Frequency Of Discontinuation Research Articles

Efficacy of chronic hepatitis C therapy with pegylated interferon and ribavirin in patients on methadone maintenance treatment

A considerable number of patients undergoing methadone maintenance treatment (MMT) are not considered for treatment against hepatitis C virus (HCV) infection due to a possible lower adherence and efficacy in this population. We aimed to compare the response rates to HCV treatment in patients with or without MMT. HCV-infected patients who initiated pegylated interferon plus ribavirin were included in this prospective cohort study. The relation between sustained virologic response (SVR) and MMT was analyzed. A total of 214 patients were included in the study [81 (37.9%) with and 133 (62.1%) without MMT]. No differences in HCV and interleukin 28B (rs12979860) genotype distribution were observed between the two groups. Of these patients, 103 (48.1%) achieved SVR. Among the patients who received MMT, 39 (48.1%) reached SVR compared to 64 (48.1%) subjects without MMT (p = 0.99). The frequency of voluntary drop-out and treatment discontinuations due to adverse events was comparable between the patients with and without MMT [10 (12.3%) versus 14 (10.5%), p = 0.68, and 4 (4.9%) versus 9 (6.8%), p = 0.59, respectively]. The efficacy of HCV therapy in MMT patients is similar to that found in subjects not taking methadone. MMT patients should be equally considered for treatment with pegylated interferon plus ribavirin in HCV-infected patients.

Safety and efficacy of sorafenib in hepatocellular carcinoma: the impact of the Child-Pugh score

Sorafenib increases median survival and time to radiological progression in patients with advanced hepatocellular carcinoma, but its benefit for Child-Pugh B patients remains uncertain. To evaluate the safety and efficacy of sorafenib in real-life clinical practice conditions and to assess the influence of Child-Pugh class B on safety and efficacy. All patients treated with sorafenib for advanced hepatocellular carcinoma in our institution were included prospectively. Adverse events, overall survival and time to progression were recorded. A case control study was performed to compare outcome of patients with comparable stages of hepatocellular carcinoma, but a different Child-Pugh class. From March 2007 to May 2009, 120 patients were included. Overall survival was 11.1 months, Child-Pugh A patients (n=100) had significantly higher median survival than Child-Pugh B patients (n=20) (13 vs. 4.5 months, P=0.0008). In multivariate analysis, Child-Pugh class B, α-fetoprotein level and total size of lesions were independent predictive factors of death. Patients with radiological progression in the first 3 months had shorter median survival (5.4 vs. 17.4 months). In a case control study, time to symptomatic progression (2.5 vs. 3.6 months), frequency of adverse events and discontinuation of sorafenib were not correlated with Child-Pugh class. Patients with advanced hepatocellular carcinoma treated with sorafenib had a median survival of 11 months. Sorafenib therapy must be considered with caution in Child-Pugh B patients due to their poor survival. Radiological assessment of tumour progression at an early stage may be advantageous when tailoring sorafenib therapy.

High-Pressure Spectroscopic Study of Hydrous and Anhydrous Cs-Exchanged Natrolites

Structural phase transitions in hydrous Cs-exchanged natrolite (Cs-NAT-hyd) and anhydrous Cs-exchanged natrolite (Cs-NAT-anh) have been investigated as a function of pressure and temperature using micro-Raman scattering and synchrotron infrared (IR) spectroscopy with pure water as the penetrating pressure medium. The spectroscopic results indicate that Cs-NAT-hyd undergoes a reversible phase transition around 4.72 GPa accompanied by the discontinuous frequency shifts of the breathing vibrational modes of the four-ring and helical eight-ring units of the natrolite framework. On the other hand, we observe that Cs-NAT-anh becomes rehydrated at 0.76 GPa after heating to 100 °C and then transforms into two distinctive phases at 2.24 and 3.41 GPa after temperature treatments at 165 and 180 °C, respectively. Both of these high-pressure phases are characterized by the absence of the helical eight-ring breathing modes, which suggests the collapse of the natrolite channel and formation of dense high-pressure polymo...

