Primary Care Medical Abstracts

Nordestgaard, B.G., J Am Coll Cardiol 70(13):1637, September 26, 2017

This Danish author reviews the impact of a fasting versus nonfasting state on lipid profile testing. He addresses the pros and cons of fasting or nonfasting lipid profiles, the impact on individual lipid parameters, and the implications for diagnosing and treating cardiovascular disease (CVD). Testing lipid profiles in the nonfasting state is increasingly common, in part because it is simpler, given that (typically) 16 hours per day are nonfasting. In addition, a nonfasting lipid profile is more accurate for measuring total atherogenic lipoproteins in plasma because it includes those of hepatic origin in the fasting state and those of intestinal origin in the nonfasting state. Maximum mean differences in lipid parameters measured in nonfasting versus fasting patients are +26mg/dL for triglycerides, -8mg/dL for total cholesterol, -8mg/dL for LDL cholesterol, +8mg/dL for remnant cholesterol, and -8mg/dL for non-HDL cholesterol. The reductions in total, LDL and non-HDL cholesterol are mainly due to fluid intake and not food consumption. A nonfasting condition has no appreciable effect on HDL cholesterol, lipoprotein(a), or apolipoproteins A1 and B. Nonfasting lipid profiles have equal predictive ability for CVD and should not affect treatment decisions (e.g., statin use) for most patients. Testing of nonfasting samples is simpler for all parties (patients, clinicians and laboratories), safer for patients who cannot fast, increases efficiency, and saves money. International guidelines since 2009 are increasingly recommending nonfasting lipid profiles. The author notes that testing of fasting lipid profiles continues largely because “we have always done it this way.” He recommends that nonfasting blood samples be routinely tested, except in selected patients who require fasting samples. 55 references ([email protected] – no reprints)

Nordestgaard, B.G., J Am Coll Cardiol 70(13):1637, September 26, 2017

This Danish author reviews the impact of a fasting versus nonfasting state on lipid profile testing. He addresses the pros and cons of fasting or nonfasting lipid profiles, the impact on individual lipid parameters, and the implications for diagnosing and treating cardiovascular disease (CVD). Testing lipid profiles in the nonfasting state is increasingly common, in part because it is simpler, given that (typically) 16 hours per day are nonfasting. In addition, a nonfasting lipid profile is more accurate for measuring total atherogenic lipoproteins in plasma because it includes those of hepatic origin in the fasting state and those of intestinal origin in the nonfasting state. Maximum mean differences in lipid parameters measured in nonfasting versus fasting patients are +26mg/dL for triglycerides, -8mg/dL for total cholesterol, -8mg/dL for LDL cholesterol, +8mg/dL for remnant cholesterol, and -8mg/dL for non-HDL cholesterol. The reductions in total, LDL and non-HDL cholesterol are mainly due to fluid intake and not food consumption. A nonfasting condition has no appreciable effect on HDL cholesterol, lipoprotein(a), or apolipoproteins A1 and B. Nonfasting lipid profiles have equal predictive ability for CVD and should not affect treatment decisions (e.g., statin use) for most patients. Testing of nonfasting samples is simpler for all parties (patients, clinicians and laboratories), safer for patients who cannot fast, increases efficiency, and saves money. International guidelines since 2009 are increasingly recommending nonfasting lipid profiles. The author notes that testing of fasting lipid profiles continues largely because “we have always done it this way.” He recommends that nonfasting blood samples be routinely tested, except in selected patients who require fasting samples. 55 references ([email protected] – no reprints)

