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Purpose: Patients with hypothyroidism are increasingly enquiring about the benefit of using combination therapy of levothyroxine (LT4) and liothyronine (LT3) as a potential treatment for hypothyroidism. Combination therapy, however, remains controversial. The purpose of this study was to systematically review available hypothyroidism treatment recommendations from clinical practice guidelines from around the world to identify the consensus regarding combination therapy. Source: Clinical practice guidelines were obtained from searches of PubMed, EMBASE, and MEDLINE, using several combinations of MeSH terms. The search was limited to clinical guidelines in English-language publications, published between January 1, 1990 and May 1, 2015. A quantitative approach was utilized for data synthesis. Principal Findings: Thirteen guidelines were identified, including three regarding pregnancy, two regarding pediatric populations and eight regarding adult populations. There were six guidelines from North America, four guidelines from Europe and three guidelines from South America. Twelve of the guidelines were published after 2010. Nine guidelines addressed combination therapy of LT4 plus LT3, and all nine concluded that LT4 therapy alone is the standard of care, with insufficient evidence to recommend widespread combination therapy. Only the 2012 ETA Guidelines and the 2015 BTA Guidelines concluded that combination therapy could be used, although only in certain circumstances and as an experimental treatment. Conclusion: This systematic review illustrates that clinical practice guidelines worldwide do not recommend and do not support routine use of combination LT4 and LT3 therapy to treat hypothyroidism.

Purpose: The purpose of this study was to explore the ten-year trends in utilization of bioequivalent doses of statin amongst elderly patients with diabetes according to sex/gender in Ontario, Canada. Methods: A cohort of patients with diabetes (>65 years) was constructed using the Ontario Diabetes Database Statin utilization data (2003-2012) was obtained from the Ontario Drug Benefit Program for both women and men. Bioequivalent doses for statins were calculated according to the dosing conversion factor in therapeutic interchange programs in clinical practice. Utilization pattern of high potency (Atorvastatin and Rosuvastatin) vs. low potency statins (Simvastatin, Lovastatin, Fluvastatin, Pravastatin) were also analyzed. Results: The average bioequivalent Simvastatin utilization in 2003 was 29.22 mg/day for women and 30.35 mg/day for men. By 2008, this gap in dosing was higher for both women and men and by 2013 it had increased to 47.75 mg/day for women and 52.98 mg/day for men. For average number of day supply per year, there was no significant trend of changes over the 10-year period, although the use of high potency statins increased significantly (P

Purpose: Patients with hypothyroidism are increasingly enquiring about the benefit of using combination therapy of levothyroxine (LT4) and liothyronine (LT3) as a potential treatment for hypothyroidism. Combination therapy, however, remains controversial. The purpose of this study was to systematically review available hypothyroidism treatment recommendations from clinical practice guidelines from around the world to identify the consensus regarding combination therapy. Source: Clinical practice guidelines were obtained from searches of PubMed, EMBASE, and MEDLINE, using several combinations of MeSH terms. The search was limited to clinical guidelines in English-language publications, published between January 1, 1990 and May 1, 2015. A quantitative approach was utilized for data synthesis. Principal Findings: Thirteen guidelines were identified, including three regarding pregnancy, two regarding pediatric populations and eight regarding adult populations. There were six guidelines from North America, four guidelines from Europe and three guidelines from South America. Twelve of the guidelines were published after 2010. Nine guidelines addressed combination therapy of LT4 plus LT3, and all nine concluded that LT4 therapy alone is the standard of care, with insufficient evidence to recommend widespread combination therapy. Only the 2012 ETA Guidelines and the 2015 BTA Guidelines concluded that combination therapy could be used, although only in certain circumstances and as an experimental treatment. Conclusion: This systematic review illustrates that clinical practice guidelines worldwide do not recommend and do not support routine use of combination LT4 and LT3 therapy to treat hypothyroidism.

