Showing papers by "Bruce Neal published in 2010"
TL;DR: Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes, including respiratory, digestive, and skin conditions, and no relationship was found between repeated episodes of severe hypglycemia and vascular outcomes or death.
Abstract: Background Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes. Methods We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes, using Cox proportional-hazards models with adjustment for covariates measured at baseline and after randomization. Results During a median follow-up period of 5 years, 231 patients (2.1%) had at least one severe hypoglycemic episode; 150 had been assigned to intensive glucose control (2.7% of the 5571 patients in that group), and 81 had been assigned to standard glucose control (1.5% of the 5569 patients in that group). The median times from the onset of severe hypoglycemia to the first major macrovascular event, the first major microvascular event, and death were 1.56 years (interquartile range, 0.84 to 2.41), 0.99 years (interquartile range, 0.40 to 2.17), and 1.05 years (interquartile range, 0.34 to 2.41), respectively. During follow-up, severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events (hazard ratio, 2.88; 95% confidence interval [CI], 2.01 to 4.12), major microvascular events (hazard ratio, 1.81; 95% CI, 1.19 to 2.74), death from a cardiovascular cause (hazard ratio, 2.68; 95% CI, 1.72 to 4.19), and death from any cause (hazard ratio, 2.69; 95% CI, 1.97 to 3.67) (P<0.001 for all comparisons). Similar associations were apparent for a range of nonvascular outcomes, including respiratory, digestive, and skin conditions (P<0.01 for all comparisons). No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death. Conclusions Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.)
1,280 citations
TL;DR: Fibrates can reduce the risk of major cardiovascular events predominantly by prevention of coronary events, and might have a role in individuals at high risk of cardiovascular events and in those with combined dyslipidaemia.
821 citations
TL;DR: Many products, particularly breads, processed meats, and sauces, have salt amounts above reasonable benchmarks, and the variation in salt concentrations between comparable products suggests that reformulation is highly feasible for many foods.
216 citations
TL;DR: BP-lowering treatment is likely to provide protection against all types of ICH, and there was no evidence of differences in the magnitude of the effects of treatment among different types ofICH.
Abstract: Background and Purpose—Patients with cerebral amyloid angiopathy (CAA) are at high risk for intracerebral hemorrhage (ICH), but no effective prevention strategies have been established. The objective is to determine whether lowering of blood pressure (BP) provides protection for this high-risk patient group. Methods—This study is a subsidiary analysis of the PROGRESS trial—a randomized, placebo-controlled trial that established the beneficial effects of BP lowering in patients with cerebrovascular disease; 6105 patients were randomly assigned to either active treatment (perindopril for all participants plus indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo. Outcomes were probable CAA-related ICH as defined by the Boston criteria, probable hypertension-related ICH, and unclassified ICH. Results—Over a mean follow-up of 3.9 years, 16 probable CAA-related ICH, 51 probable hypertension-related ICH, and 44 unclassified ICH occurred. Active treatment r...
193 citations
TL;DR: To compare the effects of a management strategy of early intensive blood pressure lowering with a more conservative guideline-based blood pressure management policy in patients with acute intracerebral hemorrhage, the second, main phase, INTERACT2 is described.
Abstract: Rationale:The INTERACT pilot study demonstrated the feasibility of the protocol, safety of early intensive blood pressure lowering and effects on haematoma expansion within 6h of onset of intracere...
125 citations
TL;DR: In this paper, the authors evaluated the performance of the Framingham and UK Prospective Diabetes Study (UKPDS) risk equations in participants who took part in the Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial.
Abstract: Aims/hypothesis
Available multivariable equations for cardiovascular risk assessment in people with diabetes have been derived either from the general population or from populations with diabetes Their utility and comparative performance in a contemporary group of patients with type 2 diabetes are not well established The aim of this study was to evaluate the performance of the Framingham and UK Prospective Diabetes Study (UKPDS) risk equations in participants who took part in the Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial
103 citations
TL;DR: In this cohort of men with type 2 diabetes, ED was associated with a range of CVD events, and men who experienced ED at baseline and at 2-year follow-up had the highest risk for these outcomes.
