University of Florida Health Science Center

BACKGROUND: Literature searches underlie the foundations of systematic reviews and related review types. Yet, the literature searching component of systematic reviews and related review types is often poorly reported. Guidance for literature search reporting has been diverse, and, in many cases, does not offer enough detail to authors who need more specific information about reporting search methods and information sources in a clear, reproducible way. This document presents the PRISMA-S (Preferred Reporting Items for Systematic reviews and Meta-Analyses literature search extension) checklist, and explanation and elaboration. METHODS: The checklist was developed using a 3-stage Delphi survey process, followed by a consensus conference and public review process. RESULTS: The final checklist includes 16 reporting items, each of which is detailed with exemplar reporting and rationale. CONCLUSIONS: The intent of PRISMA-S is to complement the PRISMA Statement and its extensions by providing a checklist that could be used by interdisciplinary authors, editors, and peer reviewers to verify that each component of a search is completely reported and therefore reproducible.

BACKGROUND: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy. METHODS: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause). RESULTS: At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone. CONCLUSIONS: Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).

Emotional reactions are organized by underlying motivational states--defensive and appetitive--that have evolved to promote the survival of individuals and species. Affective responses were measured while participants viewed pictures with varied emotional and neutral content. Consistent with the motivational hypothesis, reports of the strongest emotional arousal, largest skin conductance responses, most pronounced cardiac deceleration, and greatest modulation of the startle reflex occurred when participants viewed pictures depicting threat, violent death, and erotica. Moreover, reflex modulation and conductance change varied with arousal, whereas facial patterns were content specific. The findings suggest that affective responses serve different functions-mobilization for action, attention, and social communication-and reflect the motivational system that is engaged, its intensity of activation, and the specific emotional context.

The affective dimension of pain is made up of feelings of unpleasantness and emotions associated with future implications, termed secondary affect. Experimental and clinical studies show serial interactions between pain sensation intensity, pain unpleasantness, and secondary affect. These pain dimensions and their interactions relate to a central network of brain structures that processes nociceptive information both in parallel and in series. Spinal pathways to limbic structures and medial thalamic nuclei provide direct inputs to brain areas involved in affect. Another source is from spinal pathways to somatosensory thalamic and cortical areas and then through a cortico-limbic pathway. The latter integrates nociceptive input with contextual information and memory to provide cognitive mediation of pain affect. Both direct and cortico-limbic pathways converge on the same anterior cingulate cortical and subcortical structures whose function may be to establish emotional valence and response priorities.

Increasingly, consumers engage in health information seeking via the Internet. Taking a communication perspective, this review argues why public health professionals should be concerned about the topic, considers potential benefits, synthesizes quality concerns, identifies criteria for evaluating online health information and critiques the literature. More than 70 000 websites disseminate health information; in excess of 50 million people seek health information online, with likely consequences for the health care system. The Internet offers widespread access to health information, and the advantages of interactivity, information tailoring and anonymity. However, access is inequitable and use is hindered further by navigational challenges due to numerous design features (e.g. disorganization, technical language and lack of permanence). Increasingly, critics question the quality of online health information; limited research indicates that much is inaccurate. Meager information-evaluation skills add to consumers' vulnerability, and reinforce the need for quality standards and widespread criteria for evaluating health information. Extant literature can be characterized as speculative, comprised of basic 'how to' presentations, with little empirical research. Future research needs to address the Internet as part of the larger health communication system and take advantage of incorporating extant communication concepts. Not only should research focus on the 'net-gap' and information quality, it also should address the inherently communicative and transactional quality of Internet use. Both interpersonal and mass communication concepts open avenues for investigation and understanding the influence of the Internet on health beliefs and behaviors, health care, medical outcomes, and the health care system.

Chronic hepatitis C (non-A, non-B hepatitis) is a common and often progressive viral liver disease. To assess the efficacy of therapy with the antiviral agent interferon alfa, we randomly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks, or to no treatment. The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon (P less than 0.001) and 28 percent in those treated with 1 million units (P less than 0.02), but only 8 percent in untreated patients. The serum alanine aminotransferase level became completely normal in 22 of the 26 patients (85 percent) who responded to treatment with 3 million units of interferon and 9 of the 16 patients (56 percent) who responded to treatment with 1 million units. The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation. Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units. We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C, although relapse after the cessation of treatment is common.

