Erik Totté

Contraceptive treatment after biliopancreatic diversion needs consensus.

Background: An important population of patients who undergo biliopancreatic diversion (BPD) are fertile women. A consensus is needed with regard to contraceptive therapy after BPD by evaluating the risks of pregnancy, the safety of oral contraception and the changes in fertility after this bariatric surgery. Method: From May 1997 until May 1998, 40 women who underwent a BPD were included in a prospective study evaluating the hormone status preoperatively and postoperatively after 2 and 7 days, 3 and 6 months and 1 year. An extensive questionnaire, with regard to fertility and obstetric history, was sent at least 2 years after inclusion. A literature search was performed to understand the complex physiology of hormone changes after excess weight loss, as well as absorption and metabolism of oral contraceptives. Results: Our laboratory results are consistent with hormone changes found in the literature, which show that rising levels of serum sex-hormone-binding globulin, follicle stimulating hormone and luteinizing hormone and decreasing levels of testosterone and dehydroepiandrosterone sulphate result in an improved fertility status, regulated through complex interactions, in particular with the gonatotropin-releasing-hormone pulse generator. The questionnaire shows the use of different types of contraception. From the 9 patients who only used oral contraception, 2 patients developed an unforeseen pregnancy after BPD. Although miscarriages and neonatal complications were seen in other patients in our hospital, none of these problems were seen in our study. Conclusion: Pregnancy should be avoided for 12 to 18 months after BPD. Fertility increases after BPD. As oral contraception is most popular and less reliable, we strongly believe that large multi-centre, prospective, randomized studies are necessary to come to a consensus about the use of contraceptive therapy after BPD.

Biliopancreatic diversion for treatment of morbid obesity: experience in 180 consecutive cases.

Background: Biliopancreatic diversion (BPD) by Scopinaros method is used by many as a surgical treatment for morbid obesity. The authors present their results in 180 consecutive cases. Method: Between June 1995 and May 1998, the authors performed BPD by Scopinaros method on 180 patients (36 men) with morbid obesity, mean age 35.8 years (range 18-58 years), mean body mass index (BMI) 48.8 kg/m2 (range 35-66 kg/m2). Results: In all cases, a gradual decrease in weight was obtained: the mean BMI at 1 month was 40.3 kg/m2, at 6 months 34 kg/m2, at 1 years 32 kg/m2, at 18 months 30.2 kg/m2, and at 36 months 28.8 kg/m2. At the same time a significant improvement in the pathologic conditions associated with morbid obesity was observed. Postoperative complications were two duodenum blowout syndromes requiring prolonged intensive care, and an 18% rate of incisional hernias. Conversion to normal small bowel continuity was necessary in three cases. Protein malnutrition developed in 2 patients (1.1%), in 1 patient coinciding with addiction to cocaine. One patient could not psychologically accept the physical changes and requested conversion. Anastomotic ulceration was seen in 11% of the patients. Operation for late obstruction occurred in 2 patients. There was no mortality. Conclusions: Although BPD by Scopinaros method is technically complex, it is safe and effective.

Influence of Bariatric Surgery on the Use and Pharmacokinetics of Some Major Drug Classes

The purpose of this review is to evaluate the influence of bariatric surgery on the use and pharmacokinetics of some frequently used drugs. A PubMed literature search was conducted. Literature was included on influence of bariatric surgery on pharmacoepidemiology and pharmacokinetics. Drug classes to be searched for were antidepressants, antidiabetics, statins, antihypertensive agents, corticosteroids, oral contraceptives, and thyroid drugs. A reduction in the use of medication by patients after bariatric surgery has been reported for various drug classes. Very few studies have been published on the influence of bariatric surgery on the pharmacokinetics of drugs. After bariatric surgery, theoretically, reduced drug absorption may occur. Correct dosing and choosing the right dosage form for drugs used by patients after bariatric surgery are necessary for optimal pharmacotherapy. Therefore, more clinical studies are needed on the influence of bariatric surgery on the pharmacokinetics of major drugs.

Long-term self-reported symptom prevalence of early and late dumping in a patient population after sleeve gastrectomy, primary, and revisional gastric bypass surgery

BACKGROUND Early and late dumping are side effects of bariatric surgery. Almost no data are available on the prevalence of dumping after different surgical procedures. OBJECTIVES Comparison of the relative risks of dumping in a large population of patients having undergone primary Roux-en-Y gastric bypass (pRYGB), sleeve gastrectomy (SG), or revisional RYGB (rRYGB; after removal of band). SETTING Bariatric center of a teaching hospital. METHODS In this descriptive cohort study, all patients who underwent a pRYGB (n = 615), SG (n = 157), or rRYGB (n = 274) between 2008 and 2011 were approached by mail and asked to complete and return a questionnaire of general and disease-specific questions related to dumping syndrome. Relative risks (RR) were calculated (mean with 95% confidence intervals) by comparing the prevalence of high suspicion for early and late dumping between different surgical procedure groups and primary gastric bypass surgery. RESULTS The questionnaire was completed and returned by 593 (57%) of 1046 patients. Fewer patients with SG were at high suspicion of early dumping than after pRYGB (RR [95% confidence interval] .46 [.22-.99], P = .049). No differences for early dumping were seen between rRYGB and pRYGB (RR 1.21 [.77-1.91], P = .40). More patients were at high suspicion for late dumping after rRYGB compared with after pRYGB (RR 1.78 [1.09-2.90] P = .021). No differences for late dumping were seen between SG and pRYGB (RR .59 [.22-1.61], P =.30). CONCLUSION Fewer complaints of early dumping are reported after SG, while patients report more complaints of late dumping after rRYGB compared with pRYGB.