Nordestgaard, B.G., J Am Coll Cardiol 70(13):1637, September 26, 2017

This Danish author reviews the impact of a fasting versus nonfasting state on lipid profile testing. He addresses the pros and cons of fasting or nonfasting lipid profiles, the impact on individual lipid parameters, and the implications for diagnosing and treating cardiovascular disease (CVD). Testing lipid profiles in the nonfasting state is increasingly common, in part because it is simpler, given that (typically) 16 hours per day are nonfasting. In addition, a nonfasting lipid profile is more accurate for measuring total atherogenic lipoproteins in plasma because it includes those of hepatic origin in the fasting state and those of intestinal origin in the nonfasting state. Maximum mean differences in lipid parameters measured in nonfasting versus fasting patients are +26mg/dL for triglycerides, -8mg/dL for total cholesterol, -8mg/dL for LDL cholesterol, +8mg/dL for remnant cholesterol, and -8mg/dL for non-HDL cholesterol. The reductions in total, LDL and non-HDL cholesterol are mainly due to fluid intake and not food consumption. A nonfasting condition has no appreciable effect on HDL cholesterol, lipoprotein(a), or apolipoproteins A1 and B. Nonfasting lipid profiles have equal predictive ability for CVD and should not affect treatment decisions (e.g., statin use) for most patients. Testing of nonfasting samples is simpler for all parties (patients, clinicians and laboratories), safer for patients who cannot fast, increases efficiency, and saves money. International guidelines since 2009 are increasingly recommending nonfasting lipid profiles. The author notes that testing of fasting lipid profiles continues largely because “we have always done it this way.” He recommends that nonfasting blood samples be routinely tested, except in selected patients who require fasting samples. 55 references ([email protected] – no reprints)

Pinkerton, J. V., et al, Menopause 24(10):1099, October 2017

The authors, writing for the North American Menopause Society (NAMS), protest the recent guideline recommendations regarding postmenopausal hormone therapy (HT) from the US Preventive Services Task Force (USPSTF). The USPSTF draft guidance gives HT (both combined regimens and estrogen alone) a D recommendation for preventing chronic disease because of harms outweighing benefits. The NAMS panel contends that the USPSTF opinion does not distinguish between approved and unapproved indications for HT. They note that the conclusions are based on the Women’s Health Initiative (WHI) trial, from which certain patient populations who may benefit (bothersome hot flashes, high osteoporosis risk, genitourinary symptoms) were omitted. The WHI tested a single dose of a single formulation in women having an average age of 63 who were 13 years past menopause. According to NAMS, the USPSTF should acknowledge that HT relieves vasomotor symptoms, helps prevent bone loss and fracture, and may improve quality of life in women younger than 60 years who take HT within ten years of menopause. Women younger than 60 years who have had a hysterectomy benefit from early estrogen monotherapy, having a lower incidence of breast cancer, cardiovascular disease and mortality. Further, the panel feels that the USPSTF should state that the findings of harm were based on higher-dose formulations, and that the results may not apply to lower doses, different and newer formulations (e.g., natural progesterone, bazedoxifene), and different dosing routes (e.g., transdermal administration). NAMS agrees that HT does not prevent heart disease, but indicates that its use (and insurance coverage) should not be precluded for women with early menopause, bothersome hot flashes, genitourinary symptoms and/or a high risk of fracture. 12 references

Pinkerton, J. V., et al, Menopause 24(10):1099, October 2017

The authors, writing for the North American Menopause Society (NAMS), protest the recent guideline recommendations regarding postmenopausal hormone therapy (HT) from the US Preventive Services Task Force (USPSTF). The USPSTF draft guidance gives HT (both combined regimens and estrogen alone) a D recommendation for preventing chronic disease because of harms outweighing benefits. The NAMS panel contends that the USPSTF opinion does not distinguish between approved and unapproved indications for HT. They note that the conclusions are based on the Women’s Health Initiative (WHI) trial, from which certain patient populations who may benefit (bothersome hot flashes, high osteoporosis risk, genitourinary symptoms) were omitted. The WHI tested a single dose of a single formulation in women having an average age of 63 who were 13 years past menopause. According to NAMS, the USPSTF should acknowledge that HT relieves vasomotor symptoms, helps prevent bone loss and fracture, and may improve quality of life in women younger than 60 years who take HT within ten years of menopause. Women younger than 60 years who have had a hysterectomy benefit from early estrogen monotherapy, having a lower incidence of breast cancer, cardiovascular disease and mortality. Further, the panel feels that the USPSTF should state that the findings of harm were based on higher-dose formulations, and that the results may not apply to lower doses, different and newer formulations (e.g., natural progesterone, bazedoxifene), and different dosing routes (e.g., transdermal administration). NAMS agrees that HT does not prevent heart disease, but indicates that its use (and insurance coverage) should not be precluded for women with early menopause, bothersome hot flashes, genitourinary symptoms and/or a high risk of fracture. 12 references

