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Introduction: A Canadian research team is conducting a multi-centered, non-interventional national study with the objective of charting the course of arm morbidity after breast cancer surgery. This paper examined the relationship between arm morbidity and leisure and recreational activities of affected women.Methods: Five hundred and forty seven women with stage I-III breast cancer were recruited in four centers across Canada: Surrey (BC); Winnipeg (MB), Montreal (QB) and Fredericton (NB). Participants were enrolled in the study 6-12 months post surgery. Physical examination was used to assess arm and shoulder functioning and questionnaires were used to assess disability, pain, and participation in recreational and leisure activities.Results: At the first clinical assessment (T1), the mean number of months post breast cancer surgery was 8.4. At T1 49% of women reported difficulty with recreational activities that involved "some force or impact" and 29% experienced negative changes to their involvement in leisure activities. A hierarchical multiple regression analysis found that several arm morbidity variables were significant predictors of difficulty with participation in recreational activities. A second hierarchical regression found also that arm morbidity factors were significant predictors of negative changes in leisure activities. Follow-up analyses found that arm morbidity, was most closely related to difficulty with recreational activities requiring free movement of the arm and using force.Conclusion: Many women treated for breast cancer experience arm morbidity. Arm morbidity is related to difficulties with recreational activities and negative changes in leisure activity participation.Implications: Breast cancer survivors should engage in recreational and leisure activities that are compatible with reduced range of motion and pain, and avoid those that exacerbate their arm morbidity. [ABSTRACT FROM AUTHOR]

Twenty family physicians (11 female and 9 male) were interviewed about their experiences in treating depressed patients. Interview transcripts were analyzed thematically with respect to physicians' understanding of women's depression and their treatment strategies with depressed women. Stress arising in the social context of women's lives was perceived as a key precipitant of depression in women, with familyrelated, gender-specific and practical sources of stress as the main contributors. Physicians' treatment strategies had the aims of alleviating depressive symptoms and stress reduction. Implications of the findings for primary health care delivery and community-based interventions with depressed women are discussed. [ABSTRACT FROM AUTHOR]

The purpose of this study was to find out, from the patient's perspective and using qualitative methodology, how cancer follow-up care is managed in a New Brunswick health region.From focus group discussions with 23 participants 1-year post-cancer diagnosis, 3 prominent themes emerged: fear of recurrence, cancer surveillance/testing and support issues. The fear of recurrence permeates day-to-day life for many patients. To allay these fears, some patients feel a need to be subjected to extensive cancer surveillance. Emotional support, which is important for survivors, is complex.The majority of the participants in this study received cancer follow-up care from specialists. More rural than urban participants received their follow-up care from their family physicians (FPs). Participants had high expectations for follow-up care, regard-less of which type of physician -- specialist or FP -- provided it. If physicians did not provide the level and intensity of care expected by their patients, they were considered uncaring. We advocate a 'transition of care' or 'shared care' protocol between the acute cancer treatment provider and the FP, particularly in rural areas. This would ensure that cancer patients have a clear understanding of where to turn for ongoing surveillance, when they fear cancer recurrence or need support. For optimized cancer follow-up care, physicians must be cognizant that careful emotional and clinical management over an indefinite period of time is required, and they must recognize the individual needs of each patient. [ABSTRACT FROM AUTHOR]

This qualitative research aims to understand, from the standpoint of the family physician, the barriers to treating depression in the office setting. Three primary barriers to treating depression in the family physician's office were identified: systemic, physician-related, and patient-related. The systemic barriers involved the shortage of qualified, publicly-funded counsellors, lack of locally available counselling, and the cost of medication. Physician-related barriers included lack of time and expertise, and inadequacies of the reimbursement system. Patient-related barriers were rooted in the stigma attached to depression and failure to comply with treatment. [ABSTRACT FROM AUTHOR]

The hypothalamic-pituitary-gonadal (HPG) axis is an important regulatory mechanism involved primarily in the development and regulation of the reproductive systems. The suppression of the HPG axis by gonadotropin-releasing hormone (GnRH) analogues is expected to be effective for the treatment of sex hormone-dependent diseases, such as endometriosis, uterine fibroid, prostate cancer, benign prostatic hyperplasia (BPH) and polycystic ovary syndrome (PCOS). Despite the established involvement of GnRH signalling in these disorders, the therapeutic efficacy of small molecular GnRH antagonists for BPH and PCOS has not been adequately evaluated in non-clinical studies. Therefore, the purpose of the present study was to evaluate the potential of linzagolix, a small molecular GnRH antagonist, as a potential new treatment option for BPH and PCOS. Dogs and rats exhibiting normal prostates and dogs diagnosed with prostatic hyperplasia were used to evaluate the effects of linzagolix in BPH. The effects of linzagolix were also examined in a rat model of PCOS induced by repeated administration of letrozole, an aromatase inhibitor. Linzagolix reduced serum luteinizing hormone and testosterone levels in male rats and normal or BPH model dogs and suppressed prostate weight without testosterone depletion, suggesting the existence of an optimal therapeutic testosterone level for BPH treatment. In a PCOS rat model, linzagolix improved both insulin resistance and ovarian dysfunction. Treatment with linzagolix decreased follicle-stimulating hormone levels, but did not alter serum luteinizing hormone and testosterone levels. These results indicate that linzagolix may provide a new treatment option for GnRH-related disorders, such as BPH and PCOS., (© 2023 John Wiley & Sons Australia, Ltd.)

