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1.  Partial Agonism of 5-HT3 Receptors: A Novel Approach to the Symptomatic Treatment of IBS-D 
ACS Chemical Neuroscience  2012;4(1):43-47.
Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain, discomfort, and altered bowel habits, which have a significant impact on quality of life for approximately 10–20% of the population. IBS can be divided into three main types IBS-D (diarrhea predominant), IBS-C (constipation predominant), and mixed or alternating IBS. 5-HT3 receptor antagonism has proved to be an efficacious treatment option for IBS-D. For example, alosetron displays efficacy in the treatment of multiple symptoms, including abdominal pain, discomfort, urgency, stool frequency and consistency. However, significant constipation occurred in approximately 25% of patients, leading to withdrawal of up to 10% of patients in clinical trials. Targeting compounds with partial agonist activity at the 5-HT3 receptor represents a mechanistic departure from the classic 5-HT3 receptor antagonist approach and should result in agents that are applicable to a broader array of IBS patient populations. Attenuation of the activity of the ion channel without completely abolishing its function may control or normalize bowel function without leading to a total block associated with severe constipation. We have identified a new class of selective, orally active 5-HT3 receptor ligands with high 5-HT3 receptor affinity and low partial agonist activity currently in preclinical development that should offer a significant advantage over existing therapies.
PMCID: PMC3548414  PMID: 23342199
5-HT3 receptor; partial agonist; irritable bowel syndrome; IBS
2.  Impact of therapy escalation on ambulatory care costs among patients with type 2 diabetes in France 
This study compares annual ambulatory care expenditures per patient with type 2 diabetes mellitus (T2DM) in France according to treatment phase and renal function status.
Records from patients with T2DM were extracted from a health insurance database. Patients were classified in subgroups, by treatment phase: oral/GLP1 monotherapy, double therapy, triple therapy or insulin therapy, and according to renal function status (identified using pharmacy, lab and consultation claims). Annual ambulatory expenditures were estimated from the national insurance perspective by year (from 2005 to 2010) and subgroup.
The number of patients ranged from 9,682 to 11,772 between 2005 and 2010. The average annual expenditure per individual in 2010 ranged from €3,017 (standard deviation: €3,829) for monotherapy to €3,609 ± €3,801 for triple therapy, and €7,398 ± €5,487 with insulin (adjusted ratio insulin therapy/monotherapy: 2.36, p < 0.001). Similar differences between treatement stages were found in previous years. Additional costs for insulin were mainly related to nursing care (multiplied by 18.42, p < 0.001), medical devices and pharmacy costs. DM-attributable drug costs were mainly related to antidiabetic drugs (28% for monotherapy to 71% for triple therapy), but also to cardiovascular system drugs (21% for monotherapy to 51% with insulin) and nervous system drugs (up to 8% with insulin). Declining renal function was associated with an increase in expenses by 12% to 53% according to treatment stage.
Overall, ambulatory care expenditures increase with treatment escalation and declining renal function amongst patients with T2DM. Insulin therapy is associated with substantially increased costs, related to pharmacy, nursing care and medical device costs.
PMCID: PMC3653727  PMID: 23627403
Cost analysis; Type 2 diabetes mellitus; Oral antidiabetics; Insulin; Renal function
3.  Transplantation for Acute Liver Failure in Patients Exposed to NSAIDs or Paracetamol (Acetaminophen) 
Drug Safety  2013;36(2):135-144.
Most NSAIDs are thought to be able to cause hepatic injury and acute liver failure (ALF), but the event rates of those leading to transplantation (ALFT) remain uncertain.
The aim of the study was to estimate population event rates for NSAID-associated ALFT
This was a case-population study of ALFT in 57 eligible liver transplant centres in seven countries (France, Greece, Ireland, Italy, The Netherlands, Portugal and the UK). Cases were all adults registered from 2005 to 2007 for a liver transplant following ALFT without identified clinical aetiology, exposed to an NSAID or paracetamol (acetaminophen) within 30 days before the onset of clinical symptoms. NSAID and paracetamol population exposures were assessed using national sales data from Intercontinental Marketing Services (IMS). Risk was estimated as the rate of ALFT per million treatment-years (MTY).
