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Byline: T. P. van Staa (1), T. P. van Staa (2), T. P. van Staa (3), H. G. M. Leufkens (2), C. Cooper (1) Keywords: Key words:Bone -- Bone density -- Fracture -- Glucocorticoids -- Iatrogenic disease -- Meta-analysis -- Review Abstract: Studies of oral corticosteroid dose and loss of bone mineral density have reported inconsistent results. In this meta-analysis, we used information from 66 papers on bone density and 23 papers on fractures to examine the effects of oral corticosteroids on bone mineral density and risk of fracture. Strong correlations were found between cumulative dose and loss of bone mineral density and between daily dose and risk of fracture. The risk of fracture was found to increase rapidly after the start of oral corticosteroid therapy (within 3 to 6 months) and decrease after stopping therapy. The risk remained independent of underlying disease, age and gender. We conclude that oral corticosteroid treatment using more than 5 mg (of prednisolone or equivalent) daily leads to a reduction in bone mineral density and a rapid increase in the risk of fracture during the treatment period. Early use of preventive measures against corticosteroid-induced osteoporosis is recommended. Author Affiliation: (1) MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK, GB (2) Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands, NL (3) Procter &amp Gamble Pharmaceuticals, Staines, UK, GB Article note: Received: 14 January 2001 / Accepted: 25 March 2002

Byline: T. P. van Staa (1), T. P. van Staa (2), T. P. van Staa (3), H. G. M. Leufkens (2), C. Cooper (1) Keywords: Key words:Epidemiology -- Fracture risk -- Fractures -- Osteoporosis -- Risk factors Abstract: The extent to which a fracture at one skeletal site predicts further fractures at other sites remains uncertain. We addressed this issue using information from the UK General Practice Research Database, which contains the medical records of general practitioners our study population consisted of all patients aged 20 years or older with an incident fracture during 1988 to 1998. We identified 222369 subjects (119317 women, 103052 men) who had sustained at least one fracture during follow-up. There was a 2- to 3-fold increase in the risk of subsequent fractures at different skeletal sites. A patient with a radius/ulna fracture had a standardized incidence ratio (SIR) of 3.0 (95% confidence interval 2.9--3.1) for fractures at a different skeletal site for initial vertebral fracture, this ratio was 2.9 (2.8--3.1) and for initial femur/hip fracture it was 2.6 (2.5--2.7). The SIRs were generally higher among men than women. Men aged 65--74 years with a radius/ulna fracture or vertebral fracture had substantially higher rates of subsequent femur/hip fractures than expected SIRs were 6.0 (3.4--9.9) and 13.4 (7.3--22.5). Corresponding SIRs among women of similar age were 3.3 (2.8--3.9) and 5.8 (4.1--8.1), respectively. Men and women aged 65 years or older with a vertebral fracture had a 5-year risk of femur/hip fracture of 6.7% and 13.3%, respectively. Our results indicate that fractures at any site are strong risk factors for subsequent fractures, among both elderly men and women. Author Affiliation: (1) MRC Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK, GB (2) Department of Pharmacoepidemiology and Pharmacotherapy, University of Utrecht, Utrecht, The Netherlands , NL (3) Procter &amp Gamble Pharmaceuticals, Staines, UK, GB Article note: Received: 19 November 2001 / Accepted: 13 February 2002

Objective: Turkey's health reforms started in 2003 with providing changes in regulatory, financing, and healthcare services. Access to health care and pharmaceuticals increased rapidly, and this resulted with an increase in public pharmaceutical expenditures. Our study aims to quantify and to evaluate the impact of a specific process within the Turkish system called "Medicines Brought From Abroad" (MBFA).Methods: We reviewed the general reimbursement legislations of Social Security Institution (SSI), the guideline on MBFA, the SSI reimbursement list, the list of MBFA published by the Ministry of Health to describe the current supply mechanism of medicines and, in particular, the role of MBFA.Results: Total costs of the of MBFA medicines over the period 2011-17 went up to more than $520 million, which takes 7.5 percent of total public pharmaceutical expenditure for 2017. Our results showed that MBFA provides access to many orphan drugs and in total, forty-two orphan drugs listed in MBFA accounted for 83 percent of all MBFA budget in the year 2017. Nine of the top ten MBFA medicines were orphan drugs and total costs were $408 million. The highest budget impact was for eculizumab for "paroxysmal nocturnal hemoglobinuria" (PNH), covering 31 percent of total MBFA costs and 2.3 percent of overall drug costs in 2017.Conclusions: Turkey faced significant challenges for creating an access pathway for innovative medicines while continuing the sustainability of the public pharmaceutical budget like many other countries. Therefore, it may be argued that Turkey needs to create an independent health technology assessment organization to provide sustainable access to medicines in the future. [ABSTRACT FROM AUTHOR]