Pinkerton, J. V., et al, Menopause 24(10):1099, October 2017

The authors, writing for the North American Menopause Society (NAMS), protest the recent guideline recommendations regarding postmenopausal hormone therapy (HT) from the US Preventive Services Task Force (USPSTF). The USPSTF draft guidance gives HT (both combined regimens and estrogen alone) a D recommendation for preventing chronic disease because of harms outweighing benefits. The NAMS panel contends that the USPSTF opinion does not distinguish between approved and unapproved indications for HT. They note that the conclusions are based on the Women’s Health Initiative (WHI) trial, from which certain patient populations who may benefit (bothersome hot flashes, high osteoporosis risk, genitourinary symptoms) were omitted. The WHI tested a single dose of a single formulation in women having an average age of 63 who were 13 years past menopause. According to NAMS, the USPSTF should acknowledge that HT relieves vasomotor symptoms, helps prevent bone loss and fracture, and may improve quality of life in women younger than 60 years who take HT within ten years of menopause. Women younger than 60 years who have had a hysterectomy benefit from early estrogen monotherapy, having a lower incidence of breast cancer, cardiovascular disease and mortality. Further, the panel feels that the USPSTF should state that the findings of harm were based on higher-dose formulations, and that the results may not apply to lower doses, different and newer formulations (e.g., natural progesterone, bazedoxifene), and different dosing routes (e.g., transdermal administration). NAMS agrees that HT does not prevent heart disease, but indicates that its use (and insurance coverage) should not be precluded for women with early menopause, bothersome hot flashes, genitourinary symptoms and/or a high risk of fracture. 12 references

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)

Leclerc, J., et al, Circ Cardiovasc Qual Outcomes 10(10):e003891, October 2017

BACKGROUND: Generic formulations are generally less expensive than their brand-name counterparts, but they must also be clinically equivalent as well as bioequivalent.

METHODS: This retrospective, interrupted time-series analysis, coordinated at the National Institute of Public Health of Quebec, explored adverse events after commercialization of three generic angiotensin II receptor blockers (ARBs). A large Quebec disease surveillance database provided population data on 136,177 elderly patients (aged 66 or older; mean 76 years; 60% female) using losartan, valsartan or candesartan, as well as 16 generic analogs, each month for 24 months before and 12 months after generic market entry. The primary study outcome was all-cause hospitalization and emergency room visits from before to after introduction of the generics.

RESULTS: Brand-name drug utilization decreased to less than 5% of the total within two to three years after introduction of the generics. At baseline, adverse event rates (per 1000 person-months) were 107 for losartan, 104 for valsartan and 89 for candesartan. Adverse event rates increased for generic losartan users versus brand-name losartan users during the month after generic commercialization (8.0% increase versus 0.5% increase; p=0.064). Valsartan generic users had significantly elevated adverse event rates versus brand-name valsartan users (11.7% increase versus 5.4% decrease; p<0.0001), and the same was true for candesartan generic users versus brand-name users (14.0% increase versus 2.6% decrease; p<0.0001). The difference in adverse event rates at one year follow-up was statistically significant only for losartan (p=0.003).

CONCLUSIONS: In this large study, generic substitution of ARBs was associated with an increase in adverse events. 41 references ([email protected] – no reprints)

Nachum, Z., et al, Diab Care 40(3):332, March 2017

METHODS: These Israeli authors performed an open-label trial of the efficacy and safety of glyburide, metformin and their combination for gestational diabetes mellitus (GDM).  The study included 104 women aged 18-45 (mean age, 33) with elevated blood glucose due to GDM diagnosed at 13-33 weeks’ gestation who were randomized to begin treatment with glyburide or metformin.  Treatment was changed as follows: the patient was switched to the other drug in case of adverse events, changed to combination therapy in the event of treatment failure (preprandial glucose above 95mg/dL, postprandial glucose above 130mg/dL, or daily glucose above 100mg/dL), changed to insulin if both drugs failed.  The primary outcome was treatment failure (adverse events or poor glycemic control) after the first study drug based on patients’ daily glucose charts.