In the 52 participating centres, 9479 patients were registered for transplantation, with 600 for ALFT, 301 of whom, without clinical aetiology, had been exposed to a drug within 30 days. Of these 301 patients, 40 had been exposed to an NSAID and 192 to paracetamol (81 of whom were without overdose).
Event rates per MTY were 1.59 (95 % CI 1.1–2.2) for all NSAIDs pooled, 2.3 (95 % CI 1.2–3.9) for ibuprofen, 1.9 (95 % CI 0.8–3.7) for nimesulide, 1.6 (95 % CI 0.6–3.4) for diclofenac and 1.6 (95 % CI 0.3–4.5) for ketoprofen. For paracetamol, the event rate was 3.3 per MTY (95 % CI 2.6–4.1) without overdoses and 7.8 (95 % CI 6.8–9.0) including overdoses.
ALF leading to registration for transplantation after exposure to an NSAID was rare, with no major difference between NSAID. Non-overdose paracetamol-exposed liver failure was twice more common than NSAID-exposed liver failure.
Electronic supplementary material
The online version of this article (doi:10.1007/s40264-012-0013-7) contains supplementary material, which is available to authorized users.
PMCID: PMC3568201  PMID: 23325533
4.  Contribution of prolonged-release melatonin and anti-benzodiazepine campaigns to the reduction of benzodiazepine and z-drugs consumption in nine European countries 
Benzodiazepines (BZD) and benzodiazepine receptor agonists (zolpidem, zaleplon, zopiclone, altogether Z-drugs) are most commonly prescribed for the treatment of insomnia. However, long-term use of BZD/Z-drugs is associated with major adverse events including, but not limited to, falls and fractures, domestic and traffic accidents, confusion, cognitive impairment, Alzheimer's disease and cancer. The prolonged use of these drugs is thought to be related to severe withdrawal symptoms and potential dependency. The chronic and extensive use of BZD/Z drugs has become a public health issue and has led to multiple campaigns to reduce both prescription and consumption of BZD/Z-drugs. Prolonged-release (PR) melatonin is the first of a new class of melatonin receptor agonist drugs that has demonstrated clinically relevant efficacy on improving quality of sleep and morning alertness, with a good safety profile.
This study aimed to analyze and evaluate the impact of anti-BZD/Z-drugs campaigns and the availability of alternative pharmacotherapy (PR-melatonin) on the consumption of BZD and Z-drugs in several European countries.
Annual sales data from nine European countries were extracted from the IMS sales database and analyzed to determine whether trends in use of these treatment options were attributed to campaigns and/or availability and affordability of safer alternatives on the market.
Campaigns aiming to reduce the use of BZD/Z-drugs failed when they were not associated with the availability and market uptake of PR-melatonin. The reimbursement of PR-melatonin supports better penetration rates and a higher reduction in sales for BZD/Z-drugs.
PMCID: PMC3610030  PMID: 23114457
Insomnia; Benzodiazepines (BZD); Benzodiazepine receptor agonists; Z-drugs; Prolonged-release (PR) melatonin; Addiction
5.  Immunomodulatory and antitumour effects of abnormal Savda Munziq on S180 tumour-bearing mice 
Abnormal Savda Munziq (ASMq), a traditional uyghur medicine, has shown anti-tumour properties in vitro. This study attempts to confirm these effects in vivo and measure effects on the immune system.
Kunming mice transplanted with Sarcoma 180 cells were treated with ASMq (2–8 g/kg/day) by intra-gastric administration compared to model and cyclophosphamide (20 mg/kg/day). After the 14th day post tumour implant, thymus, liver, spleen and tumours were removed, weighed, and processed for histopathological analysis. Blood samples were also taken for haematological and biochemical analyses including TNF-α , IL-1 β and IL-2. Splenic lymphocyte function was measured with MTT; lymphocyte subpopulations were measured by flow cytometry.