87 citations
TL;DR: Even small improvements in composition could produce important health gains if implemented across all product categories by all companies in unison.
85 citations
TL;DR: Intensive BP reduction to systolic levels between 130 and 140 mm Hg is likely to provide the maximum protection against hematoma growth after intracerebral hemorrhage.
Abstract: The pilot phase of the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT) showed that rapid blood pressure (BP) lowering can attenuate hematoma growth in acute intracerebral hemorrhage. We sought to define the systolic BP level associated with greatest attenuation of hematoma growth. INTERACT included 404 patients with computed tomographic-confirmed intracerebral hemorrhage, elevated systolic BP (150 to 220 mm Hg), and capacity to commence BP lowering treatment within 6 hours of onset. Computed tomography was done at baseline and at 24 hours using standardized techniques, with digital images analyzed centrally, blinded to clinical data. Associations of baseline and achieved on-treatment (mean during the first 24 hours) systolic BP levels with the primary outcome of increase in hematoma volume were explored. There were 346 patients with duplicate computed tomographic scans. There was no significant association between baseline systolic BP levels and either the absolute or proportional growth in hematoma volume (P trend=0.26 and 0.12, respectively). By contrast, achieved on-treatment systolic BP levels in the first 24 hours were clearly associated with both absolute and proportional hematoma growth (both P trend=0.03). Maximum reduction in hematoma growth occurred in the one third of participants with the lowest on-treatment systolic BP levels (median: 135 mm Hg). Intensive BP reduction to systolic levels between 130 and 140 mm Hg is likely to provide the maximum protection against hematoma growth after intracerebral hemorrhage.
75 citations
TL;DR: The treatment benefits of a routine administration of a fixed combination of perindopril-indapamide to patients with type 2 diabetes on cardiovascular and renal outcomes, and death, are consistent across all stages of CKD at baseline.
Abstract: Aims Individuals with diabetes and chronic kidney disease (CKD) are at high risk for cardiovascular disease. In these analyses of the ADVANCE trial, we assessed the effects of a fixed combination of perindopril–indapamide on renal and cardiovascular outcomes in patients with type 2 diabetes according to baseline CKD stage.
Methods and results Patients with type 2 diabetes were randomized to perindopril–indapamide (4 mg/1.25 mg) or placebo. Treatment effects on cardiovascular (cardiovascular death, myocardial infarction, or stroke) and renal outcomes were compared in subgroups defined by baseline Kidney Disease Outcome Quality Initiative CKD stage. Homogeneity in treatment effect was tested by adding interaction terms to the relevant Cox models. The study included 10 640 participants with known CKD status, of whom 6125 did not have CKD, 2482 were classified as CKD stage 1 or 2, and 2033 as CKD stage ≥3. The relative treatment effects on major cardiovascular events were similar across all stages of CKD, with no heterogeneity in the magnitude of the effects for any outcome. In contrast, the absolute treatment effects approximately doubled in those with CKD stage ≥3 when compared to those with no CKD. For every 1000 patients with CKD stage ≥3 treated for 5 years, active treatment prevented 12 cardiovascular events when compared with six events per 1000 patients with no CKD.
Conclusion The treatment benefits of a routine administration of a fixed combination of perindopril–indapamide to patients with type 2 diabetes on cardiovascular and renal outcomes, and death, are consistent across all stages of CKD at baseline. Absolute risk reductions are larger in patients with CKD highlighting the importance of blood pressure-lowering in this population.
70 citations
TL;DR: Consumer education will be one part of the effort necessary to reduce salt intake in Australia and will require government investment in a targeted campaign to achieve improvements in knowledge and behaviours.
