Theoretical impact of the AT(N) framework on dementia using a community autopsy sample.

The AT(N) research framework categorizes eight biomarker profiles using amyloid (A), tauopathy (T), and neurodegeneration (N), regardless of dementia status. We evaluated associations with dementia risk in a community-based cohort by approximating AT(N) profiles using autopsy-based neuropathology correlates, and considered cost implications for clinical trials for secondary prevention of dementia based on AT(N) profiles. We used Consortium to Establish a Registry for Alzheimer's Disease (moderate/frequent) to approximate A+, Braak stage (IV-VI) for T+, and temporal pole lateral ventricular dilation for (N)+. Outcomes included dementia prevalence at death and incidence in the last 5 years of life. A+T+(N)+ was the most common profile (31%). Dementia prevalence ranged from 14% (A-T-[N]-) to 79% (A+T+[N]+). Between 8% (A+T-[N]-) and 68% (A+T+[N]-) of decedents developed incident dementia in the last 5 years of life. Clinical trials would incur substantial expense to characterize AT(N). Many people with biomarker-defined preclinical Alzheimer's disease will never develop clinical dementia during life, highlighting resilience to clinical expression of AD neuropathologic changes and the need for improved tools for prediction beyond current AT(N) biomarkers.

Mid-term Results of Femoral and Tibial Osteotomies and Fassier-Duval Nailing in Children With Osteogenesis Imperfecta.

BACKGROUND: Patients with osteogenesis imperfecta (OI) have significant burden of both fractures and bony deformities. The present approach to care in this disorder is a combination of surgical care with intramedullary rod fixation, cyclic bisphosphonate therapy, and rehabilitation with goal of maximizing patient function and quality of life. METHODS: Retrospective chart review identified 58 children with OI who had realignment osteotomies with Fassier-Duval (FD) intramedullary nailing of the lower extremity by a single surgeon. This is a consecutive series treated between 2003 and 2010. Postoperatively, patients were followed up clinically and radiologically. Motor function was assessed using the Brief Assessment of Motor Function score and the walking scale subset of the Gillette Functional Assessment Questionnaire. RESULTS: Fifty-eight patients had 179 lower extremity FD intramedullary rods placed. This technique allowed for intervention on multiple long bones, with 29% having bilateral femur and tibial rodding in the same procedure. Revisions were required in 53% of patients, which occurred at a mean time of 52 months after initial rodding surgery. In most cases, revision surgery was related to patient growth and subsequent fracture, although rod migration did occur in a minority of patients. Nonunion or incomplete union was 14.5% in this series. Bisphosphonate infusion was not postponed after surgical procedures. Patients had improvement in mobility status at the latest follow-up. CONCLUSIONS: This series lends evidence to the medium-term utility of FD intramedullary rods as an effective and less invasive platform for stabilization and correction of deformity in long bones of patients with OI. Relatively low blood loss and relatively short hospitalizations were noted. Nonunion rate was comparable with existing literature noting that our patients did not have postsurgical postponement of bisphosphonate therapy. LEVEL OF EVIDENCE: Therapeutic study to investigate the results of treatment with FD rods. Retrospective case series model of Level IV evidence quality.

The primary care extension program: a catalyst for change.

The Affordable Care Act authorized, but did not fund, the Primary Care Extension Program (PCEP). Much like the Cooperative Extension Program of the US Department of Agriculture sped the modernization of farming a century ago, the PCEP could speed the transformation of primary care. It could also help achieve other goals such as integrating primary care with public health and translating research into practice. The urgency of these goals and their importance to achieving the Triple Aim for health care should increase interest in rapidly building the PCEP, much as the need to feed the country did a century ago.

A needs-based method for estimating the behavioral health staff needs of community health centers.