ASMq treated animals had reduced tumour volume compared to model and increased concentrations of TNF-α, IL-1β and IL-2 compared to untreated and to cyclophosphamide-treated animals. No histopathological alterations were observed. The absence of viable S180 cells and the presence of necrotic cells and granulation tissue were observed in tumour tissue of treated animals. The effect on T lymphocytes was unclear.
ASMq confirmed in vivo anti-tumour effects observed in vitro, which may be at least in part mediated by increased immune activity.
PMCID: PMC3489790  PMID: 22978453
6.  The impact of the Uighur medicine abnormal savda munziq on antitumor and antioxidant activity in a S180 and Ehrlich ascites carcinoma mouse tumor model 
Pharmacognosy Magazine  2012;8(30):141-148.
This study was designed to study the antitumor and antioxidant activity of Uighur medicine abnormal savda munziq (ASMq) in the S180 and Ehrlich ascites carcinoma mice tumor model.
Materials and Methods:
The serum levels of superoxide dismutase (SOD), malonaldehyde (MDA), and glutathione-catalase (GSH-PX) were analyzed, and the mice were also subjected to a hypoxia tolerance test. Their climbing ability was also analyzed.
The findings of the study revealed that ASMq-treatment leads to an increase in blood serum SOD and GSH-PX levels but a decrease in blood serum MDA levels. Moreover, ASMq-treatment enhanced the survival time of mice maintained under hypoxic conditions and improved their mice climbing ability.
The results of this study indicate that ASMq has obvious antitumor and antioxidative effects.
PMCID: PMC3371436  PMID: 22701288
Abnormal savda munziq; antioxidant; antitumor
7.  Ethanol Extract of Abnormal Savda Munziq, a Herbal Preparation of Traditional Uighur Medicine, Inhibits Caco-2 Cells Proliferation via Cell Cycle Arrest and Apoptosis 
Aims. Study the effect of Abnormal Savda Munziq (ASMq) ethanol extract on the proliferation, apoptosis, and correlative gene, expression in colon cancer cells (Caco-2) to elucidate the molecular mechanisms responsible for the anticancer property of Abnormal Savda Munziq. Materials and Methods. ASMq ethanol extract was prepared by a professional pharmacist. Caco-2 cells were treated with different concentration of ASMq ethanol extract (0.5–7.5 mg/mL) for different time intervals (48 and 72 h). Antiproliferative effect of ASMq ethanol extract was determined by MTT assay; DNA fragmentation was determined by gel electrophoresis assay; cell cycle analysis was detected by flow cytometer; apoptosis-related gene expression was detected by RT-PCR assay. Results. ASMq ethanol extract possesses an inhibition effect on Caco-2 cells proliferation, induction of cell apoptosis, cell cycle arrest in sub-G1 phase, and downregulation of bcl-2 and upregulation of Bax gene expression. Conclusion. The anticancer mechanism of ASMq ethanol extract may be involved in antiproliferation, induction of apoptosis, cell cycle arrest, and regulation of apoptosis-related gene expression such as bcl-2 and Bax activity pathway.
