sj-xlsx-1-anp-10.1177_00048674231203898 – Supplemental material for Ensuring the affordable becomes accessible–lessons from ketamine, a new treatment for severe depression

Supplemental material, sj-xlsx-1-anp-10.1177_00048674231203898 for Ensuring the affordable becomes accessible–lessons from ketamine, a new treatment for severe depression by Anthony Rodgers, Dilara Bahceci, Christopher G Davey, Mary Lou Chatterton, Nick Glozier, Malcolm Hopwood and Colleen Loo in Australian & New Zealand Journal of Psychiatry</p

Distribution of Attributable Cardiovascular Disease Burden Due to BMI, Blood Pressure, and Cholesterol by Exposure Level, Age, and Level of Development

<p>Conventions as for <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0010027#pmed-0010027-g001" target="_blank">Figure 1</a>.</p

Distribution by Exposure Level of Attributable Disease Burden Due to Selected Continuous Risk Factors

<p>Figure 1 shows the distribution of the estimated cardiovascular disease (CVD) burden of disease (in DALYs) attributable to four major continuous risk factors, by exposure levels. Half the attributable burden occurs to the left of the solid vertical line and half occurs to the right. The dashed vertical lines indicate commonly used thresholds—150 mm Hg for hypertension, 6.0 mmol/l for hypercholesterolemia, and 30 kg/m² for obesity. The blood pressure and cholesterol levels plotted are the estimated usual levels [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0010027#pmed-0010027-b22" target="_blank">22</a>], which tend to have a smaller SD than levels based on one-off measurements commonly used in population surveys, because of normal day-to-day and week-to-week fluctuations. For example, the distribution of usual blood pressure is about half as wide as the distribution of one-off blood pressure measures, and so many fewer people would be classified as hypertensive (or hypotensive) if classifications were based on usual rather than one-off blood pressure. Thus, if a population mean SBP was 134 mm Hg, the SD of once-only measures might be 17 mm Hg (with about 18% of the population having one-off SBP over 150 mm Hg), and the SD of usual SBP based on many measures would be about 9 mm Hg (hence about 5% of the population would have usual SBP over 150 mm Hg).</p

Forest Plots of Polypills versus Control for Change in Total Cholesterol and LDL-cholesterol.

<p>Forest Plots of Polypills versus Control for Change in Total Cholesterol and LDL-cholesterol.</p

Polypills Meta-analysis ‘PRISMA’ Flow Diagram.

<p>Polypills Meta-analysis ‘PRISMA’ Flow Diagram.</p

Actual vs Expected Reductions in Systolic Blood Pressure and LDL-cholesterol in Trials of ‘Polypills’.

*<p>rounded to nearest 10 mm Hg;</p>**<p>based on mean baseline SBP &amp; standard dose equivalence (from Law 2009) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052145#pone.0052145-Law1" target="_blank">[4]</a>;</p>∧<p>mean baseline LDL × percentage reduction in LDL cholesterol for the statin at that dose (from Law 2003) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052145#pone.0052145-Law2" target="_blank">[5]</a></p>#<p>estimate: two drugs at half dose therefore an overestimate of likely effect;</p>##<p>estimate: two drugs at half dose therefore an underestimate of likely effect; 12.7 mmHg for two drugs at standard dose;</p>β<p>estimate: three drugs at standard dose; 15.2 mmHg for three drugs at half standard dose.</p

Forest Plots of Polypills versus Control for Change in Discontinuation of Study Medication and Side Effects.

<p>Forest Plots of Polypills versus Control for Change in Discontinuation of Study Medication and Side Effects.</p

Baseline Characteristics and Study Quality of included Randomised Controlled Trials.

*<p>BP not assessed in meta-analysis as both arms contained an anti-hypertensive;</p>**<p>Following placebo 12 weeks of cross-over RCT;</p>#<p>Double-blind 9-arm with varying medication components and number of components. Only three arms were used in this meta-analysis: the polycap, aspirin and simvastatin arms;</p><p>BP = blood pressure and measured in mmHg; SBP = systolic blood pressure; DBP = Diastolic blood pressure; Total chol. = total cholesterol in mmol/L; LDL = LDL cholesterol in mmol/L; AE = adverse events; TLC = therapeutic lifestyle changes; SD = standard deviation; CVD = cardiovascular disease.</p

Global Mortality and Burden of Disease Attributable to Cardiovascular Diseases and Their Major Risk Factors for People 30 y of Age and Older

<p>The size of each circle is proportional to the number of deaths (left) or burden of disease (right; measured in disability-adjusted life years) (in millions). Overweight and obesity affect non-cardiovascular diseases, including diabetes, endometrial and colon cancers, post-menopausal breast cancer, and osteoarthritis, shown as the portions of yellow circles that fall outside the cardiovascular disease circle [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020133#pmed-0020133-b57" target="_blank">57</a>]. The mortality estimates exclude osteoarthritis, which results in morbidity but not direct deaths. Disease burden does include nonfatal health outcomes associated with diabetes and osteoarthritis (hence the larger size of the circle for overweight and obesity relative to those for blood pressure and cholesterol). Source: re-analysis of data from Ezzati et al. [<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020133#pmed-0020133-b57" target="_blank">57</a>,<a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020133#pmed-0020133-b58" target="_blank">58</a>].</p

Relationship of Mean Population BMI, SBP, and Total Cholesterol with Average National Income, Food Share of Household Expenditure, and Proportion of Population in Urban Areas

<p>Relationships were estimated using local regression models applied to the data in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020133#pmed-0020133-g002" target="_blank">Figure 2</a>. Results for (A) males and (B) females are shown. National income was measured as gross domestic product (GDP). The following outlier countries were dropped (see also Results): United States for males and females in the income–BMI relationship, and Russian Federation and Tajikistan for males and females in the food share of household expenditure–BMI relationship.</p