Abstract: Australians are eating far more salt than is good for health. In May 2007, the Australian Division of World Action on Salt and Health (AWASH) launched a campaign to reduce population salt intake. A consumer survey was commissioned to quantify baseline aspects of awareness and behaviour related to salt and health amongst Australians. A total of 1084 individuals aged 14 years or over were surveyed by ACA Research using an established consumer panel. Participants were selected to include people of each sex, within different age bands, from major metropolitan and other areas of all Australian states and territories. Participants were invited via email to complete a brief questionnaire online. Two-thirds knew that salt was bad for health but only 14% knew the recommended maximum daily intake. Seventy percent correctly identified that most dietary salt comes from processed foods but only a quarter regularly checked food labels for salt content. Even fewer reported their food purchases were influenced by the salt level indicated (21%). The survey showed a moderate understanding of how salt effects health but there was little evidence of action to reduce salt intake. Consumer education will be one part of the effort necessary to reduce salt intake in Australia and will require government investment in a targeted campaign to achieve improvements in knowledge and behaviours.
TL;DR: Routine administration of perindopril–indapamide lowers blood pressure safely and reduces the risk of major clinical outcomes in patients of at least 75 years with type 2 diabetes.
Abstract: OBJECTIVE: The efficacy and safety of blood pressure lowering in elderly patients have not been sufficiently investigated in patients with diabetes. Using data from the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation study, we assessed the efficacy and safety of routine blood pressure lowering to prevent major clinical outcomes in elderly patients with type 2 diabetes. METHODS: Eleven thousand one hundred and forty patients aged at least 55 years with type 2 diabetes (mean 66+/-6 years) were randomly assigned to perindopril-indapamide or placebo. The primary endpoint was a composite of major macrovascular and microvascular disease. The effects of active treatment on outcomes were estimated in subgroups according to age: below 65, 65-74 and at least 75 years. RESULTS: During a mean 4.3-year follow-up, 1799 (16.1%) patients experienced a major event. Active treatment produced similar relative risk reductions for the primary outcome, major macrovascular disease, death and renal events across age groups (all P heterogeneity >0.3). Over 5 years, active treatment was estimated to prevent one primary outcome in every 21, 71 and 118 patients of at least 75, 65-74 and below 65 years, respectively. Similar patterns of benefits were observed for secondary outcomes. There were no differences in the tolerability between randomized allocations across age groups (all P heterogeneity >0.6) CONCLUSION: Routine administration of perindopril-indapamide lowers blood pressure safely and reduces the risk of major clinical outcomes in patients of at least 75 years with type 2 diabetes. The greater absolute benefits in older patients in this age group were not offset by an increased risk of side effects.
TL;DR: In people with type 2 diabetes, oral disease, as indexed by fewer teeth, was related to an increased risk of death from all causes and of death due to CVD and non-CVD.
Abstract: Aims/hypothesis
While there are plausible biological mechanisms linking oral health with cardiovascular disease (CVD) and mortality rates, no study, to our knowledge, has examined this association in a representative population of people with type 2 diabetes.
TL;DR: The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated.
Abstract: Background
The Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP) Study aims to examine whether a polypill-based strategy (using a single capsule containing aspirin, a statin and two blood pressure-lowering agents) amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline-indicated therapies, and lower blood pressure and cholesterol levels.
TL;DR: Intensive glucose control with a gliclazide MR-based regimen was well tolerated and consistently effective in lowering HbA1c across a broad range of patient with type 2 diabetes.
TL;DR: In this article, the authors investigated the association between alcohol consumption and diabetic retinopathy and deterioration of visual acuity in individuals with Type 2 diabetes and found that moderate and heavy consumption of alcohol was associated with increased risk of deterioration of vision.