PMCID: PMC3138059  PMID: 21785650
8.  Inhibition of Cell Growth and Cellular Protein, DNA and RNA Synthesis in Human Hepatoma (HepG2) Cells by Ethanol Extract of Abnormal Savda Munziq of Traditional Uighur Medicine 
Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation, commonly used for the treatment and prevention of cancer. We tested the effects of ethanol extract of ASMq on cultured human hepatoma cells (HepG2) to explore the mechanism of its putative anticancer properties, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide, neutral red and lactate dehydrogenase (LDH) leakage assays, testing the incorporation of 3[H]-leucine and 3[H]-nucleosides into protein, DNA and RNA, and quantifying the formation of malondialdehyde-thiobarbituric acid (MDA) adducts. ASMq ethanol extract significantly inhibited the growth of HepG2 and cell viability, increased the leakage of LDH after 48 hours or 72 hours treatment, in a concentration- and time-dependent manner (P < .05). Cellular protein, DNA and RNA synthesis were inhibited in a concentration- and time-dependent manner (P < .05). No significant MDA release in culture medium and no lipid peroxidation in cells were observed. The results suggest that the cytotoxic effects of ASMq ethanol extract might be related to inhibition of cancer cell growth, alteration of cell membrane integrity and inhibition of cellular protein, DNA and RNA synthesis.
PMCID: PMC3136333  PMID: 18955370
9.  Abnormal Savda Munziq, an Herbal Preparation of Traditional Uighur Medicine, May Prevent 1,2-dimethylhydrazine-Induced Rat Colon Carcinogenesis 
The study tried to assess the chemoprotective effect of abnormal Savda Munziq (ASMq) on 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis. Male F344 rats were randomized into eight groups: Group 1 was served as control, no DMH injection was given and treated daily with normal saline. Rats in Groups 2–8 were given a single intraperitoneal injection of DMH (20 mg/kg body weight) at the beginning of the study. Group 2 was served as negative control, administered with normal saline until the end of the experiment after the single DMH injection. Groups 3–5 were served as pretreatment group, administered with ASMq ethanol extract at 400, 800 and 1600 mg/kg body weight, respectively, until the 45th day, continued by normal saline administration for another 45 days. Groups 6–8 were served as the treatment group, administered with normal saline for the first 45 days from the day of DMH injection, ASMq ethanol extract at three different doses to be administered until the end of the second 45th day. All rats were sacrificed at 91st day and the colons were analyzed for aberrant crypt foci (ACF) formation and crypt multiplicity. Results showed that ASMq ethanol extract reduced the number of ACF, AC and crypt multiplicity significantly (P < .05). It suggested that ASMq ethanol extract had chemoprotective effects on DMH-induced colon carcinogenesis, by suppressing the development of preneoplastic lesions, and probably exerted protection against the initiation and promotion steps of colon carcinogenesis.
PMCID: PMC3136791  PMID: 19561161
10.  Anti-Inflammatory, Immunomodulatory, and Heme Oxygenase-1 Inhibitory Activities of Ravan Napas, a Formulation of Uighur Traditional Medicine, in a Rat Model of Allergic Asthma 
Ravan Napas (RN) is a traditional formula used to treat pulmonary symptoms and diseases such as coughing, breathing difficulty, and asthma in traditional Uighur medicine. The purpose of this study was to investigate the anti-inflammatory, and immuno-modulatory activity of RN in a well-characterized animal model of allergic asthma. Rats were sensitized with intraperitoneal (ip) ovalbumin (OVA) and alum, and then challenged with OVA aerosols. The asthma model rats were treated with RN; saline- and dexamethasone- (DXM-) treated rats served as normal and model controls. The bronchoalveolar lavage fluid (BALF) cellular differential and the concentrations of sICAM-1, IL-4, IL-5, TNF-α, INF-γ, and IgE in serum were measured. Lung sections underwent histological analysis. The immunohistochemistry S-P method was used to measure the expression of ICAM-1 and HO-1 in the lung. RN significantly reduced the number of inflammatory cells in BALF and lung tissues, decreased sICAM-1, IL-4, IL-5, TNF-α, and IgE in serum, and increased serum INF-γ. There was a marked suppression of ICAM-1 and HO-1 expression in the lung. Our results suggest that RN may have an anti-inflammatory and immuneregulatory effect on allergic bronchial asthma by modulating the balance between Th1/Th2 cytokines.
PMCID: PMC2952321  PMID: 20953388
11.  Phytalgic®, a food supplement, vs placebo in patients with osteoarthritis of the knee or hip: a randomised double-blind placebo-controlled clinical trial 
Arthritis Research & Therapy  2009;11(6):R192.
