Children\u27s memory for painful procedures: the relationship of pain intensity, anxiety, and adult behaviors to subsequent recall.

OBJECTIVE: To examine whether children\u27s experience of pain intensity and anxiety, and adult behaviors during venepuncture, were related to children\u27s memories of the procedure. METHODS: Participants were 48 children (24 males, 24 females) between the ages of 5 and 10 years who underwent venepuncture. The venepunctures were videotaped and adult behaviors were coded. Children self-reported their pain intensity and anxiety immediately and 2 weeks following venepuncture and answered contextual questions at follow-up. RESULTS: Children who initially reported higher levels of pain tended to over-estimate their anxiety at follow-up, whereas children who reported lower levels of pain accurately- or under-estimated their anxiety. Staff coping-promoting behaviors predicted the accuracy of children\u27s contextual memories. Staff and parent behaviors did not predict children\u27s recalled pain intensity and anxiety. CONCLUSIONS: Results indicate that children\u27s direct experience of pain intensity and staff behaviors during venepuncture are related to their memories. These data highlight the importance of effective pain management during medical procedures

Parent–child interactions during pediatric venipuncture: Investigating the role of parent traits, beliefs, and behaviors in relation to child outcomes

Background: The social context is critical to children’s pain, and parents frequently form a major aspect of this context. We addressed several gaps in our understanding of parent–child interactions during painful procedures and identified intrapersonal contributions to parental affective responses and behaviors. We used the pain empathy model framework to examine parent–child interactions during venipuncture to determine predictors of parent distraction and reassurance. Aims: We examined relations among parent and child behaviors along with parent fear and child pain and fear. We empirically tested the contribution of top-down influences in predicting the use of two common parent utterances, reassurance and distraction during venipuncture, including parent beliefs about these behaviors. Methods: Venipunctures of 100 5- to 10-year-old children were filmed, and parent–child interactions were coded using the full 35 item Child Adult Medical Procedure Interaction Scale. Two codes were of particular interest: reassurance and distraction. Self-report measures included child fear and pain, parent fear, trait anxiety, empathy, pain catastrophizing, and beliefs about reassurance and distraction. Results: Findings supported original Child–Adult Medical Procedure Interaction Scale codes linking parent “distress-promoting” behaviors with poorer child outcomes and parent “coping-promoting” behaviors with improved child outcomes. Parent traits accounted for a small portion of the variance in parent reassurance and distraction. Conclusions: Findings are consistent with research on coping and distress promoting behaviors. Using a novel framework of the pain empathy model, we found that parent traits largely did not predict their procedural behaviors, which were more strongly related to child distress behaviors during the needle and parent beliefs about the behaviors

Metals and metallothionein in the liver of raccoons: utility for environmental assessment and monitoring

The relationship between metallothionein levels and concentrations of several metals and radionuclides was examined in liver tissues of raccoons (Procyon lotor, n = 47) from the Department of Energy’s Savannah River Site in South Carolina to determine the applicability of metallothioneins as an initial screening device for exposure assessment in free-living mammals and environmental monitoring. Using a fluorescent marker and a cell sorter to measure metallothionein, a significant positive correlation was found across animals between levels of metallothioneins and concentrations of selenium (Pearson’s r = .30) , mercury (Pearson’s r = .31) , and copper (Pearson’s r = .30) in liver tissue. Arsenic, cobalt, silver, thallium, and tin were below detection limits in most or all liver samples. Other metals, including cadmium, chromium, radiocesium ( 137Cs) , copper, lead, manganese, strontium, and vanadium, showed only weak and nonsignificant correlations with metallothionein. Concentrations of mercury were correlated with concentrations of selenium (Pearson’s r = .73) , manganese (Pearson’s r = .56) , and strontium (Pearson’s r = .57). In an a posteriori test, there was a still unexplained positive correlation between mercury (Pearson r = .56) , selenium (Pearson r = .54) , and radiocesium (Pearson’s r = .38) concentrations and background cellular autofluorescence, and a negative correlation of strontium with the latter (Kendall tau = –.38) . Background cellular autofluorescence may represent a generalized cellular stress response, or a yet unidentified biomarker. To better understand which metals contribute to the induction of metallothionein, principle component analysis (PCA) was performed. The first three principle components explained 78% of the variance, with highest loadings being from mercury and radiocesium. Metallothionein levels did not correlate well with the principal components from the metals and radiocesium, while autofluorescent background levels tended to correlate better

