Detection of potentially inappropriate prescribing in older patients with the GheOP³S-tool: completeness and clinical relevance.

OBJECTIVES: The Ghent Older People's Prescriptions community Pharmacy Screening (GheOP3S-) tool was recently developed as an explicit screening method to detect Potentially Inappropriate Prescribing (PIP) in the community pharmacy. We aimed to validate the GheOP3S-tool as an effective screening method for PIP. METHODS: All patients admitted to the acute geriatric ward of the Sint-Vincentius hospital (Belgium) were consecutively screened for inclusion (≥70 years,≥5 drugs chronically). PIP prevalence was evaluated by applying the GheOP3S-tool on the complete medication history. For each PIP-item, clinical relevance of the detected item, relevance of proposed alternative and subsequent acceptance by the treating geriatrician and a general practitioner were evaluated. Additionally, contribution to the current admission and preventability was assessed by the geriatrician. The completeness of a PIP-screening with the GheOP3S-tool was evaluated through comparison with the adapted Medication Appropriateness Index (aMAI). RESULTS: We detected 250 GheOP3S-items in 57 of 60 included patients (95%) (median: four PIP-items per patient; IQR: 3-5). Both the geriatrician and the general practitioners scored the clinical relevance of the detected items 'serious' or 'significant' in over 70% of cases. Proposed alternative treatment plans were accepted for 79% of the PIP-items (n = 198). The aMAI detected 536 items, of which 145 were also detected by the GheOP3S-tool. A total of 119 PIP-items were additionally detected by the GheOP3S-tool. CONCLUSION: The clinical relevance of the PIP-items detected with the GheOP3S-tool is high, likewise the acceptance rate of proposed alternatives.

Development of clinical pharmacy in Belgian hospitals through pilot projects funded by the government.

Objectives The goal is to develop clinical pharmacy in the Belgian hospitals to improve drug efficacy and to reduce drug-related problems. Methods From 2007 to 2014, financial support was provided by the Belgian federal government for the development of clinical pharmacy in Belgian hospitals. This project was guided by a national Advisory Working Group. Each funded hospital was obliged to describe yearly its clinical pharmacy activities. Results In 2007, 20 pharmacists were funded in 28 pilot hospitals; this number was doubled in 2009 to 40 pharmacists over 54 institutions, representing more than half of all acute Belgian hospitals. Most projects (72%) considered patient-related activities, whereas some projects (28%) had a hospital-wide approach. The projects targeted patients at admission (30%), during hospital stay (52%) or at discharge (18%). During hospital stay, actions were mainly focused on geriatric patients (20%), surgical patients (15%), and oncology patients (9%). Experiences, methods, and tools were shared during meetings and workshops. Structure, process, and outcome indicators were reported and strengths, weaknesses, opportunities, and threats were described. The yearly reports revealed that the hospital board was engaged in the project in 87% of the cases, and developed a vision on clinical pharmacy in 75% of the hospitals. In 2014, the pilot phase was replaced by structural financing for clinical pharmacy in all acute Belgian hospitals. Conclusion The pilot projects in clinical pharmacy funded by the federal government provided a unique opportunity to launch clinical pharmacy activities on a broad scale in Belgium. The results of the pilot projects showed clear implementation through case reports, time registrations, and indicators. Tools for clinical pharmacy activities were developed to overcome identified barriers. The engagement of hospital boards and the results of clinical pharmacy activities persuaded the government to start structural financing of clinical pharmacy.

Fibromyalgia and unexplained widespread pain: The idiopathic cerebrospinal pressure dysregulation hypothesis.

