Ocular Pathology Relevant to Glaucoma in a Gja1(Jrt) Mouse Model of Human Oculodentodigital Dysplasia

PURPOSE. Oculodentodigital dysplasia (ODDD) is a human disorder caused by mutations in the gap junction alpha 1 (GJA1) gene encoding the connexin43 (Cx43) gap junction protein. Causal links between GJA1 mutations and glaucoma are not understood. The purpose in this study was to examine the ocular phenotype for Gja1(Jrt/+) mice harboring a Cx43 G60S mutation. METHODS. In young Gja1(Jrt/+) mice, Cx43 abundance was assessed with a Western blot, and Cx43 localization was visualized using immunohistochemistry and confocal microscopy. Intraocular pressure (IOP) was measured by rebound tonometry, and eye anatomy was imaged using ocular coherence tomography (OCT). Hematoxylin and eosin (H&E)-stained eye sections were examined for ocular histopathology related to the development of glaucoma. RESULTS. Decreased Cx43 protein levels were evident in whole eyes from Gja1(Jrt/+) mice compared with those of wild-type mice at postnatal day 1 (P = 0.005). Cx43 immunofluorescence in ciliary bodies of Gja1(Jrt/+) mice was diffuse and intracellular, unlike the gap junction plaques prevalent in wildtype mice. IOP in Gja1(Jrt/+) mice changed during postnatal development, with significantly lower IOP at 21 weeks of age in comparison to the IOP of wild-type eyes. Microphthalmia, enophthalmia, anterior angle closure, and reduced pupil diameter were observed in Gja1(Jrt/+) mice at all ages examined. Ocular histology showed prominent separations between the pigmented and nonpigmented ciliary epithelium of Gja1(Jrt/+) mice, split irides, and alterations in the number and distribution of nuclei in the retina. CONCLUSIONS. Detailed phenotyping of Gja1(Jrt/+) eyes offers a framework for elucidating human ODDD ocular disease mechanisms and evaluating new treatments designed to protect ocular synaptic network integrity

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Factors associated with HPV awareness among mothers of low-income ethnic minority adolescent girls in Los Angeles.

Among caregivers of adolescent girls, awareness of human papillomavirus (HPV) is strongly associated with vaccine uptake. Little is known, however, about the predictors of HPV awareness among low-income ethnic minority groups in the U.S. The purpose of this study is to understand demographic factors associated with HPV awareness among low-income, ethnic minority mothers in Los Angeles County. We conducted a cross-sectional study of caregivers of adolescent girls through the Los Angeles County Department of Public Health Office of Women's Health's hotline. The majority of the participants were foreign-born (88%), one quarter lacked a usual source of care, and one quarter lacked public or private health insurance for their daughter. We found that one in three participants had never heard of HPV or the vaccine. Mothers that were unaware of HPV were significantly more likely to conduct the interview in a language other than English and to lack health insurance for their daughters. HPV vaccine awareness was much lower in our caregiver sample (61%) than in a simultaneous national survey of caregivers (85%). The associations between lack of awareness and use of a language other than English, as well as lack of health insurance for their daughter indicate the need for HPV vaccine outreach efforts tailored to ethnic minority communities in the U.S

Increasing HPV Vaccination among Low-income, Ethnic Minority Adolescents: Effects of a Multicomponent System Intervention through a County Health Department Hotline

BackgroundIntroduction of the human papillomavirus (HPV) vaccine in 2006 was a game-changing advance in cancer control. Despite the vaccine's potential cancer prevention benefits, uptake remains low. We utilized a randomized design to evaluate a multicomponent intervention to improve HPV vaccine uptake among low-income, ethnic minority adolescents seeking services through a county health department telephone hotline.MethodsHotline callers who were caregivers of never-vaccinated adolescents (11-17 years) were randomized by call-week to intervention or control conditions. The intervention included brief telephone and print education, delivered in multiple languages, and personalized referral to a low-cost/free vaccine provider. Participants completed baseline (n = 238), 3-month (n = 215), and 9-month (n = 204) telephone follow-up surveys.ResultsHPV vaccine initiation rates increased substantially by 9-month follow-up overall, although no differences were observed between intervention and control groups (45% vs. 42%, respectively, P > 0.05). We also observed significant improvements in perceived HPV risk, barriers to vaccination, and perceived knowledge in both study conditions (P < 0.05).ConclusionsA low-intensity county hotline intervention did not produce a greater increase in HPV vaccination rates than routine practice. However, 44% of unvaccinated adolescents in both conditions received at least one dose of the vaccine, which can be viewed as a successful public health outcome. Future studies should evaluate more intensive interventions that address accessing and utilizing services in complex safety net settings.ImpactStudy results suggest the need for investigators to be aware of the potential priming effects of study participation, which may obscure the effect of low-intensity interventions

Effects of Patient Empowerment Programme (PEP) on clinical outcomes and health service utilization in type 2 diabetes mellitus in primary care: an observational matched cohort study.

To evaluate the effects of a large population-based patient empowerment programme (PEP) on clinical outcomes and health service utilization rates in type 2 diabetes mellitus (T2DM) patients in the primary care setting.A stratified random sample of 1,141 patients with T2DM enrolled to PEP between March and September 2010 were selected from general outpatient clinics (GOPC) across Hong Kong and compared with an equal number of T2DM patients who had not participated in the PEP (non-PEP group) matched by age, sex and HbA1C level group.Clinical outcomes of HbA1c, SBP, DBP and LDL-C levels, and health service utilization rates including numbers of visits to GOPC, specialist outpatient clinics (SOPC), emergency department (ED) and inpatient admissions, were measured at baseline and at 12-month post-recruitment. The effects of PEP on clinical outcomes and health service utilization rates were assessed by the difference-in-difference estimation, using the generalized estimating equation models.Compared with non-PEP group, PEP group achieved additional improvements in clinical outcomes over the 12-month period. A significantly greater percentage of patients in the PEP group attained HbA1C≤7% or LDL-C≤2.6 mmol/L at 12-month follow-up compared with the non-PEP group. PEP group had a mean 0.813 fewer GOPC visits in comparison with the non-PEP group.PEP was effective in improving the clinical outcomes and reduced the general outpatient clinic utilization rate over a 12-month period. Empowering T2DM patients on self-management of their disease can enhance the quality of diabetes care in primary care.ClinicalTrials.gov NCT01935349

Flow of Participants on the Subject Assignment, Follow-up and Analysis.

<p>Flow of Participants on the Subject Assignment, Follow-up and Analysis.</p