Cancellous and cortical autografts histologically have three differences: (1) cancellous grafts are revascularized more rapidly and completely than cortical grafts; (2) creeping substitution of cancellous bone initially involves an appositional bone formation phase, followed by a resorptive phase, whereas cortical grafts undergo a reverse creeping substitution process; (3) cancellous grafts tend to repair completely with time, whereas cortical grafts remain as admixtures of necrotic and viable bone. Physiologic skeletal metabolic factors influence the rate, amount, and completeness of bone repair and graft incorporation. The mechanical strengths of cancellous and cortical grafts are correlated with their respective repair processes: cancellous grafts tend to be strengthened first, whereas cortical grafts are weakened. Bone allografts are influenced by the same immunologic factors as other tissue grafts. Fresh bone allografts may be rejected by the host's immune system. The histoincompatibility antigens of bone allografts are presumably the proteins or glycoproteins on cell surfaces. The matrix proteins may or may not elicit graft rejection. The rejection of a bone allograft is considered to be a cellular rather than a humoral response, although the humoral component may play a part. The degree of the host response to an allograft may be related to the antigen concentration and total dose. The rejection of a bone allograft is histologically expressed by the disruption of vessels, an inflammatory process including lymphocytes, fibrous encapsulation, peripheral graft resorption, callus bridging, nonunions, and fatigue fractures.

Incidental memory performance for pictures that varied along the affective dimensions of pleasantness and arousal was assessed. For both an immediate and delayed (1 year later) free-recall task, only the arousal dimension had a stable effect on memory performance: Pictures rated as highly arousing were remembered better than low-arousal stimuli. This effect was corroborated in a speeded recognition test, in which high-arousal materials encoded earlier in the experiment produced faster reaction times than their low-arousal counterparts. Pleasantness affected reaction time decisions only for pictures not encoded earlier. These results suggest that whereas both the dimensions of pleasantness and arousal are processed at initial encoding, long-term memory performance is mainly affected by arousal.

Over the past twenty years, polypyrrole has appeared as the most extensively studied conducting polymer. However, despite the volume of work already done in this area, there has been little focus put on the mechanism of polypyrrole synthesis, especially concerning the most efficient method, electropolymerization. Numerous analytical techniques have been used to study polypyrrole electrodeposition and/or doping. However, the mechanism itself is still a controversial subject as there is not one mechanism which is universally accepted. The mechanism proposed by Diaz is the one most commonly referred to in the literature although several other mechanisms are not lacking in support. The controversy lies in the initiation step as each mechanism proposes a different way of beginning the reaction, varying between electron transfer, proton transfer and direct radical pyrrole formation. Without considering the initiation step, there are many other factors including electrolyte, solvent, temperature and pH which can influence the reaction mechanism during the electropolymerization of pyrrole, thus impacting the characteristics of the polymer formed at the electrode.

Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying central nervous system involvement by SARS-CoV-2.

Adhering to the view that emotional reactivity is organized in part by underlying motivational states--defensive and appetitive--we investigated sex differences in motivational activation. Men's and women's affective reactions were measured while participants viewed pictures with varied emotional and neutral content. As expected, highly arousing contents of threat, mutilation, and erotica prompted the largest affective reactions in both men and women. Nonetheless, women showed a broad disposition to respond with greater defensive reactivity to aversive pictures, regardless of specific content, whereas increased appetitive activation was apparent for men only when viewing erotica. Biological and sociocultural factors in shaping sex differences in emotional reactivity are considered as possible mediators of sex differences in emotional response.