Fibromyalgia (FM) is a debilitating, widespread pain disorder that is assumed to originate from inappropriate pain processing in the central nervous system. Psychological and behavioral factors are both believed to underlie the pathogenesis and complicate the treatment. This hypothesis, however, has not yet been sufficiently supported by scientific evidence and accumulating evidence supports a peripheral neurological origin of the symptoms. We postulate that FM and several unexplained widespread pain syndromes are caused by chronic postural idiopathic cerebrospinal hypertension. Thus, the symptoms originate from the filling of nerve root sleeves under high pressure with subsequent polyradiculopathy from the compression of the nerve root fibers (axons) inside the sleeves. Associated symptoms, such as bladder and bowel dysfunction, result from compression of the sacral nerve root fibers, and facial pain and paresthesia result from compression of the cranial nerve root fibers. Idiopathic Intracranial Hypertension, Normal Pressure Hydrocephalus and the clinical entity of symptomatic Tarlov cysts share similar central and peripheral neurological symptoms and are likely other manifestations of the same condition. The hypothesis presented in this article links the characteristics of fibromyalgia and unexplained widespread pain to cerebrospinal pressure dysregulation with support from scientific evidence and provides a conclusive explanation for the multitude of symptoms associated with fibromyalgia.

[Medication screening by the community pharmacist in Belgium]. / Revue de la medication par le pharmacien d'officine en Belgique: pourquoi, comment et situation actuelle.

About 20% of the European population is older than 65 years. Because of multimorbidity (i.e. multiple chronic condition within a patient), older patients are often prescribed multiple drugs [i.e. polypharmacy). Both older age and polypharmacy significantly increase the risk for adverse drug events. International research showed that more or less 5% of all unplanned hospital admissions is related to the use of medication. About 70% of these drug related admissions happened in patients older than 65 years. Moreover, about half of the admissions could have been avoided. These preventable hospital admissions were caused by the intake of medication without an indication, problems with medication adherence, interactions and/or insufficient monitoring. We define this as (potential Drug Related Problems [DRPI. DRPs can occur on multiple occasions during the medication management process: prescribing, dispensing, intake and monitoring. When DRPs can be detected in an early stage, significant consequences can be avoided. To accomplish this, multiple strategies are possible. One of the possibilities is performing a periodic medication screening by the community pharmacist in patient groups at risk. During such a medication screening, the pharmacotherapy is critically evaluated in a systematic and structured way. The implementation of medication screening in first-line health care is currently limited. The community pharmacist is nevertheless ideally placed to perform this task. There is an important relation of trust between him and the patient and the community pharmacist has access to a full medication history. Furthermore, as an expert in drug-related issues, he possesses all necessary knowledge to perform the pharmacotherapeutic analysis.

[A practical program for outpatient parenteral antimicrobial therapy]. / Un modèle pratique pour l'antibiothérapie parentérale ambulatoire.

Some infections require prolonged parenteral antimicrobial therapy, which can be continued in an outpatient setting. The Ghent University Hospital has fifteen years of experience with Outpatient Parenteral Antimicrobial Therapy [OPAT) in the patient own home setting. As a quality improvement initiative, this process was critically reviewed in a multidisciplinary approach. Several challenges and barriers were identified, including regulatory obstacles for OPAT in Belgium, such as Lack of uniformity in ambulatory reimbursement of parenteral antimicrobials. There is no financial incentive for the patient with OPAT, as costs for the patient of outpatient therapy can be higher as compared with hospitalization. Other barriers include delayed approval of the certificate for reimbursement, low availability of medicines in the community pharmacies and limited knowledge of the medical devices for administration in ambulatory setting. All critical steps in the revised OPAT program are summarized in a flowchart with a checklist for all stakeholders. Firstly, a list with specific criteria to include patients in an OPAT program is provided. Secondly, the Multidisciplinary Infection Team received a formal mandate to review all eligible OPAT patients. In order to select the most appropriate catheter a decision tree was developed and standardized packages with medical devices were developed. Thirdly, patients receive oral and written information about the treatment with practical and financial implications. Fourthly, information is provided towards the general practitioners, community pharmacists and home care nurses. Standardization of the OPAT-program aims at improving quality and safety of intravenous antimicrobial therapy in the home setting.