Going Home on the Right Medications

TRANSITIONS OF CARE—WHEN PATIENTS MOVE ACROSS care sites within the health system—pose both an opportunity and a threat to patient welfare. These transitions are an opportunity because they provide a chance to freshly reevaluate the patient’s medical needs in a new clinical setting. In the case of hospital admission, transitions also offer an opportunity to leverage an acute illness to increase healthy behaviors. To borrow a term from medical education, they are a “teachable moment” in which the threat of a medical illness may facilitate lifestyle changes, medication adherence, or other healthy actions on the part of the patient. However, transitions of care are also a threat, especially for patients with chronic diseases and complex treatment regimens. Either because of miscommunication or simple error, patients may experience unwarranted changes in treatment with potentially deleterious effects on their health. This reality is demonstrated by Bell et al in their report in this issue of JAMA. The authors used a novel populationbased data set containing both hospitalization and outpatient prescription records to study the incidence of potentially unintentional medication discontinuation among Canadian patients aged 66 years or older. The study group included 396 380 patients assessed continuously using 1 of 5 selected medication classes for at least 1 year. Half of the patients were hospitalized at some point during the study period, and the other half acted as matched controls. The authors then compared the frequency of medication discontinuation between hospitalized and nonhospitalized patients, controlling for patient characteristics and excluding patients for whom medication discontinuation was clinically indicated (for example, stopping an anticoagulant for a patient admitted for bleeding). For the 5 medication classes, hospitalization was associated with high rates of medication discontinuation ranging from 4.5% to 19.4%. Moreover, compared with patients who were not hospitalized, hospitalized patients were at increased risk for discontinuing medications from all 5 medication classes, even after adjusting for important confounders. The highest risk was observed among patients admitted to the intensive care unit (ICU). These patients are more severely ill than other hospitalized patients and are subject to more care transitions. The finding of increased risk among ICU patients suggests a provocative dose effect that strengthens the putative link between care transitions and unintentional medication discontinuation. For statins and bloodthinning agents, discontinuing the medication was associated with an increased adjusted composite risk of death, emergency department visit, or emergency hospitalization. Thus, the medication discontinuations were not only common but were also associated with real health consequences. The major limitation of this type of study is that the medication discontinuation may have been intentional. There are a number of valid reasons these medications may have been stopped during the index hospitalization. New contraindications may have arisen that were not captured in the investigators’ administrative database. Physicians may have used the admission as an opportunity to rethink the original medication indication, deciding that the patient was better off without the medication. Patient preferences might also have played a role in that patients may have decided the medication’s adverse effects outweighed any perceived benefits in light of their new clinical condition. However, the authors took a number of steps to minimize these possibilities. All patients had taken the medications continuously for more than 1 year prior to their index hospitalization date, presumably providing ample opportunity for adverse effects to manifest. Almost all patients had an outpatient visit during the year prior to hospitalization, at which the medication indication could have been reevaluated. The investigators only studied medications with solid evidentiary bases and strong benefit-torisk profiles that are unlikely to be stopped without good clinical reasons. The authors also avoided including medications with relatively soft indications and common adverse effects, such as benzodiazepines or nonsteroidal antiinflammatory agents. Ultimately, given the high incidence of medication discontinuation in this study, even if some

Who Is Paying the Price? Loss of Health Insurance Coverage Early in Psychosis

Who Is Paying the Price? Loss of Health Insurance Coverage Early in Psychosis

Discontinuous Galerkin frequency domain forward modelling for the inversion of electric permittivity in the 2D case

