"They Just Tell Me to Abstain:" Variable Access to and Uptake of Sexual and Reproductive Health Services Among Adolescents Living With HIV in Kenya.

Background: To improve holistic care for adolescents living with HIV (ALHIV), including integration of sexual and reproductive health services (SRHS), the Kenya Ministry of Health implemented an adolescent package of care (APOC). To inform optimized SRH service delivery, we sought to understand the experiences with SRHS for ALHIV, their primary caregivers, and health care workers (HCWs) following APOC implementation. Methods: We completed a mixed methods evaluation to characterize SRHS provided and personal experiences with access and uptake using surveys conducted with facility managers from 102 randomly selected large HIV treatment facilities throughout Kenya. Among a subset of 4 APOC-trained facilities in a high burden county, we conducted in-depth interviews (IDIs) with 40 ALHIV and 40 caregivers of ALHIV, and 4 focus group discussions (FGDs) with HCWs. Qualitative data was analyzed using thematic analysis. Facility survey data was analyzed using descriptive statistics. Results: Of 102 surveyed facilities, only 56% reported training in APOC and 12% reported receiving additional adolescent-related SRHS training outside of APOC. Frequency of condom provision to ALHIV varied, with 65% of facilities providing condoms daily and 11% never providing condoms to ALHIV. Family planning (FP) was provided to ALHIV daily in 60% of facilities, whereas 14% of facilities reported not providing any FP services to ALHIV. Screening and treatment for STIs for adolescents were provided at all clinics, with 67% providing STI services daily. Three key themes emerged characterizing experiences with adolescent SRHS access and uptake: (1) HCWs were the preferred source for SRH information, (2) greater adolescent autonomy was a facilitator of SRH discussions with HCWs, and (3) ALHIV had variable access to and limited uptake of SRHS within APOC-trained health facilities. The primary SRHS reported available to ALHIV were abstinence and condom use education. There was variable access to FP, condoms, pregnancy and STI testing, and partner services. Adolescents reported limited utilization of SRHS beyond education. Conclusions: Our results indicate a gap in SRHS offered within APOC trained facilities and highlight the importance of adolescent autonomy when providing SRHS and further HCW training to improve SRHS integration within HIV care for ALHIV.

Optimising the use of EEG in non-epileptic attack disorder: Results of a UK national service evaluation.

PURPOSE: To produce an evidence base to formulate guidelines for optimal performance of EEG in patients referred with a possible diagnosis of non-epileptic attack disorder (NEAD). METHODS: 51 UK EEG departments participated in the prospective study. A pro-forma was completed for all consecutive patients aged 5 years and over referred for EEG over a six month period. Information obtained included referral diagnosis, occurrence/type of attack during EEG, the use of suggestion, length of recording and who was present during the EEG. RESULTS: 11,298 patients were entered into the study. 376 psychogenic non-epileptic seizures (PNES) occurred of which 337 were considered to be of the habitual type. In those patients suspected of having NEAD prior to referral, the use of verbal suggestion increased the yield of habitual attacks by a factor of three in both adults and children. Using suggestive techniques twice, improved the yield further. Non-habitual attacks occurred equally whether or not suggestion was used. At least 90% of habitual PNES occurred within the first 30 min of recording even in those patients having prolonged EEGs. In EEGs where additional professional personnel were present, PNES occurred more frequently. CONCLUSION: This large multicentre study provides evidence to inform recommendations for EEG to investigate NEAD. We recommend the use of verbal suggestion at least twice and where practical the presence of additional professional staff. A thirty minute recording is sufficient to record a habitual PNES in most instances.

Compounds identified by virtual docking to a tetrameric EGFR extracellular domain can modulate Grb2 internalization.

