Colorectal cancer in patients under close colonoscopic surveillance

BACKGROUND & AIMS: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia. METHODS: Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored. RESULTS: CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia. CONCLUSIONS: CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.     

P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: implications for age-associated vascular dysfunction

The p66shc adaptor protein mediates age-associated oxidative stress. We examined the role of p66shc in endothelial nitric oxide synthase (eNOS) signaling. Overexpression of p66shc inhibited eNOS-dependent NO production. RNAi-mediated down-regulation of endogenous p66shc led to activation of the proto-oncogene ras, and Akt kinase, with a corresponding increase in phosphorylation of eNOS at S1177 (S1179 on bovine eNOS). In rat aortic rings, down-regulation of p66shc suppressed the vasoconstrictor response to phenyephrine that was abrogated by treatment with the NOS inhibitor l-NAME, and enhanced vasodilation induced by sub-maximal doses of acetylcholine. These findings highlight a pivotal role for p66shc in inhibiting endothelial NO production, and endothelium-dependent vasorelaxation, that may provide important mechanistic information about endothelial dysfunction seen with aging.     

Adherence to Antiretroviral Therapy and Clinical Outcomes Among Young Adults Reporting High-Risk Sexual Behavior, Including Men Who Have Sex with Men, in Coastal Kenya

African men who have sex with men (MSM) face significant stigma and barriers to care. We investigated antiretroviral therapy (ART) adherence among high-risk adults, including MSM, participating in a clinic-based cohort. Survival analysis was used to compare attrition across patient groups. Differences in adherence, weight gain, and CD4 counts after ART initiation were assessed. Among 250 HIV-1-seropositive adults, including 108 MSM, 15 heterosexual men, and 127 women, patient group was not associated with attrition. Among 58 participants who were followed on ART, 40 % of MSM had less than 95 % adherence, versus 28.6 % of heterosexual men and 11.5 % of women. Although MSM gained less weight after ART initiation than women (adjusted difference ?3.5 kg/year), CD4 counts did not differ. More data are needed on barriers to adherence and clinical outcomes among African MSM, to ensure that MSM can access care and derive treatment and prevention benefits from ART.     

Pharmacogenetic Treatments for Drug Addiction: Alcohol and Opiates

Aims: Psychiatric pharmacogenetics involves the use of genetic tests that can predict the effectiveness of treatments for individual patients with mental illness such as drug dependence. This review aims to cover these developments in the pharmacotherapy of alcohol and opiates, two addictive drugs for which we have the majority of our FDA approved pharmacotherapies. Methods: We conducted a literature review using Medline searching terms related to these two drugs and their pharmacotherapies crossed with related genetic studies. Results: Alcohol's physiological and subjective effects are associated with enhanced β-endorphin release. Naltrexone increases baseline β-endorphin release blocking further release by alcohol. Naltrexone's action as an alcohol pharmacotherapy is facilitated by a putative functional single nucleotide polymorphism (SNP) in the opioid mu receptor gene (Al18G) which alters receptor function. Patients with this SNP have significantly lower relapse rates to alcoholism when treated with naltrexone. Caucasians with various forms of the CYP2D6 enzyme results in a ‘poor metabolizer’ phenotype and appear to be protected from developing opioid dependence. Others with a “ultra-rapid metabolizer” phenotype do poorly on methadone maintenance and have frequent withdrawal symptoms. These patients can do well using buprenorphine because it is not significantly metabolized by CYP2D6. Conclusions: Pharmacogenetics has great potential for improving treatment outcome as we identify gene variants that affect pharmacodynamic and pharmacokinetic factors. These mutations guide pharmacotherapeutic agent choice for optimum treatment of alcohol and opiate abuse and subsequent relapse.     

Prevalence of Orthohantavirus-Reactive Antibodies in Humans and Peri-Domestic Rodents in Northern Ethiopia

In 2012, Tigray orthohantavirus was discovered in Ethiopia, but its seasonal infection in small mammals, and whether it poses a risk to humans was unknown. The occurrence of small mammals, rodents and shrews, in human inhabitations in northern Ethiopia is affected by season and presence of stone bunds. We sampled small mammals in two seasons from low- and high-density stone bund fields adjacent to houses and community-protected semi-natural habitats in Atsbi and Hagere Selam, where Tigray orthohantavirus was first discovered. We collected blood samples from both small mammals and residents using filter paper. The presence of orthohantavirus-reactive antibodies in blood was then analyzed using immunofluorescence assay (human samples) and enzyme linked immunosorbent assays (small mammal samples) with Puumala orthohantavirus as antigen. Viral RNA was detected by RT-PCR using small mammal blood samples. Total orthohantavirus prevalence (antibodies or virus RNA) in the small mammals was 3.37%. The positive animals were three Stenocephalemys albipes rats (prevalence in this species = 13.04%). The low prevalence made it impossible to determine whether season and stone bunds were associated with orthohantavirus prevalence in the small mammals. In humans, we report the first detection of orthohantavirus-reactive IgG antibodies in Ethiopia (seroprevalence = 5.26%). S. albipes lives in close proximity to humans, likely increasing the risk of zoonotic transmission.     

