Portfolios of Biomedical HIV Interventions in South Africa: A Cost-Effectiveness Analysis

BACKGROUND

Recent clinical trials of male circumcision, oral pre-exposure prophylaxis (PrEP), and a vaginal microbicide gel have shown partial effectiveness at reducing HIV transmission, stimulating interest in implementing portfolios of biomedical prevention programs.

OBJECTIVE

To evaluate the effectiveness and cost-effectiveness of combination biomedical HIV prevention and treatment scale-up in South Africa, given uncertainty in program effectiveness.

DESIGN

Dynamic HIV transmission and disease progression model with Monte Carlo simulation and cost-effectiveness analysis.

PARTICIPANTS

Men and women aged 15 to 49 years in South Africa.

INTERVENTIONS

HIV screening and counseling, antiretroviral therapy (ART), male circumcision, PrEP, microbicide, and select combinations.

MAIN MEASURES

HIV incidence, prevalence, discounted costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios.

KEY RESULTS

Providing half of all uninfected persons with PrEP averts 28 % of future HIV infections for $9,000/QALY gained, but the affordability of such a program is questionable. Given limited resources, annual HIV screening and ART utilization by 75 % of eligible infected persons could avert one-third of new HIV infections, for approximately $1,000/QALY gained. Male circumcision is more cost-effective, but disproportionately benefits men. A comprehensive portfolio of expanded screening, ART, male circumcision, microbicides, and PrEP could avert 62 % of new HIV infections, reducing HIV prevalence from a projected 14 % to 10 % after 10 years. This strategy doubles treatment initiation and adds 31 million QALYs to the population. Despite uncertainty in program effectiveness, a comprehensive portfolio costs less than $10,000/QALY gained in 33 % of simulation iterations and less than $30,000/QALY gained in 90 % of iterations, assuming an annual microbicide cost of $100.

CONCLUSIONS

A portfolio of modestly-effective biomedical HIV prevention programs, including male circumcision, vaginal microbicides, and oral PrEP, could substantially reduce HIV incidence and prevalence in South Africa and be likely cost-effective. Given limited resources, PrEP is the least cost-effective intervention of those considered.     

Cost-Effectiveness of Chemoprevention with Proton Pump Inhibitors in Barrett’s Esophagus

Background

Proton pump inhibitors (PPIs) may reduce the risk of esophageal adenocarcinoma (EAC) in patients with Barrett’s esophagus. PPIs are prescribed for virtually all patients with Barrett’s esophagus, irrespective of the presence of reflux symptoms, and represent a de facto chemopreventive agent in this population. However, long-term PPI use has been associated with several adverse effects, and the cost-effectiveness of chemoprevention with PPIs has not been evaluated.

Aim

The purpose of this study was to assess the cost-effectiveness of PPIs for the prevention of EAC in Barrett’s esophagus without reflux.

Methods

We designed a state-transition Markov microsimulation model of a hypothetical cohort of 50-year-old white men with Barrett’s esophagus. We modeled chemoprevention with PPIs or no chemoprevention, with endoscopic surveillance for all treatment arms. Outcome measures were life-years, quality-adjusted life years (QALYs), incident EAC cases and deaths, costs, and incremental cost-effectiveness ratios.

Results

Assuming 50 % reduction in EAC, chemoprevention with PPIs was a cost-effective strategy compared to no chemoprevention. In our model, administration of PPIs cost $23,000 per patient and resulted in a gain of 0.32 QALYs for an incremental cost-effectiveness ratio of $12,000/QALY. In sensitivity analyses, PPIs would be cost-effective at $50,000/QALY if they reduce EAC risk by at least 19 %.

Conclusions

Chemoprevention with PPIs in patients with Barrett’s esophagus without reflux is cost-effective if PPIs reduce EAC by a minimum of 19 %. The identification of subgroups of Barrett’s esophagus patients at increased risk for progression would lead to more cost-effective strategies for the prevention of esophageal adenocarcinoma.     

Decreasing Trend of Upper Gastrointestinal Bleeding Mortality Risk Over Three Decades

Background

Upper gastrointestinal bleeding (UGIB) causes over $1 billion in medical expenses annually.

Aims

The purpose of this study was to examine changes of UGIB mortality risks and trends over the last three decades.

Methods

We analyzed the National Hospital Discharge Sample from 1979 to 2009. Patients with primary ICD-9 code representing a diagnosis of UGIB were included. The UGIB mortality risks and trends in each decade by anatomical sites, bleeding causes, comorbidities, and other important variables were analyzed.