Background: Post-treatment hypothyroidism is common in Graves’ disease, and clinical guidelines recommend monitoring for it; however, thyroid stimulating hormone (TSH) can remain suppressed in these patients following treatment. The objectives of this study were to explore the proposed pathophysiology behind the phenomenon of post-therapy TSH suppression and to systematically review existing clinical data on post-therapy TSH suppression in patients with Graves’ disease. Source: A systematic literature search was performed using EMBASE and PubMed databases, with several combinations of MeSH terms. Bibliography mining was also done on relevant articles to be as inclusive as possible. Principal findings: A total of 18 articles described possible mechanisms for post-therapy TSH suppression. Several of the studies demonstrate evidence of thyrotroph atrophy and hypothesize that this contributes to the ongoing suppression. TSH receptors have been identified in folliculo-stellate cells of the pituitary as well as astroglial cells of the hypothalamus, mediating paracrine feedback. A few studies have demonstrated inverse correlation between autoantibody titres and TSH levels, suggestive of their role in mediating ongoing TSH suppression in patients with Graves’ disease. In addition, five studies were identified that provided clinical data on the duration of TSH suppression. Combined data show that 45.5% of patients recover TSH by 3 months after treatment, increasing to 69.3% by 6 months, and plateauing to 73.8% by 12 months (p>0.0001). Sub-analysis also shows that for patients who are TBII negative, 80.7% recover their TSH by 6 months compared with only 58.7% in those who are TBII positive (p= 0.003). Conclusion: Clinical data suggests that TSH recovery is most likely to occur within the first 6 months after treatment, with recovery plateauing at approximately 70% of patients, suggesting that reliance on this assay for monitoring can be very misleading. Furthermore, TBII posi

Purpose: Pharmacotherapy for diabetes in real-world clinical settings is very complex and is posing a challenge for residents in training. The purpose of this study was to explore the views of residents in Canada regarding educational priorities for pharmacotherapy in diabetes management. Methods: A questionnaire was developed to explore different domains of pharmacotherapy in diabetes management, including different clinic>al settings, combination pharmacotherapy with different classes of medications and patients’ characteristics, including comorbidities and cardiovascular risk factors. The questionnaire and the letter of invitation was sent to residents through their program directors. The results were gathered through an online survey system. Due to the study design, response rate could not be determined. For data analysis, SPSS Software was used for statistical analysis. Chi-square testing was utilized for comparisons of proportions. Results: Thirty-four residency programs in Canada were contacted and 165 residents completed the study. A significant number of the residents (59%) viewed combination pharmacotherapy for diabetes management as the most important educational priority (p < 0.001). Regarding insulin therapy, combination of insulin with another class of agents was recognized as the most important educational priority by 51% of residents (p < 0.001). Among all classes of medication for blood glucose management the education on the use of newer class of medication such as GLP1 agonists, DPP4 inhibitors and SGLT2 inhibitors was recognized as a priority by 77% of residents (p < 0.001). Conclusion: This study provides new data and insights into residents’ views on diabetes pharmacotherapy. Educational curriculums may incorporate these views from residents on the educational priorities that were identified in this study.

Purpose: The purpose of this study was to explore the ten-year trends in utilization of bioequivalent doses of statin amongst elderly patients with diabetes according to sex/gender in Ontario, Canada. Methods: A cohort of patients with diabetes (>65 years) was constructed using the Ontario Diabetes Database Statin utilization data (2003-2012) was obtained from the Ontario Drug Benefit Program for both women and men. Bioequivalent doses for statins were calculated according to the dosing conversion factor in therapeutic interchange programs in clinical practice. Utilization pattern of high potency (Atorvastatin and Rosuvastatin) vs. low potency statins (Simvastatin, Lovastatin, Fluvastatin, Pravastatin) were also analyzed. Results: The average bioequivalent Simvastatin utilization in 2003 was 29.22 mg/day for women and 30.35 mg/day for men. By 2008, this gap in dosing was higher for both women and men and by 2013 it had increased to 47.75 mg/day for women and 52.98 mg/day for men. For average number of day supply per year, there was no significant trend of changes over the 10-year period, although the use of high potency statins increased significantly (P

Purpose: The purpose of this study was to explore the ten-year trends in utilization of bioequivalent doses of statin amongst elderly patients with diabetes according to sex/gender in Ontario, Canada. Methods: A cohort of patients with diabetes (>65 years) was constructed using the Ontario Diabetes Database Statin utilization data (2003-2012) was obtained from the Ontario Drug Benefit Program for both women and men. Bioequivalent doses for statins were calculated according to the dosing conversion factor in therapeutic interchange programs in clinical practice. Utilization pattern of high potency (Atorvastatin and Rosuvastatin) vs. low potency statins (Simvastatin, Lovastatin, Fluvastatin, Pravastatin) were also analyzed. Results: The average bioequivalent Simvastatin utilization in 2003 was 29.22 mg/day for women and 30.35 mg/day for men. By 2008, this gap in dosing was higher for both women and men and by 2013 it had increased to 47.75 mg/day for women and 52.98 mg/day for men. For average number of day supply per year, there was no significant trend of changes over the 10-year period, although the use of high potency statins increased significantly (P

