Randomized Controlled Trial of Personalized Colorectal Cancer Risk Assessment vs Education to Promote Screening Uptake.

INTRODUCTION: Risk stratification has been proposed as a strategy to improve participation in colorectal cancer (CRC) screening, but evidence is lacking. We performed a randomized controlled trial of risk stratification using the National Cancer Institute's Colorectal Cancer Risk Assessment Tool (CCRAT) on screening intent and completion. METHODS: A total of 230 primary care patients eligible for first-time CRC screening were randomized to risk assessment via CCRAT or education control. Follow-up of screening intent and completion was performed by record review and phone at 6 and 12 months. We analyzed change in intent after intervention, time to screening, overall screening completion rates, and screening completion by CCRAT risk score tertile. RESULTS: Of the patients, 61.7% of patients were aged <60 years, 58.7% female, and 94.3% with college or higher education. Time to screening did not differ between arms (hazard ratio 0.78 [95% confidence interval (CI) 0.52-1.18], P = 0.24). At 12 months, screening completion was 38.6% with CCRAT vs 44.0% with education (odds ratio [OR] 0.80 [95% CI 0.47-1.37], P = 0.41). Changes in screening intent did not differ between the risk assessment and education arms (precontemplation to contemplation: OR 1.52 [95% CI 0.81-2.86], P = 0.19; contemplation to precontemplation: OR 1.93 [95% CI 0.45-8.34], P = 0.38). There were higher screening completion rates at 12 months in the top CCRAT risk tertile (52.6%) vs the bottom (32.4%) and middle (31.6%) tertiles (P = 0.10). DISCUSSION: CCRAT risk assessment did not increase screening participation or intent. Risk stratification might motivate persons classified as higher CRC risk to complete screening, but unintentionally discourage screening among persons not identified as higher risk.

A Case of Epstein-Barr Virus-Negative Post-transplant Lymphoproliferative Disorder in a Solid Organ Transplant Recipient With Untreated Chronic Hepatitis C.

Post-transplant lymphoproliferative disorder (PTLD) is one of the most common malignancies affecting solid organ transplant recipients. The disease is frequently associated with Epstein-Barr virus (EBV) infection (70% of cases) and cases are often delineated by EBV positivity status. The oncogenesis of EBV-positive PTLD is well-described in the literature; however, the etiology of the EBV-negative subtype is poorly understood. This report describes a case of EBV-negative PTLD developing in a combined kidney-pancreas transplant recipient with an incidental finding of untreated chronic hepatitis C virus (HCV). Our experience suggests an association between HCV and EBV-negative PTLD. Additional well-designed studies are needed to further investigate this association.

Acute Immune Thrombocytopenia Following Influenza Vaccination in a Patient With Untreated Helicobacter pylori Infection.

A 70-year-old man with previously normal comprehensive blood counts (CBCs) was referred to our hospital for acute thrombocytopenia. Following a negative workup for secondary causes, we diagnosed immune thrombocytopenia (ITP). Aside from the influenza vaccine administered six days before presentation, there was no discernable precipitant on history. His only risk factor for ITP was untreated Helicobacter â€‹â€‹â€‹â€‹â€‹â€‹pylori diagnosed over two months prior. With treatment, the patient's platelets normalized within three days. ITP following influenza vaccination has been documented in the literature and reported to regulatory bodies. Our case indicates that individuals with untreated H. pylori infection might be particularly vulnerable to such occurrences.

A Case of Accidental Isoniazid Overdose Presenting With Nonspecific Symptoms.

A 68-year-old male with a history of end-stage renal disease and latent tuberculosis on isoniazid (INH), and no psychiatric history presented with a five-day history of anorexia, fatigue, and nausea. Physical exam in the emergency department was notable for somnolence, right upper extremity tremor, and diffuse abdominal pain. Initial workup revealed an anion gap metabolic acidosis with elevated lactate, prompting admission to the general ward for empiric IV antibiotics for suspected bacteremia from his permacath. Within a few hours of admission, he became increasingly encephalopathic and had two episodes of copious hematemesis. Repeat studies revealed a cholestatic pattern of liver injury and new-onset coagulopathy. With an overall clinical picture consistent with fulminant hepatic failure, our pharmacy team initiated a comprehensive pill count of all his medications, which established that he had been inadvertently taking up to six times the recommended dose of INH. With INH discontinuation and supportive therapy, he improved and was discharged on hospital day eight. Our experience provides lessons in the timely recognition and management of this rarely reported toxidrome in the United States.

Refractory pain in a schizophrenic patient on clozapine.

A 36-year-old man with schizophrenia, on two times per day clozapine, presented with a 2-year history of diffuse intermittent body pain.Per chart review-and on presentation-his physical examination had been consistently unremarkable, without point-tenderness elicited at any major muscle groups or focal neurological deficits. Workup for myopathy, neuropathy and supratherapeutic clozapine levels had similarly been unrevealing.Given that prior interventions had been unsuccessful in alleviating these symptoms, we queried whether clozapine might have been contributory. As a result, we adopted a previously described strategy of scheduling the bulk of patients' medication during non-waking hours.At 1-month follow-up, the patient reported about a 50% improvement in his symptoms. At 6-month follow-up, this improvement in symptoms had been sustained.Our findings add to the limited anecdotal reports of this side effect whose true prevalence remains unknown. Timely recognition has the potential to promote adherence to therapy among patients in the maintenance phase.

