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Purpose: Hip subluxation and dislocation are known problems for children with spinal muscular atrophy (SMA). Medical complexity of these children typically results in absence of monitoring and intervention for pathologic hips. Patterns of hip migration and acetabular morphology in SMA have not been described. This study examines the natural progression of hip instability across all types of SMA in a pediatric population., Methods: Following institutional review board approval, a retrospective chart review of all children with SMA at our institution was performed. All x-rays taken before the age of 18 years containing adequate projections of the pelvis were measured for Reimer migration index (MI), acetabular depth ratio (ADR), and acetabular index (AI). Demographics and clinical data were collected including use of nusinersen, ambulatory status, contractures, and hip pain. Linear mixed effects model was fit to serial MI measures of individual hips with fixed effects consisting of SMA type, age at x-ray, and their interaction. ADR and AI measures were similarly modeled following conversion of raw values to z-scores based on the model developed by Novais et al Slope indicated rate of measure change as a function of age., Results: Forty-five children (22 males) with SMA types 1 to 3 were included in this retrospective study. Six children were classified as type 1, 25 were type 2, and 14 were type 3. The interaction of age by SMA type was statistically significant (P=0.01), indicating a difference in the rate of hip subluxation between the 3 SMA types as measured by MI. By age 4, MI values were different from one another across all 3 groups (P<0.01). ADR decreased with age across all SMA types. The slopes of ADR regression lines were negative and statistically significant between the 3 groups (P=0.002). AI values were higher for all types of SMA, which is the opposite of expected in normal hips., Conclusions: Hip subluxation occurs across all SMA types, most rapidly in SMA type 1. Regression lines of ADR and AI compared with those seen in unaffected populations suggest hips in children with SMA demonstrate a difference in morphology of the acetabulum and do not follow normal adaptive remodeling. As treatments advance and the population of SMA patients becomes more mobile, there is an increased need to monitor hip instability in children with SMA, thus making orthopaedic management an important consideration., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Breast cancer is a common type of cancer in South Asian women. Early detection by mammographic screening plays a significant role in improving survival rates. South Asian minorities in many countries have reported low mammographic screening rates., Objective: This study aimed to understand the factors that influence mammographic screening uptake among South Asian women in Hong Kong., Methods: This was a qualitative exploratory descriptive study. South Asian women 40 years or older with no history of breast cancer were recruited. In-depth face-to-face interviews were conducted following a semistructured interview guide. Thematic analysis was conducted to analyze the data., Results: A total of 31 South Asian women consented to participate. Among them, only 7 had ever undergone mammographic screening. The following themes of facilitating factors were identified: (1) influence of doctors, family, and friends; (2) strong sense of commitment to the family; and (3) accessibility and availability of mammographic screening information and services. The following themes for barriers to screening were identified: (1) beliefs about health management and social norms, (2) lack of knowledge and understanding of breast cancer and mammographic screening, (3) logistical barriers, and (4) physical barriers., Conclusion: This study identified important facilitators and barriers that influence the uptake of mammographic screening among South Asian women in Hong Kong., Implications for Practice: The study findings can be used to guide the development and implementation of culturally relevant interventions to address barriers to screening, including the expected gender roles and responsibilities among women in their respective families., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Research exploring the unmet supportive care needs of Arab cancer survivors is limited, with most conducted with immigrant groups. No study has compared the unmet supportive care needs of immigrant Arab cancer survivors with Arab cancer survivors living in their native country., Objective: To explore the unmet supportive care needs of both Arab Australian and Arab Jordanian cancer survivors., Methods: Arab people living in Sydney, Australia, and Amman, Jordan, and diagnosed with cancer within the last 5 years were invited to complete a questionnaire that measured unmet supportive care needs, depression, and language acculturation. Multiple regression analysis was performed to identify predictors of unmet supportive care needs., Results: Seventy-seven Arab Jordanian and 66 Arab Australian cancer survivors were recruited. Australian participants were older than their Jordanian counterparts (61.5 vs 52.3 years; P < .001) and reported higher levels of overall unmet needs (44.9 vs 36.1; P = .012). Controlling for age and stage of cancer diagnosis, higher levels of depression (β = .34) and living in Australia (β = .26) were significant predictors of unmet needs and explained almost 17% of the variance., Conclusions: These findings have extended our understanding of the unmet supportive care needs of Arab cancer survivors and confirm disparities in unmet needs in immigrant populations., Implications for Practice: Greater attention is needed to ensure the supportive care needs are met for immigrant patients with cancer. Additional strategies to address physical and psychological needs are particularly needed in this group.