Abstract: Aims We investigated the association between alcohol consumption and diabetic retinopathy and deterioration of visual acuity in individuals with Type 2 diabetes. Methods We conducted a cohort analysis of 1239 participants with Type 2 diabetes aged 55-81 years enrolled in the AdRem study, a sub-study of the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial. Current and past consumption of wine, spirits and beer was measured by self-report. Moderate and heavy alcohol consumption was defined as 1-14 and > 14 drinks/week, respectively. Diabetic retinopathy, measured by mydriatic stereoscopic seven-field retinal photography, was defined by a 2-step progression in the Early Treatment of Diabetic Retinopathy Study (ETDRS) score or the presence of any retinal vascular lesions. Deterioration of visual acuity was defined by a decrease of two lines in best vision in either eye, measured corrected, or through a pinhole using a Snellen chart. Results In a mean follow-up of 5.5 years, we identified 182 participants with a 2-step progression in the ETDRS score, 640 participants with the presence of any retinal vascular lesions and 693 participants with a deterioration of visual acuity. Current moderate consumption of alcohol, compared with no current consumption, was not associated with presence or progression of diabetic retinopathy; however, it was associated with higher risk of deterioration of visual acuity (multivariable-adjusted OR 1.83; 95% CI 1.34-2.48; P < 0.001). Conclusions Alcohol consumption is associated with increased risk of deterioration of visual acuity, but not with retinopathy in individuals with Type 2 diabetes.
TL;DR: Most of the apparent variation in response is not because of true variation but is a consequence of background within-person fluctuation in day-to-day blood pressure levels, and a better approach may be to simply assume the mean treatment effect.
Abstract: Most clinicians monitor blood pressure to estimate a patient's response to blood pressure-lowering therapy. However, the apparent change may not actually reflect the effect of the treatment, because a person's blood pressure varies considerably even without the administration of drug therapy. We estimated random background within-person variation, apparent between-person variation, and true between-person variation in blood pressure response to angiotensin-converting enzyme inhibitors after 3 months. We used meta-analytic mixed models to analyze individual patient data from 28 281 participants in 7 randomized, controlled trials from the Blood Pressure Lowering Trialists Collaboration. The apparent between-person variation in response was large, with SDs for change in systolic blood pressure/diastolic blood pressure of 15.2/8.5 mm Hg. Within-person variation was also large, with SDs for change in systolic blood pressure/diastolic blood pressure of 14.9/8.45 mm Hg. The true between-person variation in response was small, with SDs for change in systolic blood pressure/diastolic blood pressure of 2.6/1.0 mm Hg. The proportion of the apparent between-person variation in response that was attributed to true between-person variation was only 3% for systolic blood pressure and 1% for diastolic blood pressure. In conclusion, most of the apparent variation in response is not because of true variation but is a consequence of background within-person fluctuation in day-to-day blood pressure levels. Instead of monitoring an individual's blood pressure response, a better approach may be to simply assume the mean treatment effect.
TL;DR: BP lowering reduces the risk of major vascular events, with separately significant reductions, in both Asia and the West, with particular emphasis on stroke subtypes and cardiac outcomes.
Abstract: ObjectiveTo assess the benefits of blood pressure (BP) lowering on vascular events separately for Asian and for Western participants with particular emphasis on stroke subtypes and cardiac outcomes.MethodsThis is a subsidiary analysis of Perindopril Protection Against Recurrent Stroke Study (PROGRES
TL;DR: In conclusion, blood pressure–lowering therapy produced comparable risk reductions in vascular disease across the whole range of body mass indices in participants with a history of stroke, and the greater baseline level of cardiovascular risk in those with higher body mass index meant that these patients obtained the greatest benefit.
