metabolism of tyramine in tyramine-rich foods and lead to adverse circulatory reactions. These and other examples of when the ingestion of medication together with food can cause clinically relevant problems are discussed in this article.

Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in the diagnosis of heart failure.

OBJECTIVES: The concentration of atrial natriuretic peptide (ANP) in the circulation is approximately 10- to 50- fold higher than B-type natriuretic peptide (BNP). We sought to compare the accuracy of midregional pro-atrial natriuretic peptide (MRproANP) measured with a novel sandwich immunoassay with N-terminal pro-B-type natriuretic peptide (NTproBNP) in the diagnosis of heart failure. DESIGN: The diagnosis of heart failure was adjudicated by two independent cardiologists using all available clinical data (including BNP levels) in 287 consecutive patients presenting with dyspnoea to the emergency department (ED). MRproANP and NTproBNP levels were determined at presentation in a blinded fashion. RESULTS: Heart failure was the adjudicated final diagnosis in 154 patients (54%). Median MRproANP was significantly higher in patients with heart failure as compared to patients with other causes of dyspnoea (400 vs. 92 pmol L(-1), P < 0.001). The diagnostic accuracy of MRproANP was very high with an area under the receiver operating characteristic curve of 0.92 and was comparable with that of NTproBNP (0.92, P = 0.791). Moreover, MRproANP provided incremental diagnostic information to BNP and NTproBNP in patients presenting with BNP levels in the grey zone between 100 and 500 pg mL(-1). CONCLUSION: Midregional pro-atrial natriuretic peptide is as accurate in the diagnosis of heart failure as NTproBNP. MRproANP seems to provide incremental information on top of BNP or NT-proBNP in some subgroups and should be further investigated in other studies.

["Real-life"-data on asthma control using budesonide/formoterol for both maintenance and relief: the Swiss experience]. / "Real-life"-Daten zur Asthmakontrolle mit Budesonid/Formoterol als Erhaltungs- und Bedarfstherapie: die Erfahrung in der Schweiz.

BACKGROUND: Asthma is not adequately controlled in many patients. A new approach in asthma treatment, known as Budesonide/Formoterol Maintenance and Reliever Therapy has shown improvement in asthma control compared to conventional therapy regimens. As Switzerland was the first European country to formally approve budesonide/formoterol maintenance and reliever therapy, a patient follow-up programme was commenced in January 2006 to investigate its efficacy and safety in a "real-life" environment. METHODS: A non randomized uncontrolled post-marketing survey involving 420 physicians in all language regions in Switzerland was carried out. 2035 patients with asthma were enrolled. Data on current asthma treatment, asthma control and unscheduled visits due to worsening asthma were recorded. Asthma control was assessed subjectively by both the patients and the physicians as well as by means of the validated 5-item Asthma Control Questionnaire (ACQ5). An ACQ score of 0.75 or less indicates well-controlled asthma. RESULTS: Data from 2006 out of 2035 patients were analysed (mean age 44.9 +/- 19.6 years, 50.5% female). With budesonide/formoterol maintenance and reliever therapy the mean ACQ5 score improved by more than 3-fold the defined minimal important difference (MID). The percentage of patients with an ACQ score < or =0.75 increased from 4.8% at baseline to 58.0% at the end of the follow-up programme. Patient satisfaction with budesonide/formoterol for both maintenance and relief was high. CONCLUSIONS: Budesonide/formoterol maintenance and reliever therapy improves asthma control in a non randomised real-life setting.

Single-nucleotide polymorphisms in the SPARC gene are not associated with susceptibility to scleroderma.

OBJECTIVE: SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that modulates cell-cell and cell-extracellular matrix interactions. SPARC expression is restricted mainly to sites of tissue remodelling and wound repair, and is prominent in fibrotic disorders. Single-nucleotide polymorphisms (SNPs) in the SPARC gene are reportedly linked to scleroderma in four ethnic groups: Choctaw Indians, Caucasians, African Americans and Mexican Americans. We set out to reproduce and to positionally clone these disease associations in a set of UK Caucasian scleroderma patients and ethnically matched controls. METHODS: One hundred and twenty-one scleroderma subjects and 200 controls were genotyped by polymerase chain reaction with sequence-specific primers differing only in the 3' nucleotide corresponding to each allele of the biallelic SNPs. Scleroderma patients were analysed against controls and on the basis of their fibrosing alveolitis status as judged by high-resolution computed tomography evaluation and the extent of cutaneous involvement. RESULTS: Eight biallelic SNPs were genotyped: three from the last untranslated exon, which had been described previously, and an additional five novel SNPs: two in the promoter region, one in exon three and two in the 3' untranslated region. Six major haplotypes were constructed across all eight SNP positions. No significant differences in genotype, allele or haplotype frequency were observed between scleroderma and controls or within scleroderma subgroups. CONCLUSIONS: SNPs in the SPARC gene are not associated with susceptibility to scleroderma. This research adds to the genetic knowledge of the SPARC gene by identifying five novel SNPs spanning the whole gene and inserting these within the context of clearly defined haplotypes.