RESULTS: Treatment failed in 18 glyburide patients (34%) and 15 metformin patients (29%), a nonsignificant difference (p=0.6). Failure with glyburide was due to hypoglycemia in 11% and poor glycemic control in 23%; metformin failure was due to gastrointestinal events in 2% and poor glycemic control in 28%. Second-line treatment with metformin was more effective than second-line glyburide (87% versus 50%; p=0.03), and glyburide patients were more likely to require insulin (17% versus 4%; p=0.03). Combining the drugs reduced the need for insulin from 32% to 11% (p=0.0002). Safety parameters and obstetric outcomes were similar between groups.

CONCLUSIONS: In this study, glyburide and metformin were generally comparable in efficacy and safety for treating GDM. There may be a slight advantage to starting with metformin. Combining the two agents reduced the risk of treatment failure and the need for insulin. 22 references ([email protected] – no reprints)

Nachum, Z., et al, Diab Care 40(3):332, March 2017

METHODS: These Israeli authors performed an open-label trial of the efficacy and safety of glyburide, metformin and their combination for gestational diabetes mellitus (GDM).  The study included 104 women aged 18-45 (mean age, 33) with elevated blood glucose due to GDM diagnosed at 13-33 weeks’ gestation who were randomized to begin treatment with glyburide or metformin.  Treatment was changed as follows: the patient was switched to the other drug in case of adverse events, changed to combination therapy in the event of treatment failure (preprandial glucose above 95mg/dL, postprandial glucose above 130mg/dL, or daily glucose above 100mg/dL), changed to insulin if both drugs failed.  The primary outcome was treatment failure (adverse events or poor glycemic control) after the first study drug based on patients’ daily glucose charts.

RESULTS: Treatment failed in 18 glyburide patients (34%) and 15 metformin patients (29%), a nonsignificant difference (p=0.6). Failure with glyburide was due to hypoglycemia in 11% and poor glycemic control in 23%; metformin failure was due to gastrointestinal events in 2% and poor glycemic control in 28%. Second-line treatment with metformin was more effective than second-line glyburide (87% versus 50%; p=0.03), and glyburide patients were more likely to require insulin (17% versus 4%; p=0.03). Combining the drugs reduced the need for insulin from 32% to 11% (p=0.0002). Safety parameters and obstetric outcomes were similar between groups.

CONCLUSIONS: In this study, glyburide and metformin were generally comparable in efficacy and safety for treating GDM. There may be a slight advantage to starting with metformin. Combining the two agents reduced the risk of treatment failure and the need for insulin. 22 references ([email protected] – no reprints)

Nachum, Z., et al, Diab Care 40(3):332, March 2017

METHODS: These Israeli authors performed an open-label trial of the efficacy and safety of glyburide, metformin and their combination for gestational diabetes mellitus (GDM).  The study included 104 women aged 18-45 (mean age, 33) with elevated blood glucose due to GDM diagnosed at 13-33 weeks’ gestation who were randomized to begin treatment with glyburide or metformin.  Treatment was changed as follows: the patient was switched to the other drug in case of adverse events, changed to combination therapy in the event of treatment failure (preprandial glucose above 95mg/dL, postprandial glucose above 130mg/dL, or daily glucose above 100mg/dL), changed to insulin if both drugs failed.  The primary outcome was treatment failure (adverse events or poor glycemic control) after the first study drug based on patients’ daily glucose charts.

RESULTS: Treatment failed in 18 glyburide patients (34%) and 15 metformin patients (29%), a nonsignificant difference (p=0.6). Failure with glyburide was due to hypoglycemia in 11% and poor glycemic control in 23%; metformin failure was due to gastrointestinal events in 2% and poor glycemic control in 28%. Second-line treatment with metformin was more effective than second-line glyburide (87% versus 50%; p=0.03), and glyburide patients were more likely to require insulin (17% versus 4%; p=0.03). Combining the drugs reduced the need for insulin from 32% to 11% (p=0.0002). Safety parameters and obstetric outcomes were similar between groups.