BACKGROUND: Federally Qualified Health Centers are expanding to increase access for millions of more Americans with a goal of doubling capacity to serve 40 million people. Health centers provide a lot of behavioral health services but many have difficulty accessing mental health and substance use professionals for their patients. To meet the needs of the underserved and newly insured it is important to better estimate how many behavioral health professionals are needed. METHODS: Using health center staffing data and behavioral health service patterns from the 2010 Uniform Data System and the 2010 National Survey on Drug Use and Health, we estimated the number of patients likely to need behavioral health care by insurance type, the number of visits likely needed by health center patients annually, and the number of full time equivalent providers needed to serve them. RESULTS: More than 2.5 million patients, 12 or older, with mild or moderate mental illness, and more than 357,000 with substance abuse disorders, may have gone without needed behavioral health services in 2010. This level of need would have required more than 11,600 full time providers. This translates to approximately 0.9 licensed mental health provider FTE, 0.1 FTE psychiatrist, 0.4 FTE other mental health staff, and 0.3 FTE substance abuse provider per 2,500 patients. These estimates suggest that 90% of current centers could not access mental health services or provide substance abuse services to fully meet patients' needs in 2010. If needs are similar after health center expansion, more than 27,000 full time behavioral health providers will be needed to serve 40 million medical patients, and grantees will need to increase behavioral health staff more than four-fold. CONCLUSIONS: More behavioral health is seen in primary care than in any other setting, and health center clients have greater behavioral health needs than typical primary care patients. Most health centers needed additional behavioral health services in 2010, and this need will be magnified to serve 40 million patients. Further testing of these workforce models are needed, but the degree of current underservice suggests that we cannot wait to move on closing the gap.

Distal humerus atrophic nonunion in a child with osteogenesis imperfecta.

UNLABELLED: Atrophic nonunion of the distal humerus in children with osteogenesis imperfecta is a vexing and disabling problem. Traditional treatments, including casting, intramedullary nailing, plating and bone grafting have not been universally successful. We report on a case of successful treatment of one atrophic nonunion of the distal humerus in ad 2 year 10 month old child with type III OI who had failed more traditional treatments. The treatment used a combination of telescoping intramedullary nails, locking plate fixation and bone morphogenic protein. LEVEL OF EVIDENCE: Level IV.

From precision medicine to precision care: Choosing and using precision medicine in the context of multimorbidity.

Rapid advances in precision medicine promise dramatic reductions in morbidity and mortality for a growing array of conditions. To realize the benefits of precision medicine and minimize harm, it is necessary to address real-world challenges encountered in translating this research into practice. Foremost among these is how to choose and use precision medicine modalities in real-world practice by addressing issues related to caring for the sizable proportion of people living with multimorbidity. Precision medicine needs to be delivered in the broader context of precision care to account for factors that influence outcomes for specific therapeutics. Precision care integrates a person-centered approach with precision medicine to inform decision making and care planning by taking multimorbidity, functional status, values, goals, preferences, social and societal context into account. Designing dissemination and implementation of precision medicine around precision care would improve person-centered quality and outcomes of care, target interventions to those most likely to benefit thereby improving access to new therapeutics, minimize the risk of withdrawal from the market from unanticipated harms of therapy, and advance health equity by tailoring interventions and care to meet the needs of diverse individuals and populations. Precision medicine delivered in the context of precision care would foster respectful care aligned with preferences, values, and goals, engendering trust, and providing needed information to make informed decisions. Accelerating adoption requires attention to the full continuum of translational research: developing new approaches, demonstrating their usefulness, disseminating and implementing findings, while engaging patients throughout the process. This encompasses basic science, preclinical and clinical research and implementation into practice, ultimately improving health. This article examines challenges to the adoption of precision medicine in the context of multimorbidity. Although the potential of precision medicine is enormous, proactive efforts are needed to avoid unintended consequences and foster its equitable and effective adoption.

The incidence of spondylolysis and spondylolisthesis in children with osteogenesis imperfecta.

