Brian Perry

Complication rate of minimally invasive cochlear implantation

Objectives To assess the complication rate of minimally invasive cochlear implantation (MICI). Study Design and Setting Data for this study were obtained via a retrospective analysis of records at the Ear Medical Group, San Antonio, TX, after IRB approval at the University of Texas Health Science Center at San Antonio. The surgical complications of MICI were recorded in a spreadsheet format; 176 patients were included in the study. Results A total of 22 (12.5%) complications were noted in the study. There were 0 life-threatening, 7 major, and 15 minor complications. Of the 7 major complications, 3 were device failures, 2 developed delayed mastoiditis, 1 required receiver/stimulator repositioning, and 1 involved facial paralysis. Conclusions MICI is as safe as standard cochlear implantation (SCI) and affords with it other benefits. Eliminating the scalp flap avoids devascularization and minimizes the opportunity of flap infection or necrosis. Complications not related to the flap are similar to SCI. EBM rating: C-4

Attenuation of Neomycin Ototoxicity by Iron Chelation

Increasing evidence suggests that aminoglycoside ototoxicity is mediated by the formation of an aminoglycoside‐iron complex and that the creation of this complex is a preliminary step in generation of free radical species and subsequent hair cell death. In this study we have assessed the ability of the iron chelator deferoxamine to attenuate the hearing loss induced by an ototoxic dose of the aminoglycoside neomycin (100 mg/kg per day for 14 days). Experiments were carried out on pigmented guinea pigs weighing 250 to 300 g. Changes in auditory sensitivity were characterized by monitoring shifts in compound action potential(CAP) thresholds, recorded through indwelling electrodes implanted at the round window, vertex, and contralateral mastoid. Results show that animals receiving neomycin alone suffered a mean threshold shift exceeding 35 dB at all test frequencies (2.0, 4.0, and 8.0 kHz) 30 days after initiation of treatment. In comparison, all animals receiving cotherapy of neomycin and deferoxamine (150 mg/kg twice daily for 14 days) maintained their CAP threshold, suggesting significant protection from neomycin ototoxicity. A statistical comparison of treatment groups showed that in the animals receiving cotherapy with neomycin and deferoxamine, deferoxamine produced a significant protective effect against neomycin‐induced ototoxicity (P < 0.001). These results provide further evidence of the intrinsic role of iron in aminoglycoside ototoxicity and suggest that deferoxamine may have a therapeutic role in attenuating the cytotoxic action of aminoglycoside antibiotics.

Narrowing critical regions and determining penetrance for selected 18q- phenotypes.

One of our primary goals is to help families who have a child with an 18q deletion anticipate medical issues in order to optimize their childs medical care. To this end we have narrowed the critical regions for four phenotypic features and determined the penetrance for each of those phenotypes when the critical region for that feature is hemizygous. We completed molecular analysis using oligo‐array CGH and clinical assessments on 151 individuals with deletions of 18q and made genotype–phenotype correlations defining or narrowing critical regions. These nested regions, all within 18q22.3 to q23, were for kidney malformations, dysmyelination of the brain, growth hormone stimulation response failure, and aural atresia. The region for dysmyelination and growth hormone stimulation response failure were identical and was narrowed to 1.62 Mb, a region containing five known genes. The region for aural atresia was 2.3 Mb and includes an additional three genes. The region for kidney malformations was 3.21 Mb and includes an additional four genes. Penetrance rates were calculated by comparing the number of individuals hemizygous for a critical region with the phenotype to those without the phenotype. The kidney malformations region was 25% penetrant, the dysmyelination region was 100% penetrant, the growth hormone stimulant response failure region was 90% penetrant with variable expressivity, and the aural atresia region was 78% penetrant. Identification of these critical regions suggest possible candidate genes, while penetrance calculations begin to create a predictive phenotypic description based on genotype.

How to create successful vasectomy programs.

Background While there is considerable variability with respect to attendance at the postpartum visit, not much is known about women’s preferences with respect to postpartum care. Likewise, there is also limited information on providers’ practices regarding the postpartum visit and care including the delivery of contraception. To understand and address deficits in the delivery and utilization of postpartum care, we examined the perceptions of low-income postpartum women with respect to barriers to and preferences for the timing and location of the postpartum visit and receipt of contraception. We also examined providers’ current prenatal and postnatal care practices for promoting the use of postpartum care and their attitudes toward alternative approaches for delivering contraceptive services in the postpartum period. Methods Qualitative face-to-face interviews were completed with 20 postpartum women and in-depth qualitative phone interviews were completed with 12 health care providers who had regular contact with postpartum women. Interviews were coded using Atlas.ti software and themes were identified. Results Women believed that receiving care during the postpartum period was an important resource for monitoring physical and mental health and also strongly supported the provision of contraception earlier than the 6-week postpartum visit. Providers reported barriers to women’s use of postpartum care on the patient, provider, and system levels. However, providers were receptive to exploring new clinical practices that may widen the reach of postpartum care and increase access to postpartum contraception. Conclusion Approaches that increase the flexibility and convenience of postpartum care and the delivery of postpartum contraception may increase the likelihood that women will take advantage of essential postpartum services.