The medicinal treatment of osteoarthritis (OA) is mostly symptomatic to relieve pain and incapacity with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), drugs with well-known risks. Complementary medicines might reduce the symptoms of OA and decrease the need for NSAIDs. This study tested the effects of a food supplement, Phytalgic®, on pain and function in patients with osteoarthritis and their use of analgesic and NSAIDs.
A randomized double-blind parallel-groups clinical trial compared Phytalgic® (fish-oil, vitamin E, Urtica dioica) to a placebo for three months, in 81 patients with OA of the knee or hip using NSAIDs and/or analgesics regularly. The main outcome measures were use of NSAIDs (in Defined Daily Doses per day - DDD/day) or analgesics (in 500 mg paracetamol-equivalent tablets per week (PET/week) measured each month, and Western Ontario-McMaster University Osteo-Arthritis Index (WOMAC) function scales.
After three months of treatment, the mean use of analgesics in the active arm (6.5 PET/week) vs. the placebo arm (16.5) was significantly different (P < 0.001) with a group mean difference of -10.0 (95% CI: -4.9 to -15.1). That of NSAIDs in the active arm (0.4 DDD/day) vs the placebo arm (1.0 DDD/day) was significantly different (P = 0.02) with a group mean difference of - 0.7 DDD/day (95% CI: -0.2 to -1.2). Mean WOMAC scores for pain, stiffness and function in the active arm (respectively 86.5, 41.4 and 301.6) vs the placebo arm (resp. 235.3, 96.3 and 746.5) were significantly different (P < 0.001) with group mean differences respectively of -148.8 (95% CI: -97.7 to -199.9), -54.9 (95% CI: -27.9 to -81.9) and -444.8 (95% CI: -269.1 to -620.4).
The food supplement tested appeared to decrease the need for analgesics and NSAIDs and improve the symptoms of osteoarthritis.
Trial registration NCT00666523.
PMCID: PMC3003499  PMID: 20015358
12.  The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies 
To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area.
Data sources
The bibliographic search was done in Medline electronic database using the keywords: ((accident* or crash*) and traffic and drug*) leading to 1141 references. Additional references were retrieved from the Safetylit website and the reference lists of selected studies. Original articles published in English or French, between April 1st, 1979 and July 31st, 2008, were considered for inclusion. We excluded descriptive studies, studies limited to alcohol or illicit drug involvement, and investigations of injuries other than from traffic crashes. Studies based on laboratory tests, driving simulators or on-the-road driving tests were also excluded. Eligible studies had to evaluate the causal relationship between the use of medicinal drugs and the risk of traffic crashes. Study quality was assessed by two independent experts, according to a grid adapted from the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.
22 studies of variable methodological quality were included. Definition of drug exposure varied across studies and depended on the data sources. Potential confounding due to the interaction between the effects of the medicinal drug and disease-related symptoms was often not controlled. The risk of motor-vehicle crashes related to benzodiazepines has been amply studied and demonstrated. Results for other medicinal drugs remain controversial.
There is a need for large studies, investigating the role of individual substances in the risk of road traffic crashes.
PMCID: PMC2780583  PMID: 19418468
Accidents, Traffic; statistics & numerical data; Benzodiazepines; adverse effects; Bias (Epidemiology); Epidemiologic Research Design; Humans; Odds Ratio; Pharmaceutical Preparations; adverse effects; Risk Assessment; Risk Factors;  traffic crashes; medicinal drugs; methodology
13.  The self-reported Montgomery-Åsberg depression rating scale is a useful evaluative tool in major depressive disorder 
BMC Psychiatry  2009;9:26.
The use of Patient-reported Outcomes (PROs) as secondary endpoints in the development of new antidepressants has grown in recent years. The objective of this study was to assess the psychometric properties of the 9-item, patient-administered version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S).