Surveying Gut Microbiome Research in Africans: Toward Improved Diversity and Representation.

Descriptive and translational investigations into the human gut microbiome (GM) are rapidly expanding; however, studies are largely restricted to industrialized populations in the USA and Europe. Little is known about microbial variability and its implications for health and disease in other parts of the world. Populations in Africa are particularly underrepresented. What limited research has been performed has focused on a few subject domains, including the impact of long-term lifestyle and dietary factors on GM ecology, its maturation during infancy, and the interrelationships between the microbiome, infectious disease, and undernutrition. Recently, international consortia have laid the groundwork for large-scale genomics and microbiome studies on the continent, with a particular interest in the epidemiologic transition to noncommunicable disease. Here, we survey the current landscape of GM scholarship in Africa and propose actionable recommendations to improve research capacity and output.

Analyzing Ras-associated cell proliferation signaling.

Ras-dependent signaling is an important regulator of cell cycle progression, proliferation, senescence, and apoptosis. Several of the downstream effectors of Ras play dual roles in each of these processes. Under one set of conditions, they promote cell cycle progression and proliferation; yet, in a different paradigm, they drive cell cycle arrest and apoptosis. Furthermore, there is cross talk between certain downstream effectors of Ras including the PI3K-AKT and Raf-MEK-ERK pathways. Here we describe a series of experiments used to dissect the effect of different Ras-dependent signaling pathways on cell cycle progression, proliferation, senescence, and apoptosis. Furthermore, we highlight the importance of consistent growth conditions of cells in culture when studying Ras-dependent signaling as we show that the activation of downstream effectors of Ras changes with the confluency at which the cells are grown.

Three types of self-efficacy associated with medication adherence in patients with co-occurring HIV and substance use disorders, but only when mood disorders are present.

BACKGROUND: Adherence with medication regimens for human immunodeficiency virus (HIV) is a life-saving behavior for people with HIV infection, yet adherence is challenging for many individuals with co-occurring substance use and/or mood disorders. Medication-taking self-efficacy, which is the confidence that one can take one's medication as prescribed, is associated with better adherence with HIV medication. However, little is known about the influence that other kinds of self-efficacy have on adherence with HIV medication, especially among HIV-infected individuals with co-occurring substance use and/or mood disorders. We sought to examine the relationship between adherence with HIV medication among substance users and three specific kinds of self-efficacy, ie, one's confidence that one can communicate with medical providers, get support, and manage one's mood. We further sought to examine whether symptoms of depression and anxiety moderate these relationships. METHODS: Patients were recruited from three HIV clinics in the southeastern United States as part of an integrated study of treatment for HIV and substance use. RESULTS: We interviewed 154 patients with HIV and substance use who reported taking HIV medications. Based on symptoms of depression and anxiety using the Patient Health Questionnaire-9 and the Hospital Anxiety and Depression Scale-Anxiety, 63% had probable depression and/or anxiety. Higher levels of self-efficacy in provider communication (ß = 3.86, P < 0.01), getting needed support (ß = 2.82, P < 0.01), and mood management (ß = 2.29, P < 0.05) were related to better self-reported adherence with HIV medication among study participants with probable depression and/or anxiety. The three kinds of self-efficacy were not associated with medication adherence among participants with HIV and substance use only. CONCLUSION: In the search for mutable factors to improve medication adherence among individuals triply diagnosed with HIV, substance use, and mood disorders, these findings support previous research indicating the benefit of enhancing self-efficacy, and further point to three specific kinds of self-efficacy that may benefit medication adherence, ie, provider communication, getting support, and mood management.

Stratified whole genome linkage analysis of Chiari type I malformation implicates known Klippel-Feil syndrome genes as putative disease candidates.

Chiari Type I Malformation (CMI) is characterized by displacement of the cerebellar tonsils below the base of the skull, resulting in significant neurologic morbidity. Although multiple lines of evidence support a genetic contribution to disease, no genes have been identified. We therefore conducted the largest whole genome linkage screen to date using 367 individuals from 66 families with at least two individuals presenting with nonsyndromic CMI with or without syringomyelia. Initial findings across all 66 families showed minimal evidence for linkage due to suspected genetic heterogeneity. In order to improve power to localize susceptibility genes, stratified linkage analyses were performed using clinical criteria to differentiate families based on etiologic factors. Families were stratified on the presence or absence of clinical features associated with connective tissue disorders (CTDs) since CMI and CTDs frequently co-occur and it has been proposed that CMI patients with CTDs represent a distinct class of patients with a different underlying disease mechanism. Stratified linkage analyses resulted in a marked increase in evidence of linkage to multiple genomic regions consistent with reduced genetic heterogeneity. Of particular interest were two regions (Chr8, Max LOD = 3.04; Chr12, Max LOD = 2.09) identified within the subset of "CTD-negative" families, both of which harbor growth differentiation factors (GDF6, GDF3) implicated in the development of Klippel-Feil syndrome (KFS). Interestingly, roughly 3-5% of CMI patients are diagnosed with KFS. In order to investigate the possibility that CMI and KFS are allelic, GDF3 and GDF6 were sequenced leading to the identification of a previously known KFS missense mutation and potential regulatory variants in GDF6. This study has demonstrated the value of reducing genetic heterogeneity by clinical stratification implicating several convincing biological candidates and further supporting the hypothesis that multiple, distinct mechanisms are responsible for CMI.