BACKGROUND: Overexpression or mutation of the epidermal growth factor receptor (EGFR) potently enhances the growth of many solid tumors. Tumor cells frequently display resistance to mechanistically-distinct EGFR-directed therapeutic agents, making it valuable to develop therapeutics that work by additional mechanisms. Current EGFR-targeting therapeutics include antibodies targeting the extracellular domains, and small molecules inhibiting the intracellular kinase domain. Recent studies have identified a novel prone extracellular tetrameric EGFR configuration, which we identify as a potential target for drug discovery. METHODS: Our focus is on the prone EGFR tetramer, which contains a novel protein-protein interface involving extracellular domain III. This EGFR tetramer is computationally targeted for stabilization by small molecule ligand binding. This study performed virtual screening of a Life Chemicals, Inc. small molecule library of 345,232 drug-like compounds against a molecular dynamics simulation of protein-protein interfaces distinct to the novel tetramer. One hundred nine chemically diverse candidate molecules were selected and evaluated using a cell-based high-content imaging screen that directly assessed induced internalization of the EGFR effector protein Grb2. Positive hits were further evaluated for influence on phosphorylation of EGFR and its effector ERK1/2. RESULTS: Fourteen hit compounds affected internalization of Grb2, an adaptor responsive to EGFR activation. Most hits had limited effect on cell viability, and minimally influenced EGFR and ERK1/2 phosphorylation. Docked hit compound poses generally include Arg270 or neighboring residues, which are also involved in binding the effective therapeutic cetuximab, guiding further chemical optimization. CONCLUSIONS: These data suggest that the EGFR tetrameric configuration offers a novel cancer drug target.

Osteopenia in children who have undergone posterior fossa or craniospinal irradiation for brain tumors.

OBJECTIVES: To determine lumbar spine and total body bone mineral density (BMD) in pediatric patients who have undergone cranial or craniospinal irradiation for posterior fossa tumors, specifically medulloblastoma and ependymoma and to analyze the association between degree of osteopenia and factors that may affect BMD. METHODS: Retrospective and prospective data collection included medical record review and examination, including pubertal, dietary, and activity assessment. Lumbar spine and total body BMD were measured by means of dual energy x-ray absorptiometry. Patients were routinely observed by the endocrinology department, and hormone deficiencies were corrected promptly. A subset of patients received calcium and vitamin D supplementation and underwent repeat BMD measurement 1 year later. RESULTS: Of 24 patients aged 4 to 20 years, 11 of whom were male, recruited from 1996 through 1999, 19 had medulloblastoma. All 19 underwent craniospinal radiotherapy plus a boost to the posterior fossa (mean +/- SD of 5410 +/- 130 rad [54.1 +/- 1.3 Gy] to the posterior fossa, mean +/- SD of 3470 +/- 460 rad [34.7 +/- 4.6 Gy] to the whole brain and spinal axis), and 8 of 19 underwent chemotherapy. The remaining 5 patients had ependymoma and underwent irradiation to the posterior fossa only (mean +/- SD of 5680 +/- 720 rad [56.8 +/- 7.2 Gy]). Therefore, there were 3 treatment groups: craniospinal irradiation and chemotherapy, only craniospinal irradiation, and only posterior fossa irradiation. Bone mineral studies were performed a mean +/- SD of 5.42 +/- 3.23 years after therapy. Our patients had lower total body BMD (mean z score, -0.47; 95% confidence interval, -0.85 to -0.09) and lumbar spine BMD (mean z score, -1.27; 95% confidence interval, -1.81 to -0.73) as compared with those of the the general population. There was no significant difference in mean lumbar spine BMD between patients in the 3 groups. Our patients consumed a diet deficient in vitamin D and calcium (mean +/- SD 53.6% +/- 24.1% and 70.0% +/- 37.4% of the amount recommended, respectively). Of 7 patients who underwent measurements 1 year later, 5 had in increase in BMD that was parallel to normal curves, with no compensatory increase. Four patients were hypothyroid, 6 were growth hormone deficient, and 6 were both. All hormones were replaced, with the exception of growth hormone in 1 patient. By using regression analysis, the factors that affected lumbar spine BMD, protectively in both cases, were calcium intake (beta = 0.015, 95% confidence interval, 0.001-0.029) and female sex (beta = 1.422, 95% confidence interval, 0.456-2.388). CONCLUSIONS: Children who have undergone irradiation for posterior fossa tumors have diminished total body and lumbar spine BMD, as compared with those of the general population. This reduction was similar within all 3 treatment groups, which suggests that chemotherapy did not play a major role and that localized irradiation may have systemic effects. This population often has balance and gait problems, so the risk of falling, coupled with osteopenia, may place them at considerably increased risk of fractures.