Data from a multicentre, double-blind, 8-week, randomised controlled trial of 278 outpatients diagnosed with Major Depressive Disorder were used to evaluate the validity, reliability and sensitivity to change of the MADRS-S using psychometric methods. A Receiver Operating Characteristic (ROC) curve was plotted to identify the most appropriate threshold to define perceived remission.
No missing values were found at the item level, indicating good acceptability of the scale. The construct validity was satisfactory: all items contributed to a common underlying concept, as expected. The correlation between MADRS-S and physicians' MADRS was moderate (r = 0.54, p < 0.001) indicating that MADRS-S is complementary rather than redundant to the MADRS. Cronbach's alpha was 0.84, and the stability over time of the scale, estimated on a sub-sample of patients whose health status did not change during the first week of the study, was good (intraclass correlation coefficient of 0.78). MADRS-S sensitivity to change was shown. Using a threshold value of 5, the definition of "perceived remission" reached a sensitivity of 82% and a specificity of 75%.
Taking account of patient's perceptions of the severity of their own symptoms along with the psychometric properties of the MADRS-S enable its use for evaluative purposes in the development of new antidepressant drugs.
PMCID: PMC2701427  PMID: 19473506
14.  Physicochemical characteristics and bronchial epithelial cell cytotoxicity of Folpan 80 WG® and Myco 500®, two commercial forms of folpet 
Pesticides, in particular folpet, have been found in rural and urban air in France in the past few years. Folpet is a contact fungicide and has been widely used for the past 50 years in vineyards in France. Slightly water-soluble and mostly present as particles in the environment, it has been measured at average concentration of 40.1 μg/m3 during its spraying, 0.16–1.2 μg/m3 in rural air and around 0.01 μg/m3 in urban air, potentially exposing both the workers and the general population. However, no study on its penetration by inhalation and on its respiratory toxicity has been published. The objective of this study was to determine the physicochemical characteristics of folpet particles (morphology, granulometry, stability) in its commercial forms under their typical application conditions. Moreover, the cytotoxic effect of these particles and the generation of reactive oxygen species were assessed in vitro on respiratory cells.
Granulometry of two commercial forms of folpet (Folpan 80WG® and Myco 500®) under their typical application conditions showed that the majority of the particles (>75%) had a size under 5 μm, and therefore could be inhaled by humans. These particles were relatively stable over time: more than 75% of folpet remained in the particle suspension after 30 days under the typical application conditions. The inhibitory concentration (IC50) on human bronchial epithelial cells (16HBE14o-) was found to be between 2.89 and 5.11 μg/cm2 for folpet commercial products after 24 h of exposure. Folpet degradation products and vehicles of Folpan 80 WG® did not show any cytotoxicity at tested concentrations. At non-cytotoxic and subtoxic concentrations, Folpan 80 WG® was found to increase DCFH-DA fluorescence.
These results show that the particles of commercial forms of folpet are relatively stable over time. Particles could be easily inhaled by humans, could reach the conducting airways and are cytotoxic to respiratory cells in vitro. Folpet particles may mediate its toxicity directly or indirectly through ROS-mediated alterations. These data constitute the first step towards the risk assessment of folpet particles by inhalation for human health. This work confirms the need for further studies on the effect of environmental pesticides on the respiratory system.
PMCID: PMC2211752  PMID: 17883864
15.  Online music model could work for journals 
BMJ : British Medical Journal  2005;330(7504):1391.
PMCID: PMC558303  PMID: 15947419
16.  Assessing drug safety 
BMJ : British Medical Journal  2005;330(7490):539-540.
PMCID: PMC552852  PMID: 15746143
17.  Prescription channeling of COX-2 inhibitors and traditional nonselective nonsteroidal anti-inflammatory drugs: a population-based case–control study 
Arthritis Research & Therapy  2005;7(2):R333-R342.