Results

UGIB mortality risk decreased by 35.4 % from 4.8 % in the first decade to 3.1 % in the third decade (P < 0.001). Age and number of hospitalization days were significant risk factors in all decades. Most significant decreases were observed in patients over 65 years and during the first day of admission. Gastric (P < 0.001) and esophageal (P = 0.018) bleedings showed significant decreasing mortality risk trends. Duodenal bleeding mortality risk was stable in three decades. Mortality risk declined significantly among patients with renal failure (from 50.0 to 4.0 %) and heart failure (from 17.9 to 5.2 %; both P < 0.001) while changes in cases with ischemic heart disease, cancer, and liver failure were less significant.

Conclusion

UGIB morality risks, especially of the first hospital day and geriatric patients, significantly decreased over the last three decades, presumably from recent advances in emergency medical care. Mortality risk of gastric, but not duodenal, bleeding had the most significant reduction. Critical care improvements in patients with various comorbidities may explain significant UGIB mortality risk reductions. This study provides invaluable insight into the causes and trends of UGIB mortality risks for future studies.     

Diabetes, prediabetes and cancer mortality

Aims/hypothesis

We aimed to investigate the risk of cancer mortality in relation to the glucose tolerance status classified according to the 2 h OGTT.

Methods

Data from 17 European population-based or occupational cohorts involved in the DECODE study comprising 26,460 men and 18,195 women aged 25–90 years were collaboratively analysed. The cohorts were recruited between 1966 and 2004 and followed for 5.9 to 36.8 years. Cox proportional hazards analysis with adjustment for cohort, age, BMI, total cholesterol, blood pressure and smoking status was used to estimate HRs for cancer mortality.

Results

Compared with people in the normal glucose category, multivariable adjusted HRs (95% CI) for cancer mortality were 1.13 (1.00, 1.28), 1.27 (1.02, 1.57) and 1.71 (1.35, 2.17) in men with prediabetes, previously undiagnosed diabetes and known diabetes, respectively; in women they were 1.11 (0.94, 1.30), 1.31 (1.00, 1.70) and 1.43 (1.01, 2.02), respectively. Significant increases in deaths from cancer of the stomach, colon–rectum and liver in men with prediabetes and diabetes, and deaths from cancers of the liver and pancreas in women with diabetes were also observed. In individuals without known diabetes, the HR (95% CI) for cancer mortality corresponding to a one standard deviation increase in fasting plasma glucose was 1.06 (1.02, 1.09) and in 2 h plasma glucose was 1.07 (1.03, 1.11).

Conclusions/interpretation

Diabetes and prediabetes were associated with an increased risk of cancer death, particularly death from liver cancer. Mortality from all cancers rose linearly with increasing glucose concentrations.     

Adult mortality or morbidity is not increased in childhood-onset growth hormone deficient patients who received pediatric GH treatment: an analysis of the Hypopituitary Control and Complications Study (HypoCCS)

Background

The French Safety and Appropriateness of Growth Hormone treatments in Europe (SAGhE) cohort has raised concern of increased mortality risk during follow-up into adulthood in certain patients who had received growth hormone (GH) treatment during childhood. The Hypopituitary Control and Complications Study monitored mortality and morbidity of adult GH-deficient patients including those with childhood-onset GH deficiency (COGHD) who received GH treatment as children.

Purpose

Evaluate risk of mortality, cancer, myocardial infarction (MI) and stroke in a prospective observational study.

Methods

COGHD patients [n = 1,204, including 389 diagnosed with idiopathic COGHD (ICOGHD)] had received pediatric GH treatment. Standardized mortality ratios (SMRs), and cancer standardized incidence ratios (SIRs) in patients without a prior cancer were estimated relative to reference populations. Crude incidence rates were estimated for MI and stroke.

Results

No increased mortality or cancer incidence was observed, as compared with reference populations, during a follow-up of 3.7 ± 3.3 years (mean ± SD). The overall SMR for COGHD was 1.14 [95 % confidence interval (CI) 0.55–2.10], and for ICOGHD, 0.33 (0.01–1.84). The overall cancer SIR for COGHD was 0.27 (0.01–1.50), and for ICOGHD, 0.00 (0.00–2.45). No incident case of MI was reported. The crude stroke incidence rate [181.3 per 100,000 person-years] in COGHD patients was consistent with the rates reported in reference populations. No incident case of stroke was identified in ICOGHD patients who are presumed to have no increased stroke risk factors.

Conclusions

The results indicate no increased risk of mortality or incidence of cancer, stroke, or MI in adult GH-deficient patients who had previously received pediatric GH treatment.     

Racial Disparities in Gastrointestinal Cancers-Related Mortality in the US Population

Background

Racial difference in cancer-related mortality has been described in epidemiological studies and evidence points towards higher mortalities in the minorities. To determine the magnitude of racial disparities and sex differences in GI cancer-related mortalities in the US population, we analyzed the data using the third National Health and Nutrition Examination Survey (NHANES III) and related mortality data files.

Methods

NHANES III and its related public linked mortality files were used for this study. Our study cohort included subjects who were ≥18 years and were part of the longitudinal mortality follow-up database. The overall GI cancers related mortality was calculated using combined mortality from malignant neoplasm of esophagus, stomach, colon, liver and pancreas. The evaluation of independent predictors of overall GI cancer-related mortality and of each individual GI cancer was carried out using the Cox proportional hazards model.

Results

A total of 13,221 individuals were included in the analyses with the average person year follow-up of 13.9 years. During the follow-up period, 4,146 subjects died. Of these, 199 were from GI-related cancers. Non-Hispanic black (NHB) had significantly higher overall GI-cancer related mortality compared to non-Hispanic white (NHW, adjusted hazard ratio, aHR: 2.31, 95 % CI 1.57–3.38, p < 0.001). Subgroup analyses by sex demonstrated higher mortality from gastric, colorectal and primary liver cancer related mortality in NHB men compared to NHW men. Esophageal and pancreatic cancer mortalities were higher in NHB women compared to NHW women.

Conclusion

Overall GI cancer-related mortality is significantly higher among NHB compared to NHW in the US population.     

Population-based assessment of the incidence, risk factors, and outcomes of anaerobic bloodstream infections

Background

Anaerobes are a relatively uncommon but important cause of bloodstream infection. However, their epidemiology has not been well defined in non-selected populations. We sought to describe the incidence of, risk factors for, and outcomes associated with anaerobic bacteremia.

Methods

Population-based surveillance for bacteremia with anaerobic microorganisms was conducted in the Calgary area (population 1.2 million) during the period from 2000 to 2008.

Results

A total of 904 incident cases were identified, for an overall population incidence of 8.7 per 100,000 per year; 231 (26 %) were nosocomial, 300 (33 %) were healthcare-associated community-onset, and 373 (41 %) were community-acquired. Elderly males were at the greatest risk. The most common pathogens identified were: Bacteroides fragilis group (3.6 per 100,000), Clostridium (non-perfringens) spp. (1.1 per 100,000), Peptostreptococcus spp. (0.9 per 100,000), and Clostridium perfringens (0.7 per 100,000). Non-susceptibility to metronidazole was 2 %, to clindamycin 17 %, and to penicillin 42 %. Relative to the general population, risk factors for anaerobic bloodstream infection included: male sex, increasing age, a prior diagnosis of cancer, chronic liver disease, heart disease, diabetes mellitus, stroke, inflammatory bowel disease, human immunodeficiency virus (HIV) infection, chronic obstructive pulmonary disease (COPD), and/or hemodialysis-dependent chronic renal failure (HDCRF). The 30-day mortality was 20 %. Increasing age, nosocomial acquisition, presence of malignancy, and several other co-morbid illnesses were independently associated with an increased risk of death.

Conclusion

Anaerobic bloodstream infection is responsible for a significant burden of disease in general populations. The data herein establish the extent to which anaerobes contribute to morbidity and subsequent mortality. This information is key in developing preventative, empiric treatment and research priorities.     

Cost–Effectiveness of Different Strategies for Stroke Prevention in Patients with Atrial Fibrillation in a Health Resource-Limited Setting

Purpose

To compare the lifetime cost and effectiveness of five alternative chronic atrial fibrillation (AF) management strategies: rivaroxaban, warfarin, aspirin plus clopidogrel, aspirin and no prevention.

Methods

An individual-level state-transition model was developed to track the lifetime disease course associated with AF. The clinical and utility data were derived from published studies. The cost data were estimated based on local charges and current Chinese practices. Sensitivity analyses were used to explore the impact of uncertainty on the results.

Results

For base-case patients with a CHADS₂ score of 3, the cost per additional quality-adjusted life-years (QALYs) gained for rivaroxaban compared with no prevention, aspirin, aspirin plus clopidogrel and warfarin was $116,884, $153,944, $155,979 and $216,273, respectively. CHADS₂ score had a substantial impact on the model outcomes for different prevention strategies. The time distribution of warfarin international normalised ratio (INR), stroke and intracranial haemorrhage (ICH) risks, cost of rivaroxaban and utility of warfarin therapy had substantial impacts on the results. Based on a willingness-to-pay threshold of $16,350/QALY, no prevention strategy was the preferred therapy for a patient with a low risk for stroke and a high risk for ICH; aspirin was preferred for patients with a moderate risk for stroke and ICH; and warfarin was preferred for patients with a high risk for stroke and a low risk of ICH.

Conclusion

In the context of limited health resources, rivaroxaban is unlikely to be cost-effective, although it provided more health benefits comparing with other strategies. Additionally, warfarin with good INR control might be more suitable for AF patients in developing regions.     

Accuracy of Ovarian and Colon Cancer Risk Assessments by U.S. Physicians

BACKGROUND

Studies have shown a mismatch between published cancer screening and genetic counseling referral recommendations and physician-reported screening and referral practices. Inaccurate cancer risk assessment is one potential cause of this mismatch.

OBJECTIVE

To assess U.S. physicians’ ability to accurately determine a woman’s colon and ovarian cancer risk level.

DESIGN, PARTICIPANTS

Cross-sectional survey of U.S. family physicians, general internists, and obstetrician-gynecologists. A twelve-page questionnaire with a vignette of a woman’s annual examination included a question about the patient’s level of colon and ovarian cancer risk. The final study sample included 1,555 physicians weighted to represent practicing U.S. physicians nationally.

MAIN MEASURE

Accuracy of physicians’ ovarian and colon cancer risk assessments.

KEY RESULTS

Overall, most physicians accurately assessed women’s risk of ovarian (57.0 %, CI 54.3, 59.6) and colon cancer (62.0 %, CI 59.4, 64.6). However, 27.1 % (CI 23.0, 31.6) of physicians overestimated the ovarian cancer risk among women at the same risk as the general population, and 65.1 % (CI 60.2, 69.7) underestimated ovarian cancer risk among women at much higher risk than the general population. Physicians overestimated colon more than ovarian cancer risk (38.0 %, CI 35.4, 40.6 vs. 27.1 %, CI 23.0, 31.6) for women at the same risk as the general population.

CONCLUSIONS

Physicians’ misestimation of patient ovarian and colon cancer risk may put average risk patients in jeopardy of unnecessary screening and higher risk patients in jeopardy of missed opportunities for prevention or early detection of cancers.     

Circulating tumor cell detection in high-risk non-metastatic prostate cancer

Purpose

The detection of circulating tumor cells (CTCs) provides important prognostic information in men with metastatic prostate cancer. We aim to determine the rate of detection of CTCs in patients with high-risk non-metastatic prostate cancer using the CellSearch^® method.

Method

Samples of peripheral blood (7.5 mL) were drawn from 36 men with newly diagnosed high-risk non-metastatic prostate cancer, prior to any initiation of therapy and analyzed for CTCs using the CellSearch^® method.

Results

The median age was 70 years, median PSA was 14.1, and the median Gleason score was 9. The median 5-year risk of progression of disease using a validated nomogram was 39 %. Five out of 36 patients (14 %, 95 % CI 5–30 %) had CTCs detected in their circulation. Four patients had only 1 CTC per 7.5 mL of blood detected. One patient had 3 CTCs per 7.5 mL of blood detected, which included a circulating tumor microemboli. Both on univariate analysis and multivariate analysis, there were no correlations found between CTC positivity and the classic prognostic factors including PSA, Gleason score, T-stage and age.

Conclusion

This study demonstrates that patients with high-risk, non-metastatic prostate cancer present infrequently with small number of CTCs in peripheral blood. This finding is consistent with the limited literature available in this setting. Other CTC isolation and detection technologies with improved sensitivity and specificity may enable detection of CTCs with mesenchymal phenotypes, although none as yet have been validated for clinical use. Newer assays are emerging for detection of new putative biomarkers for prostate cancer. Correlation of disease control outcomes with CTC detection will be important.     

Risk of cancer and secondary proctectomy after colectomy and ileorectal anastomosis in familial adenomatous polyposis

Purpose

The aim of our retrospective study was to review the outcome of patients undergoing colectomy with ileorectal anastomosis (IRA) due to familial adenomatous polyposis (FAP) in Finland during the last 50 years.

Methods

The cumulative risk of rectal cancer and the rate of anus preservation were analyzed. A total of 140 FAP patients with previous colectomy combined with ileorectal anastomosis were included. Kaplan–Meier analysis was performed to evaluate cumulative risks.

Results

Secondary proctectomy was performed for 39 (28 %) of 140 patients. The cumulative risk of secondary proctectomy was 53 % at 30 years after colectomy with IRA. A total of 17 (44 %) secondary proctectomies were performed due to cancer or suspicion of cancer, and another 17 (44 %) secondary proctectomies were performed due to uncontrollable rectal polyposis. During our study, the anus preservation rate in secondary proctectomies was 49 %. The cumulative risk of rectal cancer was 24 % at 30 years after colectomy with IRA. Therefore, the cumulative rectal cancer mortality 30 years after colectomy with IRA was 9 %.

Conclusions

Proctocolectomy and ileal pouch-anal anastomosis (IPAA) should be favored as a primary operation for patients not having technical or medical contraindications for it because colectomy with IRA carried a rectal cancer risk of 13 % with a mortality of 7 % during our study, and because IPAA is likely to succeed better at earlier phase of the disease. Patients with attenuated FAP had no rectal cancer in our study, and they may form a group where IRA should still be the first choice as an exception.     

Cost-Effectiveness of Long-Term Outpatient Buprenorphine-Naloxone Treatment for Opioid Dependence in Primary Care

BACKGROUND

Primary care physicians with appropriate training may prescribe buprenorphine-naloxone (bup/nx) to treat opioid dependence in US office-based settings, where many patients prefer to be treated. Bup/nx is off patent but not available as a generic.

OBJECTIVE

We evaluated the cost-effectiveness of long-term office-based bup/nx treatment for clinically stable opioid-dependent patients compared to no treatment.

DESIGN, SUBJECTS, AND INTERVENTION

A decision analytic model simulated a hypothetical cohort of clinically stable opioid-dependent individuals who have already completed 6 months of office-based bup/nx treatment. Data were from a published cohort study that collected treatment retention, opioid use, and costs for this population, and published quality-of-life weights. Uncertainties in estimated monthly costs and quality-of-life weights were evaluated in probabilistic sensitivity analyses, and the economic value of additional research to reduce these uncertainties was also evaluated.

MAIN MEASURES

Bup/nx, provider, and patient costs in 2010 US dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness (CE) ratios ($/QALY); costs and QALYs are discounted at 3% annually.

KEY RESULTS

In the base case, office-based bup/nx for clinically stable patients has a CE ratio of $35,100/QALY compared to no treatment after 24?months, with 64% probability of being < $100,000/QALY in probabilistic sensitivity analysis. With a 50% bup/nx price reduction the CE ratio is $23,000/QALY with 69% probability of being < $100,000/QALY. Alternative quality-of-life weights result in CE ratios of $138,000/QALY and $90,600/QALY. The value of research to reduce quality-of-life uncertainties for 24-month results is $6,400 per person eligible for treatment at the current bup/nx price and $5,100 per person with a 50% bup/nx price reduction.

CONCLUSIONS

Office-based bup/nx for clinically stable patients may be a cost-effective alternative to no treatment at a threshold of $100,000/QALY depending on assumptions about quality-of-life weights. Additional research about quality-of-life benefits and broader health system and societal cost savings of bup/nx therapy is needed.     

Mortality after cancer among patients with diabetes mellitus: effect of diabetes duration and treatment

Aims/hypothesis

The prognostic role of different diabetes treatment types has not been studied in detail. We compared mortality rates among cancer patients with and without diabetes, accounting for diabetes treatment and diabetes duration.

Methods

This register-based study included all cancer patients diagnosed in Denmark during 1995–2009. The patients were classified into four groups according to diabetes status at the time of cancer diagnosis: no diabetes, diabetes without medication, diabetes with only oral hypoglycaemic agent (OHA) or diabetes with insulin treatment. Poisson models were used to examine the association between pre-existing diabetes in cancer patients and mortality relative to the non-diabetic cancer population.

Results

Among 426,129 patients with incident cancer, we identified 42,205 patients with diabetes prior to cancer diagnosis. Overall, cancer patients with diabetes had higher mortality rates than non-diabetic cancer patients, highest among OHA- or insulin-treated patients. For all cancers combined and diabetes duration of 2 years at cancer diagnosis, insulin-treated patients experienced the highest mortality rate ratios starting from 3.7 (95% CI 2.7, 5.1) for men and 4.4 (3.1, 6.5) for women 1 year after cancer diagnosis, increasing to 5 (3.5, 7.0) for men and 6.5 (4.2, 9.3) for women 9 years after cancer diagnosis.

Conclusions/interpretation

Our study provides strong evidence that cancer patients with pre-existing diabetes experience higher mortality than cancer patients without diabetes. The higher mortality seen among cancer patients treated with OHAs or insulin is in accordance with the existing evidence that more intensive diabetes treatment reflects a larger degree of comorbidity at the time of cancer diagnosis, and hence poorer survival.     

Improved survival for older patients undergoing surgery for colorectal cancer between 2008 and 2011

Introduction

Older colorectal cancer patients have a higher risk of postoperative complications, and the impact of adverse events on survival is also significantly higher. Innovations like laparoscopic surgery which improve short-term outcome for older patients can also benefit their overall prognosis. We set out to analyse the impact of an increased utilisation of laparoscopic surgery for colorectal cancer in the Netherlands on overall survival.

Methods

All patients diagnosed with stages I–III colorectal cancer in the Netherlands between 2008 and 2011 were selected from the Netherlands Cancer Registry. Changes in perioperative mortality, 3-month mortality and 1-year mortality rates were analysed using year of diagnosis as an instrumental variable.

Results

Over 33,000 patients were included in the analyses. Data on surgical approach were not precisely known for 2008 and 2009; in 2010, 36.6 % of definitive surgical procedures were performed laparoscopically and 45.9 % in 2011. A laparoscopic approach was used less frequently in the patients aged ≥75 years (in 2011, 40.3 versus 49.2 % of younger patients; p?p?=?0.02), 3-month mortality from 4.8 to 3.9 % (p?=?0.01) and 1-year mortality from 9.6 to 8.3 % (p?Conclusion Between 2008 and 2011, the utilisation of a laparoscopic approach increases significantly, resulting in reduced mortality rates, particularly for the elderly. Therefore, a laparoscopic approach should be used whenever possible, which may allow for further improvement of outcomes.     

Hyperglycaemia is associated with cancer-related but not non-cancer-related deaths: evidence from the IPC cohort

Aims/hypothesis

Hyperglycaemia has been associated with the incidence of all and specific types of cancer, distinct from the risks related to diabetes. The relationships between blood glucose and mortality rates related to all and specific cancers were analysed in comparison with all-cause or non-cancer-related mortality rates in a large, general primary care population in France.

Methods

Between January 1991 and December 2008, 301,948 participants (193,221 men and 108,727 women), aged 16–95 years (mean ± SD 44.8?±?12.0 years for men and 45.1?±?14.2 years for women), had a health check at the IPC Centre. All data collected in standard conditions during the health checks-up were used for statistical analysis All examinations were performed under fasting conditions and included a blood glucose measurement. Participants with known diabetes (<9%) were excluded from the analysis. Participants were classified into quintiles based on their blood glucose measurement and were followed for a maximum of 17 years (mean ± SD 9.2?±?4.7 years) to assess all-cause, cancer and non-cancer mortality rates.

Results

A non-linear relationship was observed between cancer mortality rates and blood glucose quintile after adjustment for age and sex. There was a significant association between the group with the highest blood glucose level and cancer-related death (multivariate Cox model, HR [95% CI] 1.17 [1.03, 1.34]), while the group with normoglycaemia showed no association with cancer-related deaths. We did not observe a relationship between blood glucose and all-cause or non-cancer mortality rates. An excess risk of death was observed in the highest blood glucose quintile for gastrointestinal cancer and leukaemia. Adjustments for diabetes and aspirin use did not modify the results. However, this excess risk disappeared with use of glucose-lowering agents (HR [95% CI] 1.03 [0.74, 1.43]).

Conclusions/interpretation

Hyperglycaemia is associated with significantly higher rates of cancer-related deaths, particularly in gastrointestinal cancer and leukaemia, but not with non-cancer-related deaths. The association is retained when taking into account confounding factors, including chronic aspirin treatment.

     

Out-of-Pocket Spending in the Last Five Years of Life

BACKGROUND

A key objective of the Medicare program is to reduce risk of financial catastrophe due to out-of-pocket healthcare expenditures. Yet little is known about cumulative financial risks arising from out-of-pocket healthcare expenditures faced by older adults, particularly near the end of life.

DESIGN

Using the nationally representative Health and Retirement Study (HRS) cohort, we conducted retrospective analyses of Medicare beneficiaries’ total out-of-pocket healthcare expenditures over the last 5 years of life.