CONCLUSIONS: In this study, glyburide and metformin were generally comparable in efficacy and safety for treating GDM. There may be a slight advantage to starting with metformin. Combining the two agents reduced the risk of treatment failure and the need for insulin. 22 references ([email protected] – no reprints)

Spyropoulos, A.C., et al, Clin Appl Thromb Hemost 23(6):532, September 2017

BACKGROUND: The American College of Chest Physicians (ACCP) recommends three months or at least six months of oral anticoagulant therapy, depending on history and risk factors, to prevent recurrent venous thromboembolism (VTE) events.

METHODS: This retrospective study coordinated at Hofstra School of Medicine evaluated adherence to the ACCP guidelines and associated clinical and economic outcomes. A US health care claims database identified 81,827 adults (median age 56 years; 52% male) with at least one claim for deep vein thrombosis or pulmonary embolism in 2008-2014, use of anticoagulation therapy after the index event, and continuous insurance coverage for one year before and after the event. Patients were classified as adherent (n=60,550; 74%) or nonadherent (n=21,277) with the ACCP minimum treatment durations. The primary study outcomes were VTE recurrence, all-cause and bleeding-related hospitalizations, and medical costs.

RESULTS: Most patients (94%) received warfarin. Nonadherent patients had significantly more VTE recurrences, resource use, bleeding complications, and costs during follow-up. On multivariate analysis controlling for patient characteristics, adherent patients had lower risks of all-cause hospitalization (adjusted odds ratio [AOR] 0.85; 95% CI 0.82-0.88; p<0.0001), bleeding-related hospitalization (AOR 0.74; 95% CI 0.69-0.78; p<0.0001), and VTE recurrence (AOR 0.92; 95% CI 0.88-0.97; p=0.0014), as well as lower total health care costs (mean difference -$2121; p=0.0003), VTE-related costs (-$2294; p<0.0001), and bleeding-related costs (-$248; p<0.0001).

CONCLUSIONS: In this large study, compliance with ACCP anticoagulant guidelines was associated with a reduction in VTE morbidity and health care costs. 16 references ([email protected] – no reprints)

Spyropoulos, A.C., et al, Clin Appl Thromb Hemost 23(6):532, September 2017

BACKGROUND: The American College of Chest Physicians (ACCP) recommends three months or at least six months of oral anticoagulant therapy, depending on history and risk factors, to prevent recurrent venous thromboembolism (VTE) events.

METHODS: This retrospective study coordinated at Hofstra School of Medicine evaluated adherence to the ACCP guidelines and associated clinical and economic outcomes. A US health care claims database identified 81,827 adults (median age 56 years; 52% male) with at least one claim for deep vein thrombosis or pulmonary embolism in 2008-2014, use of anticoagulation therapy after the index event, and continuous insurance coverage for one year before and after the event. Patients were classified as adherent (n=60,550; 74%) or nonadherent (n=21,277) with the ACCP minimum treatment durations. The primary study outcomes were VTE recurrence, all-cause and bleeding-related hospitalizations, and medical costs.

RESULTS: Most patients (94%) received warfarin. Nonadherent patients had significantly more VTE recurrences, resource use, bleeding complications, and costs during follow-up. On multivariate analysis controlling for patient characteristics, adherent patients had lower risks of all-cause hospitalization (adjusted odds ratio [AOR] 0.85; 95% CI 0.82-0.88; p<0.0001), bleeding-related hospitalization (AOR 0.74; 95% CI 0.69-0.78; p<0.0001), and VTE recurrence (AOR 0.92; 95% CI 0.88-0.97; p=0.0014), as well as lower total health care costs (mean difference -$2121; p=0.0003), VTE-related costs (-$2294; p<0.0001), and bleeding-related costs (-$248; p<0.0001).