BACKGROUND: Standard chemotherapy is associated with low response rates and short progression-free survival among patients with pretreated metastatic triple-negative breast cancer. Sacituzumab govitecan-hziy is an antibody-drug conjugate that combines a humanized monoclonal antibody, which targets the human trophoblast cell-surface antigen 2 (Trop-2), with SN-38, which is conjugated to the antibody by a cleavable linker. Sacituzumab govitecan-hziy enables delivery of high concentrations of SN-38 to tumors. METHODS: We conducted a phase 1/2 single-group, multicenter trial involving patients with advanced epithelial cancers who received sacituzumab govitecan-hziy intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxic effects. A total of 108 patients received sacituzumab govitecan-hziy at a dose of 10 mg per kilogram of body weight after receiving at least two previous anticancer therapies for metastatic triple-negative breast cancer. The end points included safety; the objective response rate (according to Response Evaluation Criteria in Solid Tumors, version 1.1), which was assessed locally; the duration of response; the clinical benefit rate (defined as a complete or partial response or stable disease for at least 6 months); progression-free survival; and overall survival. Post hoc analyses determined the response rate and duration, which were assessed by blinded independent central review. RESULTS: The 108 patients with triple-negative breast cancer had received a median of 3 previous therapies (range, 2 to 10). Four deaths occurred during treatment; 3 patients (2.8%) discontinued treatment because of adverse events. Grade 3 or 4 adverse events (in ≥10% of the patients) included anemia and neutropenia; 10 patients (9.3%) had febrile neutropenia. The response rate (3 complete and 33 partial responses) was 33.3% (95% confidence interval [CI], 24.6 to 43.1), and the median duration of response was 7.7 months (95% CI, 4.9 to 10.8); as assessed by independent central review, these values were 34.3% and 9.1 months, respectively. The clinical benefit rate was 45.4%. Median progression-free survival was 5.5 months (95% CI, 4.1 to 6.3), and overall survival was 13.0 months (95% CI, 11.2 to 13.7). CONCLUSIONS: Sacituzumab govitecan-hziy was associated with durable objective responses in patients with heavily pretreated metastatic triple-negative breast cancer. Myelotoxic effects were the main adverse reactions. (Funded by Immunomedics; IMMU-132-01 ClinicalTrials.gov number, NCT01631552.).

A pictorial instrument was developed to examine perceptions of body figure in a cross-sectional survey of 1118 preadolescent children. Hypothesis testing related to differences in figure selections by gender, grade, race, and school/community setting revealed males selected Ideal Self slightly thinner than Self. However, females selected Ideal Self significantly thinner than Self, as well as thinner than males' selection of Ideal Self and Ideal Girl. Additionally, females made thinner Ideal Adult figure selections than males. Though blacks chose heavier figures than whites, females of both races desired thinner figures. Bias toward thinness among females occurred across all levels of age, weight, race, and school/community setting, with 42% desiring thinner figures. Results of this study suggest that the onset of disparate figure perceptions and expectations regarding thinness among females may be evident as early as 6 and 7 years of age.

BACKGROUND: The World Health Organization's (WHO's) Health Promoting Schools (HPS) framework is an holistic, settings-based approach to promoting health and educational attainment in school. The effectiveness of this approach has not been previously rigorously reviewed. OBJECTIVES: To assess the effectiveness of the Health Promoting Schools (HPS) framework in improving the health and well-being of students and their academic achievement. SEARCH METHODS: We searched the following electronic databases in January 2011 and again in March and April 2013: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, CINAHL, Campbell Library, ASSIA, BiblioMap, CAB Abstracts, IBSS, Social Science Citation Index, Sociological Abstracts, TRoPHI, Global Health Database, SIGLE, Australian Education Index, British Education Index, Education Resources Information Centre, Database of Education Research, Dissertation Express, Index to Theses in Great Britain and Ireland, ClinicalTrials.gov, Current controlled trials, and WHO International Clinical Trials Registry Platform. We also searched relevant websites, handsearched reference lists, and used citation tracking to identify other relevant articles. SELECTION CRITERIA: We included cluster-randomised controlled trials where randomisation took place at the level of school, district or other geographical area. Participants were children and young people aged four to 18 years, attending schools or colleges. In this review, we define HPS interventions as comprising the following three elements: input to the curriculum; changes to the school's ethos or environment or both; and engagement with families or communities, or both. We compared this intervention against schools that implemented either no intervention or continued with their usual practice, or any programme that included just one or two of the above mentioned HPS elements. DATA COLLECTION AND ANALYSIS: At least two review authors identified relevant trials, extracted data, and assessed risk of bias in the trials. We grouped different types of interventions according to the health topic targeted or the approach used, or both. Where data permitted, we performed random-effects meta-analyses to provide a summary of results across studies. MAIN RESULTS: We included 67 eligible cluster trials, randomising 1443 schools or districts. This is made up of 1345 schools and 98 districts. The studies tackled a range of health issues: physical activity (4), nutrition (12), physical activity and nutrition combined (18), bullying (7), tobacco (5), alcohol (2), sexual health (2), violence (2), mental health (2), hand-washing (2), multiple risk behaviours (7), cycle-helmet use (1), eating disorders (1), sun protection (1), and oral health (1). The quality of evidence overall was low to moderate as determined by the GRADE approach. 'Risk of bias' assessments identified methodological limitations, including heavy reliance on self-reported data and high attrition rates for some studies. In addition, there was a lack of long-term follow-up data for most studies.We found positive effects for some interventions for: body mass index (BMI), physical activity, physical fitness, fruit and vegetable intake, tobacco use, and being bullied. Intervention effects were generally small but have the potential to produce public health benefits at the population level. We found little evidence of effectiveness for standardised body mass index (zBMI) and no evidence of effectiveness for fat intake, alcohol use, drug use, mental health, violence and bullying others; however, only a small number of studies focused on these latter outcomes. It was not possible to meta-analyse data on other health outcomes due to lack of data. Few studies provided details on adverse events or outcomes related to the interventions. In addition, few studies included any academic, attendance or school-related outcomes. We therefore cannot draw any clear conclusions as to the effectiveness of this approach for improving academic achievement. AUTHORS' CONCLUSIONS: The results of this review provide evidence for the effectiveness of some interventions based on the HPS framework for improving certain health outcomes but not others. More well-designed research is required to establish the effectiveness of this approach for other health topics and academic achievement.

