Longitudinal Outcomes of GastroIntestinal symptoms in Canada (LOGIC): key factors for an effective patient retention in observational studies.

BACKGROUND: Longitudinal Outcomes of GastroIntestinal symptoms in Canada (LOGIC) is an ongoing study on irritable bowel syndrome (IBS) treatment patterns and health outcomes in routine Canadian clinical practice. Advancements in understanding IBS, a chronic multifaceted GI disorder, may be possible through methodical observational studies. The objective of this paper is to describe site recruitment techniques and extensive subject follow-up methodology used to facilitate a high return rate of questionnaires from this population-based study of subjects with IBS. METHODS: Invitation letters along with protocol synopses and preliminary site assessment questionnaires were faxed to potential sites across Canada. There were 1,556 subjects enrolled in this study from general practitioner sites (GP) and specialist sites (SP) in Canada. Subjects were compensated for the return of questionnaires reporting symptoms, quality of life, productivity, healthcare and resource utilization at baseline, Month 1, 3, 6, 9, and 12. Upon the return of questionnaires, subjects received thank you cards which included a reminder of the next questionnaire's due date. If subject questionnaires were not received within 2 weeks after the due date, the subjects received a reminder letter in the mail. RESULTS: The methodology in the LOGIC study allowed for a high patient questionnaire return rate (89%) through extensive subject reminders and follow-up. Subject participation throughout the study was not found to be linked to study site size or type (GP or SP). CONCLUSION: Questionnaire based observational studies may benefit from focusing resources on increasing questionnaire return rates to effectively maintain data reliability and also reduce non-response bias.

Adherence to weekly oral bisphosphonate therapy: cost of wasted drugs and fractures.

UNLABELLED: In an observational cohort of patients treated with biphosphonates (BP), we observed that poor adherence to these drugs causes important expenditures in terms of avoidable fractures. Of particular interest are the amounts of money wasted by patients who did not take their BPs long enough to obtain a clinical benefit. INTRODUCTION: A large proportion of patients initiated with oral weekly BP therapy stop their treatment within the first year. The objective of this study was to estimate the impact of the poor adherence to BPs in terms of drug wasted and avoidable fractures. METHODS: The study was done on primary and secondary prevention cohorts from the Régie de l'assurance maladie du Québec (Québec). The concept of the "point of visual divergence" was used to determine the amount of wasted drug. The risk of fracture was estimated using Cox regression models. The hazard ratios of compliant patients (+80%) versus non compliant patients were used to estimate the number of fractures saved. RESULTS: The cost of wasted drugs was $25.87 per patient initiated in the primary prevention cohort and $30.52 in the secondary prevention cohort. If all patients had been compliant, 110 fractures would have been avoided in the primary prevention cohort and 19 fractures in the secondary prevention cohort. The cost of these avoidable fractures per patient initiated on BP therapy was $62.95 in primary prevention cohort and $330.84 in secondary prevention cohort. CONCLUSIONS: This study confirms that poor adherence to oral BPs leads to a significant waste of money and avoidable fractures.

Differences in persistence among different weekly oral bisphosphonate medications.

SUMMARY: We evaluated the differences in persistence with weekly oral bisphosphonate therapy according to the initial drug. Persistence to weekly oral preparations remains suboptimal, particularly in patients who receive generic alendronate. Alternative solutions are needed to improve the real life effectiveness of osteoporosis therapies. INTRODUCTION: Poor persistence is widespread with oral osteoporosis (OP) therapy. The objective of this study was to evaluate the persistence among OP patients started on weekly oral bisphosphonates (BP). METHODS: Patients newly initiated on branded risedronate, branded alendronate, or generic alendronate once weekly were selected from the Régie de l'Assurance Maladie du Québec databases. The cohort included patients with and without a previous OP fracture. The probability and the risk factors for early discontinuation were estimated using Cox regression models. RESULTS: The study cohort included 32,804 patients. After 1 year, a significant difference in persistence on oral BP therapy was found. The patients started on branded risedronate were 11% more likely to stop OP therapy than patients started on branded alendronate. Risk of discontinuation doubled in patients initiated with generic alendronate compared to patients started on branded alendronate. Male gender was associated with a 25% increase risk of early discontinuation. No statistical association was found between previous OP fracture and early discontinuation. CONCLUSION: This study provides further evidence of poor persistence to newly initiated oral weekly BP therapies, particularly for the patients started on generic alendronate.