CONCLUSIONS: In this large study, compliance with ACCP anticoagulant guidelines was associated with a reduction in VTE morbidity and health care costs. 16 references ([email protected] – no reprints)

Spyropoulos, A.C., et al, Clin Appl Thromb Hemost 23(6):532, September 2017

BACKGROUND: The American College of Chest Physicians (ACCP) recommends three months or at least six months of oral anticoagulant therapy, depending on history and risk factors, to prevent recurrent venous thromboembolism (VTE) events.

METHODS: This retrospective study coordinated at Hofstra School of Medicine evaluated adherence to the ACCP guidelines and associated clinical and economic outcomes. A US health care claims database identified 81,827 adults (median age 56 years; 52% male) with at least one claim for deep vein thrombosis or pulmonary embolism in 2008-2014, use of anticoagulation therapy after the index event, and continuous insurance coverage for one year before and after the event. Patients were classified as adherent (n=60,550; 74%) or nonadherent (n=21,277) with the ACCP minimum treatment durations. The primary study outcomes were VTE recurrence, all-cause and bleeding-related hospitalizations, and medical costs.

RESULTS: Most patients (94%) received warfarin. Nonadherent patients had significantly more VTE recurrences, resource use, bleeding complications, and costs during follow-up. On multivariate analysis controlling for patient characteristics, adherent patients had lower risks of all-cause hospitalization (adjusted odds ratio [AOR] 0.85; 95% CI 0.82-0.88; p<0.0001), bleeding-related hospitalization (AOR 0.74; 95% CI 0.69-0.78; p<0.0001), and VTE recurrence (AOR 0.92; 95% CI 0.88-0.97; p=0.0014), as well as lower total health care costs (mean difference -$2121; p=0.0003), VTE-related costs (-$2294; p<0.0001), and bleeding-related costs (-$248; p<0.0001).

CONCLUSIONS: In this large study, compliance with ACCP anticoagulant guidelines was associated with a reduction in VTE morbidity and health care costs. 16 references ([email protected] – no reprints)

Tsodikov, A., et al, Ann Intern Med 167(7):449, October 3, 2017

BACKGROUND: In 2012 the U.S. Preventive Services Task Force recommended against routine prostate cancer screening because its lack of effect on long-term mortality. Their recommendations (which are being updated) were based mainly on the ERSPC (European Randomized Study of Screening for Prostate Cancer) and PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) trials. However, these two trials are substantially different in terms of design, settings, screening intensity, baseline risk and screening effect on mortality (a relative reduction of 21% vs. no reduction, respectively).

METHODS: To evaluate whether the mortality difference persisted after accounting for implementation and practice setting differences, these multinational authors combined data from both trials to conduct a traditional statistical analysis that adjusted for participant age and trial setting, and extended analyses that overcame variability in screening intensity by considering mean lead times, which indicated increased prostate cancer incidence and earlier diagnosis with vs. without screening. Follow-up was restricted to eleven years for both trials.

RESULTS: The traditional analysis demonstrated a marginally different screening effect on mortality between trials (p=0.087), and an overall relative risk reduction of 16% (p=0.010). Extended analyses indicated no difference in screening effect on mortality between trials (p=0.37 to 0.47), and an overall association of longer mean lead times with a lower risk of prostate cancer specific death (p=0.0027 to 0.0032). Screening was estimated to lead to a 25-31% and a 27-32% relative reduction in risk of prostate cancer death in the two trials, respectively, vs. no screening (NNT = ~ 1,111 for 11 years of regular screening).

CONCLUSIONS: This analysis of data from two large prostate cancer-screening trials found that screening significantly reduced prostate cancer mortality risk compared with no screening. 18 references ([email protected] for reprints)

Tsodikov, A., et al, Ann Intern Med 167(7):449, October 3, 2017

BACKGROUND: In 2012 the U.S. Preventive Services Task Force recommended against routine prostate cancer screening because its lack of effect on long-term mortality. Their recommendations (which are being updated) were based mainly on the ERSPC (European Randomized Study of Screening for Prostate Cancer) and PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) trials. However, these two trials are substantially different in terms of design, settings, screening intensity, baseline risk and screening effect on mortality (a relative reduction of 21% vs. no reduction, respectively).

