The development of a social-sexual education program for adults with neurodevelopmental disabilities: starting the discussion

Sexuality and Disability - People with neurodevelopmental disabilities, including intellectual disabilities and autism, want to have relationships but few are given the tools and opportunity to...     

A randomized controlled trial evaluating combination detection of HIV in Malawian sexually transmitted infections clinics

IntroductionHIV diagnosis is the necessary first step towards HIV care initiation, yet many persons living with HIV (PLWH) remain undiagnosed. Employing multiple HIV testing strategies in tandem could increase HIV detection and promote linkage to care. We aimed to assess an intervention to improve HIV detection within socio‐sexual networks of PLWH in two sexually transmitted infections (STI) clinics in Lilongwe, Malawi.MethodsWe conducted a randomized controlled trial to evaluate an intervention combining acute HIV infection (AHI) screening, contract partner notification and social contact referral versus the Malawian standard of care: serial rapid serological HIV tests and passive partner referral. Enrolment occurred between 2015 and 2019. HIV‐seropositive persons (two positive rapid tests) were randomized to the trial arms and HIV‐seronegative (one negative rapid test) and ‐serodiscordant (one positive test followed by a negative confirmatory test) persons were screened for AHI with HIV RNA testing. Those found to have AHI were offered enrolment into the intervention arm. Our primary outcome of interest was the number of new HIV diagnoses made per index participant within participants’ sexual and social networks. We also calculated total persons, sexual partners and PLWH (including those previously diagnosed) referred per index participant.ResultsA total of 1230 HIV‐seropositive persons were randomized to the control arm, and 561 to the intervention arm. Another 12,713 HIV‐seronegative or ‐serodiscordant persons underwent AHI screening, resulting in 136 AHI cases, of whom 94 enrolled into the intervention arm. The intervention increased the number of new HIV diagnoses made per index participant versus the control (ratio: 1.9; 95% confidence interval (CI): 1.2 to 3.1). The intervention also increased the numbers of persons (ratio: 2.5; 95% CI: 2.0 to 3.2), sexual partners (ratio: 1.7; 95% CI: 1.4 to 2.0) and PLWH (ratio: 2.3; 95% CI: 1.7 to 3.2) referred per index participant.ConclusionsCombining three distinct HIV testing and referral strategies increased the detection of previously undiagnosed HIV infections within the socio‐sexual networks of PLWH seeking STI care. Combination HIV detection strategies that leverage AHI screening and socio‐sexual contact networks offer a novel and efficacious approach to increasing HIV status awareness.     

Understanding the financial impact of a diagnosis of young onset dementia on individuals and families in the United Kingdom: Results of an online survey

Although literature on postdiagnostic support for people affected by young onset dementia acknowledges financial concerns, this topic has remained underresearched. The aim of this study was to explore the financial impact of a diagnosis of young onset dementia on individuals and families. An online survey, comprising binary yes/no, multiple-response and open-ended questions, was codesigned with people living with young onset dementia. The survey was promoted via networks and online platforms. Data were collected from August to October 2019. Survey respondents across the United Kingdom (n = 55) who had received a diagnosis of young onset dementia were aged between 45 and 64, were at different stages of dementia and had been diagnosed with thirteen different types of dementia. Of the 55 respondents, 71% (n = 39) had received assistance from family members when completing the survey. The main financial impact of a diagnosis of young onset dementia resulted from premature loss of income and reduced and often deferred pension entitlements. In some cases, care-costs became unaffordable. Lack of clarity of processes and procedures around needs assessments, carers' assessments and financial assessments by different organisations resulted in some families having to ask for legal advice and, in some cases, involved lengthy appeal processes. Future research needs to involve Adult Social Care and Third Sector organisations to help codesign and test financial management interventions to support people affected by this progressive health condition.     

