Obesity uncovered: diagnosis without treatment in plans offered on the 2015 health insurance marketplace

Background: Obesity is a public health problem that currently affects more than one-third of American adults. The Patient Protection and Affordable Care Act (ACA) requires all private health plans to cover diagnostic screening and counseling for obesity. However, the ACA does not guarantee access to effective treatment for obesity. Objective: To examine the health plans sold on the 2015 Health Insurance Marketplace (Marketplace) by describing the coverage and access barriers for surgical and non-surgical treatments for obesity. Methods: Using data from the 2015 Marketplace Public Use Files that consist of a census of all health plans sold on the 2015 Marketplace in 37 states, which excludes plans sold on the 14 State-based Marketplaces. Descriptive statistics are employed to characterize the plans’ coverage, exclusions, limitations, and out-of-pocket costs for bariatric surgery (surgical category), dietician services, nutritional counseling, gym access, gym membership, gym membership reimbursement, and weight loss programs (non-surgical category). Results: Bariatric surgery was covered by 30.4% of plans. Of these plans, over one-third applied a limit on the coverage amount. Of the plans covering bariatric surgery with a copayment, 60.3% of these plans had a copayment of $1,000 or more. In contrast, the non-surgical treatments were covered by more than 80$1 and $49. Of the plans covering treatments in the surgical or non-surgical categories, coinsurance rates were more prevalent than copayments, with almost two-thirds of plans having a coinsurance rate of 50% or more. Conclusions: A majority of plans on the 2015 Marketplace covered non-surgical obesity treatments. However, bariatric surgery, the treatment that results in the greatest amount of weight loss, was covered by less than one-third of plans. Furthermore, bariatric surgery, even when covered, may be less accessible to patients with a Marketplace plan due to high cost sharing and limits on the coverage amount. This study is significant to public health because it provides an early description of the coverage and access barriers to obesity treatments available to Marketplace enrollees, highlighting the importance of promoting policy that expands coverage of and access to obesity treatments given the high prevalence of obesity in the U.S

Caregiver Integration During Discharge Planning for Older Adults to Reduce Resource Use: A Metaanalysis

Objectives To determine the effect of integrating informal caregivers into discharge planning on postdischarge cost and resource use in older adults. Design A systematic review and metaanalysis of randomized controlled trials that examine the effect of discharge planning with caregiver integration begun before discharge on healthcare cost and resource use outcomes. MEDLINE, EMBASE, and the Cochrane Library databases were searched for all English‐language articles published between 1990 and April 2016. Setting Hospital or skilled nursing facility. Participants Older adults with informal caregivers discharged to a community setting. Measurements Readmission rates, length of and time to post‐discharge rehospitalizations, costs of postdischarge care. Results Of 10,715 abstracts identified, 15 studies met the inclusion criteria. Eleven studies provided sufficient detail to calculate readmission rates for treatment and control participants. Discharge planning interventions with caregiver integration were associated with a 25% fewer readmissions at 90 days (relative risk (RR) = 0.75, 95% confidence interval (CI) = 0.62–0.91) and 24% fewer readmissions at 180 days (RR = 0.76, 95% CI = 0.64–0.90). The majority of studies reported statistically significant shorter time to readmission, shorter rehospitalization, and lower costs of postdischarge care among discharge planning interventions with caregiver integration. Conclusion For older adults discharged to a community setting, the integration of caregivers into the discharge planning process reduces the risk of hospital readmission

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation

Investigating biochemical and structural changes in animal models of multiple sclerosis using Fourier transform infrared imaging and small angle x-ray scattering