Objectives: Pharmacological treatment options for underactive bladder (UAB) syndrome are limited. Urapidil is the only alpha 1 -adrenoceptor (AR) antagonist that can be used for urinary disorders in women in some countries. However, no studies have directly verified the effects of alpha 1 -AR antagonists on the female urethra and UAB-like dysfunctions. We investigated the effects of silodosin (alpha 1A -AR antagonist) and urapidil (nonselective alpha 1 -AR antagonist) on the voiding function in female rats with diabetes mellitus (DM)., Methods: Changes in intraurethral pressure (IUP) induced by midodrine (alpha 1 -AR agonist) and mean blood pressure (MBP) were continuously measured in normal female rats to verify the pharmacological profiles of the drugs. To establish a DM model, rats were administered streptozotocin (STZ; 50 mg/kg, intravenous). Eight weeks after STZ administration, drugs were subcutaneously delivered through an osmotic pump. Four weeks after drug administration, emptied bladder blood flow (BBF), intravesical pressure, and the micturition volume were measured., Results: Both silodosin and urapidil inhibited the midodrine-induced increase in IUP and decreased MBP in a dose-dependent manner. Silodosin had a more substantial effect on the lower urinary tract than on MBP. Twelve weeks after STZ administration, DM rats exhibited UAB-like dysfunction (increased bladder capacity/bladder weight and residual volume and decreased bladder voided efficiency) and decreased BBF. Both drug treatments controlled this dysfunction., Conclusions: Alpha 1 -AR antagonists induced dose-dependent urethral relaxation in female rats. These drugs ameliorated UAB-like dysfunction in STZ-induced DM rats. In addition, alpha 1A -AR antagonists such as silodosin, which have limited effects on blood pressure, appear to be useful for treating UAB., (© 2022 John Wiley & Sons Australia, Ltd.)

Renal anemia is predominantly caused by a relative deficiency in erythropoietin (EPO). Conventional treatment for renal anemia includes the use of recombinant human EPO (rhEPO) or a long-acting erythropoiesis-activating agent named darbepoetin alfa, which is a modified rhEPO with a carbohydrate chain structure that differs from native hEPO. We have developed a biosimilar to darbepoetin alfa designated JR-131. Here, we comprehensively compare the physicochemical and biological characteristics of JR-131 to darbepoetin alfa. JR-131 demonstrated similar protein structure to the originator, darbepoetin alfa, by peptide mapping and circular dichroism spectroscopy. Additionally, mass spectroscopic analyses and capillary zone electrophoresis revealed similar glycosylation patterns between the two products. Human bone marrow-derived erythroblasts differentiated and proliferated to form colonies with JR-131 to a similar degree as darbepoetin alfa. Finally, JR-131 stimulated erythropoiesis and improved anemia in rats similarly to darbepoetin alfa. Our data show the similarity in physicochemical and biological properties of JR-131 to those of darbepoetin alfa, and JR-131 therefore represents a biosimilar for use in the treatment of renal anemia., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Junya Tani, Yae Ito, Makoto Yamakami, Tsuyoshi Fukui, Yukichi Hatano, Shinji Kakimoto, Ayaka Kotani, Atsushi Sugimura, Kazutoshi Mihara, Ryuji Yamamoto, Noboru Tanaka, Kohtaro Minami, Kenichi Takahashi, and Tohru Hirato are employees of JCR Pharmaceuticals. Satoshi Tatemichi is an employee of Kissei Pharmaceutical. This study was funded by JCR Pharmaceuticals and Kissei Pharmaceutical. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate., Methods: For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2-8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance., Results: In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic., Conclusions: These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Sucroferric oxyhydroxide (P-TOL ® chewable tablets, 250 and 500 mg) is a phosphate binder for oral use; it is composed of polynuclear iron (III)-oxyhydroxide, sucrose, and starches, and is currently indicated for alleviating hyperphosphatemia in patients with chronic kidney disease (CKD) on dialysis. The results of non-clinical pharmacological studies have suggested that P-TOL consistently decreases serum phosphorus levels in the aqueous environment at pH levels similar to those in the gastrointestinal tract, thereby suppressing the progression of secondary hyperparathyroidism, aberrant calcification, and abnormal bone metabolism associated with hyperphosphatemia. Since the diameter of the P-TOL tablet exceeds 15 mm, it is manufactured with a doughnut-shape to minimize choking hazards. From the results of pharmaceutical studies, it was indicated that the P-TOL tablets promptly disintegrated in the gastrointestinal tract and excessive iron uptake from this product is unlikely to occur. In clinical studies, P-TOL (one tablet/dose, t.i.d.) decreased serum phosphorus levels during treatment Week 1 and allowed stable, long-term control of serum phosphorus levels. Furthermore, P-TOL was expected to reduce the tablet burden on patients and to improve medication adherence. The most common adverse reaction was diarrhea. However, in most cases, the symptoms were mild and oral administration of P-TOL could be continued. Although iron-related parameters tended to increase, iron uptake from this product was low, and the risk of iron overload was considered to be low. These findings confirm the efficacy and safety of P-TOL in CKD patients with hyperphosphatemia. Therefore, sucroferric oxyhydroxide therapy is a potentially useful treatment option for hyperphosphatemia.

We examined the effects of combining the rapid insulin secretagogue, mitiglinide, with various oral hypoglycaemic drugs including biguanides, pioglitazone, α-glucosidase inhibitors, and sodium-glucose co-transporter 2 inhibitors in a rat model of type 2 diabetes. The oral glucose tolerance test (OGTT) using glucose, sucrose, or a liquid meal was used to compare the effects of mitiglinide with those of the four oral hypoglycaemic drugs and examine their combined effects on blood glucose levels and insulin secretion in the rat model. The combination of mitiglinide with other oral hypoglycaemic drugs suppressed the plasma glucose levels more than either agent did alone. Furthermore, the combination of these agents decreased insulin secretion more than mitiglinide did alone. These results indicate that mitiglinide is suitable for use in combination with other hypoglycaemic drugs because it inhibits postprandial hyperglycaemia by rapidly stimulating insulin secretion., (© 2017 John Wiley & Sons Australia, Ltd.)

Background: Patients with diabetes experience lower urinary tract symptoms. Cystopathy may evolve into underactive bladder (UAB), depending on the degree and duration of the symptoms. In the present study, we aimed to investigate the effects of silodosin, an alpha 1A -adrenoceptor (AR) antagonist, on UAB in a rat model of diabetes mellitus (DM)., Methods: Female Sprague-Dawley rats (6 weeks old) were administered streptozotocin (STZ) (50 mg/kg, i.v.) to establish a DM model. One week after STZ administration, vehicle or silodosin (0.3 or 1 mg/kg/day) was delivered subcutaneously through an osmotic pump. Nine weeks after STZ administration (8 weeks after drug treatment), a catheter was implanted into the bladder under urethane anesthesia. After the measurement of emptied bladder blood flow (BBF), saline was continuously infused into the bladder and intravesical pressure and micturition volume were measured. In another experiment, the bladder was isolated and nerve markers were quantified., Results: A cystometrogram showed that bladder capacity (BC), residual volume (RV), and bladder extension (BC/bladder weight) increased by 7.43, 10.47, and 3.59 times, respectively, in vehicle rats in comparison with normal rats. These findings suggested the occurrence of UAB-like symptoms in this model. Silodosin (1 mg/kg/day) inhibited the increase in BC and RV by 49.0% and 46.8%, respectively, and caused a decrease in BBF of approximately 25.5% (when the difference between normal and vehicle was set as 100%) in STZ rats. The nerve marker expression levels tended to be decreased in the bladders of STZ rats and these effects were ameliorated by silodosin., Conclusions: The STZ rats showed increased bladder extension and RV, symptoms that were suggestive of UAB, and these symptoms were ameliorated by silodosin. These results suggested that the alpha 1A -AR antagonist would be useful for the prevention or treatment of UAB.