Supportive and Negative Responses in the Partner Relationship: Their Association with Psychological Adjustment Among Individuals with Cancer

This study examined the association between positive and negative aspects of spouse responses and psychological adjustment among 15S individuals with cancer. Two contextual variables, gender and disease-related functional impairment, were taken into account when examining the association between spouse responses and patient psychological distress and well-being. Results indicated that negative aspects of close relationships played a comparatively stronger role than positive aspects in their associations with both psychological distress and well-being. For negative spouse responses, patient gender did not moderate the effects of these responses upon psychological outcomes. For positive aspects of spouse support, both gender and functional disability moderated the association between spouse support and psychological outcomes. These findings are integrated with the general literature on positive and negative aspects of close relationships. Implications for clinical interventions are also discussed.     

Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties

1. 15-Lipoxygenase (15-LO) has been implicated in the pathogenesis of atherosclerosis because of its localization in lesions and the many biological activities exhibited by its products. To provide further evidence for a role of 15-LO, the effects of PD 146176 on the development of atherosclerosis in cholesterol-fed rabbits were assessed. This novel drug is a specific inhibitor of the enzyme in vitro and lacks significant non specific antioxidant properties.
2. PD 146176 inhibited rabbit reticulocyte 15-LO through a mixed noncompetitive mode with a K_i of 197 nM. The drug had minimal effects on either copper or 2,2′-azobis(2-amidinopropane)hydrochloride (ABAP) induced oxidation of LDL except at concentrations 2 orders higher than the K_i.
3. Control New Zealand rabbits were fed a high-fat diet containing 0.25% wt./wt. cholesterol; treated animals received inhibitor in this diet (175 mg kg⁻¹, b.i.d.). Plasma concentrations of inhibitor were similar to the estimated K_i (197 nM). During the 12 week study, there were no significant differences in weight gain, haematocrit, plasma total cholesterol concentrations, or distribution of lipoprotein cholesterol.
4. The drug plasma concentrations achieved in vivo did not inhibit low-density lipoprotein (LDL) oxidation in vitro. Furthermore, LDL isolated from PD 146176-treated animals was as susceptible as that from controls to oxidation ex vivo by either copper or ABAP.
5. PD 146176 was very effective in suppressing atherogenesis, especially in the aortic arch where lesion coverage diminished from 15±4 to 0% (P<0.02); esterified cholesterol content was reduced from 2.1±0.7 to 0 μg mg⁻¹ (P<0.02) in this region. Immunostainable lipid-laden macrophages present in aortic intima of control animals were totally absent in the drug-treated group.
6. Results of these studies are consistent with a role for 15-LO in atherogenesis.

     

The effect of midazolam on median nerve somatosensory evoked potentials

Objective. To quantify the effect of an induction dose of midazolam on median nerve somatosensory evoked potentials.Methods. We studied 10 patients undergoing lumbar spine surgery. After an induction dose of intravenous midazolam was given, MNEPs were collected for ten minutes. After ten minutes the patients were intubated and their anesthetic was supplemented with 0.5% isoflurane, narcotic, and N₂O.Results. We found a clinically significant decrease in amplitude and an insignificant delay in latency.Conclusion. When midazolam is used as an anesthetic induction agent, a decrease in amplitude can be expected.     

Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer

The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m², peak plasma concentration 5.6±2.5 g/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal E_max equation. A good fit was found between day 1 AUC and neutrophil toxicity (R ²=0.77). All patients who had a day 1 AUC>2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m²). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R ²=98.9%). The equation AUC_pr=–0.376+0.631×C_4h+0.336×C_6h was validated on the test set with a relative mean predictive error of –0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Locked Bag 1, A'Beckett St, Melbourne 3000, Australia     

Current management of AIDS related non Hodgkin’s lymphoma

Non Hodgkin’s lymphoma is the AIDS defining illness in 3-3.5% of patients and is increasing in incidence as the survival of HIV infected people improves. The incidence of these intermediate/high grade B cell malignancies is sixty times higher than in the general population. The most important prognostic factors are a CD4 positive lymphocyte count of <100 cells/mm3, a prior AIDS defining diagnosis, an ECOG performance status >2 and primary cerebral origin. Patients with any of these factors are most likely to benefit from palliative rather than radical treatment. Good prognosis patients have a 30-40% chance of cure from their lymphoma with carefully administered intensive chemotherapy.