The medical records of general practitioners (GPs) in the UK (from the General Practice Research Database) were used to evaluate the risk of colorectal cancer (CRC) in patients with a [...]

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Background Drug-induced photosensitivity is difficult to predict and remains a challenge for both the dermatological clinical practice and pharmacovigilance. Purpose To assess the association between spectroscopic and molecular characteristics and the occurrence of photosensitivity reactions. Methods For 143 well-known photosensitisers (e.g. tetracyclines, diuretics), we retrieved information on spectroscopic and molecular parameters, including: absorption maximum λmax, molar absorption coefficient ε, area under the absorption curve (AUC), molecular weight and configuration, hetero and aromatic halogen atoms, lipophilicity (log P) and acid/base status (pKa). In the WHO-ADR database, all reports with suspected adverse drug reactions of the study drugs were selected. We identified all reports on photosensitivity reactions and defined them as cases. All other reports were selected as non-cases. A case-non-case approach was performed to assess the spectroscopic and molecular exposure variables as a factor for photosensitivity reactions. Logistic regression was used to calculate odds ratios (OR) with 95% confidence intervals (CI). Results A λmax between 290 and 320 nm (OR 3.74, 95% CI 3.45-4.06), and an ε > 20 000 M−1 cm−1 (OR 5.49, 95% CI 5.10-5.92) were highly associated with the reporting of photosensitivity reactions. Risk of the photosensitivity reactions was significantly increased among intermediate or high AUCs compared to low AUC. Low molecular weight and aromatic halogen atoms were associated with photosensitivity reactions (OR 2.37, 95% CI 2.07-2.71 resp. OR 3.37, 95% CI 3.15-3.61) as were log p < 1 and pKa < 7. Conclusion The reporting of photosensitivity reactions to established phototoxic drug classes is strongly influenced by spectroscopic and physicochemical characteristics of individual drugs. Copyright © 2009 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Souverein PC, Van Staa TP, Egberts ACG, De la Rosette JJMCH, Cooper C, Leufkens HGM. (Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands; Southampton University Hospital, Southampton, UK; and Academic Medical Centre, Amsterdam, The Netherlands). Use of α-blockers and the risk of hip/femur fractures. J Intern Med 2003; 254: 548–554. To study the association between use of α-blockers and risk of hip/femur fractures. Population-based case–control study. General Practice Research Database. Cases were defined as men, aged 40 years and older with a first diagnosis for hip/femur fracture. Controls were matched 1 : 1 on gender, year of birth and general practitioner-practice. In all, 4571 cases and an equal number of controls were identified. Current use of α-blockers (prazosin, doxazosin, indoramin, terazosin, alfuzosin and tamsulosin) was compared with non-use of α-blockers. Current use of α-blockers on the index date was associated with an increased risk of hip/femur fracture [adjusted odds ratio (OR) 1.9, 95% confidence interval (CI): 1.1–3.0] in the overall analysis. The effect was particularly strong for first prescriptions within a treatment episode (adjusted OR 5.1, 95% CI: 1.0–31.7) and during the first month of treatment (adjusted OR 4.1, 95% CI: 0.7–23.9). Stratification according to indication of use showed that current use of α-blockers was not associated with hip/femur fracture in men with a diagnosis of benign prostatic hyperplasia (adjusted OR 1.0, 95% CI: 0.4–2.5), but was associated in men who used α-blockers for cardiovascular disease (adjusted OR 2.8, 95% CI: 1.4–5.4). Current use of α-blockers was associated with an increased risk of hip/femur fracture and with the start of a new treatment episode. The effect seemed to be confined to patients who used α-blockers for cardiovascular disease. Caution with respect to first-dose effects related to the initiation of a new episode of α-blocker treatment is advised. [ABSTRACT FROM AUTHOR]