Observational study of the acceptability of Sayana® Press among intramuscular DMPA users in Uganda and Senegal

BACKGROUND Sayana® Press (SP), a subcutaneous formulation of depot medroxyprogesterone acetate (DMPA) in Uniject™, has potential to be a valuable innovation in family planning (FP) because it may overcome logistic and safety challenges in delivering intramuscular DMPA (DMPA IM). However, SPs acceptability is unknown. We measured acceptability of SP among DMPA IM users. STUDY DESIGN This open-label observational study was conducted in clinics in three districts in Senegal and community-based distribution services in two districts in Uganda. Experienced DMPA IM users were offered SP by community health workers (CHWs) or clinic-based providers. SP decliners were asked to discuss their reasons. Those who received SP were interviewed pre- and postinjection and 3 months later, when they were asked if they would select SP over DMPA IM if it were available. RESULTS One hundred twenty women in Uganda and 242 in Senegal received SP (117 and 240 were followed up, respectively). Nine Ugandan and seven Senegalese SP decliners were interviewed. Three months after receiving SP, 84% [95% confidence interval (CI)=75%-93%] of Ugandan participants and 80% (95% CI=74%-87%) of Senegalese participants said they would select SP over DMPA IM. Main reasons for selecting SP were fewer side effects, liking the method, fast administration, less pain and method effectiveness. Thirty-four adverse events were reported but were not serious. No pregnancies were reported. CONCLUSION Current DMPA IM users in Senegal and Uganda accepted SP, and most preferred SP over DMPA IM. SP can be safely introduced into FP programs and administered by trained CHWs, with expectation of client uptake. IMPLICATIONS We found SP acceptable and safe in diverse settings among current intramuscular DMPA users, including those who received SP from CHWs. This provides evidence that SP would be used and could therefore reduce unmet family planning needs if introduced into family planning programs.

The science of being a study participant: FEM-PrEP participants' explanations for overreporting adherence to the study pills and for the whereabouts of unused pills.

Background:FEM-PrEP was unable to determine whether once-daily, oral emtricitabine/tenofovir disoproxil fumarate reduces the risk of HIV acquisition among women because of low adherence. Self-reported adherence was high, and pill-count data suggested good adherence. Yet, drug concentrations revealed limited pill use. We conducted a follow-up study with former participants in Bondo, Kenya, and Pretoria, South Africa, to understand factors that had influenced overreporting of adherence and to learn the whereabouts of unused pills. Methods:Qualitative, semistructured interviews were conducted with 88 participants, and quantitative, audio computer-assisted self-interviews were conducted with 224 participants. We used thematic analysis and descriptive statistics to analyze the qualitative and quantitative data, respectively. Results:In audio computer-assisted self-interviews, 31% (n = 70) said they had overreported adherence; the main reason was the belief that nonadherence would result in trial termination (69%, n = 48). A considerable percentage (35%, n = 78) acknowledged discarding unused pills. Few acknowledged giving their pills to someone else (4%, n = 10), and even fewer acknowledged giving them to someone with HIV (2%, n = 5). Many participants in the semistructured interviews said other participants had counted and removed pills from their bottles to appear adherent. Conclusions:Despite repeated messages that nonadherence would not upset staff, participants acknowledged several perceived negative consequences of reporting nonadherence, which made it difficult to report accurately. Uneasiness continued in the follow-up study, as many said they had not overreported during the trial. Efforts to improve self-reported measures should include identifying alternative methods for creating supportive environments that allow participants to feel comfortable reporting actual adherence.

Tetrasomy 18p: report of the molecular and clinical findings of 43 individuals.

Thus far, the phenotype of tetrasomy 18p has been primarily delineated by published case series and reports. Findings reported in more than 25% of these cases include neonatal feeding problems, growth retardation, microcephaly, strabismus, muscle tone abnormalities, scoliosis/kyphosis, and variants on brain MRI. Developmental delays and cognitive impairment are universally present. The purpose of this study was to more fully describe tetrasomy 18p at both the genotypic and the phenotypic levels. Array CGH was performed on 43 samples from individuals with tetrasomy 18p diagnosed via routine karyotype. The medical records of 42 of these 43 individuals were reviewed. In order to gain additional phenotypic data, 31 individuals with tetrasomy 18p underwent a series of clinical evaluations at the Chromosome 18 Clinical Research Center. Results from the molecular analysis indicated that 42 of 43 samples analyzed had 4 copies of the entire p arm of chromosome 18; one individual was also trisomic for a section of proximal 18q. The results of the medical records review and clinical evaluations expand the phenotypic description of tetrasomy 18p to include neonatal jaundice and respiratory distress; recurrent otitis media; hearing loss; seizures; refractive errors; constipation and gastroesophageal reflux; cryptorchidism; heart defects; and foot anomalies. Additional findings identified in a small number of individuals include hernias, myelomeningocele, kidney defects, short stature, and failure to respond to growth hormone stimulation testing. Additionally, a profile of dysmorphic features is described. Lastly, a series of clinical evaluations to be considered for individuals with tetrasomy 18p is suggested.