ABSTRACTWe have recently developed a discontinuous Galerkin frequency domain modelling algorithm for the solution of the 2D transverse magnetic Maxwell equations. This method is formulated on an unstructured triangular discretization of the computational domain and makes use of a high order polynomial interpolation of the electromagnetic field components within each triangular element. The discontinuous nature of the approximation naturally allows for a local definition of the interpolation order that is, in combination with a possibly non‐conforming local refinement of the mesh, a key ingredient for obtaining a flexible and accurate discretization method. Moreover, heterogeneity of the propagation media is easily dealt with by assuming element‐wise values of the electromagnetic parameters. In this paper, we propose the use of this discontinuous Galerkin frequency domain method as the forward modelling algorithm for solving the inverse problem for the electric permittivity in the 2D case. The inversion process is based on a gradient minimization technique developed by Pratt for seismological applications. Preliminary numerical results are presented for the imaging of a simplified subsurface model with the aim of assessing the performances of the proposed inversion methodology with regards to the number of frequencies, the number of recorded data and the number of sources.

Cilostazol in Acute Ischemic Stroke Treatment (CAIST Trial): A Randomized Double-Blind Non-Inferiority Trial

Background: Aspirin is a proven antiplatelet agent in acute ischemic stroke, and there are no current guidelines for other antiplatelet treatments. We aimed to compare the efficacy and safety of cilostazol with aspirin in acute stroke. Methods: Patients with measurable neurological deficits (NIHSS score ≤15) within 48 h of onset were randomly assigned to cilostazol (200 mg/day) or aspirin (300 mg/day) for 90 days. The primary endpoint was a modified Rankin Scale (mRS) score of 0–2 at 90 days. Cardiovascular events, bleeding complications, and other functional outcomes were also assessed. Statistical analysis was carried out by intention-to-treat and per-protocol bases. This trial is registered with ClinicalTrials.gov (NCT00272454). Results: In total, 458 patients were enrolled (mean age of 63 years, median NIHSS of 3), and mRS at 90 days was obtained in 447 patients. The primary endpoint was achieved in 76% (173/228) of those randomized to cilostazol and in 75% (165/219) assigned to aspirin, which supported the pre-specified non-inferiority of cilostazol to aspirin (95% CI of proportion difference: –6.15 to 7.22%, p = 0.0004). These results were also supported by per-protocol analysis (p = 0.045). Cardiovascular events occurred in 6 patients (3%) treated with cilostazol, and in 9 patients (4%) treated with aspirin (p = 0.41). Adverse events were more common in cilostazol-treated patients during the trial (91 vs. 85%, p = 0.055), while the frequencies of bleeding complications (cilostazol 11%, aspirin 13%, p = 0.43) or drug discontinuation (cilostazol 10%, aspirin 7%, p = 0.32) were not different. Conclusion: Cilostazol is feasible in acute ischemic stroke, and comparable to aspirin in its efficacy and safety.

B-type natriuretic peptide blood levels identify patients with non-ST elevation acute coronary syndromes at high risk for complications during intravenous beta-blocker infusion

We hypothesized that measurement of B-type natriuretic peptide could identify patients with non-ST elevation acute coronary syndromes at high risk for complications during beta-blocker (esmolol) infusion. We reviewed the records of 340 consecutive patients admitted with a non-ST elevation acute coronary syndrome. Seventy three (47 males, aged 62 ± 14 years) received esmolol up to a maximum dose of 300 μg/ kg/min until the symptoms were relieved or an adverse event occurred. The median infusion rate at steady state was 175 μg/kg/min (median infusion time 18 h). Infusion was halted in 14 patients. The frequency of drug discontinuation increased across admission BNP quartiles. BNP > 141 pg/ml at admission had a 95% predictive value for subsequent withdrawal of esmolol. The presence of BNP > 141 pg/ml in combination with systolic blood pressure < 130 mmHg and left ventricular ejection fraction < 50% identified a group of patients at high risk for drug interruption (interruption frequency = 83%, 95% CI: 55-95%). In conclusion, BNP measurement in combination with systolic blood pressure and 2D echocardiography may identify patients with non-ST elevation acute coronary syndromes at high risk for adverse events during esmolol infusion.