[Major drug related problems leading to hospital admission in the elderly]. / Principaux problèmes liés aux médicaments conduisant a une hospitalisation chez les personnes âgées.

Drug related problems represent an important problem in geriatric patients, and contribute to hospitalization in 15 to 30% of the admissions. In most cases this concerns adverse drug reactions (normal dose and overdose) but also drug therapy failures (e.g. undertreatment) are common. The main pharmacological classes involved are cardiovascular drugs and drugs for the central nervous system. Drug related problems can be prevented by regular medication review to decide if all drugs have to be continued, and to check for adverse drug reactions. Clinical pharmacists in hospitals can detect drug related problems (over-, under- and misuse using a systematic approach) and recommend changes to improve pharmacotherapy. The community pharmacist can help by elaborating drug schemes, by screening for medication interactions, and by resolving practical problems.

Sunitinib for metastatic renal cell cancer patients: observational study highlighting the risk of important drug-drug interactions.

WHAT IS KNOWN AND OBJECTIVE: Sunitinib, a CYP3A4 substrate, is standard of care treatment in metastatic renal cell carcinoma (mRCC) and is administered orally as a single dose of 50 mg, in a 4 weeks on/2 weeks off regimen. Frequently, dose reduction is necessary because of toxicity, as is the association of comedication to treat side effects. In addition, existing comorbidities in these patients necessitate the intake of various classes of chronic medication. Only limited data are available on the risk of drug-drug interactions (DDI). The objective of our paper was to evaluate prescribed dose, comedication, risk of drug-drug interactions and outcome among patients with mRCC treated with sunitinib. METHODS: A single-centre, retrospective analysis was performed for patients with mRCC treated with sunitinib. The drug interaction databases 'Clinical Pharmacology' and 'Lexicomp' were used to screen for possible interactions. RESULTS AND DISCUSSION: The hospital files of 36 patients with mRCC were evaluated. Twenty-two patients received sunitinib as first-line treatment. Progression-free survival (PFS) in this first-line group was longer for patients that started with full-dose sunitinib (21·1 months; n = 12) than for patients started on reduced dose (3·5 months; n = 10). In the whole group of 36 patients, an average of 6·8 comedications was taken. Possible pharmacodynamic drug-drug interactions were most frequently found (47%) and reported as major interactions (QT prolongation). Risk of pharmacokinetic interactions due to co-administration of CYP inhibitors, CYP inducers, CYP substrates and PgP substrates was reported for 8%, 11%, 53% and 19%, respectively. These interactions were reported as major or moderate. WHAT IS NEW AND CONCLUSION: Patients with mRCC under treatment with sunitinib at a reduced starting dose had a decreased PFS compared with patients started with full-dose sunitinib. Due to adverse drug reactions and comorbidity, patients under sunitinib, a CYP3A4 substrate, took an average of 6·8 comedications provoking an important risk of major-to-moderate drug-drug interactions. With the help of a multidisciplinary team, avoidance of drug-drug interactions could be obtained. Moreover, serial ECG monitoring is recommended for patients at high risk of QT prolongation.

Prevalence of orthostatic hypotension and relationship with drug use amongst older patients.