Recurrent interstitial deletions of proximal 18q: A new syndrome involving expressive speech delay

Most deletions of the long arm of chromosome 18 involve some part of the most distal 30 Mb. We have identified five individuals with cytogenetically diagnosed interstitial deletions that are all proximal to this commonly deleted region. The extent of their deletions was characterized using molecular and molecular cytogenetic techniques. Each participant was assessed under the comprehensive clinical evaluation protocol of the Chromosome 18 Clinical Research Center. Three of the five individuals were found to have apparently identical interstitial deletions between positions of 37.5 and 42.5 Mb (18q12.3 → 18q21.1). One individuals deletion was much larger and extended from a more proximal breakpoint position of 23 Mb (18q11.2) to a more distal breakpoint at 43 Mb (18q21.1). The fifth individual had a proximal breakpoint identical to the other three, but a distal breakpoint at 43.5 Mb (18q21.1). The clinical findings were of interest because the three individuals with the smaller deletions lacked major anomalies. All five individuals were developmentally delayed; however, the discrepancy between their expressive and receptive language abilities was striking, with expressive language being much more severely affected. This leads us to hypothesize that there are genes in this region of chromosome 18 that are specific to the neural and motor planning domains necessary for speech. Additionally, this may represent a previously underappreciated syndrome since these children do not have the typical clinical abnormalities that would lead to a chromosome analysis.

Selective Expression of β Tubulin Isotypes in Gerbil Vestibular Sensory Epithelia and Neurons

The seven mammalian isotypes of β tubulin are strikingly similar in amino acid sequence. The differences in isotypic sequence, although small, are nonetheless conserved in evolution, which suggests that they may confer distinct functional roles. If so, such roles should be reflected in the selective expression of isotypes by cell type, or even in the sorting of isotypes to within-cell pools. Hair cells of the vestibular sensory epithelia each possess a kinocilium, a microtubule-based organelle that could represent a distinct microtubule compartment, separate from the extensive microtubule network in the soma. The afferent neurons that innervate the vestibular sensory epithelia may also be functionally divided into dendritic, somatic, and axonal compartments, each with its own complement of microtubules. We have examined the distribution of β tubulin isotypes in gerbil vestibular epithelia using isotype-specific antibodies to four isotypes and indirect immunofluorescence. We found that hair cells selectively express βI and βIV tubulin, while supporting cells express βI, βII, and βIV tubulin. However, no sorting of isotypes between somatic and kinocilia compartments was found in hair cells. Vestibular ganglion cells display three isotypes in the soma, axon, and terminal dendrite compartments (βI, βII, and βIII tubulin), but only βIII tubulin was found in calyceal nerve endings. The implication of these findings is that β tubulin isotypes are not sorted to within-cell compartments in hair cells but are sorted in some vestibular neurons.

Facilitators of Adherence to the Study Pill in the FEM-PrEP Clinical Trial

Introduction FEM-PrEP did not demonstrate a reduction in HIV acquisition because of low study pill adherence. Yet, plasma and intracellular drug concentrations indicated that some participants had evidence of recent pill use. We conducted a follow-up study to identify, among other topics, participants’ reasons for taking the study pill. Methods Qualitative, semi-structured interviews (SSIs) were conducted with 88 FEM-PrEP participants. Participants were purposefully selected based on their adherence drug concentrations collected during FEM-PrEP and placed into three adherence interview groups: “high,” “moderate,” and “none/scarce.” Participants in the high and moderate groups described reasons why they adhered most or some of the time, including factors that facilitated their adherence. Participants in all groups described what they believed made it possible for other FEM-PrEP participants to adhere. In addition, 224 FEM-PrEP participants reported on their reasons for taking the study pills through a quantitative, audio computer-assisted self-interview (ACASI). Thematic analysis and descriptive statistics were used to analyze the qualitative and quantitative data, respectively. Results Five themes were identified from the SSIs as facilitating factors of adherence: 1) participants’ support for the research, 2) HIV risk reduction, 3) routine formation and use of tools, 4) adherence counseling, and 5) partner awareness and support. Participants described similar facilitators when they spoke about other participants’ adherence. Among the 172 participants who reported in ACASI that they had taken a study pill, wanting to help answer the research question was the most frequently stated reason for taking the pills (94%, n = 161). We also found evidence of preventive misconception. Conclusions Adherence was facilitated by personal motivations, such as risk reduction and interest in the research outcome, and by adherence strategies consisting of external cues, reminders, and support. These findings can inform future HIV prevention clinical trials and the rollout of effective antiretroviral-based HIV prevention technologies for women.