The effects of PA21, a novel iron-based and non-calcium-based phosphate binder, on hyperphosphatemia and its accompanying bone abnormality in chronic kidney disease-mineral and bone disorder (CKD-MBD) were evaluated. Rats with adenine-induced chronic renal failure (CRF) were prepared by feeding them an adenine-containing diet for four weeks. They were also freely fed a diet that contained PA21 (0.5, 1.5, and 5%), sevelamer hydrochloride (0.6 and 2%) or lanthanum carbonate hydrate (0.6 and 2%) for four weeks. Blood biochemical parameters were measured and bone histomorphometry was performed for femurs, which were isolated after drug treatment. Serum phosphorus and parathyroid hormone (PTH) levels were higher in the CRF rats. Administration of phosphate binders for four weeks decreased serum phosphorus and PTH levels in a dose-dependent manner and there were significant decreases in the AUC0-28 day of these parameters in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups compared with that in the CRF control group. Moreover, osteoid volume improved significantly in 5% of the PA21 group, and fibrosis volume and cortical porosity were ameliorated in 5% PA21, 2% sevelamer hydrochloride, and 2% lanthanum carbonate hydrate groups. These results suggest that PA21 is effective against hyperphosphatemia, secondary hyperparathyroidism, and bone abnormalities in CKD-MBD as sevelamer hydrochloride and lanthanum carbonate hydrate are, and that PA21 is a new potential alternative to phosphate binders.

We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats. Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed. These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare in connection with the contents of this manuscript., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background/aims: This study was performed to investigate the detailed mechanism underlying the effects of the selective α(1A)-adrenoceptor antagonist, silodosin, on bladder function in a rat model of atherosclerosis-induced chronic bladder ischemia (CBI)., Methods: The CBI model was prepared by balloon endothelial injury of the bilateral iliac arteries in male rats. Using an osmotic pump, the CBI rats received either silodosin or vehicle alone subcutaneously for 8 weeks. Rats received a 2% cholesterol diet throughout the experiment. Bladder blood flow (BBF) was measured. Immunohistochemical staining was performed to determine the nerve distribution and nerve growth factor expression in the bladder. Bladders were used for muscle strip contraction analysis. The expression levels of muscarinic M2 and M3 receptors were measured., Results: Silodosin abrogated the decrease in BBF in CBI rats. Silodosin prevented the decrease in nerve distribution and increase in nerve growth factor expression in the CBI model. Bladder contractile response was reduced in the CBI group. Silodosin ameliorated the effect on the bladder contractile response. The level of muscarinic M3 receptor mRNA present in the bladder of CBI rats was increased by silodosin., Conclusion: The results of this study suggest that silodosin ameliorates the denervation of the bladder and effects on detrusor contractile function under ischemic conditions by restoring BBF., (© 2016 S. Karger AG, Basel.)

The impact of arm morbidity on leisure and quality of life is an understudied area in cancer survivorship. The purpose of this study was to qualitatively describe the impact of breast cancer-related arm morbidity on leisure participation in Canadian women. A grounded theory approach was used to generate thematic categories and a model. Drawing on participants from a larger cohort study (n = 740), 40 women with arm morbidity symptoms were purposively sampled and interviewed. Three themes emerged: a sense of loss, adapting participation, and new directions. Women with arm morbidity may experience an abrupt loss of previously enjoyed leisure activities and engage in a process of adapting to discover new meanings and directions. Comprehensive, person-centred cancer survivorship programs may assist with adaptation to arm morbidity.

This study was performed to investigate the effects of silodosin (selective α1A-adrenoceptor antagonist) on bladder blood flow (BBF) and bladder function in a rat model of bladder outlet obstruction (BOO) and to determine the expression of α1-adrenoceptor subtype mRNA in human and rat bladder microvessels. BOO was produced by partial ligature of the proximal urethra, which was maintained for 2 weeks. The BOO rats received either silodosin at a rate of 0.3mg/kg/day or vehicle subcutaneously via an osmotic pump for 2 weeks after BOO surgery. A metabolic cage study was performed in conscious animals. BBF was measured using a Laser Speckle Blood Flow Imager. Urinary levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and nerve growth factor (NGF) were measured. Immunohistological examinations of nerve distribution and NGF expression in the rat bladder were conducted. The expression of each α1-adrenoceptor subtype mRNA in human and rat bladder microvessels was determined by in situ hybridization. Silodosin ameliorated the increase in voiding frequency and decrease in mean voided volume in BOO rats in the metabolic cage study. Silodosin also abrogated the decrease in BBF in BOO rats. The levels of 8-OHdG and NGF in BOO rats were significantly decreased by administration of silodosin. Silodosin prevented the decrease in nerve distribution and increase in NGF expression. Human and rat bladder microvessels showed expression of all α1-adrenoceptor subtype mRNAs. The results presented here suggest that silodosin improves voiding behavior in rat models with BOO by inducing recovery of BBF., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background/aims: To evaluate the effects of silodosin (α1A-adrenoceptor antagonist) and distigmine (acetylcholinesterase inhibitor), alone or in combination, on voiding dysfunction in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model, by pressure flow study., Methods: Male ZDF rats were anesthetized with urethane and a catheter was implanted into the bladder through the dome. Saline was continuously infused into the bladder at 6 ml/h to induce the micturition reflex. Intravesical pressure and micturition volume were recorded continuously and various urodynamic parameters were calculated using a waveform analysis system., Results: Increased bladder capacity, residual volume, and urethral resistance and decreased maximum detrusor contraction velocity and urine flow rate, considered to be detrusor underactivity-like symptoms, were observed in ZDF rats. Although both silodosin and distigmine improved impaired voiding function, administration of both drugs in combination was more effective than either drug alone., Conclusions: ZDF rats showed symptoms suggestive of detrusor underactivity, and silodosin tended to ameliorate these symptoms in ZDF rats. These results suggested that an α1A-adrenoceptor antagonists may be effective against the voiding disorder accompanying not only bladder outlet obstruction but also deficiency of bladder function. Moreover, combined administration of an α1A-adrenoceptor antagonist with an acetylcholinesterase inhibitor may have additive efficacy in clinical use.