Validating reasons for medication discontinuation in electronic patient records at hospital discharge

The accuracy of health care professionals in reporting safety events determines their usefulness for both system improvement and research. The study objectives were to: (1) validate (assess the accuracy of) the reasons recorded by doctors and pharmacists for discontinuing medication orders at discharge in a hospital's electronic patient records (EPR); (2) investigate the causes of any detected recording inaccuracy; and (3) collect preliminary data on the frequency and types of medication discontinuation. This was a validation study in one English hospital. The study comprised two steps: extraction of discontinued medication orders from the EPR followed by short structured interviews with doctors and pharmacists who made the discontinuation. A total of 104 discontinued orders were discussed during 15 face-to-face and six telephone interviews. The software package spss was used for data analysis. Duplication of therapy (27, 25.2%), omission of drug (23, 21.5%) and dosage regimen change (19, 17.8%) were the three most frequent reasons given for discontinuing medications. The majority of recorded discontinuation reasons were correct (100, 96.2%) and complete (101, 97.1%), and hence were judged accurate (97, 93.3%). The difference in accurate recording between doctors (15, 88.2%) and pharmacists (82, 94.3%) was not statistically significant. Potential causes of recording inaccuracy included: slip or lapse, lack of training, carelessness and electronic system rigidity. This study showed that doctors and pharmacists recorded accurate reasons for the majority of the discontinued medication orders. It also showed that utilizing pharmacists' recorded reasons during clinical interventions using EPR was beneficial in understanding and characterizing prescribing errors. Although they require further research, the reasons identified present preliminary data about the most prevalent types of pharmacists' interventions during hospital discharge.

Telaprevir in Combination with Peginterferon and Ribavirin In Genotype 1 HCV Treatment-Naïve Patients, Prior Relapsers and Prior Non-Responders: Pooled Analysis Of PROVE1, PROVE2, PROVE3 and Study 107