OBJECTIVES: Because the detection of SARS-CoV-2 RNA in aerosols but failure to isolate viable (infectious) virus are commonly reported, there is substantial controversy whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted through aerosols. This conundrum occurs because common air samplers can inactivate virions through their harsh collection processes. We sought to resolve the question whether viable SARS-CoV-2 can occur in aerosols using VIVAS air samplers that operate on a gentle water vapor condensation principle. METHODS: Air samples collected in the hospital room of two coronavirus disease-2019 (COVID-19) patients, one ready for discharge and the other newly admitted, were subjected to RT-qPCR and virus culture. The genomes of the SARS-CoV-2 collected from the air and isolated in cell culture were sequenced. RESULTS: units/L of air. CONCLUSIONS: Patients with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus.

Actigraphy is a method used to study sleep-wake patterns and circadian rhythms by assessing movement, most commonly of the wrist. These evidence-based practice parameters are an update to the Practice Parameters for the Use of Actigraphy in the Clinical Assessment of Sleep Disorders, published in 1995. These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. Recommendations are based on the accompanying comprehensive review of the medical literature regarding the role of actigraphy, which was developed by a task force commissioned by the American Academy of Sleep Medicine. The following recommendations serve as a guide to the appropriate use of actigraphy. Actigraphy is reliable and valid for detecting sleep in normal, healthy populations, but less reliable for detecting disturbed sleep. Although actigraphy is not indicated for the routine diagnosis, assessment, or management of any of the sleep disorders, it may serve as a useful adjunct to routine clinical evaluation of insomnia, circadian-rhythm disorders, and excessive sleepiness, and may be helpful in the assessment of specific aspects of some disorders, such as insomnia and restless legs syndrome/periodic limb movement disorder. The assessment of daytime sleepiness, the demonstration of multiday human-rest activity patterns, and the estimation of sleep-wake patterns are potential uses of actigraphy in clinical situations where other techniques cannot provide similar information (e.g., psychiatric ward patients). Superiority of actigraphy placement on different parts of the body is not currently established. Actigraphy may be useful in characterizing and monitoring circadian rhythm patterns or disturbances in certain special populations (e.g., children, demented individuals), and appears useful as an outcome measure in certain applications and populations. Although actigraphy may be a useful adjunct to portable sleep apnea testing, the use of actigraphy alone in the detection of sleep apnea is not currently established. Specific technical recommendations are discussed, such as using concomitant completion of a sleep log for artifact rejection and timing of lights out and on; conducting actigraphy studies for a minimum of three consecutive 24-hour periods; requiring raw data inspection; permitting some preprocessing of movement counts; stating that epoch lengths up to 1 minute are usually sufficient, except for circadian rhythm assessment; requiring interpretation to be performed manually by visual inspection; and allowing automatic scoring in addition to manual scoring methods.