METHODS: To evaluate whether the mortality difference persisted after accounting for implementation and practice setting differences, these multinational authors combined data from both trials to conduct a traditional statistical analysis that adjusted for participant age and trial setting, and extended analyses that overcame variability in screening intensity by considering mean lead times, which indicated increased prostate cancer incidence and earlier diagnosis with vs. without screening. Follow-up was restricted to eleven years for both trials.

RESULTS: The traditional analysis demonstrated a marginally different screening effect on mortality between trials (p=0.087), and an overall relative risk reduction of 16% (p=0.010). Extended analyses indicated no difference in screening effect on mortality between trials (p=0.37 to 0.47), and an overall association of longer mean lead times with a lower risk of prostate cancer specific death (p=0.0027 to 0.0032). Screening was estimated to lead to a 25-31% and a 27-32% relative reduction in risk of prostate cancer death in the two trials, respectively, vs. no screening (NNT = ~ 1,111 for 11 years of regular screening).

CONCLUSIONS: This analysis of data from two large prostate cancer-screening trials found that screening significantly reduced prostate cancer mortality risk compared with no screening. 18 references ([email protected] for reprints)

Tsodikov, A., et al, Ann Intern Med 167(7):449, October 3, 2017

BACKGROUND: In 2012 the U.S. Preventive Services Task Force recommended against routine prostate cancer screening because its lack of effect on long-term mortality. Their recommendations (which are being updated) were based mainly on the ERSPC (European Randomized Study of Screening for Prostate Cancer) and PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) trials. However, these two trials are substantially different in terms of design, settings, screening intensity, baseline risk and screening effect on mortality (a relative reduction of 21% vs. no reduction, respectively).

METHODS: To evaluate whether the mortality difference persisted after accounting for implementation and practice setting differences, these multinational authors combined data from both trials to conduct a traditional statistical analysis that adjusted for participant age and trial setting, and extended analyses that overcame variability in screening intensity by considering mean lead times, which indicated increased prostate cancer incidence and earlier diagnosis with vs. without screening. Follow-up was restricted to eleven years for both trials.

RESULTS: The traditional analysis demonstrated a marginally different screening effect on mortality between trials (p=0.087), and an overall relative risk reduction of 16% (p=0.010). Extended analyses indicated no difference in screening effect on mortality between trials (p=0.37 to 0.47), and an overall association of longer mean lead times with a lower risk of prostate cancer specific death (p=0.0027 to 0.0032). Screening was estimated to lead to a 25-31% and a 27-32% relative reduction in risk of prostate cancer death in the two trials, respectively, vs. no screening (NNT = ~ 1,111 for 11 years of regular screening).

CONCLUSIONS: This analysis of data from two large prostate cancer-screening trials found that screening significantly reduced prostate cancer mortality risk compared with no screening. 18 references ([email protected] for reprints)

Silverman, M., et al, Ann Intern Med 166(11):765, June 6, 2017

BACKGROUND: Overuse of antibiotics increases healthcare costs and contributes to the emergence of resistance, but these agents continue to be prescribed heavily for nonbacterial acute upper respiratory infections. Factors influencing physicians may include patient expectations, decision fatigue, fear of complications and unintended financial incentives.

METHODS: In this retrospective analysis of administrative healthcare data, the authors from the University of Western Ontario included 185,014 patients aged 66 or older (mean age 74.6 years) presenting to 8990 primary care physicians who were diagnosed with a first episode of nonbacterial acute upper respiratory infection that did not otherwise warrant antibiotic treatment. More than 90% of the episodes were managed by one physician and involved one visit. The primary outcome was antibiotic prescription within 30 days. Episode, patient and physician factors, in the context of antibiotic prescription, were evaluated.