INTRODUCTION: Orthostatic hypotension (OH) is said to be highly prevalent in older people. Drugs are often involved as causative factor. Nevertheless, few data are available about the prevalence of OH and its relationship with drugs in olders. OBJECTIVES: To review data about (i) the prevalence and characteristics of OH in older patients; and (ii) the relationship between OH and drugs. METHODS: Review of publications from Ovid (PubMed) from 1980 to May 2011 using the following key words: "orthostatic hypotension" combined with "elderly" or equivalent for the analysis of prevalence (first search) and "orthostatic hypotension" combined with "drugs" or equivalent to assess the relationship between OH and drugs (second search). RESULTS: Fifty-one publications (of which 14 with original data) were retrieved from the prevalence search, 31 for the second search (8 with original data: 7 retrospective studies and 1 prospective cohort study) and 12 reviews or experts opinions. Prevalence of OH varies according to the characteristics of the subjects, the settings of the studies, and the procedures of blood pressure measurement. In acute geriatrics units, two studies reported a prevalence of over 30% and one study mentioned that 68% of the patients presented with at least one episode during the day. OH was associated with several geriatric problems: gait disorders, balance disorders, falls, cerebral hypoperfusion, transient ischemic attacks, cognitive impairment, acute myocardial infarct and systolic hypertension. OH can also be asymptomatic or with atypical presentation: falls, gait disorders and confusion. Psychotropic agents (antipsychotics, sedatives, antidepressants), and cardiovascular drugs (antihypertensive agents, vasodilators, diuretics) were associated with OH. DISCUSSION: If the hypothesis of causality between drug treatment and OH is confirmed, the identification of the involved drugs could be of value for the prevention of OH and its complications. In this context, the Working Group Pharmacology Pharmacotherapy and Pharmaceutical Care of the Belgian Society of Gerontology and Geriatrics proposes to conduct a multicentre study to assess the prevalence of OH in Belgian acute geriatrics units and its relationship with drugs.

Impact of the HIV epidemic and Anti-Retroviral Treatment policy on lymphoma incidence and subtypes seen in the Western Cape of South Africa, 2002-2009: preliminary findings of the Tygerberg Lymphoma Study Group.

The Tygerberg Lymphoma Study Group was constituted in 2007 to quantify the impact of HIV on the pattern and burden of lymphoma cases in the Western Cape of South Africa which currently has an HIV prevalence of 15%. South Africa has had an Anti-Retroviral Treatment (ART) policy and a roll-out plan since 2004 attaining 31% effective coverage in 2009. This study is designed to qualify and establish the impact of HIV epidemic and the ARV roll-out treatment program on the incidence of HIV Related Lymphoma (HRL). Early data document that despite the ART roll out, cases of HRL are increasing in this geographical location, now accounting for 37% of all lymphomas seen in 2009 which is an increase from 5% in 2002. This is in contrast to trends seen in developed environments following the introduction of ART. Also noted are the emergence of subtypes not previously seen in this location such as Burkitt and plasmablastic lymphomas. Burkitt lymphoma is now the commonest HRL seen in this population followed by diffuse large B-cell lymphoma subtypes. The reasons for this observed increase in HRL are not ascribable to improved diagnostic capacity as the tertiary institute in which these diagnoses are made has had significant expertise in this regard for over a decade. We ascribe this paradoxical finding to an ART treatment environment that is ineffective for a diversity of reasons, paramount of which are poor coverage, late commencement of ART and incomplete viral suppression.

Contribution of drug related problems to hospital admission in the elderly.

PURPOSE: To investigate the frequency and type of drug related problems (DRPs) in geriatric patients (> 65 years), and to assess their contribution to hospital admission; to explore the appropriateness of drug therapy according to the Beers' criteria. METHODS: Cross-sectional observational survey of 110 elderly patients admitted during three non-consecutive months to the geriatric ward of a university hospital. Explorative assessment of appropriateness of drug therapy prior to hospital admission based on the Beers' criteria. RESULTS: A DRP was the dominant reason for hospital admission in 14 out of the 110 patients (12.7%); for another 9 patients (8.2%), a DRP was partly contributing to hospital admission. For these 23 patients, adverse drug reactions and noncompliance were the most important types of DRPs. We found no relationship between drug related hospital admission and intake of a drug listed in the Beers criteria for inappropriate drug use in the elderly. Patients admitted for a DRP took more drugs before admission than patients admitted because of other reasons. CONCLUSIONS: DRPs are an important cause for admission on the geriatric ward of our hospital. The drugs causing DRPs in this study were not those listed in the Beers list of inappropriate drugs in the elderly.

Direct observation of the coherent spectral hole in the noise spectrum of a saturated InAs/InP quantum dash amplifier operating near 1550 nm.