Purpose: There is evidence of a social disparity pertaining to the epidemiology and burden of illness of diabetes. The purpose of this study was to assess the association between household income strata and therapeutic goal achievement rates for LDL-cholesterol (LDL-C) (< 2.5 mmol/L) in Canadian diabetic patients. Methods: Data (household income, cardiovascular risk factors, drug profile, clinical and laboratory variables) were obtained from a previous cross-sectional study of diabetic patients who filled a prescription for a lipid-lowering drug in selected pharmacies across Canada. Telephone interviews were conducted. Physicians, identified by the participating patients, were requested to complete a short questionnaire for clinical data. Achievement of LDL-C goals according to the Canadian diabetes guidelines were assessed and incorporated into regression models corresponding to household income strata. Results: Seven household income strata were defined in the cohort (from less than 20,000 CDN$, up to 70,000 CDN$ by increments of 10,000 CDN$). LDL-C goals were attained in 34% of patients in the total cohort. There were no significant differences amongst household income strata for LDL-C goal achievement (p = 0.80). There were no significant differences in patient characteristics (age, sex, BMI) and cardiovascular risks according to the household income strata in this cohort, except age more than 65 in the lower income strata. Conclusion: This study demonstrates that household income was not a factor to achieve therapeutic goals for LDL-C for patients with diabetes in this dataset, although goal attainment was less than ideal overall. Future studies should address limitations of this work including small sample size, recruitment bias and lack of data on third party insurance coverage.

Purpose: There is evidence of a social disparity pertaining to the epidemiology and burden of illness of diabetes. The purpose of this study was to assess the association between household income strata and therapeutic goal achievement rates for LDL-cholesterol (LDL-C) (< 2.5 mmol/L) in Canadian diabetic patients. Methods: Data (household income, cardiovascular risk factors, drug profile, clinical and laboratory variables) were obtained from a previous cross-sectional study of diabetic patients who filled a prescription for a lipid-lowering drug in selected pharmacies across Canada. Telephone interviews were conducted. Physicians, identified by the participating patients, were requested to complete a short questionnaire for clinical data. Achievement of LDL-C goals according to the Canadian diabetes guidelines were assessed and incorporated into regression models corresponding to household income strata. Results: Seven household income strata were defined in the cohort (from less than 20,000 CDN$, up to 70,000 CDN$ by increments of 10,000 CDN$). LDL-C goals were attained in 34% of patients in the total cohort. There were no significant differences amongst household income strata for LDL-C goal achievement (p = 0.80). There were no significant differences in patient characteristics (age, sex, BMI) and cardiovascular risks according to the household income strata in this cohort, except age more than 65 in the lower income strata. Conclusion: This study demonstrates that household income was not a factor to achieve therapeutic goals for LDL-C for patients with diabetes in this dataset, although goal attainment was less than ideal overall. Future studies should address limitations of this work including small sample size, recruitment bias and lack of data on third party insurance coverage.

Purpose: There is evidence of a social disparity pertaining to the epidemiology and burden of illness of diabetes. The purpose of this study was to assess the association between household income strata and therapeutic goal achievement rates for LDL-cholesterol (LDL-C) (< 2.5 mmol/L) in Canadian diabetic patients. Methods: Data (household income, cardiovascular risk factors, drug profile, clinical and laboratory variables) were obtained from a previous cross-sectional study of diabetic patients who filled a prescription for a lipid-lowering drug in selected pharmacies across Canada. Telephone interviews were conducted. Physicians, identified by the participating patients, were requested to complete a short questionnaire for clinical data. Achievement of LDL-C goals according to the Canadian diabetes guidelines were assessed and incorporated into regression models corresponding to household income strata. Results: Seven household income strata were defined in the cohort (from less than 20,000 CDN$, up to 70,000 CDN$ by increments of 10,000 CDN$). LDL-C goals were attained in 34% of patients in the total cohort. There were no significant differences amongst household income strata for LDL-C goal achievement (p = 0.80). There were no significant differences in patient characteristics (age, sex, BMI) and cardiovascular risks according to the household income strata in this cohort, except age more than 65 in the lower income strata. Conclusion: This study demonstrates that household income was not a factor to achieve therapeutic goals for LDL-C for patients with diabetes in this dataset, although goal attainment was less than ideal overall. Future studies should address limitations of this work including small sample size, recruitment bias and lack of data on third party insurance coverage.