We performed in vitro and in vivo experiments to evaluate the pharmacological profile of ritobegron and its effects on the bladder in rats. β(3)-AR selectivity was assessed using CHO cells expressing various subtypes of the human β-adrenoceptor (AR). Effects on isolated organs were evaluated using the organ-bath method. Effects on intravesical pressure, heart rate, and mean blood pressure were evaluated in urethane-anesthetized rats. Ritobegron increased cAMP accumulation in a concentration-dependent manner in CHO cells expressing any one of three human β-AR, its selectivity for β(3)-AR being 301-fold and 32-fold higher versus β(1)-AR and β(2)-AR, respectively. Ritobegron decreased the resting tension of the isolated bladder in a concentration-dependent manner (EC(50), 7.7 × 10(-8) mol/L; maximal relaxation, 97.0 %), and the β(3)-AR antagonist SR58894A produced a parallel rightward-shift of this concentration-response curve without altering the maximal response [pK(B) value, 6.43]. Ritobegron concentration-dependently increased atrial rate and decreased myometrial contractions in vitro, and its selectivity for the bladder was 2,078-fold higher versus the atria and 14-fold higher versus the uterus. In vivo, ritobegron induced a dose-dependent decrease in intravesical pressure (ED(50) 0.4 mg/kg), without affecting heart rate and only slightly lowering mean blood pressure. Thus, ritobegron displayed potent and selective β(3)-AR agonistic activity toward transfected human β-AR and exhibited a high selectivity for the bladder versus other organs in rats. Moreover, it decreased intravesical pressure with minimal effects on the cardiovascular system in anesthetized rats. These results suggest that ritobegron shows promise as a potential agent for the treatment of overactive bladder.

This study aimed to characterize the β-adrenoceptor (β-AR) subtype mediating relaxation of isolated human bladder strips and to explore relaxation by the novel β3-AR-selective agonist KUC-7322 for its relaxant effect on the human isolated detrusor and for its effect on the carbachol (CCh)-induced contractile response. In two parallel studies, relaxation of isolated human bladder strips was tested for the β-AR agonists isoproterenol, clenbuterol, BRL 37344, and KUC-7322. For the isoproterenol and KUC-7322 responses, antagonism by CGP 20712A, ICI 118551, and SR59230A was determined. The potency and efficacy of the reference agonists for detrusor relaxation was in line with their known β3-AR activity. KUC-7322 relative to isoproterenol was a full agonist with a pEC(50) of 5.95 ± 0.09 and 5.92 ± 0.11 in the two studies. SR59230A exhibited antagonism of the expected potency against isoproterenol (apparent pK (B) 7.2) but not against KUC-7322. Neither isoproterenol nor KUC-7322 nor forskolin significantly attenuated CCh-induced contraction. These results suggest that KUC-7322 displays full agonistic activity in relaxing the human detrusor without inhibiting the contraction induced by cholinergic stimulation. These characteristics, if proven in vivo, may be beneficial for the treatment of overactive bladder, as increased bladder capacity with a negligible effect on voiding contractions may be anticipated.

We evaluated the pharmacological profile of ritobegron [KUC-7483; (-)-ethyl 2-[4-(2-{[(1S,2R)-2-hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]amino}ethyl)-2,5-dimethylphenyloxy]acetate monohydrochloride] and its effects on the bladder in cynomolgus monkeys by in vitro and in vivo experiments. In vitro, ritobegron decreased the resting tension of the isolated bladder in a concentration-dependent manner (EC(50) 8.2 ± 2.3 × 10(-7) M; maximal relaxation 88.7 ± 3.7%). The β(3)-adrenoceptor (AR) antagonist 3-(2-allylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol hydrochloride (SR58894A) produced a rightward shift of this concentration-response curve without altering the maximal response (pK(B) value 6.56 ± 0.35). In isolated atria, ritobegron increased the atrial rate only at high concentrations (EC(50) 6.5 ± 1.2 × 10(-5) M). Ritobegron had no effect on tracheal contraction at concentrations from 10(-9) to 10(-4) M, and even at the highest concentration tested, 10(-3) M, the maximal relaxation it induced was only 26.7 ± 8.1%. Tests of the selectivity of ritobegron for the bladder gave values of 79.3- and 1200-fold higher versus atria and trachea, respectively. In the in vivo study ritobegron significantly decreased intravesical pressure (ED(50) 1.44 mg/kg) without affecting either mean blood pressure or heart rate. In conclusion, ritobegron displayed potent and selective β(3)-AR agonistic activity and relaxed the monkey isolated bladder, and in vivo it decreased intravesical pressure without affecting cardiovascular parameters. These results suggest that ritobegron may be a promising potential agent for the treatment of overactive bladder.

The objective of this study was to investigate the effects of the β3-adrenoceptor (AR) agonist ritobegron on rat bladder function following partial bladder outlet obstruction and on rat salivary secretion. In addition, the effects of ritobegron were compared with those of the anti-muscarinic agent tolterodine. After a 6-week partial bladder outlet obstruction (BOO), drug effects on bladder functions were evaluated using cystometrography. Effects on carbachol (CCh)-induced salivary secretion were evaluated in urethane-anesthetized rats. Ritobegron significantly decreased the frequency of non-voiding contractions (NVC), while both ritobegron and tolterodine each significantly decreased the amplitude of NVC. Ritobegron had no effect on either the micturition pressure (MP) or the residual volume (RV). In contrast, tolterodine dose-dependently decreased MP and increased RV. Ritobegron had no effect on CCh-induced salivary secretion, whereas tolterodine dose-dependently decreased it. Ritobegron decreased both the frequency and amplitude of NVC, which is similar to its effect on the contractions associated with detrusor overactivity (DO) in patients with an overactive bladder (OAB), without affecting MP, RV, or CCh-induced salivary secretion. Although tolterodine reduced the amplitude of NVC, it also markedly increased RV and significantly inhibited CCh-induced salivary secretion. These results suggest that use of ritobegron, a β3-AR agonist, is unlikely to lead to the residual urine and dry mouth symptoms that are associated with anti-muscarinic drugs, and that ritobegron may hold promise as a safe and effective agent for OAB treatment.