We demonstrate a direct observation of the coherent noise spectral hole in a saturated quantum dash amplifier. Its width 500-600 GHz is determined by the response time and is responsible for high speed regeneration properties.

Cross talk free multi channel processing of 10 Gbit/s data via four wave mixing in a 1550 nm InAs/InP quantum dash amplifier.

We demonstrate multi wavelength processing in a broad band 1550 nm quantum dash optical amplifier. Two 10 Gbit/s signals, spectrally separated by 30 nm are individually wavelength converted via four wave mixing (FWM) with no cross talk. High power signal levels cause depletion of high energy and wetting layer states resulting in some homogenizing of the gain medium and generation of cross FWM components near each channel due to FWM in the other channel. These do not affect the cross-talkless multichannel processing except when the two channels use equal detuning between signal and pump.

The use of hypnosedative drugs in a university hospital setting.

OBJECTIVE: The use of hypnosedatives (HSs) in the hospital and at home before admission was registered. Also, the incidence of HSs newly started in the hospital and the incidence of withdrawal in chronic users while in hospital was recorded. METHODS: The study population consisted of 517 consecutively admitted patients recruited from 10 wards of the Ghent University Hospital; 493 of them received a questionnaire and were interviewed concerning the use of HSs at home and in the hospital, about the cause and duration of treatment, the type of HSs used, the presence and nature of any concomitant sleep or anxiety disorder. Main outcome measures were the actual use of HSs during hospitalisation as compared with the reported use, the influence of hospitalisation on use of HSs and the assessment of cause and duration of use of HSs. RESULTS: Twenty-nine percent of the study sample took HSs at home and 45.2% while in the hospital. HSs were prescribed to 28.6% of the patients not habituated to chronic use of HSs at home. In contrast, 14.0% of the patients habituated to chronic use of HSs received no sleep medication while in hospital. Patients older than 60 years used more HSs than younger patients. Previous administration of HSs, sleep problems during hospital admission and female sex were predictive of HS-use. The main reason for prescription of HSs in the hospital was continuation of HSs taken at home. The most prescribed HSs were: lormetazepam, lorazepam, alprazolam, diazepam and zolpidem. Almost 10% of the patients were not informed on treatment with HSs. Among the subjects in whom HSs were newly started, 16.0% intended to continue this medication after discharge. Eleven percent took combinations of hypnosedative drugs. CONCLUSIONS: The prevalence of prescription of HSs in the university hospital setting is high. Appropriate guidelines are needed to control the use of HSs during hospitalisation and to ensure withdrawal from these drugs upon discharge.

Cost-reduction analysis of propofol versus sevoflurane: maintenance of anaesthesia for gynaecological surgery using the bispectral index.

BACKGROUND AND OBJECTIVE: The study was designed to compare the costs of propofol versus sevoflurane for the maintenance of the hypnotic component of anaesthesia during general anaesthesia, guided by the bispectral index, for gynaecological laparoscopic surgery. METHODS: Forty ASA Grade I-II female patients scheduled for gynaecological laparoscopy were randomly allocated to two groups. All patients received a continuous infusion of remifentanil (0.25 microg kg(-1) min(-1)) for 2 min. Then anaesthesia was induced with propofol 1% at 300 mL h(-1) until loss of consciousness. To guide the bispectral index between 40 and 60, Group 1 patients received propofol 10 mg kg(-1) h(-1) initially, which was increased or decreased by 2 mg kg(-1) h(-1) steps; Group 2 patients received sevoflurane, initially set at 2 vol.% and adjusted with steps of 0.2-0.4%. The time and quality of anaesthesia and recovery were assessed in two postoperative standardized interviews. RESULTS: Patient characteristics, the propofol induction dose, the bispectral index and the haemodynamic profiles during induction of anaesthesia, and its duration, were similar between the groups. In Group 1, 7.55 +/- 1.75 mg kg(-1) h(-1) propofol and in Group 2, 0.20 +/- 0.09 mL kg(-1) h(-1) liquid sevoflurane were used for maintenance. The cost for maintenance, including wasted drugs, was higher when using propofol (Euro 25.14 +/- 10.69) than sevoflurane (Euro 12.80 +/- 2.67). Postoperatively, recovery profiles tended to be better with propofol; however, the day after discharge no differences were found. CONCLUSIONS: When applying the bispectral index to guide the administration of hypnotic anaesthetic drugs, propofol-based maintenance of anaesthesia was associated with the highest cost. A trend towards a better recovery profile was obtained with propofol. However, on the day after discharge, no differences in quality were observed.