Characteristics, diagnostic and symptom profile of patients receiving tegaserod in routine clinical practice in Canada.

OBJECTIVE: This study was designed to assess the diagnostic and symptom profile of patients receiving tegaserod in routine clinical practice, and to identify their demographic characteristics, as well as the association between these characteristics and diagnosis. METHODS: This prospective, observational study collected data from physicians on the symptoms and/or diagnosis, age range and gender for patients to whom they prescribed tegaserod. Details of the physician characteristics included whether they were a family physician or a specialist, and the region of Canada in which their practice was located. RESULTS: A total of 500 patients were enrolled at 85 sites in Canada. The majority (85%) of the patients were enrolled by family physicians, and the remainder by community-based specialists. The patients were predominantly female (87%) and the highest percentages were in the 35-44 (23%) and 45-54 (25%) age groups. Nearly all patients (96%) were prescribed tegaserod on the basis of both symptoms and diagnosis. The most frequently reported symptoms were abdominal pain and/or discomfort (87%), bloating (80%) and constipation (75%). Most patients (57%) presented with all three of these symptoms. Constipation-predominant Irritable Bowel Syndrome (IBS-C) was the most common diagnosis (55%), followed by IBS alternating between constipation and diarrhea (IBS-A) (23%). Based on this, 67% of patients were given tegaserod strictly according to the label, although it was appropriately prescribed to 87%. CONCLUSIONS: In Canada, tegaserod is prescribed to patients with symptoms of abdominal pain and/or discomfort, bloating and constipation. Most of them will also have a diagnosis of either IBS-C or IBS. It is generally being prescribed appropriately.

The economic evaluation of pharmacotherapies for Parkinson's disease.

As well as the significant clinical effects of Parkinson's disease (PD), the disease places a high economic burden on society. Given the scarcity of health care resources, it is becoming increasingly necessary to demonstrate that new therapies for PD provide value for money in comparison with other potential interventions. This paper outlines the basic techniques of cost-effectiveness analysis and its application to PD. These techniques are illustrated by a recent economic evaluation of entacapone for use in Canada.

Preparation of a microcrystalline suspension formulation of Lys(B28)Pro(B29)-human insulin with ultralente properties.

The monomeric analogue, Lys(B28)Pro(B29)-human insulin (LysPro), has been crystallized using similar conditions employed to prepare extended-acting insulin ultralente formulations. In the presence of zinc ions, sodium acetate and sodium chloride, but without phenolic preservative, LysPro surprisingly forms small rhombohedral crystals with similar morphology to human insulin ultralente crystals with a mean particle size of 20 +/- 1 microm. X-ray powder diffraction studies on the LysPro crystals prior to dilution in ultralente vehicle ([NaCl] = 1.2 M) revealed the presence of T(3)R(3)(f) hexamers. Consistent with human insulin ultralente preparations, LysPro crystals formulated as an ultralente suspension ([NaCl] = 0. 12 M) contain T(6) hexamers indicating that a conformational change occurs in the hexamer units of the crystals upon dilution of the salt concentration. The pharmacological properties of subcutaneously administered ultralente LysPro (ULP) were compared to ultralente human insulin (UHI) using a conscious dog model (n = 5) with glucose levels clamped at basal. There were no statistically significant differences between the kinetic and dynamic responses of ULP compared to UHI [C(max) (ng/mL): 3.58 +/- 0.76, ULP and 3.61 +/- 0. 66, UHI; T(max) (min): 226 +/- 30, ULP and 185 +/- 42, UHI; R(max) (mg/kg min): 11.2 +/- 1.9, ULP and 13.3 +/- 2.0, UHI; and T(Rmax) (min): 336 +/- 11, ULP and 285 +/- 57, UHI]. Although the Pro to Lys sequence inversion destabilizes insulin self-assembly and greatly alters the time action of soluble LysPro preparations, this modification has now been found neither to prevent the formation of ultralente crystals in the absence of phenolics nor to compromise the protracted activity of the insulin analogue suspension.