RESULTS: Overall, 46.2% of the patients were prescribed antibiotics (broad-spectrum agents in 69.9% of these cases). Patients receiving an antibiotic prescription were more likely than those not prescribed an antibiotic to be diagnosed with acute bronchitis (45.3% vs. 19.3%) or acute sinusitis (17.1% vs. 10.6%). Patients were more likely to receive antibiotic prescriptions when physicians were mid- and late-career vs. early-career, trained outside of Canada or the United States, and seeing more than 25 patients per day. Broad-spectrum agents were more frequently prescribed by mid- and late-career physicians and those trained in Canada or the United States.

CONCLUSIONS: Almost one-half of these elderly patients with nonbacterial acute upper respiratory infections received unnecessary antibiotic prescriptions. This study sheds light on the prevalence and predictors of such prescribing. 58 references ([email protected] for reprints)

Silverman, M., et al, Ann Intern Med 166(11):765, June 6, 2017

BACKGROUND: Overuse of antibiotics increases healthcare costs and contributes to the emergence of resistance, but these agents continue to be prescribed heavily for nonbacterial acute upper respiratory infections. Factors influencing physicians may include patient expectations, decision fatigue, fear of complications and unintended financial incentives.

METHODS: In this retrospective analysis of administrative healthcare data, the authors from the University of Western Ontario included 185,014 patients aged 66 or older (mean age 74.6 years) presenting to 8990 primary care physicians who were diagnosed with a first episode of nonbacterial acute upper respiratory infection that did not otherwise warrant antibiotic treatment. More than 90% of the episodes were managed by one physician and involved one visit. The primary outcome was antibiotic prescription within 30 days. Episode, patient and physician factors, in the context of antibiotic prescription, were evaluated.

RESULTS: Overall, 46.2% of the patients were prescribed antibiotics (broad-spectrum agents in 69.9% of these cases). Patients receiving an antibiotic prescription were more likely than those not prescribed an antibiotic to be diagnosed with acute bronchitis (45.3% vs. 19.3%) or acute sinusitis (17.1% vs. 10.6%). Patients were more likely to receive antibiotic prescriptions when physicians were mid- and late-career vs. early-career, trained outside of Canada or the United States, and seeing more than 25 patients per day. Broad-spectrum agents were more frequently prescribed by mid- and late-career physicians and those trained in Canada or the United States.

CONCLUSIONS: Almost one-half of these elderly patients with nonbacterial acute upper respiratory infections received unnecessary antibiotic prescriptions. This study sheds light on the prevalence and predictors of such prescribing. 58 references ([email protected] for reprints)

Silverman, M., et al, Ann Intern Med 166(11):765, June 6, 2017

BACKGROUND: Overuse of antibiotics increases healthcare costs and contributes to the emergence of resistance, but these agents continue to be prescribed heavily for nonbacterial acute upper respiratory infections. Factors influencing physicians may include patient expectations, decision fatigue, fear of complications and unintended financial incentives.

METHODS: In this retrospective analysis of administrative healthcare data, the authors from the University of Western Ontario included 185,014 patients aged 66 or older (mean age 74.6 years) presenting to 8990 primary care physicians who were diagnosed with a first episode of nonbacterial acute upper respiratory infection that did not otherwise warrant antibiotic treatment. More than 90% of the episodes were managed by one physician and involved one visit. The primary outcome was antibiotic prescription within 30 days. Episode, patient and physician factors, in the context of antibiotic prescription, were evaluated.

RESULTS: Overall, 46.2% of the patients were prescribed antibiotics (broad-spectrum agents in 69.9% of these cases). Patients receiving an antibiotic prescription were more likely than those not prescribed an antibiotic to be diagnosed with acute bronchitis (45.3% vs. 19.3%) or acute sinusitis (17.1% vs. 10.6%). Patients were more likely to receive antibiotic prescriptions when physicians were mid- and late-career vs. early-career, trained outside of Canada or the United States, and seeing more than 25 patients per day. Broad-spectrum agents were more frequently prescribed by mid- and late-career physicians and those trained in Canada or the United States.

CONCLUSIONS: Almost one-half of these elderly patients with nonbacterial acute upper respiratory infections received unnecessary antibiotic prescriptions. This study sheds light on the prevalence and predictors of such prescribing. 58 references ([email protected] for reprints)