Purpose: Studies have demonstrated gender differences in the burden of cardiovascular outcomes for patients with dyslipidemia. Progress in identification of the sex/gender composition in Randomized Controlled Trials (RCTs) is crucial for understanding the distribution of therapeutics effectiveness in the population according to sex/gender. The purpose of this study was to investigate the evolving pattern of sex/gender disparity in participants of RCTs on statins between 1990 and 2010. A secondary objective was to evaluate changes in the pattern of the average age of participants of RCTs on statins between 1990 and 2010. Methods: This review focused on RCTs on statins that reported participants’ numbers by sex/gender. Studies were identified from an initial PubMed search using several combinations of MeSH terms. The search was limited to the RCTs on adults in English-language publications. The dates for search were set between January 1, 1990 and December 31, 2010. Results: In the 1990s, RCTs on statins with an average of more than 500 participants included 18.6% women [95% Confidence Interval (95% C.I.): 16.31%, 21.13%]. By the first decade of the 2000s, women comprised, on average, 31.45% [29.45%, 32.52% (95% C.I.)] of the total cohort of RCTs with more than 500 participants. Regression analysis illustrated a significant increase in the recruitment of women for RCTs of statins (p-value < 0.01). Furthermore, analysis of the average age of participants illustrated a significant trend (p-value = 0.03) towards an increase in the average age of the participants in RCTs on statin between 1990 and 2010: the average age of participants in the 1990s was 58 years [56, 60 (95% C.I.)] and in the 2000s it was 62 years [56, 60 (95% C.I.)]. Conclusion: This study demonstrates significant progress in the inclusion of women in RCTs on statins. This finding reflects the efforts of different agencies and groups to increase the representation of women in clinical trials.

Purpose: Studies have demonstrated gender differences in the burden of cardiovascular outcomes for patients with dyslipidemia. Progress in identification of the sex/gender composition in Randomized Controlled Trials (RCTs) is crucial for understanding the distribution of therapeutics effectiveness in the population according to sex/gender. The purpose of this study was to investigate the evolving pattern of sex/gender disparity in participants of RCTs on statins between 1990 and 2010. A secondary objective was to evaluate changes in the pattern of the average age of participants of RCTs on statins between 1990 and 2010. Methods: This review focused on RCTs on statins that reported participants’ numbers by sex/gender. Studies were identified from an initial PubMed search using several combinations of MeSH terms. The search was limited to the RCTs on adults in English-language publications. The dates for search were set between January 1, 1990 and December 31, 2010. Results: In the 1990s, RCTs on statins with an average of more than 500 participants included 18.6% women [95% Confidence Interval (95% C.I.): 16.31%, 21.13%]. By the first decade of the 2000s, women comprised, on average, 31.45% [29.45%, 32.52% (95% C.I.)] of the total cohort of RCTs with more than 500 participants. Regression analysis illustrated a significant increase in the recruitment of women for RCTs of statins (p-value < 0.01). Furthermore, analysis of the average age of participants illustrated a significant trend (p-value = 0.03) towards an increase in the average age of the participants in RCTs on statin between 1990 and 2010: the average age of participants in the 1990s was 58 years [56, 60 (95% C.I.)] and in the 2000s it was 62 years [56, 60 (95% C.I.)]. Conclusion: This study demonstrates significant progress in the inclusion of women in RCTs on statins. This finding reflects the efforts of different agencies and groups to increase the representation of women in clinical trials.