BACKGROUND: Spondylolysis and spondylolisthesis are common abnormalities of the lumbar spine. The incidence of these diagnoses is recognized in the healthy population. However, their incidence in osteogenesis imperfecta (OI) patients is less well defined. METHODS: This is a retrospective radiographic review of patients treated in the OI clinic from a single institution. Lateral radiographs were reviewed on all available patients to assess the incidence of spondylolysis and spondylolisthesis in this patient population. The morphology of the pedicle and pars interarticularis was also evaluated to identify any abnormalities or dysplasia of these structures. RESULTS: One hundred ten of the 139 patients treated in the OI clinic met the inclusion criteria for this study. Of these patients, 79% (87 of 110) were ambulatory. The overall incidence of spondylolysis in this pediatric OI population was found to be 8.2% (9 of 110) at an average age of 7.5 years. The incidence of spondylolisthesis was 10.9% (12 of 110) at an average age of 6.5 years with 75% (3 of 12) being isthmic type and 25% (3 of 12) dysplastic. The combined incidence of spondylolysis and spondylolisthesis was 19.2%. Incidentally, the pedicle length was noted to be elongated in 40.0% (44 of 110) of this OI population. CONCLUSIONS: This study found that the incidence of spondylolysis in a group of children with OI was much higher than in the normal pediatric population, which has been reported to be 2.6% to 4.0%. This incidence was also found to be higher than previously reported incidence of spondylolysis in OI patients (5.3%). The incidence of spondylolisthesis was also found to be much higher than that of the normal pediatric population (4.2%). It is important to recognize this higher incidence of these abnormalities and to anticipate future associated symptoms and potential worsening listhesis that can clinically affect the lifestyles of these children and potentially require surgical treatment. The clinical significance of these findings will necessitate long-term follow-up.

Resistance and resilience to Alzheimer's disease pathology are associated with reduced cortical pTau and absence of limbic-predominant age-related TDP-43 encephalopathy in a community-based cohort.

Alzheimer's disease neuropathologic change (ADNC) is defined by progressive accumulation of ß-amyloid plaques and hyperphosphorylated tau (pTau) neurofibrillary tangles across diverse regions of brain. Non-demented individuals who reach advanced age without significant ADNC are considered to be resistant to AD, while those burdened with ADNC are considered to be resilient. Understanding mechanisms underlying ADNC resistance and resilience may provide important clues to treating and/or preventing AD associated dementia. ADNC criteria for resistance and resilience are not well-defined, so we developed stringent pathologic cutoffs for non-demented subjects to eliminate cases of borderline pathology. We identified 14 resistant (85+ years old, non-demented, Braak stage ≤ III, CERAD absent) and 7 resilient (non-demented, Braak stage VI, CERAD frequent) individuals out of 684 autopsies from the Adult Changes in Thought study, a long-standing community-based cohort. We matched each resistant or resilient subject to a subject with dementia and severe ADNC (Braak stage VI, CERAD frequent) by age, sex, year of death, and post-mortem interval. We expanded the neuropathologic evaluation to include quantitative approaches to assess neuropathology and found that resilient participants had lower neocortical pTau burden despite fulfilling criteria for Braak stage VI. Moreover, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) was robustly associated with clinical dementia and was more prevalent in cases with high pTau burden, supporting the notion that resilience to ADNC may depend, in part, on resistance to pTDP-43 pathology. To probe for interactions between tau and TDP-43, we developed a C. elegans model of combined human (h) Tau and TDP-43 proteotoxicity, which exhibited a severe degenerative phenotype most compatible with a synergistic, rather than simply additive, interaction between hTau and hTDP-43 neurodegeneration. Pathways that underlie this synergy may present novel therapeutic targets for the prevention and treatment of AD.

Gout in Older Adults: The Atherosclerosis Risk in Communities Study.