Objective: To develop a comprehensive and easily applicable prognostic model predicting mortality risk in patients with moderate to severe heart failure. Design: Prospective follow up study. Setting: Seven general hospitals in the Netherlands. Patients: 152 outpatients with heart failure or patients admitted to hospital because of heart failure, who were included in a randomised trial to assess the impact of a pharmacist led intervention to improve drug compliance. Duration of follow up was at least 18 months. Main outcome measures: Multivariable logistic regression modelling was used to evaluate information from history, physical examination (for example, blood pressure), drug use, and quality of life questionnaires that independently contributed to the prediction of death. The area under receiver operating characteristic curves (AUC) was used to estimate the predictive ability of the prognostic models. Results: During the 18 months of follow up, 51 patients (34%) died. Independent predictors of mortality were diabetes mellitus, a history of renal dysfunction (or higher creatinine), New York Heart Association (NYHA) functional class III or IV, lower weight or body mass index, lower blood pressure, ankle oedema, and higher scores on a disease specific quality of life questionnaire. The use of β blockers was predictive of a better prognosis. These factors were used to derive various prediction formulas. A model based on medical history, weight, presence of oedema, and lower blood pressure had an AUC of 0.77. Addition of use of β blockers to this model improved the AUC to 0.80. Addition of NYHA class increased the AUC to 0.84. Data on quality of life did not improve the AUC further (AUC 0.85). Conclusions: A prognostic model produced on the basis of easily obtainable information from medical history and physical examination can adequately stratify heart failure patients according to their short term risk of death. [ABSTRACT FROM AUTHOR]

Sildenafil utilization was prospectively evaluated among 1.53 men with a history of erectile dysfunction (ED)-prescription drug use prior to starting sildenafil and 164 men who were new starters of ED-prescription drugs. Further, some determinants of sildenafil discontinuation were identified. During a median follow-up period of 18 months 45% of all patients discontinued sildenafil treatment, regardless of earlier treatment history. However, patients with a history of drug treatment for ED were nearly eight times as likely to switch or re-start another EDprescription drug after discontinuing sildenafil compared to previously untreated users. Age > 60 y, diabetes medication, nitrate use, and use of incontinence pads (a proxy for disease/surgery in the pelvic region) were associated with an increased likelihood of discontinuing sildenafil. Although the introduction of sildenafil reduced the barrier to seek medical help for erectile problems, sildenafil treatment failure in previously untreated patients results in a high dropout rate from further ED drug treatment of any kind. [ABSTRACT FROM AUTHOR]

Discusses the use of spontaneous reports of adverse events to estimate the risk for developing cardiac arrhythmias due to the systemic use of nonsedating antihistamine drugs in the Netherlands. Risk estimate before and after the regulatory action to recall the over-the-counter status of some of these drugs; Indication that nonsedating antihistamines might have an increased risk for inducing arrhythmias.

Objective: During proton pump inhibitor (PPI) use, in clinical trials, headache is one of the most frequently reported adverse events (frequency 1.3 to 8.8%), while results of one observational study indicate that headache is the fifth most frequently reported adverse event (incidence densities 2.5 to 4.6 per 1000 patient-months of exposure). However, there are no observational studies performed regarding the occurrence and features of headache during use of PPIs in daily practice. For this reason this study was set up with the aim to assess the incidence and characteristics of headache and to investigate possible associated co-factors in PPI users in daily practice.Design: Data were used from a prospective, observational study in which 10 008 lansoprazole users were followed over time. The study was designed according to the Safety Assessment of Marketed Medicines guidelines. A nested case-control design was used to compare PPI users reporting headache or not.Results: The frequency of headache was 2.5% in users of lansoprazole and the incidence density was 7.2 per 1000 patient-months of PPI lansoprazole use. Two-thirds of patients with headache had tension headache and one-third had migraine. The analysis of co-factors revealed that women, patients with previous use of analgesics and patients reporting several adverse events, were at risk to develop headache during PPI use. Patients with headache also, significantly more often, reported diarrhoea, nausea and dizziness. A discontinuation of PPI therapy resulted in a cessation or reduction of the headache in 80.0% (20 of 25).Conclusions: As can be expected, headache was reported less frequently in this study compared with clinical trials with lansoprazole. The incidence density was comparable with other observational data of lansoprazole and omeprazole users. Besides several commonly accepted co-factors such as female gender and a history of analgesic use, we also found the reporting of other adverse events to be associated with the reporting of headache during lansoprazole use. The cessation of headache after a discontinuation of use of the PPI and the observed dose relationship suggested that headache was indeed an adverse effect of lansoprazole use. [ABSTRACT FROM AUTHOR]