Objective: To assess the effects of physician-colleague and coworker abuse on family physicians in Canada., Design: A mixed-methods, bilingual study that included surveys and telephone interviews., Setting: Canada., Participants: Family physicians in active practice who were members of the College of Family Physicians of Canada in 2009., Methods: Surveys were mailed to a random sample of family physicians (N = 3802), and 37 family physicians who had been abused in the past year participated in telephone interviews., Main Findings: A total of 770 surveys (20%) were completed. A small number of respondents reported having been subjected to abuse by physician colleagues (9%) or coworkers (6%) in the previous month. Many of the respondents reported that the same physician colleagues or coworkers were repeat abusers. More than three-quarters (77%) of the physician-colleague abusers were men, whereas more than three-quarters (77%) of the other coworker abusers were women. Interviewed family physicians described feeling humiliated and unappreciated, and developed symptoms of anxiety or depression. As a result of the abuse, some family physicians terminated their employment or refused to work in certain environments. The most striking effect of this abuse was that respondents reported losing confidence in their professional abilities and skills., Conclusion: Although only a small number of family physicians experience abuse by physician colleagues and other coworkers, the effects can be considerable. Victims reported a loss of confidence in their clinical abilities and some subsequently were faced with mental health issues.

Introduction: Most longitudinal breast cancer studies have found that treatment-related sequelae such as arm morbidity [lymphedema, pain, and range of motion (ROM) restrictions] can have a significant impact on quality of life. In a previous study, we found that at 6-12 months after breast cancer surgery, 49% of participants had difficulties engaging in recreational activities and that arm morbidity significantly predicted difficulties with participation in recreation., Methods: A longitudinal national study employing clinical assessments and survey methods followed 178 women over 43 months (3.6 years) to assess issues related to arm morbidity post-breast cancer surgery. Hierarchical multiple regression analyses were conducted to identify which variables were predictive of recreational difficulties experienced by women 8 and 43 months post-surgery., Results: Between 8 months (T1) and 43 months (T2) post-breast cancer surgery, women demonstrated slight increases in lymphedema. Conversely, a significant decrease was observed in the number of ROM restrictions and pain when using the arm. Despite the overall improvements in arm morbidity, some women continued to report moderate pain and ROM restrictions. The two arm morbidity factors were found to be statistically significant (p < 0.001) predictors of recreational difficulties at both 8 and 43 months post-surgery, with pain accounting for the greatest proportion of variance., Discussion/conclusion: Pain and ROM restrictions were the only significant predictors of recreational difficulties during the first 3.6 years after breast cancer surgery. Specifically, women who still experience pain years after breast cancer surgery report difficulties in their recreational pursuits., Implications for Cancer Survivors: Pain and ROM restrictions may prohibit participation in recreational activity and targeted intervention should be sought.

Objective. The goal of this study was to examine the monthly incidence rates of abusive encounters for family physicians in Canada. Methods. A 7-page cross-sectional survey. Results. Of the entire study sample (N = 720), 29% of the physicians reported having experienced an abusive event in the last month by a patient or patient family member. Abusive incidents were classified as minor, major, or severe. Of the physician participants who reported having been abused, all reported having experienced a minor event, 26% a major, and 8% a severe event. Of the physicians who experienced an abusive event, 55% were not aware of any policies to protect them, 76% did not seek help, and 64% did not report the abusive event. Conclusion. Family physicians are subjected to significant amounts of abuse in their day-to-day practices. Few physicians are aware of workplace policies that could protect them, and fewer report abusive encounters. Physicians would benefit from increased awareness of institutional policies that can protect them against abusive patients and their families and from the development of a national policy.

We examined whether the effects (efficacy on the urethra and hypotension) of silodosin (alpha(1A)-adrenoceptor antagonist) and tamsulosin (alpha(1A+1D)-adrenoceptor antagonist) in dogs with benign prostatic hyperplasia altered with age. We used young and old dogs, diagnosed as having benign prostatic hyperplasia by veterinarian's palpation. Under anesthesia, the increase in intraurethral pressure evoked by hypogastric nerve stimulation was measured, together with the level of systemic mean blood pressure. Each drug was administered intravenously in progressively increasing doses. At the end of the experiment, the prostate was isolated from each dog, then weighed and investigated pathologically to confirm benign prostatic hyperplasia. The wet weight of the prostate was greater in old dogs with benign prostatic hyperplasia than in young dogs with benign prostatic hyperplasia. By light microscopy, hyperplasia in the prostatic epithelium was confirmed in both groups. Silodosin (0.3-300 microg/kg) dose-dependently inhibited the hypogastric nerve stimulation-induced increase in intraurethral pressure (without significant hypotensive effects) in both young and old dogs with benign prostatic hyperplasia. Tamsulosin (0.3-300 microg/kg) also dose-dependently inhibited the intraurethral pressure increase in both groups, but it had a hypotensive effect that was significantly greater in old than in young dogs with benign prostatic hyperplasia. In conclusion, as regards the effect of silodosin on intraurethral pressure, potency was similar between young and old dogs with benign prostatic hyperplasia, and it was without significant hypotensive effects. We therefore suggest that silodosin might be a good medication for lower urinary tract symptoms in patients with benign prostatic hyperplasia in all age groups.

