[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.

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.

[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.

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.

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.

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.

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.

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.

Accountability, public policy, and psychiatry.

The author identifies the direction of changes in health policy in the United States that need to be taken into account by the health professions in their dealings with government. She discusses three areas in which these changes will call for adjustment on the part of the medical profession and major health care institutions and defines the special challenge to psychiatry implicit in the changes. She concludes that the public's need for attention to the psychosocial aspects of health and the renewed interest in prevention present psychiatry with an opportunity to provide leadership in health care delivery.

"Lifecare": a viable option for long-term care for the elderly.

In the absence of any coherent US long-term care policy, the "lifecare" or "continuing care" retirement community (CCRC) has emerged as one viable model, providing housing, health care, social supports, and long-term care insurance to about 300,000 elderly Americans. Some CCRCs have also demonstrated the cost-effectiveness of a health care philosophy targeted to the maximum functional independence (MFI) of residents. Broad dissemination of the CCRC model and the philosophy of MFI depend on development of new approaches to the role of government and private health insurance along with a new understanding of, and commitment to, risk management.

Addition of human recombinant bone morphogenetic protein-2 to inactive commercial human demineralized freeze-dried bone allograft makes an effective composite bone inductive implant material.

COMMERCIAL PREPARATIONS OF HUMAN DEMINERALIZED freeze-dried bone allograft (DFDBA) vary in their ability to induce new bone formation. This study tested the hypothesis that inactive DFDBA can be used as an effective carrier of recombinant human bone morphogenetic protein-2 (rhBMP-2). Two batches of active DFDBA were used as controls. Two batches of DFDBA, previously shown to be inactive, were treated with vehicle or with 5 or 20 microg rhBMP-2 and implanted into the calf muscle of male Nu/Nu (nude) mice. Each mouse received one implant in each hind limb, both of which were of the same formulation, resulting in 8 groups of 4 mice per group: active DFDBA batch A, active DFDBA batch B, inactive DFDBA batch A, inactive DFDBA batch B, inactive DFDBA batch A plus 5 microg rhBMP-2, inactive DFDBA batch A plus 20 microg rhBMP-2, inactive DFDBA batch B plus 5 microg rhBMP-2, and inactive DFDBA batch B plus 20 microg rhBMP-2. After 56 days, the implants were removed and histologically examined. A semiquantitative bone induction index was calculated based on the amount of new bone covering each histological section. Histomorphometry was also used to evaluate the area of new bone formed and the area of residual implant material. The results showed that active DFDBA induces new bone formation, whereas inactive DFDBA does not. Addition of rhBMP-2 to inactive DFDBA results in new bone formation with a bone induction index comparable to that of active DFDBA. Histomorphometric analysis, however, revealed that the rhBMP-2-containing implants caused a dose-dependent increase in new bone area that exceeded that induced by active DFDBA. At the highest concentration of rhBMP-2, bone formation was exuberant. rhBMP-2 also caused the resorption of residual implant material to levels comparable to that seen in sites treated with active DFDBA, suggesting that this growth factor may regulate resorptive cells either directly or indirectly. This study shows that addition of rhBMP-2 to inactive DFDBA provides reproducible, consistent bone induction, and suggests that inactive commercial preparations may contain inadequate amounts of BMP to cause bone induction compared to active preparations.

Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender.

Demineralized freeze-dried bone allografts (DFDBA) have been used extensively in periodontal therapy. DFDBA is used because it contains bone morphogenetic protein (BMP), which induces new bone formation during the healing process. Most commercial bone banks do not verify the presence or activity of BMP in DFDBA nor the ability of DFDBA to induce new bone. Recently, we showed that different bone bank preparations of DFDBA, even from the same bank, varied considerably in their ability to induce new bone, suggesting inherent differences in the quality of the material. Therefore, we examined whether donor age or gender contributed to the variability seen with these preparations. Twenty-seven batches of DFDBA from different donors were donated by one bone bank which had been shown previously to supply DFDBA that was consistently able to induce new bone formation. Each batch was implanted bilaterally in the thigh muscle of nude mice. After 56 days, the implants were excised and examined by light microscopy and histomorphometry. Seventy percent of the preparations tested induced new bone formation. Most of these preparations produced ossicles containing cortical bone surrounding bone marrow-like tissue. The ability to induce bone appears to be age-dependent, with DFDBA from older donors being less likely to have strong bone-inducing activity. By contrast, no difference in ability to induce new bone was noticed between male or female donors. The results of this study confirm that commercial preparations of DFDBA differ in their ability to induce new bone formation. In fact, some of the batches had no activity at all. The ability of DFDBA to induce new bone formation is suggested to be age-dependent, but not gender-dependent by our study. These results indicate that commercial bone banks need to verify the ability of DFDBA to induce new bone formation and should reconsider the advisability of using bone from older donors.