Abstract: There is considerable uncertainty regarding the efficacy of blood pressure-lowering therapy in reducing cardiovascular risk in obese people. In this report we examine the effects of blood pressure lowering according to baseline body mass index (kilograms per meter squared) in the Perindopril Protection Against Recurrent Stroke Study. A total of 6105 participants with cerebrovascular disease were randomized to perindopril-based blood pressure-lowering therapy or placebo. The overall mean difference in systolic/diastolic blood pressure between participants assigned active therapy or placebo was 9/4 mm Hg (SE: 0.5/0.3 mm Hg), with no difference by body mass index quarters ( or = 27.9 kg/m(2)). A consistent treatment benefit was demonstrated for protection against major vascular events across quarters with the following hazard ratios (95% CIs): 0.80 (0.62 to 1.02), 0.78 (0.61 to 1.01), 0.67 (0.53 to 0.86), 0.69 (0.54 to 0.88), and 0.74 (0.66 to 0.84; P for heterogeneity=0.16). Similar results were apparent for stroke and stroke subtypes (all P for heterogeneity > or = 0.07) or with the standard definitions of overweight and obesity ( or = 30 kg/m(2); all P for heterogeneity > or = 0.28). The absolute effects of treatment were, however, more than twice that in the highest compared with the lowest body mass index quartile. Across increasing quarters of body mass index over 5 years, active therapy prevented 1 major vascular event among every 28, 23, 13, and 13 patients treated. In conclusion, blood pressure-lowering therapy produced comparable risk reductions in vascular disease across the whole range of body mass indices in participants with a history of stroke. However, the greater baseline level of cardiovascular risk in those with higher body mass index meant that these patients obtained the greatest benefit.
TL;DR: Falls are a significant public health problem facing women in rural India and fall prevention strategies should be explored and implemented within the Indian context.
Abstract: Background Little is known about the context, risk factors and severity of non-fatal fall-related injury in India. Objective To report these data for a rural population in the East and West Godavari districts of the Indian state of Andhra Pradesh. Methods In a cross-sectional population-based survey, 3686 participants aged ≥30 years (83.6% participation) selected by stratified random sampling were interviewed in 44 villages. Participants recalled injuries in the preceding 12 months that required them to stay away from their usual daily duties for at least 1 day irrespective of whether medical attention was sought for that injury. Results The annual incidence of non-fatal fall-related injury based on a 3-month recall period was 3.30% (95% CI 2.54% to 4.05%) and 9.22% (95% CI 7.74% to 10.69%) for men and women, respectively, with the incidence increasing with age. For the most recent non-fatal fall-related injury, the home was the most common place of injury for women, and the farm for men, with the former more likely to fall while climbing up/down (20.9%) compared with the latter (10.3%). Most falls were at the same level (71.7%) and slipping was the most common cause of fall (40%). Limbs (legs, 55%; hand/arm, 33.3%) were the most commonly injured body part. Fifty-six per cent reported seeking treatment outside home for injury, of whom 74.6% were women; and 8.4% reported being admitted to a hospital. Conclusion Falls are a significant public health problem facing women in rural India. Fall prevention strategies should be explored and implemented within the Indian context.
TL;DR: Monitoring blood pressure is poor at detecting nonadherence to blood pressure-lowering treatment, and a secondary analysis of the Perindopril Protection Against Recurrent Stroke Study to look at other methods of assessing adherence.
Abstract: After starting antihypertensives, blood pressure is monitored for several reasons, including assessment of adherence. We aimed to estimate the accuracy of blood pressure monitoring for detecting early nonadherence. We conducted a secondary analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a large randomized trial of blood pressure lowering to reduce the risk of recurrent stroke. We compared change in blood pressure 3 months after randomization in people who had discontinued treatment (nonadherent) with those who stayed on treatment (adherent). We also used an indirect method, assessing whether change in blood pressure discriminated between active (adherent) and placebo (nonadherent) groups. Both methods gave similar results. For the 3433 subjects, the mean (SD) of the change in systolic blood pressure was -15.8 mm Hg (SD 18.7 mm Hg) in the adherent group and -4.2 mm Hg (SD 18.1 mm Hg) in the nonadherent group. After recalibration of the mean change in the nonadherent group to 0 mm Hg and in the adherent group to -11.6 mm Hg, the absence of a fall in systolic blood pressure at 3 months had a sensitivity of 50% and a specificity of 80% for detecting nonadherence (50% of nonadherent patients and 20% of adherent patients had a rise in blood pressure). Discriminatory power was modest over the range of cutoffs (area under the receiver-operator curve 0.67). Monitoring blood pressure is poor at detecting nonadherence to blood pressure-lowering treatment. Further research should look at other methods of assessing adherence.