Pre-treatment HIV-drug resistance associated with virologic outcome of first-line NNRTI-antiretroviral therapy: A cohort study in Kenya

Background: Pre-treatment HIV-drug-resistance (PDR) to WHO-recommended 1st-line non-nucleoside reverse transcriptase inhibitors (NNRTI)-based antiretroviral treatment (ART) is increasing in low-resource communities. We evaluated the risk of PDR on treatment failure if detected at single or multiple codons, at minority (2–9%) or higher (≥10%) frequencies during efavirenz- vs. nevirapine-ART. Methods: We conducted a pooled analysis across three cohorts of Kenyans initiating 1st-line NNRTI-ART between 2006 and 2014. Mutations K103N, Y181C, G190A, M184V and K65R were detected by an oligonucleotide ligation assay (OLA) and confirmed by Sanger and next-generation sequencing (NGS). PDR was defined as detection of any mutation by OLA when confirmed by NGS. Treatment failure, defined as plasma HIV RNA ≥400 copies/mL at month-12 of ART, was compared by PDR genotypes. Findings: PDR was detected in 59/1231 (4·8%) participants. Compared to wild-type genotypes, PDR in participants prescribed nevirapine-ART was associated with increased treatment failure [PDR 69·2% (27/39) vs. wild-type 10·4% (70/674); p = 0·0001], whether detected as minority [66·7% (4/6)] or higher [69·7% (23/33)] frequencies in an individual\u27s HIV quasispecies (p = 0·002 and p \u3c 0·0001, respectively), or mutations at single [50·0% (12/24)] or multiple [100·0% (15/15)] codons (p \u3c 0·0001). During efavirenz-ART, PDR was also associated with increased virologic failure [PDR 25·0% (5/20) vs. wild-type 5·0% (25/498); p = 0·005], but only if detected at multiple drug-resistant codons [50·0% (3/6); p = 0·003] or high frequencies PDR [33·3% (5/15); p = 0·001]. Interpretation: The risk that PDR confers for treatment failure varies by number of mutant codons and their frequency in the quasispecies, with a lower risk for efavirenz- compared to nevirapine-based regimens. PDR detection and management could extend the effective use of efavirenz-ART in low-resource settings. Funding: NIH, PEPFAR

Partner Disclosure and Early CD4 Response among HIV-Infected Adults Initiating Antiretroviral Treatment in Nairobi Kenya

Background: Disclosure of HIV serostatus can have significant benefits for people living with HIV/AIDS. However, there is limited data on whether partner disclosure influences ART treatment response. Methods: We conducted a retrospective cohort study of newly diagnosed, ART-naïve HIV-infected adults (\u3e18 years) who enrolled at the Coptic Hope Center in Nairobi, Kenya between January 1st2009 and July 1st 2011 and initiated ART within 3 months. Analysis was restricted to adults who reported to have either disclosed or not disclosed their HIV status to their partner. Analysis of CD4 response at 6 and 12 months post-ART was stratified by age group. Results: Among 615 adults newly initiating ART with partner disclosure data and 12 month follow-up, mean age was 38 years and 52% were male; 76% reported that they had disclosed their HIV-status to their partner. Those who disclosed were significantly younger and more likely to be married/cohabitating than non-disclosers. At baseline, median CD4 counts were similar between disclosure groups. Among younger adults (\u3c 38 years) those who disclosed had higher CD4 recovery than those who did not at 6 months post- ART (mean difference = 31, 95% CI 3 to 58 p = 0.03) but not at 12 months (mean difference = 17, 95% CI -19 to 52, p = 0.4). Among older adults (≥ 38years) there was no observed difference in CD4 recovery at 6 or 12 months between disclosure groups. Conclusion: Among younger adults, disclosure of HIV status to partners may be associated with CD4 recovery following ART