BACKGROUND: It is unclear whether traditional and genetic risk factors in middle age predict the onset of gout in older age. METHODS: We studied the incidence of gout in older adults using the Atherosclerosis Risk in Communities study, a prospective U.S. population-based cohort of middle-aged adults enrolled between 1987 and 1989 with ongoing follow-up. A genetic urate score was formed from common urate-associated single nucleotide polymorphisms for eight genes. The adjusted hazard ratio and 95% confidence interval of incident gout by traditional and genetic risk factors in middle age were estimated using a Cox proportional hazards model. RESULTS: The cumulative incidence from middle age to age 65 was 8.6% in men and 2.5% in women; by age 75 the cumulative incidence was 11.8% and 5.0%. In middle age, increased adiposity, beer intake, protein intake, smoking status, hypertension, diuretic use, and kidney function (but not sex) were associated with an increased gout risk in older age. In addition, a 100 µmol/L increase in genetic urate score was associated with a 3.29-fold (95% confidence interval: 1.63-6.63) increased gout risk in older age. CONCLUSIONS: These findings suggest that traditional and genetic risk factors in middle age may be useful for identifying those at risk of gout in older age.

Physical Function, Hyperuricemia, and Gout in Older Adults.

OBJECTIVE: Gout prevalence is high in older adults and those affected are at risk of physical disability, yet it is unclear whether they have worse physical function. METHODS: We studied gout, hyperuricemia, and physical function in 5,819 older adults (age ≥65 years) attending the 2011-2013 Atherosclerosis Risk in Communities Study visit, a prospective US population-based cohort. Differences in lower extremity function (Short Physical Performance Battery [SPPB] and 4-meter walking speed) and upper extremity function (grip strength) by gout status and by hyperuricemia prevalence were estimated in adjusted ordinal logistic regression (SPPB) and linear regression (walking speed and grip strength) models. Lower scores or times signify worse function. The prevalence of poor physical performance (first quartile) by gout and hyperuricemia was estimated using adjusted modified Poisson regression. RESULTS: Ten percent of participants reported a history of gout and 21% had hyperuricemia. There was no difference in grip strength by history of gout (P = 0.77). Participants with gout performed worse on the SPPB test; they had 0.77 times (95% confidence interval [95% CI] 0.65, 0.90, P = 0.001) the prevalence odds of a 1-unit increase in SPPB score and were 1.18 times (95% CI 1.07, 1.32, P = 0.002) more likely to have poor SPPB performance. Participants with a history of gout had slower walking speed (mean difference -0.03; 95% CI -0.05, -0.01, P < 0.001) and were 1.19 times (95% CI 1.06, 1.34, P = 0.003) more likely to have poor walking speed. Similarly, SPPB score and walking speed, but not grip strength, were worse in participants with hyperuricemia. CONCLUSION: Older adults with gout and hyperuricemia are more likely to have worse lower extremity, but not upper extremity, function.

Proximity of providers: Colocating behavioral health and primary care and the prospects for an integrated workforce.

Integrated behavioral health and primary care is emerging as a superior means by which to address the needs of the whole person, but we know neither the extent nor the distribution of integration. Using the Centers for Medicare and Medicaid Services' National Plan and Provider Enumeration System (NPPES) Downloadable File, this study reports where colocation exists for (a) primary care providers and any behavioral health provider and (b) primary care providers and psychologists specifically. The NPPES database offers new insights into where opportunities are limited for integration due to workforce shortages or nonproximity of providers and where possibilities exist for colocation, a prerequisite for integration.

Defining intra-abdominal hypertension and abdominal compartment syndrome in acute thermal injury: a multicenter survey.

The definitions of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are not uniform despite the increasing awareness of IAH/ACS in burn patients. A short survey including definitions, resuscitation protocols, and monitoring practices was sent to every physician listed in the American Burn Association Directory. Thirty-two of 123 (26%) surveys were returned; 22 (69%) were from verified burn centers. Survey respondents said that bladder pressure indicating IAH is 19.6 mm Hg (range 12-30) and ACS is 25.9 mm Hg (range 15-40). Fifteen percentage of those responding do not include clinical sequellae in their definition of ACS. Bladder pressure is not routinely measured by 22 (69%) burn physicians, and staff at 17 centers (53%) wait until the abdomen is tense to measure abdominal pressure. Tense abdomen, along with elevated peak inspiratory pressures (PIP), is used in most centers (94%) to determine IAH/ACS, followed by oliguria (88%), and difficulty ventilating (78%). Resuscitation formulae used are primarily the Parkland/modified Parkland in 24 (75%) burn centers. Criteria for abdominal decompression is based on bladder pressures alone in 25 centers (78%); 16/32 (50%) use PIP, and 10/32 (31%) staff use other criteria including organ dysfunction or increased lactate. Eleven physicians (34%) advocate percutaneous decompression before decompressive laparotomy. Although most United States burn physicians define ACS as >or=25 mm Hg along with physiologic compromise, bladder pressure is routinely measured by only 31% of burn physicians. Most burn staff do not differentiate between IAH and ACS. Consensus definitions of IAH/ACS are necessary for burn care practitioners to compare research studies and discuss outcomes. Concise definitions will promote understanding of the pathophysiological processes involved and allow us to develop data-driven patient care protocols.

Pseudoephedrine legislation decreases methamphetamine laboratory-related burns.

Pseudoephedrine (PSE) is one of the main ingredients used to manufacture methamphetamine (MA); approximately 700 to 1000 PSE pills are necessary to "cook" a batch of MA. Steps have been taken to decrease the availability of ingredients needed to concoct MA. On May 21, 2005, the state of Iowa enacted a strict law, making PSE a Schedule V Controlled substance, restricting PSE availability, and sales. Using the same 6-month time frames in 2004 and 2005, we retrospectively compared epidemiological data on burn patients in the year before the new PSE law and again immediately after the law was enacted. Data collected between May 21 to December 31, 2004 and 2005 included sex, age, length of stay, body surface area burn, urine drug toxicity status, insurance status, and cost of hospital stay. Reports on statewide MA laboratory incidents were provided by the Office of Drug Control Policy. In 2004, Iowa ranked second in the nation for MA lab incidents, seizing an average of 120 labs per month. In 2006, Iowa ranked eighth in the nation for MA lab incidents, when only 20 labs per month were seized, an 83% decreased from the previous year. By limiting the availability of PSE, Iowa saw a marked decrease in MA laboratory-related incidents, leading to a drastic decrease in MA related burns statewide.

Methamphetamine-related burns in the cornbelt.

Methamphetamine (MA) is a highly addictive drug that is easily manufactured from everyday household products and chemicals found at local farm stores. The proliferation of small MA labs has led to a dramatic increase in patients sustaining thermal injury while making and/or using MA. We hypothesized that these patients have larger injuries with longer hospital stays, and larger, nonreimbursed hospital bills compared with burn patients not manufacturing or using MA. In a retrospective case-control study, all burn patients >or=16 years of age admitted to our burn center from January 2002 to December 2005 were stratified into two groups based on urine MA status. Of the 660 burn patients >or=16 years of age admitted during this 4 year period, urine drug screens were obtained at admission on 410 patients (62%); 10% of urine drug screens were MA (+). MA (+) patients have larger burns compared with MA (-) patients (9.3 vs 8.6% body surface area burns), have higher rates of inhalation injuries (20.4 vs 9.3%, P = .015), and more nonthermal trauma (13.0 vs 3.1%, P = .001). When compared with MA (-) patients, MA (+) patients require longer hospital stays (median 9.5 vs 7.0 days, P = .036), accrue greater hospital bills per day (dollars 4292 vs dollars 2797, P = .01), and lack medical insurance (66.7 vs 17.7%, P < .0001). The epidemic of MA use and its manufacture mandates that burn centers monitor patients for MA use and develop and institute protocols to ensure proper care of this increasingly costly population.