Dietary fish oil. Influence on lesion regression in the porcine model of atherosclerosis.

We examined the influence of dietary fish oil on lesion regression in a porcine model of atherogenesis. Thirty-two female Yucatan miniature pigs were fed an atherogenic diet for 8 months. A no-regression group (n = 8) was killed to determine the extent of atherosclerosis at 8 months. Three regression groups were switched to normal minipig chow supplemented with either MaxEPA fish oil (FO group, n = 8), a control oil with the ratio of polyunsaturated to monounsaturated to saturated fatty acid matched to that of the fish oil (CO group, n = 8), or no oil supplement (NO group, n = 8) for a further 4 months. Plasma cholesterol levels reached between 15 and 20 mmol/L during the atherogenic phase and returned to normal (2 mmol/L) within 2 months of the beginning of the regression diet. Compared with the NO group, fish oil supplementation during the regression phase caused a decrease in VLDL and HDL cholesterol and an increase in LDL cholesterol. Similarly, the control oil also caused a decrease in VLDL cholesterol; however, in contrast to the FO group, HDL cholesterol increased and LDL cholesterol was unchanged. FO LDL, which had decreased levels of 20:4 (n-6 fatty acid) and increased levels of 18:3, 20:5, and 22:6 (n-3 fatty acids), was shown to be twice as susceptible to copper-mediated oxidation as CO LDL particles. Morphological examination of the major blood vessels revealed a significant reduction in lesion area in the ascending and thoracic aorta as well as the carotid artery after the regression diet; however, there was no significant difference between the fish oil and control oil groups in any of the vessels measured. Therefore, despite increased LDL, decreased HDL, and an increased susceptibility to in vitro oxidation of LDL, fish oil supplementation of a regression diet did not influence lesion regression.

Probucol, but not MaxEPA fish oil, inhibits mononuclear cell adhesion to the aortic intima in the rat model of atherosclerosis.

We have examined the influence of both dietary fish oil and probucol on monocyte adhesion to the aortic endothelium rats fed an atherogenic diet for 2 weeks. All rats were fed a low-fat diet supplemented with 4% cholesterol, 1% cholic acid, and 0.5% 2-thiouracil. In addition to the atherogenic diet, group 1 (FO; n = 20) received a dietary supplement of the fish oil concentrate MaxEPA (5% w/w); group 2 (CO; n = 20) received a supplement of a control oil with same polyunsaturated-monounsaturated-saturated fatty acid ratio as Max-EPA; and group 3 (PR; n = 20) received both the control oil supplement (5% w/w) and a 1% (w/w) supplement of probucol. Analysis of blood samples taken at 2 weeks revealed that both fish oil and probucol lowered total plasma cholesterol by 30% compared with the CO group. In addition, fish oil supplementation caused a significant decrease in cholesterol contained in the VLDL fraction while probucol supplementation caused a significant lowered cholesterol in the HDL fraction. Analysis of mononuclear cell adhesion to the aortic endothelium in vivo revealed that, fish oil had no significant effect probucol reduced adhesion by 40%. The results of this study suggest that probucol, but not fish oil, may inhibit the initiation of lesion formation in the rat model of atherosclerosis.

[Restitution of visual function in two cases of post-anoxic occipital blindness: a long term clinical study (author's transl)]. / Etude sémiologique de la restauration de la fonction visuelle dans deux cas de cécité occipitale post-anoxique.

Two cases of post-anoxic occipital blindness, one in an adult and the other in a child, are presented. A quantitative and qualitative semiological analysis was performed using tests described in a previous paper. Mechanisms underlying restitution of visual function were chronologically followed up over three years of rehabilitation. In both cases there was a noteworthy improvement in the visual function, related to the beginning of rehabilitation therapy. Five years of an almost complete cerebral blindness had preceded the improvement in case 2. Spatial construction acquisition and ontogenetic data are compared with the present data. It is suggested that there is a similar loss of activation in Broca's aphasia and cerebral visual disturbances of occipital origin.