Aims The aim of the present study was to investigate whether use of specific antibiotic drugs decreases the risk of coronary heart disease in diabetes mellitus type 2 patients.Methods and Results Data were obtained from the PHARMO Record Linkage System comprising pharmacy records and hospitalizations for all 450000 residents of eight Dutch cities. In a nested case-control study among diabetes mellitus type 2 patients, 244 cases with a first hospitalization for coronary heart disease and 686 controls without coronary heart disease matched on age, sex, calendar time, and registration date in PHARMO RLS were selected. Use of antibiotic drugs among cases and controls was determined over 3 years prior to the event. Use of fluorquinolones for more than 14 days compared to no use of fluorquinolones was associated with a lower risk of coronary heart diseases (ORadj=0·30 (95%CI: 0·12–0·75)). No association between tetracycline, macrolide and lincosamide treatment, or other antibiotic drugs (penicillins, cephalosporines, sulphonamides and trimethoprim), and the risk of coronary heart disease was found.Conclusion Our results suggest that treatment with fluorquinolones in doses commonly prescribed in routine clinical practice is associated with a reduction in the risk of coronary heart diseases among diabetes mellitus type 2 patients. Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved. [ABSTRACT FROM PUBLISHER]

Background: Proton pump inhibitors (PPI) demonstrate high healing rates of 85 98% in clinical trials. Due to the limited knowledge regarding response and non response to lansoprazole in daily practice and for the reason that resistance to PPIs is scarce, we investigated factors possibly associated with non response. Methods: Data were used from a prospective, open label, observational follow up study in which 10,008 lansoprazole users were followed over time. The study was designed according to the SAMM guidelines. A matched nested case control design was used to compare non responding (cases) and responding (controls) lansoprazole users. Non response was defined as worsening or non improvement of symptoms at the first evaluation after at least 8 weeks of use, response as disappearance or improvement of symptoms within 8 weeks of use. Controls were matched for the evaluating physician. Results: A total of 186 non responders and 372 responders to PPI treatment were identified as cases and controls. Age of over 60 years, heavy smoking and previous use of PPIs were significantly more common in non responding patients compared with responding patients. There were no differences found between the reported diagnosis regarding response. Conclusion: In daily clinical practice, previous use of PPIs, heavy smoking and an age > 60 years were significantly associated with non response to treatment with lansoprazole. Previous use of PPIs in non responding patients might suggest resistance to PPIs. The knowledge that non response drives non response may encourage physicians to follow PPI users with previous PPI use more closely. [ABSTRACT FROM AUTHOR]

Aim of study: The role of pharmacists in today's healthcare is changing rapidly. As they are close to the prescribing process, pharmacists are in the position to identify and adjust prescribing errors before dispensing. The objective of this study was to identify relevant determinants of interventions directly linked to prescription processing in community pharmacy. Methods: As part of a yearly continuing education programme, all community pharmacies in the region of 'Zeeland' (N=23) in the south west of The Netherlands kept detailed records of all interventions directly linked to prescription processing during one week in May 1998. For every patient involved in an intervention, a control patient was matched on pharmacy practice, date, gender and age. Results: A total of 39,357 prescriptions were evaluated by the 23 pharmacies during the one week intervention programme. Out of these, one out of 10 resulted into an intervention. Being a first prescription in a new treatment episode was found to be a significant determinant (OR 1.75, 95 CI% 1.18 2.33). Variables reflecting drug therapy complexity (> 3 prescribers, > 15 prescriptions in 3 months before, > 3 different medications) showed all ORs higher than 1.00, but not significant. When looking at the individual drug categories, anti infectives, respiratory drugs and cardiovascular medicines came out as important drug classes for intervention risk. We could not find any association between the number of signals per pharmacy and the number of interventions. Conclusion: The 'whistle blower' model of pharmacy based interventions is a valid one but needs a targeted and integral way of implemented thinking and use of information technology. In such an environment, interventions are a logical step of in process quality control in the drug usage system. [ABSTRACT FROM AUTHOR]