Correlates of women's knowledge of mother-to-child transmission of HIV and its prevention in Tanzania: a population-based study

Studies that explored women's knowledge on mother-to-child transmission (MTCT) of HIV and its prevention (PMTCT) in the general population are currently lacking. This paper examined factors associated with having adequate knowledge of MTCT of HIV and PMTCT among a nationally representative sample of women in Tanzania. We conducted a cross-sectional analysis including 10,299 women from the 2011–2012 Tanzania HIV/AIDS and Malaria Indicator Survey. The outcome of interest was the presence of adequate knowledge on MTCT and PMTCT of HIV. We used multivariable logistic regression to identify factors associated with having adequate knowledge on MTCT and PMTCT of HIV. Results revealed that the overall prevalence of having adequate knowledge on MTCT and PMTCT of HIV was low (46%). We found a statistically significant difference in the proportions of having adequate knowledge between HIV-negative and HIV-positive women (45% vs. 56%; p?相似文献   

HIV/AIDS among pastoralists and refugees in north-east Africa: a neglected problem

The eight member states (Djibouti, Eritrea, Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) of the Intergovernmental Authority for Development (IGAD) have the largest proportions of cross-border mobile pastoralists and refugees in Africa. Although all IGAD countries have had national HIV/AIDS prevention, care and treatment programmes since the late 1980s, the IGAD Regional HIV & AIDS Partnership Program was (IRAPP) established in 2007 to mitigate the challenges of HIV among neglected pastoral and refugee communities. This article assesses vulnerability of pastoralists and refugee communities to HIV and interventions targeting these groups in the IGAD countries. Outcomes from this study may serve as a baseline for further research and to improve interventions. Published articles were accessed through web searches using PubMed and Google Scholar engines and unpublished documents were collected manually. The search terms were HIV risk behaviour, vulnerability, HIV prevalence and interventions, under the headings pastoralists, refugees, IGAD and north-east Africa for the period 2001–2014. Of the 214 documents reviewed, 78 met the inclusion criteria and were included. Most HIV/AIDS related studies focusing of pastoral communities in IGAD countries were found to be limited in scope and coverage but reveal precarious situations. Sero-prevalence among various pastoral populations ranged from 1% to 21% in Ethiopia, Kenya, Somalia and Uganda and from 1% to 5% among refugees in Sudan, Kenya and Uganda. Socioeconomic, cultural, logistic, infrastructure and programmatic factors were found to contribute to continuing vulnerability to HIV. Interventions need to be further contextualised to the needs of those impoverished populations and integrated into national HIV/AIDS programmes. HIV/AIDS remains a major public health concern among the pastoral and refugee communities of IGAD countries. This calls for IGAD to collaborate with national and international partners in designing and implementing more effective prevention and control programmes. Furthermore, interventions must extend beyond the health sector and improve the livelihood of these populations.     

A randomized double blind study to evaluate efficacy of palonosetron with dexamethasone versus palonosetron alone for prevention of postoperative and postdischarge nausea and vomiting in subjects undergoing laparoscopic surgeries with high emetogenic risk

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common occurrences (50%-80%) after laparoscopic surgery. Palonosetron (Pal), the newest 5-HT3 antagonist, is an effective antiemetic that has advantages in treating PDNV due to its prolonged duration of action. We hypothesized that a combination of Pal and dexamethazone (Dex) could further improve the efficacy of the treatment in comparison to Pal alone in patients at high risk for PONV. Patients scheduled to undergo laparoscopic surgeries under general anesthesia were randomized to receive 8-mg dexamethasone + 0.075-mg palonosetron (Pal + Dex) or an equivalent volume of saline + 0.075 mg palonosetron (Pal). Data was collected at defined postoperative times (2, 6, 12, 24, and 72 hours). All patients also completed an 18-question QOL-Functional Living Index-Emesis instrument at 96 hours. We enrolled 118 patients, ASA 1-2, with at least 3 PONV risk factors, who were undergoing outpatient surgery. Both groups had a low incidence of vomiting in the PACU (Pal + Dex, 1.7%; Pal, 6.8%) and at 72 hours (0.0% both groups). Complete response (no vomiting, no rescue medication) was not different between treatment groups for any time intervals. Cumulative success rates over the entire 72 hours were 60.4% (Pal + Dex) versus 60.0% (Pal). The Pal + Dex group showed a trend toward greater satisfaction on the QOL- Functional Living Index-Emesis scores with the greatest differences in the "nausea domain". The combination therapy of palonosetron + dexamethasone did not reduce the incidence of PONV or PDNV when compared with palonosetron alone. There was no change in comparative efficacy over 72 hours, most likely due to the low incidence of PDNV in both groups.