Purpose: The PROVE studies were Phase 2b randomized controlled clinical trials that evaluated the safety and efficacy of telaprevir (T), peginterferon alfa-2a (P) and ribavirin (R) in treatment-naïve (PROVE1 and PROVE2) and PR treatment-experienced (PROVE3) patients with genotype 1 hepatitis C virus (HCV) infection. Study 107 was an open-label study of T plus PR in patients who did not achieve SVR following PR treatment in the PROVE studies. We compared the efficacy and safety of T (utilized at the dose and duration currently being evaluated in Phase 3 studies) in combination with P and R to PR alone in treatment-naïve patients, and in patients with prior PR relapse or non-response (null and partial response). Methods: Treatment-naïve patients, prior PR relapsers and prior PR non-responders who received the same standard regimen (12 weeks of T 750 mg q8h plus P 180 μg/week and R 1000-1200 mg/day followed by 12 or 36 additional weeks of PR (T12PR) were compared to patients who received 48 weeks of PR (PR). Seven hundred and twenty patients were included in this pooled retrospective analysis. Results: Sustained virologic response (SVR) rates were 66% in treatment-naïve patients, 80% in prior PR relapsers and 41% in prior PR non-responders, who received the T12PR regimen, compared to 44%, 20% and 9% in treatment-naïve patients, prior PR relapsers and prior PR non-responders, respectively, who received 48 weeks of PR. Other viral responses are shown in the Table. Discontinuation of treatment due to AEs occurred in 17% of treatment-naïve patients, 10% of prior PR relapsers and 7% of prior PR non-responders who received the T-based regimen, compared with 9%, 5% and 4% of treatment-naïve patients, prior PR relapsers and prior PR non-responders, respectively, who received PR. Conclusion: Higher SVR rates were observed in all patient types who received telaprevir-based regimen compared to peginterferon alfa-2a and ribavirin. Viral responses observed in prior relapsers to peginterferon alfa-2a and ribavirin were somewhat higher to that observed in treatment-naïve patients. Higher frequency of discontinuation due to AEs was observed in patients who received telaprevir-based regimen as compared to peginterferon alfa-2a and ribavirin. Disclosure: Mitchell Shiffman, MD has received consulting and lecture fees from Abbott, Anadys, Biolex, Bristol Myers-Squibb, Celera Diagnostics, Conatus, Gilead Sciences, Human Genome Sciences, Novartis, Pfizer, Roche, Romark, Schering-Plough, Valeant, Vertex Pharmaceuticals and Zymogenetics and Grant/Research Support from Conatus, Bristol-Myers, Squibb and Zymogenetics - Thomas Berg, MD has received consulting and lecture fees from Tibotec, Vertex Pharmaceuticals, Roche, Schering-Plough, Gilead Sciences, Novartis, Bayer and Abbott - Andrew J. Muir, MD has received consulting fees from Vertex Pharmaceuticals and Schering-Plough, lecture fees from Schering-Plough and Grant/Research Support from Vertex Pharmaceuticals - John G. McHutchison, MD has received consulting fees from Schering-Plough and Vertex Pharmaceuticals and grant support from Vertex Pharmaceuticals, Schering-Plough and Hoffman-La Roche - Jean-Michel Pawlotsky, MD has received consulting fees from Abbott, AstraZeneca, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Roche, Schering-Plough, Tibotec Pharmaceuticals, Valeant Pharmaceuticals, and Vertex Pharmaceuticals; and Grant/Research Support from Gilead Science - Stefan Zeuzem, MD has received consulting and lecture fees from Vertex Pharmaceuticals, Tibotec, Roche and Schering-Plough - Leif Bengtsson, Ph.D. is an employee and stock owner of Vertex Pharmaceuticals - Nathalie Adda, MD is an employee and stock owner of Vertex Pharmaceuticals - Shelley George, MD is an employee and stock owner of Vertex Pharmaceuticals - Robert Kauffman, MD is an employee and stock owner of Vertex Pharmaceuticals - Fred F Poordad, MD has received consulting and lecture fees as well as Grants/Research Support from for Vertex Pharmaceuticals, Roche, Schering-Plough, Gilead Sciences, Bristol Myers-Squibb, Abbott, Tibotec, Valeant, Pfizer, Anadys, Idenix and Boehringer Ingelheim.Table: [274] Viral response

Elastic modulus of a rock mass based on the two parameter negative-exponential (TPNE) distribution of discontinuity spacing and trace length

The frequency, spacing and trace length of rock mass discontinuities appear to follow a negative exponential distribution. However, in some cases this distribution has limitations. To overcome this, it is necessary to choose a target distribution which is flexible enough to simulate the spacing and trace length of the discontinuities. The paper shows how the two parameter negative exponential (TPNE) distributions can meet the requirements. An improved constitutive equation of rock mass based on this new distribution has been determined from which a new method to calculate rock mass elastic modulus (Em) is proposed, taking into account the rock mass anisotropy. It was found that the geo-stresses influence Em in two ways: it varies with changes in the orientation of the geo-stress and with the size of geo-stress. The work is illustrated by a case study on the abutment slope of the 295 m high arched dam of the Xiao wan hydroelectric power station in Yunnan province, Southwest of China.

Meta-analysis Shows Extended Therapy Improves Response of Patients With Chronic Hepatitis C Virus Genotype 1 Infection

Clinical trials provided conflicting results about whether extended duration of treatment with pegylated interferon-alfa (pegIFN-alfa) and ribavirin (more than 48 weeks) improves rates of sustained virologic response (SVR) in patients infected with hepatitis C virus (HCV) genotype 1 and slow virologic response. We performed a meta-analysis to determine the overall impact of extended treatment, compared with standard treatment, on virologic response rates in these patients. We performed a literature search to identify randomized controlled trials (RCTs) that included monoinfected, treatment-naive patients infected with HCV genotype 1; data were compared between slow responding patients treated with pegIFN-alfa-2a/b plus ribavirin for 48 weeks and those that received extended treatment (as much as 72 weeks). End points included SVR rates, end-of-treatment (EOT) response and relapse rates; they were calculated according to the DerSimonian-Laird estimate. Six RCTs assessed the benefits of extended treatment with pegIFN-alfa-2a/b and ribavirin in treatment-naive patients with HCV genotype 1 that were slow responders (n = 669). The extended treatment significantly improved SVR rates in slow responders, compared with the standard of care (14.7% increase in overall SVR; 95% confidence interval, 4%-25.5%; P = .0072). Rates of viral relapse were significantly reduced by extended treatment, but EOT response rates were similar. The frequency of voluntary treatment discontinuation, but not of serious adverse events, was significantly increased by extended therapy. Extending the duration of treatment with pegIFN-alfa-2a/b and ribavirin in patients with HCV genotype 1 and a slow response to therapy improves the rate of SVR.

Performance Analysis of Selective Opportunistic Spectrum Access With Traffic Prediction

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> In cognitive radio (CR) networks, the ability to capture a frequency slot for transmission in an idle channel has a significant impact on the spectrum efficiency and quality of service (QoS) of a secondary user (SU). The radio frequency (RF) front-ends of an SU have limited bandwidth for spectrum sensing with the target frequency bands dispersed in a discontinuous manner. This results in the SU having to sense multiple target frequency bands in a short period of time before selecting an appropriate idle channel for transmission. This paper addresses this technical challenge by proposing a selective opportunistic spectrum access (SOSA) scheme. With the aid of statistical data and traffic prediction techniques, our SOSA scheme can estimate the probability of a channel appearing idle based on the statistics and choose the best spectrum-sensing order to maximize spectrum efficiency and maintain an SU's connection. By means of doing so, this SOSA scheme can preserve the QoS of an SU while improving the system efficiency. In contrast to previous work, we consider the practical issues encountered by an SU in a wireless environment, such as discontinuous target frequency bands and limited spectrum-sensing ability. We examine the spectrum-sensing scheme in terms of packet loss ratio (PLR) and throughput. The simulation results show that the proposed SOSA scheme can decrease the probability of packet losses in the discontinuous spectrum environment and improve the spectrum efficiency. </para>

An Evaluation of Frequency and Reasons of Discontinuation in Outpatient Chemotherapy in Patients with Lung Cancer

An Evaluation of Frequency and Reasons of Discontinuation in Outpatient Chemotherapy in Patients with Lung Cancer

Discontinuation of Antihyperglycemic Therapy and Clinical Outcomes After Acute Myocardial Infarction in Older Patients With Diabetes

Patients with diabetes are frequently admitted for acute myocardial infarction (AMI) on antihyperglycemic agents but may be discharged without glucose-lowering therapy. We examined the frequency of this practice and evaluated the associated outcomes of readmission and mortality. We conducted a retrospective study of 24 953 Medicare beneficiaries with diabetes discharged after hospitalization for AMI. We examined the frequency of discontinuation of antihyperglycemic agents on discharge among those patients admitted on a diabetic regimen. The independent association between discharge on versus off antihyperglycemic therapy and outcomes at 1 year was assessed in multivariable Cox proportional hazards models, adjusting for patient, physician, and hospital variables. The primary outcome was time to death within 1 year of discharge; secondary outcomes were time to first rehospitalization within 1 year for AMI, heart failure, and all causes. There were 8751 patients admitted on at least 1 antihyperglycemic agent who met our inclusion/exclusion criteria. Of these, 7581 (86.6%) were discharged on antihyperglycemic therapy and 1170 (13.4%) were discharged off antihyperglycemic therapy. After multivariable analysis, as compared with those whose diabetes therapy was continued at discharge, patients who were not prescribed a glucose-lowering agent had higher 1-year mortality rate (hazard ratio, 1.29; 95% confidence interval, 1.15 to 1.45). Readmission rates did not differ significantly between the 2 groups (hazard ratio, 0.95; 95% confidence interval, 0.87 to 1.03). In older patients with diabetes after AMI, discontinuation of antihyperglycemic therapy is common and associated with higher mortality rates. The reasons behind this practice as well as the specific effects of hyperglycemia after AMI merit further study.