Evaluation of human albumin use in a university hospital in Belgium.

UNLABELLED: In 1996-1997, a drug use evaluation (DUE) of human albumin was conducted in the Ghent University Hospital (Belgium) to determine the pattern and appropriateness of the albumin use. The DUE was followed by permanent review of the albumin consumption. This paper describes how the DUE was carried out and how the albumin use in our hospital changed over time. METHOD: The study was based on criteria for indications and end of treatment, accepted by consensus of the physicians prescribing albumin. Albumin treatment episodes were classified as appropriate or inappropriate according to these criteria. RESULTS: For 115 treatment episodes in 90 patients, the researchers found 21 (18.3%) deviations from the developed criteria. After analysis, half out of them were considered as minor. Most deviations involved starting treatment too early (n = 17). Follow-up results indicated that the overall consumption of albumin dropped by 50.1% from 1994 to 1999, while the consumption of colloid solutions during the same period remained stable. CONCLUSION: A good compliance with internally developed criteria for indications and end of treatment with human albumin was observed. Discussion with the clinicians involved led to the development of stricter criteria and a continuous decrease in albumin consumption.

Potential of porous poly-D,L-lactide-co-glycolide particles as a carrier for recombinant human bone morphogenetic protein-2 during osteoinduction in vivo.

Several different biodegradable bone graft materials are in clinical or preclinical use for the repair of bone defects in orthopedics, maxillofacial surgery, and periodontics. This study tested the hypothesis that poly-D,L-lactide-co-glycolide copolymer (PLG) can be used as an effective carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2) and that the composite has osteoinductive ability. Porous PLG rods were shredded to a particle size ranging from 250 to 850 microm. Active and inactive demineralized freeze-dried bone allografts (DFDBA) with a comparable particle size were used as positive and negative controls, respectively. PLG particles were treated with vehicle or with 5 or 20 microg rhBMP-2. DFDBA and PLG particles were placed in gelatin capsules, mixed with vehicle or rhBMP-2, and implanted at intramuscular sites in male Nu/Nu (nude) mice. Each mouse underwent bilateral implantation with implants of the same formulation, resulting in five groups of four mice per group: active DFDBA, inactive DFDBA, PLG, PLG + 5 microg rhBMP-2, and PLG + 20 microg rhBMP-2. After 56 days, the implants were recovered and processed for histology. Bone induction was assessed by use of a semiquantitative scoring system based on the amount of new bone formed in representative histological sections. Histomorphometry was also used to measure the area of new bone formed and the area of residual implant material. The results showed that active DFDBA induced the formation of ossicles containing new bone with bone marrowlike tissue, whereas inactive DFDBA or PLG particles alone did not induce new bone. The addition of rhBMP-2 to PLG particles resulted in new bone formation that had a greater bone induction score than active DFDBA. Moreover, the histomorphometric analysis showed that the addition of rhBMP-2 to PLG particles induced the formation of a greater area of new bone and bone marrowlike tissue than active DFDBA. The resorption of the PLG particles was markedly increased with the addition of rhBMP-2, suggesting that rhBMP-2 may attract and regulate resorptive cells at the implantation site. The results of the present study indicate that PLG copolymers are good carriers for BMP and promote the induction of new bone formation. Further, the PLG copolymers with rhBMP-2 had a greater effect in inducing new bone formation and resorbing the implanted material than active DFDBA alone.