PARTICIPANTS

We identified HRS decedents between 2002 and 2008; defined a 5 year study period using each subject’s date of death; and excluded those without Medicare coverage at the beginning of this period (n?=?3,209).

MAIN MEASURES

We examined total out-of-pocket healthcare expenditures in the last 5 years of life and expenditures as a percentage of baseline household assets. We then stratified results by marital status and cause of death. All measurements were adjusted for inflation to 2008 US dollars.

RESULTS

Average out-of-pocket expenditures in the 5 years prior to death were $38,688 (95 % Confidence Interval $36,868, $40,508) for individuals, and $51,030 (95 % CI $47,649, $54,412) for couples in which one spouse dies. Spending was highly skewed, with the median and 90th percentile equal to $22,885 and $89,106, respectively, for individuals, and $39,759 and $94,823, respectively, for couples. Overall, 25 % of subjects’ expenditures exceeded baseline total household assets, and 43 % of subjects’ spending surpassed their non-housing assets. Among those survived by a spouse, 10 % exceeded total baseline assets and 24 % exceeded non-housing assets. By cause of death, average spending ranged from $31,069 for gastrointestinal disease to $66,155 for Alzheimer’s disease.

CONCLUSION

Despite Medicare coverage, elderly households face considerable financial risk from out-of-pocket healthcare expenses at the end of life. Disease-related differences in this risk complicate efforts to anticipate or plan for health-related expenditures in the last 5 years of life.     

Characteristics,risk factors and outcomes of adult cancer patients with extensively drug-resistant Pseudomonas aeruginosa infections

Objective

To evaluate the characteristics and outcomes of cancer patients with extensively drug-resistant (XDR) Pseudomonas aeruginosa infections.

Methods

This was a retrospective cohort of P. aeruginosa infections in cancer patients in Crete, Greece. Patients were followed until discharge. Mortality, predictors of mortality and risk factors for XDR P. aeruginosa infection were studied.

Results

Ninety seven episodes (89 patients) of P. aeruginosa infections (52 with bacteremia) were included in the study. In 22 cases, the infection was due to XDR isolates. All XDR isolates were susceptible to colistin and variably resistant to almost all other antibiotics. The multivariate analysis showed that the independent risk factors for XDR P. aeruginosa infection were hematologic malignancy (OR 40.7, 95 % CI 4.5–367.6) and prior fluoroquinolone use (OR 11.0, 95 % CI 2.0–60.5); lymphopenia was inversely associated with XDR infections (OR 0.16, 95 % CI 0.03–0.92). Mortality was 43 %; infection-related mortality was 24 %. Bacteremia (OR 8.47, 95 % CI 2.38–30.15), infection due to XDR isolates (OR 5.11, 95 % CI 1.15–22.62) and age (OR 1.05, 95 % CI 1.00–1.09) were independently associated with mortality.

Conclusion

Mortality in cancer patients with P. aeruginosa infections was high. Infection due to XDR isolates was independently associated with mortality.     

Fasting proinsulin levels are significantly associated with 20 year cancer mortality rates. The Hoorn Study

Aims/hypothesis

Proinsulin is possibly associated with cancer through activation of insulin receptor isoform A. We sought to investigate the associations between proinsulin and 20 year cancer mortality rates.

Methods

The study was performed within the Hoorn Study, a population-based study of glucose metabolism in individuals aged 50–75 years in the Dutch population. Fasting proinsulin levels were measured twice by a double-antibody radioimmunoassay. Participants were continuously followed to register mortality; causes of death were derived from medical records. Cox survival analyses were performed to assess the 20 year risk of death from cancer in relation to proinsulin. All analyses were adjusted for age and sex, with additional adjustments for traditional risk factors. The effect modification of glucose metabolism and sex was tested.

Results

Proinsulin levels were measured in 438 individuals (41% normal glucose tolerance, 35.7% impaired glucose metabolism, 23.3% type 2 diabetes). Of these participants, 53 died from cancer. After adjustment for age and sex, proinsulin >16.5 pmol/l (the upper tertile) was significantly associated with a twofold risk of cancer mortality (HR 2.01, 95% CI 1.16, 3.46) compared with individuals with lower proinsulin levels. Additional adjustment for glucose metabolism, BMI and smoking did not substantially change the results (HR 1.91, 95% CI 1.04, 3.52). No interaction with glucose metabolism or sex was observed.

Conclusions/interpretation

Individuals with fasting proinsulin levels >16.5 pmol/l have a twofold risk of cancer mortality over a 20 year time span. These findings provide population-based evidence for the independent association between high proinsulin levels and cancer mortality rates.     

Societal Implications of Health Insurance Coverage for Medically Necessary Services in the U.S. Transgender Population: A Cost-Effectiveness Analysis

BACKGROUND

Recently, the Massachusetts Group Insurance Commission (GIC) prioritized research on the implications of a clause expressly prohibiting the denial of health insurance coverage for transgender-related services. These medically necessary services include primary and preventive care as well as transitional therapy.

OBJECTIVE

To analyze the cost-effectiveness of insurance coverage for medically necessary transgender-related services.

DESIGN

Markov model with 5- and 10-year time horizons from a U.S. societal perspective, discounted at 3 % (USD 2013). Data on outcomes were abstracted from the 2011 National Transgender Discrimination Survey (NTDS).

PATIENTS

U.S. transgender population starting before transitional therapy.

INTERVENTIONS

No health benefits compared to health insurance coverage for medically necessary services. This coverage can lead to hormone replacement therapy, sex reassignment surgery, or both.

MAIN MEASURES

Cost per quality-adjusted life year (QALY) for successful transition or negative outcomes (e.g. HIV, depression, suicidality, drug abuse, mortality) dependent on insurance coverage or no health benefit at a willingness-to-pay threshold of $100,000/QALY. Budget impact interpreted as the U.S. per-member-per-month cost.

KEY RESULTS

Compared to no health benefits for transgender patients ($23,619; 6.49 QALYs), insurance coverage for medically necessary services came at a greater cost and effectiveness ($31,816; 7.37 QALYs), with an incremental cost-effectiveness ratio (ICER) of $9314/QALY. The budget impact of this coverage is approximately $0.016 per member per month. Although the cost for transitions is $10,000–22,000 and the cost of provider coverage is $2175/year, these additional expenses hold good value for reducing the risk of negative endpoints —HIV, depression, suicidality, and drug abuse. Results were robust to uncertainty. The probabilistic sensitivity analysis showed that provider coverage was cost-effective in 85 % of simulations.

CONCLUSIONS

Health insurance coverage for the U.S. transgender population is affordable and cost-effective, and has a low budget impact on U.S. society. Organizations such as the GIC should consider these results when examining policies regarding coverage exclusions.

     

Body-Mass Index and All-Cause Mortality in US Adults With and Without Diabetes

BACKGROUND

Previous studies found normal weight compared to overweight/obese adults with type 2 diabetes had a higher mortality risk, and body-mass index (BMI)–mortality studies do not typically account for baseline diabetes status.

OBJECTIVE

To determine if diabetes influences the BMI–mortality relationship.

DESIGN

Using a prospective study design, we analyzed data from a nationally representative sample of US adults participating in the National Health Interview Survey from 1997 to 2002, and followed for mortality through 2006.

PARTICIPANTS

Excluding those with heart disease or cancer, our final analytic sample included 74,710 (34,805 never smoker) adults.

MAIN MEASURES

BMI was calculated from self-reported height and weight. Diabetes status was based on self-reported diagnosis from a health professional. We used direct age standardization to calculate all-cause mortality rates and adjusted Cox models for all-cause mortality hazard ratios by BMI quintile; this was done separately for adults with diabetes and without diabetes.

KEY RESULTS

Among never smokers, mean age was 50.1 years and 43 % were men. Mean BMI was 27.4 kg/m², 26 % were obese, and 2,035 (5 %) reported diagnosed diabetes. After 9 years, there were 4,355 deaths (754 of 4,740 with diabetes; 3,601 of 69,970 without) among 74,710 participants, and 1,238 (247 of 2,035 with diabetes; 991 of 32,770 without) among 34,805 never smokers. We observed a qualitative interaction with diabetes on the BMI–mortality relationship (p?=?0.002). Death rates were substantially higher among participants with diabetes compared to those without diabetes across all BMI quintiles. However, death rates in participants with diabetes fell with increasing BMI quintile, while rates followed a J-shaped curve among those without diabetes. In adjusted Cox models, BMI was positively associated with mortality in adults without diabetes, but inversely associated with mortality among participants with diabetes.

CONCLUSIONS

Mortality increased with increasing BMI in adults without diabetes, but decreased with increasing BMI among their counterparts with diabetes. Future studies need to be better designed to answer the question of whether normal weight adults with diabetes have a higher risk of mortality, by minimizing the possibility of reverse causation. Future studies should also account for prevalent diabetes in all investigations of the BMI–mortality relationship.