Background: Lipid-lowering therapeutics, particularly HMG Co-A reductase inhibitors, can be beneficial in primary and secondary cardiovascular prevention. The Canadian population frequently uses these medications but the manner in which they are used in community-based practice is unknown. Objectives: To assess the patient characteristics associated with lipid lowering drug use in community-based clinical practice across four geographic regions in Canada. To assess amongst lipid-lowering drugs users the proportion of patients that would meet accepted dyslipidemia management guidelines. To assess the community-based effectiveness of anti-hyperlipidemic drugs. Methods: Patients filling a prescription for any anti-hyperlipidemia therapy in selected pharmacies in Ontario (ON), Quebec (PQ), British Columbia (BC) and Nova Scotia (NS). All eligible patients were interviewed over the telephone. Physicians who were providing healthcare to the participating patients were requested to provide information from the patient’s medical record. Results: The mean patient age was > 60 yr in all four provinces. There were some differences amongst the four provinces pertaining to patient characteristics, prescription patterns and therapeutic indicators, but not to outcomes. Anti-hyperlipidemia therapy was associated with a 1.81 mmol/L decrease in LDL-Cholesterol (P < 0.001); however only 73% of patients achieved target LDL-Cholesterol concentrations. A lag time of 1.96 yr (P < 0.0001) was observed from the diagnosis of dyslipidemia until the drug treatment was initiated. Patients had an average of 2.8 cardiovascular (CV) risk factors and 86% of patients had at two or more CV risk factors. Thirty-nine percent (95% CI, 36% - 42%) of the patients were being treated for secondary prevention. Thirteen percent (11% - 16%) of patients who were being treated for primary prevention had diabetes. Metabolic syndrome was observed in 32% (29% - 35%) of patients. Conclusion: Almost all patients

Background: Lipid-lowering therapeutics, particularly HMG Co-A reductase inhibitors, can be beneficial in primary and secondary cardiovascular prevention. The Canadian population frequently uses these medications but the manner in which they are used in community-based practice is unknown. Objectives: To assess the patient characteristics associated with lipid lowering drug use in community-based clinical practice across four geographic regions in Canada. To assess amongst lipid-lowering drugs users the proportion of patients that would meet accepted dyslipidemia management guidelines. To assess the community-based effectiveness of anti-hyperlipidemic drugs. Methods: Patients filling a prescription for any anti-hyperlipidemia therapy in selected pharmacies in Ontario (ON), Quebec (PQ), British Columbia (BC) and Nova Scotia (NS). All eligible patients were interviewed over the telephone. Physicians who were providing healthcare to the participating patients were requested to provide information from the patient’s medical record. Results: The mean patient age was > 60 yr in all four provinces. There were some differences amongst the four provinces pertaining to patient characteristics, prescription patterns and therapeutic indicators, but not to outcomes. Anti-hyperlipidemia therapy was associated with a 1.81 mmol/L decrease in LDL-Cholesterol (P < 0.001); however only 73% of patients achieved target LDL-Cholesterol concentrations. A lag time of 1.96 yr (P < 0.0001) was observed from the diagnosis of dyslipidemia until the drug treatment was initiated. Patients had an average of 2.8 cardiovascular (CV) risk factors and 86% of patients had at two or more CV risk factors. Thirty-nine percent (95% CI, 36% - 42%) of the patients were being treated for secondary prevention. Thirteen percent (11% - 16%) of patients who were being treated for primary prevention had diabetes. Metabolic syndrome was observed in 32% (29% - 35%) of patients. Conclusion: Almost all patients

Background: Lipid-lowering therapeutics, particularly HMG Co-A reductase inhibitors, can be beneficial in primary and secondary cardiovascular prevention. The Canadian population frequently uses these medications but the manner in which they are used in community-based practice is unknown. Objectives: To assess the patient characteristics associated with lipid lowering drug use in community-based clinical practice across four geographic regions in Canada. To assess amongst lipid-lowering drugs users the proportion of patients that would meet accepted dyslipidemia management guidelines. To assess the community-based effectiveness of anti-hyperlipidemic drugs. Methods: Patients filling a prescription for any anti-hyperlipidemia therapy in selected pharmacies in Ontario (ON), Quebec (PQ), British Columbia (BC) and Nova Scotia (NS). All eligible patients were interviewed over the telephone. Physicians who were providing healthcare to the participating patients were requested to provide information from the patient’s medical record. Results: The mean patient age was > 60 yr in all four provinces. There were some differences amongst the four provinces pertaining to patient characteristics, prescription patterns and therapeutic indicators, but not to outcomes. Anti-hyperlipidemia therapy was associated with a 1.81 mmol/L decrease in LDL-Cholesterol (P < 0.001); however only 73% of patients achieved target LDL-Cholesterol concentrations. A lag time of 1.96 yr (P < 0.0001) was observed from the diagnosis of dyslipidemia until the drug treatment was initiated. Patients had an average of 2.8 cardiovascular (CV) risk factors and 86% of patients had at two or more CV risk factors. Thirty-nine percent (95% CI, 36% - 42%) of the patients were being treated for secondary prevention. Thirteen percent (11% - 16%) of patients who were being treated for primary prevention had diabetes. Metabolic syndrome was observed in 32% (29% - 35%) of patients. Conclusion: Almost all patients