The importance of the recognition of benign ethnic neutropenia in black patients during treatment with clozapine: case reports and database study

Clozapine is the treatment of choice in refractory schizophrenia. Its more extensive use is limited by adverse effects and the need for regular blood monitoring. However, black patients are disadvantaged with respect to clozapine usage. Lower baseline Absolute Neutrophil Count compared with Whites leads to a greater frequency of blood testing, treatment interruptions and discontinuation. This may in part be explained by Benign Ethnic Neutropenia, but too few black patients are thus registered. The four cases described in this report underline some of the difficulties if this problem is under-recognized. Moreover, in our sample of 191 clozapine recipients in an inner London hospital, black patients account for approximately half, but only a small proportion, 8/95 (8.4%) are registered as having Benign Ethnic Neutropenia. None of the Benign Ethnic Neutropenia-registered patients discontinued treatment for haematological reasons. To optimize clozapine treatment and improve long-term outcomes, a significantly greater proportion of Black patients should be registered as having Benign Ethnic Neutropenia.

Use of Organic Nitrates and the Risk of Hip Fracture: A Population-Based Case-Control Study

Use of organic nitrates has been associated with increased bone mineral density. Moreover, a large Danish case-control study reported a decreased fracture risk. However, the association with duration of nitrate use, dose frequency, and impact of discontinuation has not been extensively studied. Our objective was to evaluate the association between organic nitrates and hip fracture risk. A case-control study was conducted using the Dutch PHARMO Record Linkage System (1991-2002, n = 6,763 hip fracture cases and 26,341 controls). Cases had their first admission for hip fracture, whereas controls had not sustained any fracture after enrollment. Current users of organic nitrates were patients who had received a prescription within 90 d before the index date. The analyses were adjusted for disease and drug history. Current use of nitrates was not associated with a decreased risk of hip fracture [adjusted odds ratio (OR) = 0.93; 95% confidence interval (CI) = 0.83-1.04]. Those who used as-needed medication only had a lower risk of hip fracture (adjusted OR = 0.83; 95% CI = 0.63-1.08) compared with users of maintenance medication only (adjusted OR = 1.17; 95% CI = 0.97-1.40). No association was found between duration of nitrate use and fracture risk. Our overall analyses showed that risk of a hip fracture was significantly lower among users of as-needed organic nitrates, when compared with users of maintenance medication. Our analyses of hip fracture risks with duration of use did not further support a beneficial effect of organic nitrates on hip fracture, although residual confounding may have masked beneficial effects.

