An IV for the RCT: using instrumental variables to adjust for treatment contamination in randomised controlled trials

Although the randomised controlled trial is the “gold standard” for studying the efficacy and safety of medical treatments, it is not necessarily free from bias. When patients do not follow the protocol for their assigned treatment, the resultant “treatment contamination” can produce misleading findings. The methods used historically to deal with this problem, the “as treated” and “per protocol” analysis techniques, are flawed and inaccurate. Intention to treat analysis is the solution most often used to analyse randomised controlled trials, but this approach ignores this issue of treatment contamination. Intention to treat analysis estimates the effect of recommending a treatment to study participants, not the effect of the treatment on those study participants who actually received it. In this article, we describe a simple yet rarely used analytical technique, the “contamination adjusted intention to treat analysis,” which complements the intention to treat approach by producing a better estimate of the benefits and harms of receiving a treatment. This method uses the statistical technique of instrumental variable analysis to address contamination. We discuss the strengths and limitations of the current methods of addressing treatment contamination and the contamination adjusted intention to treat technique, provide examples of effective uses, and discuss how using estimates generated by contamination adjusted intention to treat analysis can improve clinical decision making and patient care

The Impact of Poor Health Behaviors on Workforce Disability

The effects of poor health habits on mortality have been studied extensively. However, few studies have examined the impact of these health behaviors on workforce disability. In the Health and Retirement Study, a nationally representative cohort of 6044 Americans who were between the ages of 51 and 61 and who were working in 1992, we found that both baseline smoking status and a sedentary lifestyle predict workforce disability six years later. If this relationship is causal, cost-benefit analyses of health behavior intervention that neglect workforce disability may substantially underestimate the benefits of such interventions.

Providing clinicians with a patient’s 10-year cardiovascular risk improves their statin prescribing: a true experiment using clinical vignettes

Abstract Background Statins are effective for primary prevention of cardiovascular (CV) disease, the leading cause of death in the world. Multinational guidelines emphasize CV risk as an important factor for optimal statin prescribing. However, it’s not clear how primary care providers (PCPs) use this information. The objective of this study was to determine how primary care providers use information about global CV risk for primary prevention of CV disease. Methods A double-blinded, randomized experiment using clinical vignettes mailed to office-based PCPs in the United States who were identified through the American Medical Association Physician Masterfile in June 2012. PCPs in the control group received clinical vignettes with all information on the risk factors needed to calculate CV risk. The experimental group received the same vignettes in addition to the subject’s 10-year calculated CV risk (Framingham risk score). The primary study outcome was the decision to prescribe a statin. Results Providing calculated CV risk to providers increased statin prescribing in the two high-risk cases (CV risk > 20%) by 32 percentage points (41% v. 73%; 95% CI = 23-40, p <0.001; relative risk [RR] = 1.78) and 16 percentage points (12% v. 27%, 95% CI 8.5-22.5%, p <0.001; RR = 2.25), and decreased statin prescribing in the lowest risk case (CV risk = 2% risk) by 9 percentage points [95% CI = 1.00-16.7%, p = 0.003, RR = 0.88]. Fewer than 20% of participants in each group reported routinely calculating 10-year CV risk in their patients. Conclusions Providers do not routinely calculate 10-year CV risk for their patients. In this vignette experiment, PCPs undertreated low LDL, high CV risk patients. Giving providers a patient’s calculated CV risk improved statin prescribing. Providing PCPs with accurate estimates of patient CV risk at the point of service has the potential to improve the efficiency of statin prescribing.http://deepblue.lib.umich.edu/bitstream/2027.42/134534/1/12872_2013_Article_871.pd

Modeling experiments on pacemaker interactions in scyphomedusae

Scyphozoan jellyfish are free-swimming gelatinous organisms whose nervous system includes a motor nerve net that controls swimming. Swim contractions originate in a network of distributed pacemakers found in the marginal rhopalia, which are located around the margin of the bell. Many scyphozoan jellyfish have eight rhopalia, while others have sixteen or more. At any one time, the fastest pacemaker controls the output of the swim system. The activity of a single pacemaker is irregular; however, by linking multiple irregular pacemakers the swim system exhibits regular contractions. Thus, multiple pacemakers are believed to increase the frequency and regularity of swim contractions. Pacemaker interactions in Chrysaora quinquecirrha, Stomolophus meleagris, Aurelia aurita, and the ephyra of Aurelia aurita were investigated using artificial pacemaker networks created from pacemaker ablation experiments. In all species, with increasing pacemaker number, the frequency and regularity of swimming increased. Integrate and fire pacemaker models were used to determine if the pacemaker networks of three species of scyphomedusae were resetting, independent, or semi-independent. It is concluded that Chrysaora quinquecirrha and Stomolophus meleagris have a resetting pacemaker networks. In contrast, Aurelia aurita has a semi-independent pacemaker network and the ephyra of Aurelia aurita has resetting pacemaker network

Association between hospital case volume and the use of bronchoscopy and esophagoscopy during head and neck cancer diagnostic evaluation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102212/1/cncr28379.pd

Medication cost problems among chronically ill adults in the US: did the financial crisis make a bad situation even worse?

A national internet survey was conducted between March and April 2009 among 27,302 US participants in the Harris Interactive Chronic Illness Panel. Respondents reported behaviors related to cost-related medication non-adherence (CRN) and the impacts of medication costs on other aspects of their daily lives. Among respondents aged 40–64 and looking for work, 66% reported CRN in 2008, and 41% did not fill a prescription due to cost pressures. More than half of respondents aged 40–64 and nearly two-thirds of those in this group who were looking for work or disabled reported other impacts of medication costs, such as cutting back on basic needs or increasing credit card debt. More than one-third of respondents aged 65+ who were working or looking for work reported CRN. Regardless of age or employment status, roughly half of respondents reporting medication cost hardship said that these problems had become more frequent in 2008 than before the economic recession. These data show that many chronically ill patients, particularly those looking for work or disabled, reported greater medication cost problems since the economic crisis began. Given links between CRN and worse health, the financial downturn may have had significant health consequences for adults with chronic illness

Can risk modelling improve treatment decisions in asymptomatic carotid stenosis?

Abstract Background Carotid endarterectomy (CEA) is routinely performed for asymptomatic carotid stenosis, yet its average net benefit is small. Risk stratification may identify high risk patients that would clearly benefit from treatment. Methods Retrospective cohort study using data from the Asymptomatic Carotid Atherosclerosis Study (ACAS). Risk factors for poor outcomes were included in backward and forward selection procedures to develop baseline risk models estimating the risk of non-perioperative ipsilateral stroke/TIA. Baseline risk was estimated for all ACAS participants and externally validated using data from the Atherosclerosis Risk in Communities (ARIC) study. Baseline risk was then included in a treatment risk model that explored the interaction of baseline risk and treatment status (CEA vs. medical management) on the patient-centered outcome of any stroke or death, including peri-operative events. Results Three baseline risk factors (BMI, creatinine and degree of contralateral stenosis) were selected into our baseline risk model (c-statistic 0.59 [95% CI 0.54–0.65]). The model stratified absolute risk between the lowest and highest risk quintiles (5.1% vs. 12.5%). External validation in ARIC found similar predictiveness (c-statistic 0.58 [0.49–0.67]), but poor calibration across the risk spectrum. In the treatment risk model, CEA was superior to medical management across the spectrum of baseline risk and the magnitude of the treatment effect varied widely between the lowest and highest absolute risk quintiles (3.2% vs. 10.7%). Conclusion Even modestly predictive risk stratification tools have the potential to meaningfully influence clinical decision making in asymptomatic carotid disease. However, our ACAS model requires target population recalibration prior to clinical application.https://deepblue.lib.umich.edu/bitstream/2027.42/152135/1/12883_2019_Article_1528.pd

Degree of Landscape Fragmentation Influences Genetic Isolation among Populations of a Gliding Mammal

Forests and woodlands are under continuing pressure from urban and agricultural development. Tree-dependent mammals that rarely venture to the ground are likely to be highly sensitive to forest fragmentation. The Australian squirrel glider (Petaurus norfolcensis) provides an excellent case study to examine genetic (functional) connectivity among populations. It has an extensive range that occurs in a wide band along the east coast. However, its forest and woodland habitat has become greatly reduced in area and is severely fragmented within the southern inland part of the species' range, where it is recognised as threatened. Within central and northern coastal regions, habitat is much more intact and we thus hypothesise that genetic connectivity will be greater in this region than in the south. To test this we employed microsatellite analysis in a molecular population biology approach. Most sampling locations in the highly modified south showed signatures of genetic isolation. In contrast, a high level of genetic connectivity was inferred among most sampled populations in the more intact habitat of the coastal region, with samples collected 1400 km apart having similar genetic cluster membership. Nonetheless, some coastal populations associated with urbanisation and agriculture are genetically isolated, suggesting the historic pattern observed in the south is emerging on the coast. Our study demonstrates that massive landscape changes following European settlement have had substantial impacts on levels of connectivity among squirrel glider populations, as predicted on the basis of the species' ecology. This suggests that landscape planning and management in the south should be focused on restoring habitat connectivity where feasible, while along the coast, existing habitat connectivity must be maintained and recent losses restored. Molecular population biology approaches provide a ready means for identifying fragmentation effects on a species at multiple scales. Such studies are required to examine the generality of our findings for other tree-dependent species

Informal Caregiving for Diabetes and Diabetic Complications Among Elderly Americans

Objectives: Little is known regarding the amount of time spent by unpaid caregivers providing help to elderly individuals for disabilities associated with diabetes mellitus (DM). We sought to obtain nationally representative estimates of the time, and associated cost, of informal caregiving provided to the elderly with diabetes, and to determine the complications of DM that contribute most significantly to the subsequent need for informal care. Methods: We estimated multivariable regression models using data from the 1993 Asset and Health Dynamics (AHEAD) Study, a nationally representative survey of people aged 70 or older (N=7,443), to determine the weekly hours of informal caregiving and imputed cost of caregiver time for community-dwelling elderly with and without a diagnosis of DM. Results: Those without DM received an average of 6.1 hours per week of informal care, those with DM taking no medications received 10.5 hours, those with DM taking oral medications received 10.1 hours, and those with DM taking insulin received 14.4 hours of care (P