Multiple sclerosis (MS) is a debilitating disease of the central nervous system and is the leading cause of non-traumatic neurological disability in young adults. MS affects over 2 million people worldwide and is commonly believed to arise from an autoimmune attack directed against components of the myelin sheath, resulting in multifocal lesions characterised by inflammation, demyelination and axonal damage. A complex interplay between genetic and environmental factors is thought to contribute to disease susceptibility. Although conventional histopathological assessment and magnetic resonance imaging techniques have greatly improved our understanding of lesion activity, the aetiology of MS and the mechanisms underlying lesion formation remain largely unknown. In recent decades, advances in instrumentation and multivariate analysis tools have seen Fourier transform infrared (FTIR) microspectroscopic imaging become a powerful tool for detecting discrete and subtle changes in the macromolecular composition of healthy and diseased tissues. Complementary information about the fundamental structural attributes of the myelin sheath and quantification of the relative amount of myelin within the sample can be determined using small angle X-ray scattering (SAXS). The aim of this thesis was to investigate the biochemical and structural changes underpinning the pathological, developmental and reparative processes in animal models of MS using FTIR microspectroscopic imaging and SAXS. In the first part of this thesis, laboratory based FTIR microspectroscopic imaging, bioinformatics, and synchrotron mapping were used to analyse macromolecular changes in the CNS during the course of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Using this approach, the distinct and heterogeneous tissue layers of the cerebellum and spinal cord, as well as lesion pathology, could be distinguished from one another. EAE lesions were characterised by low relative lipid concentrations and high relative nucleic acid concentrations and correlated well with regions of demyelination and inflammation identified using conventional histological and immunofluorescence staining techniques. The identification unique infrared ‘spectral phenotypes' identified allowed the training of artificial neural networks (ANNs) capable of discriminating EAE pathology from the surrounding healthy tissue, in an unbiased and automated fashion. Moreover, the integration of ANNs with the higher lateral resolution achieved using synchrotron mapping allowed the early detection and definitive identification of microlesions in the CNS of mice, prior to the onset of clinical signs of EAE. Furthermore, the potential of this technique for the evaluation of new therapeutic agents was demonstrated in lesions of animals partially protected against EAE by vaccination with Nogo-A, an inhibitor of neurite outgrowth, where subtle chemical and protein secondary structural changes, not observed by conventional histology, were identified. For the second part of this thesis, FTIR microspectroscopic imaging and SAXS, in conjunction with conventional histological and EM techniques were used to detect and characterise the natural biochemical and ultrastructural changes associated with developmental myelination in the corpus callosum of healthy mice. The onset of myelination was consistently found to occur at postnatal day 14 (P14), while the rate of myelination varied depending on the analytical employed. Myelination reached a maximum rate between P14‒P21 and P21‒P28 as determined by SAXS and EM, respectively. In contrast, the rate of myelination was found to increase at a constant rate when measured by the relative amount of lipid quantified by FTIR microspectroscopic imaging. In addition to biochemical changes, SAXS analysis revealed that the myelin sheath underwent significant compaction at the extracellular space, which coincided with alterations in protein secondary structure detected in the FTIR spectra. Together, these data suggest that proteins involved in the compaction of the myelin sheath at this site, are responsible for the observed FTIR spectroscopic changes. The identification of significant biochemical changes between the oldest animals (P140) used in this study and the mice aged P98 and younger is of considerable importance, as mice aged between P56‒P84 are often used in research and thus may still be undergoing significant developmental changes. This is particularly relevant to the CPZ intoxication animal model, which is increasingly being used in MS research to assess demyelination and remyelination of the corpus callosum of mice aged between P56 and P140. The data obtained here, therefore provide a useful benchmark against which the biochemical and ultrastructural changes occurring in the corpus callosum following CPZ intoxication can be identified and compared. The ability of FTIR microspectroscopic imaging and SAXS to detect and quantify relative biochemical and structural changes during chemically induced demyelination and following subsequent remyelination of the corpus callosum in the CPZ intoxication animal model was examined in the third part of this thesis. Changes in the relative amounts of demyelination and remyelination were easily visualised and quantified in the FTIR spectra using the integrated area of the lipid ester carbonyl band as a measure of myelin. Notably, alterations in protein secondary structure were identified following remyelination, suggesting that such differences could be used to identify remyelination in a rapid and automated fashion. Despite these protein conformational changes, the ultrastructure of the myelin sheath, including the widths of the myelin period, lipid bilayers, cytoplasmic space and extracellular space, did not significantly differ during demyelination or remyelination, when compared with the age-matched controls. Interestingly, a discrepancy between the relative amount of myelin measured by SAXS and the average number of myelinated axons within the electron micrographs was found, suggesting that the SAXS technique is only capable of detecting myelin in a highly ordered structure. Thus, the SAXS method applied here could serve as a rapid means for quantifying the relative amount of intact internodal myelin within a sample and could be used to assess the effect of novel therapies on the relative amount of myelin remaining after demyelination or accumulating following remyelination. In summary, the data presented in this thesis illustrates the power of FTIR microspectroscopic imaging and SAXS techniques to detect subtle biochemical and structural changes associated with CNS pathology. These two techniques form a powerful addition to conventional techniques, providing rich biochemical and structural information and a unique opportunity to investigate a range of CNS pathologies within tissues at the molecular level, as well as the potential to evaluate and understand new therapeutic approaches and mechanisms of action