OBJECTIVE: The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. PARTICIPANTS: Infants who were </=28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. METHODS: The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used. RESULTS: Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count <500/mm(3), and 5 patients had an absolute neutrophil count (ANC) between 500/mm(3) and 1000/mm(3). In all 6 cases, the ANC recovered during continuation of acyclovir at the same dosage or after completion of acyclovir therapy, and there were no apparent adverse sequelae of the transient neutropenia. No other drug-related adverse events were reported among ID or HD recipients, and no other laboratory aberrations could be correlated specifically with antiviral therapy. The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4-7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5-7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8-113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. CONCLUSION: These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm(3) for a prolonged period.

OBJECTIVES: The National Institutes of Health, led by the National Heart, Lung, and Blood Institute, organized a working group of experts to discuss the problem of weight regain after weight loss. A number of experts in integrative physiology and behavioral psychology were convened with the goal of merging their perspectives regarding the barriers to scientific progress and the development of novel ways to improve long-term outcomes in obesity therapeutics. The specific objectives of this working group were to: (1) identify the challenges that make maintaining a reduced weight so difficult; (2) review strategies that have been used to improve success in previous studies; and (3) recommend novel solutions that could be examined in future studies of long-term weight control. RESULTS: Specific barriers to successful weight loss maintenance include poor adherence to behavioral regimens and physiological adaptations that promote weight regain. A better understanding of how these behavioral and physiological barriers are related, how they vary between individuals, and how they can be overcome will lead to the development of novel strategies with improved outcomes. CONCLUSIONS: Greater collaboration and cross-talk between physiological and behavioral researchers is needed to advance the science and develop better strategies for weight loss maintenance.

Radiographic and histological studies of sixteen massive retrieved human allografts were carried out after the allografts had been in situ for four to sixty-five months. The studies demonstrated that union between the allograft and the host took place slowly at cortical-cortical junctions by the formation of an external callus derived from the cortex of the host, and it took place more rapidly at cancellous-cancellous junctions by internal callus advancing from the host into the allograft. Internal repair took place very slowly, was confined to the superficial surface and the ends of the graft, and had involved only 20 per cent of the graft by five years. The deep unrepaired portions of the graft retained their architecture, and where bone cement had been used to fix a prosthetic stem or an intramedullary rod to the allograft, there was no evidence of resorption of bone or loosening of the device. Soft tissues of the host became attached to the graft by deposition of a thin seam of new bone on the surface of the graft. A previous fracture of two grafts had healed before the time of retrieval. Analysis of the articular cartilage revealed no evidence that any chondrocytes had survived, even when the graft had been cryoprotected before it was preserved by freezing. The necrotic cartilage functioned well for as long as five years, and as it degenerated, it was covered by a pannus of fibrovascular reparative tissue. Two allografts that had been removed because of rejection were surrounded by an envelope of chronic inflammatory tissue that prevented union, adherence of soft tissue, and internal repair. Internal repair was more advanced about sites of fracture and adjacent to recurrent tumors than in other portions of the graft. These findings suggest that large frozen allografts in humans are osteoconductive rather than osteoinductive.

INTRODUCTION: The Chronic Care Model (CCM) uses a systematic approach to restructuring medical care to create partnerships between health systems and communities. The objective of this study was to describe how researchers have applied CCM in US primary care settings to provide care for people who have diabetes and to describe outcomes of CCM implementation. METHODS: We conducted a literature review by using the Cochrane database of systematic reviews, CINAHL, and Health Source: Nursing/Academic Edition and the following search terms: "chronic care model" (and) "diabet*." We included articles published between January 1999 and October 2011. We summarized details on CCM application and health outcomes for 16 studies. RESULTS: The 16 studies included various study designs, including 9 randomized controlled trials, and settings, including academic-affiliated primary care practices and private practices. We found evidence that CCM approaches have been effective in managing diabetes in US primary care settings. Organizational leaders in health care systems initiated system-level reorganizations that improved the coordination of diabetes care. Disease registries and electronic medical records were used to establish patient-centered goals, monitor patient progress, and identify lapses in care. Primary care physicians (PCPs) were trained to deliver evidence-based care, and PCP officd-based diabetes self-management education improved patient outcomes. Only 7 studies described strategies for addressing community resources and policies. CONCLUSION: CCM is being used for diabetes care in US primary care settings, and positive outcomes have been reported. Future research on integration of CCM into primary care settings for diabetes management should measure diabetes process indicators, such as self-efficacy for disease management and clinical decision making.