Objective: To examine harassment and abusive encounters between family physicians and their patients or colleagues in the workplace., Design: Qualitative case study using semistructured interviews., Setting: Province of New Brunswick., Participants: Forty-eight family physicians from across the province., Methods: A collective case-study approach was developed, with 24 cases of 2 individuals per case. Cases were selected based on sex, location (urban or rural), language (French or English), and number of years since medical school graduation (< 10 years, 10 to 20 years, or > 20 years). Physicians were interviewed in either French or English. Participants were recruited using the College of Physicians and Surgeons of New Brunswick's physician directory. Based on the rates of response and participation, some cases were overrepresented, while others were not completed. All interviews were audiotaped, transcribed verbatim, and analyzed thematically using a categorical aggregation approach. A coding scheme for the thematic analysis was developed by the research team before the interviews were transcribed., Main Findings: Although the original intent of this study was to examine the work environment of family physicians in light of the increasing number of women entering the profession, harassment and abusive encounters in the workplace emerged as a main theme. These encounters ranged from minor to severe. Minor abusive encounters included disrespectful behaviour and verbal threats by patients, their families, and occasionally colleagues. More severe forms of harassment involved physical threats, physical encounters, and stalking. Demanding patients, such as heavy drug users, were often seen as threatening. Location of practice, years in practice, and sex of the physician seemed to affect abusive encounters--young, female, rural physicians appeared to experience such encounters most often., Conclusion: Abusive encounters in the workplace are concerning. It is essential to address these issues of workplace harassment and abuse in order to protect physician safety and avoid workplace dissatisfaction. Abusive encounters might push family physicians to leave clinical practice prematurely or refuse to work in higher-risk environments, such as emergency departments or rural areas.

Objective: To explore the tensions between professional and personal boundaries and how they affect the work and private lives of family physicians., Design: Qualitative case study using semistructured interviews., Setting: Province of New Brunswick., Participants: Forty-eight family physicians from across the province., Methods: A collective case-study approach was developed, with 24 cases of 2 individuals per case. Cases were selected based on sex, location (urban or rural), language (French or English), and number of years since medical school graduation (< 10 years, 10 to 20 years, or > 20 years). Physicians were interviewed in either French or English. Participants were recruited using the College of Physicians and Surgeons of New Brunswick's physician directory. Based on the rates of response and participation, some cases were overrepresented, while others were not completed. All interviews were audiotaped, transcribed verbatim, and analyzed thematically using a categorical aggregation approach. A coding scheme for the thematic analysis was developed by the research team before the interviews were transcribed., Main Findings: Almost all of the family physicians interviewed discussed how their profession negatively affected their personal lives. Many struggled with issues such as heavy workloads, the adverse effects of their profession on their family lives, and the trespassing of patients onto their personal lives in small towns and rural communities. Some physicians had developed strategies to balance their personal lives with their professional demands; however, this often meant reducing work hours or terminating certain shifts, such as those in the emergency department or after-hours clinics., Conclusion: Family physicians struggle to keep their profession from intruding too much into their private lives. These struggles are important to acknowledge and address in order to avoid physician burnout and premature retirement from clinical practice.

Each year over 20,000 Canadian women are diagnosed with breast cancer. Many breast cancer survivors anticipate a considerable number of years of potential participation in the paid labour market, therefore, the link between breast cancer survivorship and productivity deserves serious consideration. The hypothesis guiding this study is that arm morbidities such as lymphedema, pain, and range of motion limitations are important explanatory variables in survivors' loss of productivity. The study draws from a larger longitudinal research project involving over 600 breast cancer survivors in four geographical locations across Canada. The study's regression results indicate that, after adjusting for fatigue, breast cancer stage, and geographical location, survivors with range of motion limitations and arm pain are more than two and half times as likely to lose some productivity capacity as compared to counterparts with no arm morbidity. The findings make a compelling argument for the necessity of adequate rehabilitation programs delivered at crucial times in breast cancer survivors' recovery. The study's unexpected finding that geographical location is a highly significant predictor of changes in productivity among breast cancer survivors is interpreted as a factor of the regulatory framework governing employment relationships in the four different jurisdictions.

Purpose: Alpha(1)-adrenoceptor antagonists relax the obstructed prostatic urethra and suppress the irritative symptoms frequently observed in patients with benign prostatic hyperplasia. We investigated the effects of 3 alpha(1)-adrenoceptor antagonists on urodynamics in rats with hormone induced benign prostatic hyperplasia to determine which alpha(1)-adrenoceptor subtype selective antagonists would suppress irritative symptoms., Materials and Methods: Rats were treated with testosterone and 17beta-estradiol by weekly intramuscular injections. After 4 weeks a pressure flow study was done and the effects of the alpha(1)-adrenoceptor antagonists KMD-3213 silodosin, tamsulosin and prazosin on urodynamics were compared. We especially investigated the involvement of the bladder and prostatic urethra to clarify the mechanism of detrusor overactivity expression., Results: Hormone treatment induced benign prostatic hyperplasia and resulted in detrusor overactivity, as determined by cystometry. Baseline perfusion urethral pressure and the phenylephrine induced increase in it were significantly higher in rats with vs without benign prostatic hyperplasia. Cystometry in hormone treated female rats did not show detrusor overactivity. KMD-3213 decreased detrusor overactivity, similar to other alpha(1)-adrenoceptor antagonists., Conclusions: These results suggest that an excessive response to sympathetic nerve stimulation, which is mainly mediated via alpha(1A)-adrenoceptor, in the hypertrophied prostate gives rise to detrusor overactivity. Furthermore, the alpha(1A)-adrenoceptor selective antagonist KMD-3213 would be suitable for improving irritative symptoms in patients with benign prostatic hyperplasia.

We compared the urethral and cardiovascular effects of silodosin (selective alpha(1A)-adrenoceptor antagonist), a novel medication for benign prostatic hyperplasia (BPH), with those of tamsulosin (selective alpha(1A)/alpha(1D)-adrenoceptor antagonist) and naftopidil (selective alpha(1D)-adrenoceptor antagonist). We evaluated the effects of these three drugs on the increase in intraurethral pressure (IUP) induced by electrical stimulation of the hypogastric nerve in anesthetized dogs with spontaneous BPH. All three drugs dose-dependently reduced both the increase in IUP and the mean blood pressure (MBP). The rank order of potencies was tamsulosin>silodosin>naftopidil for the reductions in both IUP and MBP. However, the uroselectivity (ED(15) value for hypotensive effect/ID(50) value for reduction in IUP) of silodosin (uroselectivity, 19.8) was about 21 and 4 times higher than that of tamsulosin (0.939) and naftopidil (4.94), respectively. These data suggest that silodosin might be one of the most useful medications for dysuria in BPH patients.

The duration of action of Silodosin (KMD-3213) against the phenylephrine-induced increase in intraurethral pressure in urethane-anesthetized rats was compared with that of tamsulosin hydrochloride. Silodosin, tamsulosin, or vehicle was orally administered to fasted male rats. Then, under urethane anesthesia, a cannula was inserted into the prostatic urethra. Phenylephrine, at a dose of 30 microg/kg, was infused (infusion rate: 36 ml/h; infusion time: 100 s/kg) via the femoral vein at 12 h, 18 h, or 24 h after administration of the study drug, and the intraurethral pressure in the prostate region was measured. Although the plasma silodosin concentration would have resolved within a few hours, silodosin significantly inhibited the phenylephrine-induced increase in intraurethral pressure (versus the vehicle-treated group) at 12 h, 18 h, and 24 h after its oral administration (at doses of 100 microg/kg and above, 1000 microg/kg and above, and 3000 microg/kg, respectively). On the other hand, tamsulosin hydrochloride showed no inhibitory action at 24 h after its oral administration at doses up to 3000 microg/kg. Thus, silodosin inhibits the phenylephrine-induced increase in intraurethral pressure for a longer time than tamsulosin hydrochloride.

The effects of silodosin, an alpha(1A)-adrenoceptor (AR) antagonist, and of other alpha(1)-AR antagonists on the phenylephrine (PE)-induced increase in intraurethral pressure (IUP) and on blood pressure (BP) were studied in anesthetized rats. The drugs were administered intravenously (i.v. study) or intraduodenally (i.d. study). IUP and BP were measured via catheters inserted into the prostatic urethra and common carotid artery, respectively. In the i.v. study, drugs were administered every 30 min for effects on BP, and 5 min before each PE-injection (30 microg/kg, every 60 min) with stepwise increases in dose for effects on IUP. In the i.d. study, one dose of drug was administered per rat, then IUP and BP were observed for 4 h [IUP being measured time-dependently following PE-injection (30 microg/kg)], and IUP and BP were expressed as a percentage of the values without any drugs. ID(50) for IUP and ED(15) for BP were calculated, and uroselectivity was determined as ED(15)/ID(50) for each drug. All drugs both inhibited the IUP increase and lowered BP, each effect being dose-dependent. The order of uroselectivities was silodosin (11.7)>tamuslosin (2.24)>naftopidil (0.133) in the i.v. study, and silodosin (26.0)>tamuslosin (3.82)>naftopidil (1.39) in the i.d. study. Selectivity for the lower urinary tract (LUT) was higher for silodosin than for tamsulosin (alpha(1A)/alpha(1D)-AR), naftopidil (alpha(1D)-AR), or prazosin (non-selective alpha(1)-AR). These results suggested that an alpha(1A)-AR selective antagonist like silodosin might be effective in the LUT without causing hypotension.

The selectivity of silodosin (KMD-3213), an antagonist of alpha(1)-adrenoceptor (AR), to the subtypes (alpha(1A)-, alpha(1B)- and alpha(1D)-ARs) was examined by a receptor-binding study and a functional pharmacological study, and we compared its subtype-selectivity with those of other alpha(1)-AR antagonists. In the receptor-binding study, a replacement experiment using [(3)H]-prazosin was conducted using the membrane fraction of mouse-derived LM (tk-) cells in which each of three human alpha(1)-AR subtypes was expressed. In the functional pharmacological study, the following isolated tissues were used as representative organs with high distribution densities of alpha(1)-AR subtypes (alpha(1A)-AR: rabbit prostate, urethra and bladder trigone; alpha(1B)-AR: rat spleen; alpha(1D)-AR: rat thoracic aorta). Using the Magnus method, we studied the inhibitory effect of silodosin on noradrenaline-induced contraction, and compared it with those of tamsulosin hydrochloride, naftopidil and prazosin hydrochloride. Silodosin showed higher selectivity for the alpha(1A)-AR subtype than tamsulosin hydrochloride, naftopidil or prazosin hydrochloride (affinity was highest for tamsulosin hydrochloride, followed by silodosin, prazosin hydrochloride and naftopidil in that order). Silodosin strongly antagonized noradrenaline-induced contractions in rabbit lower urinary tract tissues (including prostate, urethra and bladder trigone, with pA(2) or pKb values of 9.60, 8.71 and 9.35, respectively). On the other hand, the pA(2) values for antagonism of noradrenaline-induced contractions in rat isolated spleen and rat isolated thoracic aorta were 7.15 and 7.88, respectively. Selectivity for lower urinary tract was higher for silodosin than for the other alpha(1)-AR antagonists. Our data suggest that silodosin has a high selectivity for the alpha(1A)-AR subtype and for the lower urinary tract.

The aim of this study was to assess the cardiovascular effects of silodosin (CAS 160970-54-7, (-)-1-(3-hydroxypropyl)-5-[(2R)-2-({2-[2-(2,2,2-trifluoroethoxy) phenoxy]ethyllamino)propyll-2,3-dihy-dro-1H-indole-7-carboxamide, KMD-3213), a potent selective alpha1A-adrenoceptor (AR) antagonist used for the treatment of dysuria. In conscious dogs, orally administered silodosin, at doses (0.2, 2 and 20 mg/kg) considerably higher than the pharmacologically effective dose, decreased blood pressure. These doses, however, had no effects on heart rate or on the electrocardiogram (PR interval, QRS interval, QT interval or QTc). In addition, the cardiac effects of silodosin were evaluated in an in vitro electrophysiological study. Silodosin inhibited the human ether-a-go-go-related gene (HERG) tail current, leaving a residual tail current of 45 % control at 10 micromol/L. However, the concentration that inhibited the HERG tail current was considerably higher than its affinity for alphal-ARs. These results suggest that while the alpha1B-AR subtype is mainly involved in the regulation of blood pressure, the alphalA-AR subtype is not. There seems to exist no evidence of a correlation between the function of alphal-AR and ECG changes reflecting inhibition of the HERG current. The cardiovascular profile of silodosin suggests therefore that it is a safe and well-tolerated drug.

Aims: Our main aim was to compare the prostatic selectivity of silodosin with that of other alpha(1)-adrenoceptor (AR) antagonists., Methods: We examined uroselectivities in two sets of experiments namely, in vitro and in vivo functional studies using male dogs. In the in vitro study, after evaluating the inhibitory effects of silodosin on noradrenaline (NA)-induced contractions in the isolated prostate and isolated carotid artery using the Magnus method, we calculated prostatic selectivity. In the in vivo study, we examined the effects of drugs on the hypogastric nerve stimulation (HNS)-induced increase in intraurethral pressure (IUP) and on blood pressure. The uroselectivity of silodosin was compared with those of tamsulosin and naftopidil., Results: In vitro, all drugs antagonized NA-induced contraction in both prostate and carotid artery. The prostatic selectivity of silodosin (79.4) was much higher than those of tamsulosin (1.78), naftopidil (0.55), BMY 7378 (0.115), and prazosin (0.01). In vivo, intravenously (i.v.) administered silodosin dose-dependently inhibited the HNS-induced increase in IUP with much less hypotensive effect than either tamsulosin or naftopidil, the uroselectivity (ED(15)/ID(50)) of silodosin (237) being significantly higher than those of tamsulosin (1.21) and naftopidil (2.65)., Conclusions: Our results clearly demonstrate that silodosin is a potent and highly selective alpha(1A)-AR antagonist. A selective alpha(1A)-AR antagonist such as silodosin may have good potential as a less-hypotensive drug for the treatment of urinary dysfunction in benign prostatic hyperplasia patients., ((c) 2006 Wiley-Liss, Inc.)

Objective: To create a list of core and enhanced procedures suitable for family medicine training., Design: Mailed or e-mailed survey using a Delphi technique., Setting: Randomly selected family physician practices across Canada., Participants: Family physicians from urban, small-town, and rural practice locations and academic family physicians. All were experienced family physicians with from 3 to 36 years in practice., Interventions: Participant physicians were asked to rate each of 158 procedures as to whether they would expect a graduate from a Canadian family practice training program to have learned and be capable of performing that procedure in their own community. In a second survey, participants were asked to verify the core and enhanced procedures lists produced from the first survey., Main Outcome Measures: Physicians' opinions about a comprehensive list of skills., Results: Twenty-two physicians responded to the first survey (92% response rate) and 14 to the second (58% response rate). Sixty-five core procedures and 15 enhanced procedures were identified in the surveys. More procedures were ranked on the core list and were performed by rural and small-town physicians than by urban physicians. Physicians' agreement with placement of procedures on the core list ranged from 55% to 100% and of procedures on the enhanced list from 50% to 64%. Fifty-five of the procedures on the core list had agreement from more than 70% of participants., Conclusion: Procedure lists represent the opinions of Canadian family physicians about the importance of specific procedure skills for new family physicians in their communities. Procedure lists will be helpful for family medicine training programs to evaluate and refine their teaching of procedure skills.

Objective: To explore and describe primary care physicians' experiences in providing care to depressed patients and to increase understanding of the possibilities and constraints around diagnosing and treating depression in primary care., Design: Qualitative study using personal interviews., Setting: A hospital region in eastern Canada., Participants: A purposely diverse sample of 20 physicians chosen from among all 100 practising family physicians in the region., Method: Invitations were mailed to all physicians practising in the region. Twenty physicians were chosen from among the 39 physicians responding positively to the invitation. Location of practice, sex, and year of graduation from medical school were used as sampling criteria. The 20 physicians were then interviewed, and the interviews were audiotaped and transcribed verbatim. Data were analyzed using a constant comparative approach involving handwritten notes on transcripts and themes created using qualitative data analysis software., Main Findings: Three themes related to diagnosis emerged. The first concerns use of checklists. Physicians said they needed an efficient but effective means of diagnosing depression and often used diagnostic aids, such as checklists. Some physicians, however, were reluctant to use such aids. The second theme, interpersonal processes, involved the investment of time needed for diagnosing depression and the importance of establishing rapport. The final theme, intuition, revealed how some physicians relied on "gut sense" and years of experience to make a diagnosis., Conclusion: Diagnosis of depression by primary care physicians involves a series of often complicated negotiations with patients. Such negotiations require expertise gained through experience, yet prior research has not recognized the intricacies of this diagnostic process. Our findings suggest that future research must recognize the complex and multidisciplinary nature of physicians' approaches to diagnosis of depression in order to better reflect how they practise.

The purpose of this study was to find out, from the patient's perspective and using qualitative methodology, how cancer follow-up care is managed in a New Brunswick health region. From focus group discussions with 23 participants 1-year post-cancer diagnosis, 3 prominent themes emerged: fear of recurrence, cancer surveillance/testing and support issues. The fear of recurrence permeates day-to-day life for many patients. To allay these fears, some patients feel a need to be subjected to extensive cancer surveillance. Emotional support, which is important for survivors, is complex. The majority of the participants in this study received cancer follow-up care from specialists. More rural than urban participants received their follow-up care from their family physicians (FPs). Participants had high expectations for follow-up care, regardless of which type of physician--specialist or FP--provided it. If physicians did not provide the level and intensity of care expected by their patients, they were considered uncaring. We advocate a "transition of care" or "shared care" protocol between the acute cancer treatment provider and the FP, particularly in rural areas. This would ensure that cancer patients have a clear understanding of where to turn for ongoing surveillance, when they fear cancer recurrence or need support. For optimized cancer follow-up care, physicians must be cognizant that careful emotional and clinical management over an indefinite period of time is required, and they must recognize the individual needs of each patient.

Objective: To assess family physicians' and specialists' involvement in cancer follow-up care and how this involvement is perceived by cancer patients., Design: Self-administered survey., Setting: A health region in New Brunswick., Participants: A nonprobability cluster sample of 183 participants., Main Outcome Measures: Patients' perceptions of cancer follow-up care., Results: More than a third of participants (36%) were not sure which physician was in charge of their cancer follow-up care. As part of follow-up care, 80% of participants wanted counseling from their family physicians, but only 20% received it. About a third of participants (32%) were not satisfied with the follow-up care provided by their family physicians. In contrast, only 18% of participants were dissatisfied with the follow-up care provided by specialists. Older participants were more satisfied with cancer follow-up care than younger participants., Conclusion: Cancer follow-up care is increasingly becoming part of family physicians' practices. Family physicians need to develop an approach that addresses patients' needs, particularly in the area of emotional support.