TL;DR: Despite providing specific carefully tailored advice, this website had no detectable effect on cholesterol management strategies, which raises considerable uncertainty about the value of Internet-based tools providing tailored advice directly to consumers.
Abstract: Background: Elevated low-density lipoprotein (LDL) cholesterol is a leading risk factor for cardiovascular disease. Despite the availability of proven interventions to lower LDL cholesterol, their use remains subobtimal. Many websites provide interactive, tailored advice on cardiovascular risk in an attempt to help bridge this evidence-practice gap, yet there is little evidence that provision of such a tool is effective in changing practice. Objective: The objective was to define the effects on use of cholesterol-lowering interventions of a consumer-targeted tailored advice website. Methods: This was a prospective, double-blind, randomized controlled trial open to any adult Australian with access to the Internet. A total of 2099 participants were randomized. Of these, 45% were male, the mean age of all participants was 56, and 1385 (66%) self-reported hypercholesterolemia. Follow-up information was obtained for 1945 (93%). Participants completed a brief online questionnaire. Individuals assigned to intervention received immediate, fully automated, personally tailored advice (based on current guidelines) regarding the need for commencement of statin therapy, increased statin therapy in those already on treatment, and nondrug intervention strategies. Control group participants were directed to static Web pages providing general information about cholesterol management. Results: The primary outcome was the proportion of participants that commenced or increased use of prescribed cholesterol-lowering therapy. Of the total 2099 randomized participants, 304 (14%) met eligibility criteria for cholesterol-lowering therapy but were not prescribed treatment, and 254 (12%) were prescribed treatment but were not achieving the recommended target level. Treatment was commenced or increased in 64 (6.0%) of the 1062 intervention group participants and 79 (7.6%) of the 1037 control group participants (% difference = -1.6%, 95% confidence interval [CI] -3.75 to 0.57, P = .15). No differences were found between the randomized groups for the secondary outcomes of “discussed treatment with a health professional” (% difference = -3.8%, 95% confidence interval [CI] -8.16 to 0.19, P = .08), “had their cholesterol checked” (% difference = -1.5%, 95% CI -5.79 to 2.71, P = .48), “had their blood pressure checked” (% difference = 1.4%, 95% CI -2.55 to 5.34, P = .49) or made a lifestyle change (P values between .49 and .96). Conclusions: Despite providing specific carefully tailored advice, this website had no detectable effect on cholesterol management strategies. This finding raises considerable uncertainty about the value of Internet-based tools providing tailored advice directly to consumers. Clinical Trial: Clinicaltrials.gov ID: NCT00220974, http://clinicaltrials.gov/ct2/show/NCT00220974 [J Med Internet Res 2010;12(3):e42]
TL;DR: There is clear potential for editorial guidelines on salt use in recipes to play a role in advancing public health efforts in Australia and other such nations.
Abstract: Background: Australians currently consume too much salt causing adverse consequences for health. The media play an important role in the provision of nutrition advice to consumers. Previous research shows that many foods advertized in consumer magazines are high in salt, but little research has examined magazine recipes in this context. The aim of this project was to summarize directions for salt use in recipes in leading Australian magazines. Methods: In August 2007 and 2008, the top 10 magazines by circulation that included at least five recipes, were examined. Standardized information was collected about directions for salt use in recipes. Results: Three hundred and thirty recipes were identified in 2007 and 417 in 2008. About 68% of recipes included high-salt ingredients, 37% instructed to season with salt, 10% instructed to add a specific quantity of salt and 15% recommended selection of low-salt ingredients. There was substantial variability in directions for salt use in recipes between magazines, but no clear differences between 2007 and 2008. Conclusion : Many recipes advised to add salt in direct contradiction to national dietary guidelines. There is clear potential for editorial guidelines on salt use in recipes to play a role in advancing public health efforts in Australia and other such nations.
TL;DR: Min Jun and colleagues’ meta-analysis on the impact of statins on cardiovascular outcomes and other more important treatments in polypharmacy patients deserves comment.