This pharmacoepidemiologic study was conducted to determine whether risk factors for upper gastrointestinal bleeding influenced the prescription of cyclo-oxygenase (COX)-2 inhibitors and traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) at the time when COX-2 inhibitors were first included in the formulary of reimbursed medications. A population-based case–control study was conducted in which the prevalence of risk factors and the medical histories of patients prescribed COX-2 inhibitors and traditional nonselective NSAIDs were compared. The study population consisted of a random sample of members of the Quebec drug plan (age 18 years or older) who received at least one dispensation of celecoxib (n = 42,422; cases), rofecoxib (n = 25,674; cases), or traditional nonselective NSAIDs (n = 12,418; controls) during the year 2000. All study data were obtained from the Quebec health care databases. Adjusting for income level, Chronic Disease Score, prior use of low-dose acetylsalicylic acid, acetaminophen, antidepressants, benzodiazepines, prescriber specialty, and time period, the following factors were significantly associated with the prescription of COX-2 inhibitors: age 75 years or older (odds ratio [OR] 4.22, 95% confidence interval [CI] 3.95–4.51), age 55–74 years (OR 3.23, 95% CI 3.06–3.40), female sex (OR 1.52, 95% CI 1.45–1.58), prior diagnosis of gastropathy (OR 1.21, 95% CI 1.08–1.36) and prior dispensation of gastroprotective agents (OR 1.57, 95% CI 1.47–1.67). Patients who received a traditional nonselective NSAID recently were more likely to switch to a coxib, especially first-time users (OR 2.17, 95% CI 1.93–2.43). Associations were significantly greater for celecoxib than rofecoxib for age, chronic NSAID use, and last NSAID use between 1 and 3 months before the index date. At the time of introduction of COX-2 inhibitors into the formulary, prescription channeling could confound risk comparisons across products.
PMCID: PMC1065326  PMID: 15743481
administrative health care databases; COX-2 inhibitors; nonsteroidal anti-inflammatory drugs; pharmacoepidemiology; prescription channeling
18.  Placebos in medicine 
BMJ : British Medical Journal  2005;330(7481):45.
PMCID: PMC539890  PMID: 15626815
19.  Transparency and trust 
BMJ : British Medical Journal  2004;329(7478):1345-1346.
PMCID: PMC534893  PMID: 15576757
21.  Benzodiazepines and hip fractures in elderly people: case-control study 
BMJ : British Medical Journal  2001;322(7288):704-708.
To determine whether benzodiazepines are associated with an increased risk of hip fracture.
Case-control study.
All incident cases of hip fracture not related to traffic accidents or cancer in patients over 65 years of age. 245 cases were matched to 817 controls.
Emergency department of a university hospital.
Main outcome measures
Exposure to benzodiazepines and other potential risk or protective factors or lifestyle items.
The use of benzodiazepines as determined from questionnaires, medical records, or plasma samples at admission to hospital was not associated with an increased risk of hip fracture (odds ratio 0.9, 95% confidence interval 0.5 to 1.5). Hip fracture was, however, associated with the use of two or more benzodiazepines, as determined from questionnaires or medical records but not from plasma samples. Of the individual drugs, only lorazepam was significantly associated with an increased risk of hip fracture (1.8, 1.1 to 3.1).
Except for lorazepam, the presence of benzodiazepines in plasma was not associated with an increased risk of hip fracture. The method used to ascertain exposure could influence the results of case-control studies.
What is already known on this topicBenzodiazepines increase the risk of elderly people falling in a dose dependent wayTheir role in hip fracture remains disputed, with increased risk sometimes attributed to drugs with a longer half life or those used to induce sleepWhat this study addsBenzodiazepines were not associated with hip fracture either as a group or according to half life or to characterisation as hypnotic or anxiolyticPatients using two or more benzodiazepines may be at higher riskPatients using lorazepam or certain other benzodiazepines may also be at a higher risk of fracture
PMCID: PMC30096  PMID: 11264208

Results 1-21 (21)