Positive predictive value of fecal occult blood testing in persons taking warfarin

BACKGROUND: In clinical practice, some physicians discontinue warfarin prior to fecal occult blood testing (FOBT). Although anticoagulant use is associated with an increased risk of overt gastrointestinal bleeding, the impact of warfarin on the positive predictive value of FOBT is unknown. METHODS: During a 5-yr period, we prospectively studied all patients taking warfarin who were referred for the evaluation of a positive FOBT. For each patient taking warfarin, we enrolled one age- and gender-matched control subject with a positive FOBT who was not taking anticoagulants. A detailed clinical history was obtained, and all subjects underwent colonoscopy and esophagogastroduodenoscopy. RESULTS: Lesions consistent with occult bleeding were identified in 59.0% of the 210 patients in the warfarin group and 53.8% of the 210 control subjects (p= 0.27). Although more lesions were identified by colonoscopy in the warfarin group than in control subjects (36.2%vs 25.7%, p= 0.02), there was no difference in the frequency of lesions identified by esophagogastroduodenoscopy (35.2%vs 39.5%, p= 0.43). Overall, adenomas > or =1 cm in diameter (16.2%) and colorectal carcinoma (9.5%) were the most common lesions identified by colonoscopy, while erosive gastritis (15.5%) and erosive duodenitis (11.0%) were the most frequent lesions found by esophagogastroduodenoscopy. Among individuals with colorectal cancer, 83.3% of patients in the warfarin group had early cancers (Dukes' stage A or B) compared with 50.0% of control subjects (p= 0.046). CONCLUSIONS: Warfarin use did not decrease the positive predictive value of FOBT. These findings suggest that warfarin should not be discontinued prior to FOBT.     

A cluster randomized controlled trial of visual, cytology and human papillomavirus screening for cancer of the cervix in rural India

The impact of screening by visual inspection with acetic acid (VIA), cytology or HPV testing on cervical cancer incidence and mortality is investigated in a cluster randomized controlled trial in India. We report findings after the screening phase, when 52 clusters, with a total of 142,701 women aged 30-59 years in Osmanabad District, India, were randomized into 4 arms for a single round of screening by trained midwives with either VIA, cytology or HPV testing as well as a control group. All laboratory tests were done locally. Test-positive women underwent investigations (colposcopy/biopsy) and treatment in the base hospital. Data on participation, test positivity, positive predictive value and detection rates of cervical neoplasia were analyzed using cluster design methodology. Of the eligible women, 72-74% were screened. Test positivity rates were 14.0% for VIA, 7.0% for cytology and 10.3% for HPV. The detection rate of high-grade lesions was similar in all intervention arms (0.7% for VIA, 1.0% for cytology and 0.9% for HPV testing) (p = 0.06, Mann-Whitney test). While the detection rate for VIA dropped to 0.5% with declining test positivity during the course of the study, it remained constant for cytology and HPV testing. Over 85% of women with high-grade lesions received treatment. Our results show that a high level of participation and good-quality cytology can be achieved in low-resource settings. VIA is a useful alternative but requires careful monitoring. Detection rates obtained by HPV testing were similar to cytology, despite higher investments.     

External inferior colliculus integrates trigeminal and acoustic information: unit responses to trigeminal nucleus and acoustic stimulation in the guinea pig

The external nucleus of the inferior colliculus (ICx) receives ascending projections from both auditory and somatosensory nuclei. In the guinea pig, both the spinal trigeminal nucleus (TN) and the cochlear nucleus converge in the ventrolateral region of ICx. We investigated the function of trigeminal-collicular pathways by electrically stimulating the TN while recording unit responses from ICx. Pairing electrical stimulation with acoustic stimuli allowed us to investigate the function of converging auditory and somatosensory inputs, i.e. multisensory integration. Unit responses were recorded from ICx using a multi channel, single shank electrode. Electrical stimulation of the TN produced small changes above or below spontaneous rate, but resulted in significant suppression or enhancement of sound-evoked responses. Multisensory integration has been demonstrated in the dorsal cochlear nucleus (DCN), superior colliculus and sensory cortices and may play a role in plasticity that occurs after sensory deprivation.     

Cerebral myogenic reactivity and blood flow in type 2 diabetic rats: role of peroxynitrite in hypoxia-mediated loss of myogenic tone

Dysregulation of cerebral vascular function and, ultimately, cerebral blood flow (CBF) may contribute to complications such as stroke and cognitive decline in diabetes. We hypothesized that 1) diabetes-mediated neurovascular and myogenic dysfunction impairs CBF and 2) under hypoxic conditions, cerebral vessels from diabetic rats lose myogenic properties because of peroxynitrite (ONOO(-))-mediated nitration of vascular smooth muscle (VSM) actin. Functional hyperemia, the ability of blood vessels to dilate upon neuronal stimulation, and myogenic tone of isolated middle cerebral arteries (MCAs) were assessed as indices of neurovascular and myogenic function, respectively, in 10- to 12-week control and type 2 diabetic Goto-Kakizaki rats. In addition, myogenic behavior of MCAs, nitrotyrosine (NY) levels, and VSM actin content were measured under normoxic and hypoxic [oxygen glucose deprivation (OGD)] conditions with and without the ONOO(-) decomposition catalyst 5,10,15,20-tetrakis(4-sulfonatophenyl) prophyrinato iron (III), chloride (FeTPPs). The percentage of myogenic tone was higher in diabetes, and forced dilation occurred at higher pressures. Functional hyperemia was impaired. Consistent with these findings, baseline CBF was lower in diabetes. OGD reduced the percentage of myogenic tone in both groups, and FeTPPs restored it only in diabetes. OGD increased VSM NY in both groups, and although FeTPPs restored basal levels, it did not correct the reduced filamentous/globular (F/G) actin ratio. Acute alterations in VSM ONOO(-) levels may contribute to hypoxic myogenic dysfunction, but this cannot be solely explained by the decreased F/G actin ratio due to actin nitration, and mechanisms may differ between control and diabetic animals. Our findings also demonstrate that diabetes alters the ability of cerebral vessels to regulate CBF under basal and hypoxic conditions.     

Changes in the sexual health behaviours of New Zealand secondary school students, 2001–2012: findings from a national survey series

Objective : To describe trends in self‐reported sexual and reproductive health behaviours among New Zealand secondary school students. Methods : Nationally representative health and wellbeing surveys conducted in 2001 (n=9,699), 2007 (n=9,107) and 2012 (n=8,500) were analysed. Logistic regressions were used to explore variations in sexual health outcomes between 2001 and 2012. Results : ‘Ever had sex’ (?6.9%, p<0.001); ‘currently sexually active’ (? 2.3%, p<0.001); ‘always use condoms’ (?3.3%, p=0.006); ‘condoms at last sex’ (?7.0, p=0.002); ‘contraception at last sex’ (?5.8%, p<0.001) and sexually transmitted infections (?0.3%, p=0.001) have reduced over time. ‘Always use contraception’ did not change significantly (?1.4%, p=0.514) over time. Māori (OR 0.7), Pacific (OR 0.5) and socioeconomically deprived students (OR 0.7) less frequently used condoms. Māori (OR 0.6), Pacific (OR 0.4), Asian (OR 0.5), younger (OR 0.6), and socioeconomically deprived (OR 0.6) students less frequently used contraception. Conclusions : Students in 2012 were more likely to delay sexual activity, but were less likely to use condoms and contraception consistently, compared to students in 2001. Declining contraceptive use over an 11‐year period suggests that current strategies are inadequate, particularly for Māori, Pacific and socioeconomically deprived students. Appropriate and accessible sexual and reproductive health services are urgently required.