Risk Factors for Hypoxia and Tachypnea Among Adolescents With Vertically-acquired HIV in Nairobi

Background: Chronic lung diseases are increasingly recognized complications of vertically-acquired HIV among adolescents in sub-Saharan Africa and may manifest with hypoxia or tachypnea. We sought to determine the prevalence of and risk factors for hypoxia and tachypnea among adolescents with vertically-acquired HIV in Nairobi, Kenya. Methods: We performed a cross-sectional analysis of 258 adolescents with vertically-acquired HIV who were initiating care at the Coptic Hope Center for Infectious Diseases. Adolescents with documented pneumonia were excluded. Hypoxia was defined as resting oxygen saturation ≤92%, and tachypnea was based on the 99th percentile of age-appropriate respiratory rates. Logistic regression models adjusted for demographics, and HIV severity estimated odds ratios for risk of hypoxia and tachypnea associated with potential risk factors. Results: Overall, 11% of adolescents had hypoxia and 55% had tachypnea. Advanced HIV [adjusted odds ratio (aOR): 2.41] and low CD4 (aOR: 1.74) were associated with greater hypoxia risk, but confidence intervals (CIs) were wide and included the null (95% CI: 0.93–6.23 and 0.69–4.39, respectively). Low CD4 (aOR: 2.45, 95% CI: 1.39–4.32), current antiretroviral therapy use (aOR: 0.48, 95% CI: 0.27–0.86) and stunted growth (aOR: 3.46, 95% CI: 1.94–6.18) were associated with altered tachypnea risk. Conclusions: Hypoxia and tachypnea are common among adolescents with vertically-acquired HIV. There was a suggestion that advanced HIV and low CD4 were associated with greater hypoxia risk. Low CD4, lack of antiretroviral therapy use and stunted growth are risk factors for tachypnea. Our findings highlight the chronic lung disease burden in this population and may inform diagnostic algorithms

Increased Cervical Human Immunodeficiency Virus (HIV) RNA Shedding Among HIV-Infected Women Randomized to Loop Electrosurgical Excision Procedure Compared to Cryotherapy for Cervical Intraepithelial Neoplasia 2/3

Background Treatment of human immunodeficiency virus (HIV)–infected women to prevent cervical cancer may stimulate HIV RNA cervical shedding and risk HIV transmission. Methods From 2011 to 2014, 400 HIV-infected women diagnosed with cervical intraepithelial neoplasia 2/3 in Kenya were randomized to loop electrosurgical excision procedure (LEEP) or cryotherapy. Cervical samples were collected at baseline and 3 weekly intervals. Samples were tested for HIV RNA using the Gen-Probe Aptima HIV assay with a minimum detection level of 60 copies/swab and analyzed using generalized estimating equations. Results Women who received LEEP had significantly higher cervical HIV RNA levels than those who received cryotherapy at weeks 2 (adjusted incident rate ratio [aIRR], 1.07; P = .038) and 3 (aIRR, 1.08; P = .046). Within LEEP, significantly higher cervical shedding was found at weeks 2 (2.03 log10 copies/swab; P < .001) and 3 (2.04 log10 copies/swab; P < .001) compared to baseline (1.80 log10 copies/swab). Cervical HIV RNA was significantly higher following LEEP for up to 3 weeks among women on antiretroviral treatment (ART) (0.18 log10 copies/swab increase; P = .003) and in ART-naive women (1.13 log10 copies/swab increase; P < .001) compared to baseline. Within cryotherapy, cervical shedding increased in ART-naive women (0.72 log10 copies/swab increase; P = 0.004) but did not increase in women on ART. Conclusions Women randomized to LEEP had a larger increase in post-procedural cervical HIV shedding than cryotherapy. Benefits of cervical cancer prevention outweigh the risk of HIV sexual transmission; our findings underscore the importance of risk-reduction counseling

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits