The ASAMET trial: a randomized, phase II, double-blind, placebo-controlled, multicenter, 2 × 2 factorial biomarker study of tertiary prevention with low-dose aspirin and metformin in stage I-III colorectal cancer patients.

BACKGROUND: Epidemiological studies and cardiovascular prevention trials have shown that low-dose aspirin can reduce colorectal cancer (CRC) incidence and mortality, including inhibition of distant metastases. Metformin has also been associated with decreased colon adenoma recurrence in clinical trials and lower CRC incidence and mortality in epidemiological studies in diabetics. While both drugs have been tested as single agents, their combination has not been tested in cancer prevention trials. METHODS/DESIGN: This is a randomized, placebo-controlled, double-blind, 2 × 2 biomarker trial of aspirin and metformin to test the activity of either agent alone and the potential synergism of their combination on a set of surrogate biomarkers of colorectal carcinogenesis. After surgery, 160 patients with stage I-III CRC are randomly assigned in a four-arm trial to either aspirin (100 mg day), metformin (850 mg bis in die), their combination, or placebo for one year. The primary endpoint biomarker is the change of IHC expression of nuclear factor kappa-B (NFκB) in the unaffected mucosa of proximal and distal colon obtained by multiple biopsies in two paired colonoscopies one year apart. Additional biomarkers will include: 1) the measurement of circulating IL-6, CRP and VEGF; 2) the IHC expression of tissue pS6K, p53, beta-catenin, PI3K; 3) the associations of genetic markers with treatment response as assessed by next generation sequencing of primary tumors; 4) the genomic profile of candidate genes, pathways, and overall genomic patterns in tissue biopsies by genome wide gene expression arrays; and 5) the evaluation of adenoma occurrence at 1 year. DISCUSSION: A favorable biomarker modulation by aspirin and metformin may provide important clues for a subsequent phase III adjuvant trial aimed at preventing second primary cancer, delaying recurrence and improving prognosis in patients with CRC. TRIAL REGISTRATION: EudraCT Number: 2015-004824-77; ClinicalTrial.gov Identifier: NCT03047837 . Registered on February 1, 2017.

Perspectives on the Tertiary Prevention Strategy for Alzheimer's Disease.

Amyloid-beta (Aß) plays a pivotal role in Alzheimer's disease (AD) pathogenesis, and is the most promising disease-modifying target for AD. A succession of failures in Aß-targeting clinical trials, however, has prompted questions on whether Aß is the true cause of AD and a valid therapeutic target. Therefore, current therapeutic targets and intervention strategies must be reconsidered. In addition to Aß, multiple pathological events such as tau hyperphosphorylation, oxidative stress and neuroinflammation are involved in the disease pathogenesis and cause cross-talk between these pathological pathways, which synergistically drive disease progression. Increasing evidence also reveals that the pathogenesis varies at different stages of the disease. Therefore, targeting Aß alone at all stages of the disease would not be sufficient to halt or reverse disease progression. In the light of the pathophysiologic similarities between the development of ischemic stroke and AD, we can formulate management strategies for AD from the successful practice of ischemic stroke management, namely the tertiary prevention strategy. These new perspectives of tertiary prevention target both Aß and different pathological pathways of AD pathogenesis at different stages of the disease, and may represent a promising avenue for the effective prevention and treatment of AD.

[Most important deficits, contradictions and possibilities in suicide prevention in Hungary]. / Az öngyilkos magatartás megelozésében tapasztalt legfontosabb hiányosságok, ellentmondások és lehetoségek Magyarországon.

Suicide is not only a contradictory biological, psychological, sociocultural and spiritual phenomenon, but also a serious public health problem, which is manifold, therefore the fight against it is also complex. The aim of the present publication is to establish the current situation of the fight against suicide in Hungary, which are the most important deficits, contradictions and unexploited possibilities. The author states that although we have accomplished important steps in the prevention of suicide, we did not realise the majority of them in everyday practice. The author defines the most important problems and tasks which should be solved in the next decade. In the near future a great deal more should be done for prevention than what we have accomplished so far in order to significantly reduce the number of suicide victims in Hungary.

Prevention of rheumatic diseases: strategies, caveats, and future directions.

Rheumatic diseases affect a significant portion of the population and lead to increased health care costs, disability, and premature mortality; effective preventive measures for these diseases could lead to substantial improvements in public health. Natural history studies show that for most rheumatic diseases there is a period of preclinical disease development during which abnormal biomarkers or other processes can be detected. These changes are useful to understand mechanisms of disease pathogenesis; in addition, they may be applied to estimate a personal risk of future disease while individuals are still relatively asymptomatic and ultimately be used to identify individuals who may be targeted for preventive interventions.

Relapse prevention for addictive behaviors.

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change.

The spectrum of invasive pneumococcal disease at an adult tertiary care hospital in the early 21st century.

Despite widespread pneumococcal vaccination of children and adults, invasive pneumococcal disease (IPD) remains prominent. Using our database of all Streptococcus pneumoniae infections at the Veterans Affairs Medical Center, Houston, Texas, since 2000, we reviewed cases of IPD, defined as the isolation of pneumococci from any normally sterile body site. In 136 cases, the mean age of patients was 63 years; 43% were African American, a higher proportion than the 30% served by our hospital. One hundred sixteen patients (85%) had pneumonia, of whom 3 also had empyema. Seven had bacteremia with no apparent source, 5 meningitis, 5 spontaneous bacterial peritonitis, 3 septic arthritis, 2 endocarditis, and individual patients had osteomyelitis and/or localized abscesses. One hundred twenty-one patients (89%) had > or =1 underlying condition associated with susceptibility to pneumococcal infection, and another 8 (6%) were aged >65 years old. Thus only 5% of patients lacked a condition for which 23-valent pneumococcal polysaccharide vaccine (PPV23) is recommended. Fifty-five percent had been vaccinated; similar proportions of vaccine serotypes infected previously vaccinated and nonvaccinated patients. All but 2 isolates were fully susceptible to penicillin and cefotaxime as currently defined. Consistent with substantial replacement of infecting serotypes since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), none of the predominant infecting serotypes was included in PCV7, although all except for 6A were contained in PPV23. The overall mortality at 30 days was 16% and was similar in vaccinated and nonvaccinated subjects. IPD causes a wide spectrum of disease. Mortality is substantial. PPV23 is clearly not fully protective.

Inpatient allergy/immunology consultations in a tertiary care setting.

Few studies have examined inpatient referral patterns for fellowship training programs and none for allergy/immunology (AI) since 2003. The primary end point was the reason for consultation, and secondary end points included the AI diagnosis made and outcomes. We retrospectively reviewed all inpatient AI consultations from July 1, 2001 through June 30, 2007. These 6 years of data were combined with 14 years of data examining the reason for consult from a previous study. The data were analyzed for trends and changes over the entire 20-year period. A total of 254 AI inpatient consults were reviewed over the 6 years studied. Thirty-six percent (92/254) of inpatient consults were for evaluation of adverse drug reactions (ADRs), 22% (55/254) miscellaneous reasons, 17% (43/254) urticaria/angioedema, 13% (32/254) for possible immunodeficiency, 9% (23/254) for anaphylaxis, and 3% (8/254) for asthma. AI inpatient consults show a significant decline over the recent 6-year period (p = 0.0023) despite stable total hospital admissions since 1998. Over the last 20 years, an 85% decrease (p < 0.00001) in inpatient asthma consults and increases (p < 0.05) in immunodeficiency, rash, and urticaria/angioedema evaluations have been observed. Not following AI recommendations resulted in a 16.6 odds ratio (95% CI, 5.55-49.93) that a patient's clinical status would be worse or unchanged. Inpatient AI consults have declined with associated reduction in asthma inpatient consults. Although ADRs and anaphylaxis consults have been stable, evaluations for immunodeficiency, rash, and urticaria/angioedema have increased. Following inpatient AI recommendations is associated with improved patient outcomes.

Delays in discharge in a tertiary care pediatric hospital.

BACKGROUND: Delays in discharges affect both efficiency and timeliness of care; 2 measures of quality of inpatient care. OBJECTIVE: Describe number, length, and type of delays in hospital discharges. Characterize impact of delays on overall length of stay (LOS) and costs. DESIGN: Prospective observational cohort study. SETTING: Tertiary-care children's hospital. PATIENTS: All children on 2 medical teams during August 2004. INTERVENTION: Two research assistants presented detailed data of patient care (from daily rounds) to 2 physicians who identified delays and classified the delay type. Discharge was identified as delayed if there was no medical reason for the patient to be in the hospital on a given day. MEASUREMENTS: Delays were classified using a validated and reliable instrument, the Delay Tool. LOS and costs were extracted from an administrative database. RESULTS: Two teams cared for 171 patients. Mean LOS and costs were 7.3 days (standard deviation [SD] 14.3) and $15,197 (SD 38,395), respectively: 22.8% of patients experienced at least 1 delay, accounting for 82 delay-related hospital days (9% of total hospital days) and $170,000 in costs (8.9% of hospital costs); 42.3% of the delays resulted from physician behavior, 21.8% were related to discharge planning, 14.1% were related to consultation, and 12.8% were related to test scheduling. CONCLUSIONS: Almost one-fourth of patients in this 1-month period could have been discharged sooner than they were. Impact of delays on LOS and costs are substantial. Interventions will need to address variations in physician criteria for discharge, more efficient discharge planning, and timely scheduling of consultation and diagnostic testing.