Cyclophosphamide for Ocular Inflammatory Diseases

To evaluate the outcomes of cyclophosphamide therapy for noninfectious ocular inflammation. Retrospective cohort study. Two hundred fifteen patients with noninfectious ocular inflammation observed from initiation of cyclophosphamide. Patients initiating cyclophosphamide, without other immunosuppressive drugs (other than corticosteroids), were identified at 4 centers. Dose of cyclophosphamide, response to therapy, corticosteroid-sparing effects, frequency of discontinuation, and reasons for discontinuation were obtained by medical record review of every visit. Control of inflammation, corticosteroid-sparing effects, and discontinuation of therapy. The 215 patients (381 involved eyes) meeting eligibility criteria carried diagnoses of uveitis (20.4%), scleritis (22.3%), ocular mucous membrane pemphigoid (45.6%), or other forms of ocular inflammation (11.6%). Overall, approximately 49.2% (95% confidence interval [CI], 41.7%-57.2%) gained sustained control of inflammation (for at least 28 days) within 6 months, and 76% (95% CI, 68.3%-83.7%) gained sustained control of inflammation within 12 months. Corticosteroid-sparing success (sustained control of inflammation while tapering prednisone to 10 mg or less among those not meeting success criteria initially) was gained by 30.0% and 61.2% by 6 and 12 months, respectively. Disease remission leading to discontinuation of cyclophosphamide occurred at the rate of 0.32/person-year (95% CI, 0.24-0.41), and the estimated proportion with remission at or before 2 years was 63.1% (95% CI, 51.5%-74.8%). Cyclophosphamide was discontinued by 33.5% of patients within 1 year because of side effects, usually of a reversible nature. The data suggest that cyclophosphamide is effective for most patients for controlling inflammation and allowing tapering of systemic corticosteroids to 10 mg prednisone or less, although 1 year of therapy may be needed to achieve these goals. Unlike with most other immunosuppressive drugs, disease remission was induced by treatment in most patients who were able to tolerate therapy. To titrate therapy properly and to minimize the risk of serious potential side effects, a systematic program of laboratory monitoring is required. Judicious use of cyclophosphamide seems to be beneficial for severe ocular inflammation cases where the potentially vision-saving benefits outweigh the substantial potential side effects of therapy, or when indicated for associated systemic inflammatory diseases.

A double-blind randomized controlled trial of low doses of propranolol, nortriptyline, and the combination of propranolol and nortriptyline for the preventive treatment of migraine

Few trials have evaluated combination of two or more drugs in the preventive treatment of migraine. In this study three therapeutic regimens were compared: (a) propranolol, at a dose of 40 mg per day, (b) nortriptyline, at a dose of 20 mg per day, and (c) the combination of these two drugs in these dosages. The groups were matched according to age, gender, and frequency of migraine attacks prior to treatment. The period of treatment was two months and the frequency and intensity of headache attacks of the 30 days pre-treatment period were compared with the frequency of headaches in the treatment period. Fourteen patients in groups A and B and sixteen patients in group C have completed the study. Treatment with propranolol, alone or in combination, was shown to be effective. Treatment with nortriptyline alone was not effective. All three therapeutic regimens were safe and side effects were minimal. The frequency of discontinuation of the study was the same in the 3 groups but no patient left the study due to adverse reactions. The combined therapy proved to be as safe as the monotherapy. Further studies evaluating this and other possible combinations of drugs in higher doses and for longer periods, should more clearly elucidate the role of combined therapy in the treatment of migraine.

Utilisation des biothérapies dans le psoriasis modéré à sévère : expérience du service de dermatologie du CHU de Besançon (2004–2008)

The course of biological therapy (BT) in clinical practice may differ markedly from treatment schedules in clinical trials. Treatment modifications and patient characteristics can affect treatment safety and efficacy. In addition, long-term results concerning the use of BT in clinical practice are lacking. To report our experience of BT in terms of short- and long-term efficacy and safety. The retrospectively analysed cohort consisted of psoriasis patients receiving BT between 2004 and 2008. Patients in clinical trials were excluded. Mean body surface area (BSA) and Dermatology Life Quality Index were recorded. Fifty-eight patients undergoing 86 courses of BT were enrolled. Thirty-three patients were treated with efalizumab, 21 with infliximab and 32 with etanercept. During the study period, 40% of patients were switched to another BT. The number of patients attaining BSA-75 at 3and 6months respectively was 38% and 75% for efalizumab, 62% and 61% for infliximab, and 36% and 61% for etanercept. After 24months of follow-up, only 33% of patients (34% of patients with efalizumab, 52% with infliximab and 22% with etanercept) were still following their initial BT, with treatment being discontinued in 52% of patients due to adverse events or treatment failure. Our study confirms the efficacy and feasibility of BT in clinical practice. However, the high frequency of BT discontinuation for adverse events or non-response led to sequential therapy using different biological treatments.