VD hotline: an evaluation.

A VD hotline started in January 1973 at Monmouth Medical Center, Long Branch, N.J., was evaluated with the following results. Hotline operators handled 260 calls in 1973. The typical caller was a 20-year-old employed male who heard about the hotline from a friend, wanted information about clinic hours and costs, and had questions about symptoms of venereal disease. At Monmouth Medical Center, venereal disease patients who go to the emergency room receive specific diagnosis and therapy, and in the clinic they receive broader medical care. The hotline encourages patients to go to the clinic or to their private physicians. Visits to Monmouth Medical Center for venereal disease increased during the second half of 1972 from 356 to 545 (53%). For the emergency room alone, the rise was 17% and for the clinic, 68%. There was an increase of 20% in the number of patients treated in the emergency room, but the number treated in the clinic leveled. Thus, there was a substantial increase in visits, especially to the clinics where the most care is provided, and a modest increase in treated patients. The causal contribution of the hotline to these increases cannot be stated with certainty. The cost of operating the hotline was $14.70 per call. While high, it might be defended on the basis of avoiding the higher costs of untreated disease. The cost can be reduced by making the hotline serve multiple health purposes. The hotline appeared useful but costly. This retrospective evaluation was hampered by the unavailability of some critical data.

Aging in the 21st century: projections, personal preferences, public policies--a consumer view.

The demographic revolutions of the recent past and projections of continuing increases in the number and proportion of elderly in the United States and other advanced nations pose extremely difficult economic, political, and ethical issues. However, there is growing evidence-based on changing public and professional attitudes-that humane solutions are economically feasible. Of special importance is the new emphasis on "productive aging", "successful aging", "preventive gerontology" and related policies and programs which already give promise of postponing the average age of incidence of chronic illness and disability and extending the productive lifespan. Simultaneously there is growing attention to the "right to die" and other indications of a new focus on the quality of life rather than the length. Such developments also offer hope for the feasibility of adequate long-term care benefits for the victims of Alzheimers and other disabling conditions that we do not now know how to prevent. However, adoption of this approach to national health policy remains an option, not a prediction.

The changing demand for health services: a historical perspective and some thoughts for the future.

Among the many factors contributing to the rise in health care costs, recent attention has concentrated on the supply side. Demand factors have generally been neglected or misunderstood. Developments discussed in this paper include: growing public skepticism toward new therapies and drugs; increasing emphasis on patient autonomy and other indications of willingness by the public to assume greater responsibility for its own health; changing relations between income, education, and health care use; the aging of the population and the concomitant rise in chronic conditions; the recent reversal of the former quest for greater equity in health care; and the shrinking American family. Despite the complexity and contradictions within these developments, I perceive a leveling off of demand, especially for acute hospital care, even apart from external financial constraints, accompanied by a rising demand for preventive services and primary and long-term care. It is time to recognize the policy implications of these developments and begin to reorganize our health care system accordingly. But is it too late? Have we the will to do so?

And who shall be the gatekeeper? The role of the primary physician in the health care delivery system.

In a speech at the Duke University Medical Center, the author discussed the growing interest in a primary care "gatekeeper" to monitor and/or control patient use of hospital and specialist services. She pointed out that there have been advocates for such a system for over 50 years-partly to assure appropriate levels of care to the entire population, partly to reduce the costs of more expensive specialist care. She went on to discuss the issues inherent in such a concept.

Teaching geriatric care: report on an experimental second-year elective.

To help fill the growing need for medical school instruction in geriatric care, the Departments of Family Medicine and Community Medicine at the College of Medicine and Dentistry of New Jersey-Rutgers Medical School, in cooperation with Roosevelt Hospital, a nearby county-supported chronic disease facility, joined to develop an experimental second-year elective, given for the first time in the fall of 1976. The curriculum involved 11 three-hour sessions covering a variety of medical and socioeconomic topics. Enrollment was limited to 12 students. Reaction was positive on the part of students, patients, and faculty, especially with respect to student attitudes toward the elderly. Improvements are suggested in six major areas.

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.