Influence of bariatric surgery on the use of some major drug classes

Objective Medication errors in ambulatory care are frequent. Because the process of prescribing and medication therapy is more complex than in hospital settings adequate methods to avoid medication errors are difficult to implement. In our study we investigated a campaign from a health insurance company that had the aim to increase medication safety within insurants with polypharmacy and multimorbidity. Method An expert team consisting of clinical pharmacologists and a pharmacist analysed the medication of insurants for risk prescriptions who had an additional telephonic health coaching. Attending physicians received a report and were offered to contact the experts for counselling. Results of medication analyses of 400 insurants were categorized in eight types of prescribing errors and feedback from the physicians was recorded. Differences in medication therapy after counselling were scanned. Main outcome measure The frequency of medication errors in eight categories and physicians’ feedback, further changes in medications of physicians responding. Results Insurants were 48% female and 52% male and took an average of 13.4 drugs regularly. 16.8% of the physicians contacted replied, 13.3% had a counselling conversation. 29.2% of the physicians replying gave a positive response to the campaign, 13.8 % a negative and for 56.9 % a neutral feedback was given. Out of a total of n=2524 errors 26.8% occurred in the category missing indication, 6.8% in PRISCUS medication, 33.3% in interactions, 15.3% in wrong dosage, 0.9% in contraindication, 2.8% in dosage adaption to renal function, 6.9% in double medication and 7.2% in gap of prescribing. Conclusion A large number of medication errors appear in ambulatory care and consequently adverse drug events and hospital admissions are more likely to happen. Medication check by pharmacotherapy experts and pharmacological consulting with a high response of physicians can be a key tool to reduce these errors. Cooperation of a health insurance company and clinical pharmacologists is an effective association but needs to be optimized for better acceptance and more rapid ability to react.

A GASTROINTESTINAL SIMULATION SYSTEM (GISS) FOR DISSOLUTION OF DRUGS BEFORE AND AFTER ROUX-EN-Y GASTRIC BYPASS: FIRST RESULTS

S OF THE DUTCH SOCIETY OF CLINICAL PHARMACOLOGY AND BIOPHARMACY MEETING OF MARCH 26, 2013 DOPAMINE D2 AGONIST INDUCED CARDIOVASCULAR CHANGES IN YOUNG HEALTHY MEN. A PHASE I CLINICAL TRIAL EXPERIENCE K Abou Farha, S van Os, C Balje & W Tamminga QPS B.V, the Netherlands and Synthon BV, the Netherlands Introduction Dopamine D2 (DA2) agonists are a first line treatment option in young Parkinson’s patients with mild to moderate symptoms. DA2 agonists are known to cause depression of cardiac functions with decrease in heart rate. A recent European multicentre study [1] found a relationship between the use of DA2 agonists in Parkinson’s disease (PD) and heart failure (HF) especially in early phase of therapy. Results Here we present data of a Phase I study where we evaluated supine (SU) and standing (ST) blood pressure (BP) and brachial pulse rate (PR) levels, obtained from 40 healthy male volunteers, aged 18–55 year, after administration of a selective DA2 agonist. Full medical screening indicated the healthy status of all participants. The DA2 agonist was administered in an escalating dose level design over 30 days, 13 up-titration (UPT) days; 12 steady state (SS) days, and 5 down titration days. An oral dose of 10 mg domperidone tid was given to prevent potential D2 cardiovascular and gastrointestinal peripheral effects. Data were categorised into 2 age groups,G1 (18–40 years) and G2 (40–55 years). Statistical comparison between BP and brachial PR obtained in SU and ST positions during screening (BL), UPT phase and SS period revealed significant results (Table 1). All 40 subjects showed an increase in both SU and resting ST PR as compared to base line (with a zenith of 239 bpm in resting ST position vs. 60 bpm (BL). Increased SU Systolic (S)BP was observed in 36 subjects (26 G1 and 10 G2) with a zenith of 175 mmHg in 1 subject vs.138 mmHg). Increased ST SBP was observed in 33 subjects (24 G1 and 9 G2) with a zenith of 202 mmHg in 1 subject vs. 125 mmHg at BL. Seven of the 28 G1 subjects were removed prematurely from the trial because of clinically significant symptomatic increase in BP (up to 202/95 mmHg, ca. 81 mmHg and 20 mmHg increase respectively in SBP and DPB above BL) and tachycardia of 151 bpm, obtained from a 12leads ECG. In 3 of the 7 subjects non-specific ST-segment depression was seen in the inferior limb leads of concurrently obtained ECG (Figure 1). The clinical condition implied immediate administration of I.V. rescue medications including a selective β-1 blocker in all 7 subjects. In 1 subject with an inadequate response an I.V. α-β-1 blocking agent was added to therapy. Table 1 Systolic blood pressure (SBP) and brachial pulse rate (PR) for group 1 (18–40 years) and group 2 (40–55 years) in supine and standing position during screening (BL), UPT and SS phase Parameter Supine Standing