Background: Despite advances in immunosuppressive therapies, the rate of chronic transplant loss remains substantial. Organ injury involves various forms of cell death including apoptosis and necrosis. We now recognize that early injury of cardiac transplants involves a newly described form of programmed necrotic cell death, termed necroptosis. Because this involves receptor-interacting protein (RIP) kinase 1/3, this study aimed to establish the role of RIP3 in chronic cardiac allograft rejection., Methods: We used major histocompatibility complex class II mismatched C57BL/6N (H-2; B6) or B6.RIP3 (H-2; RIP3) mice to B6.C-H-2 (H2-Ab1; bm12) mouse cardiac transplantation. Microvascular endothelial cells (MVEC) were developed from B6 and RIP3 cardiac grafts., Result: CD4 T cell-mediated cardiac graft rejection is inhibited using RIP3 deficient donor grafts, with reduced cellular infiltration and vasculopathy compared with wild type cardiac grafts. Alloreactive CD4 T cell-mediated MVEC death involves TNFα, Fas ligand (FasL) and granzyme B. Although necroptosis and release of danger molecule high-mobility group box 1 are eliminated by the absence of RIP3, CD4 T cells had attenuated MVEC death through granzyme B and FasL., Conclusions: CD4 T cell-mediated MVEC death involves in TNFα, FasL and granzyme B. Necroptotic cell death and release of the danger molecule may promote inflammatory responses and transplant rejection. Although loss of RIP3 does not eliminate alloimmune responses, chronic graft injury is reduced. RIP3 is an important therapeutic target but additional granzyme and caspases inhibition is required for sufficiently improving long-term graft survival.

Background: Korean immigrant women have been consistently reported as having low participation in breast cancer screening practices. A valid and reliable instrument to explore factors that affect their cancer screening behaviors is essential., Objective: The aim of this study was to report the psychometric properties of the Korean version of the Breast Cancer Screening Beliefs Questionnaire (BCSBQ)., Methods: A convenience sample of 249 Korean Australian women was recruited through a number of Korean community organizations in Sydney., Results: Exploratory factor analysis supports a similar fit for the original 3-factor structure of our data set. A significant association was found between the attitudes of these women toward general health checkups and the frequency of their performance of the breast awareness practices and having mammograms. Furthermore, it was found that knowledge and perceptions about the breast cancer scales were significantly associated with education level and that barriers to mammographic screening were much less evident among women who engaged in the 3 screening practices. The results indicated that the Korean version of the BCSBQ had satisfactory validity and internal consistency. The Cronbach's α of the 3 subscales ranged between .80 and .88., Conclusion: The Korean version of the BCSBQ was confirmed to be a culturally appropriate, valid, and reliable instrument for assessing the beliefs, knowledge, and attitudes to breast cancer and breast cancer screening practices among women of Korean background living in Australia., Implication for Practice: The Korean version of the BCBSQ can provide nurses with insights into the development of culturally sensitive breast health education programs.

Objectives: This multicenter, randomized, open-label, phase II trial evaluated the efficacy and safety of AEG35156 in addition to sorafenib in patients with advanced hepatocellular carcinoma (HCC), as compared with sorafenib alone., Methods: Eligible patients were randomly assigned in a 2:1 ratio to receive AEG35156 (300 mg weekly intravenous infusion) in combination with sorafenib (400 mg twice daily orally) or sorafenib alone. The primary endpoint was progression-free survival (PFS). Other endpoints include overall survival (OS), objective response rates (ORR), and safety profile., Results: A total of 51 patients were enrolled; of them, 48 were evaluable. At a median follow-up of 16.2 months, the median PFS and OS were 4.0 months (95% CI, 1.2-4.1) and 6.5 months (95% CI, 3.9-11.5) for combination arm, and 2.6 (95% CI, 1.2-5.4) and 5.4 months (95% CI, 4.3-11.2) for sorafenib arm. Patients who had the study treatment interrupted or had dose modifications according to protocol did significantly better, in terms of PFS and OS, than those who had no dose reduction in combination arm and those in sorafenib arm. The ORR based on Choi and RECIST criteria were 16.1% and 9.7% in combination arm, respectively. The ORR was 0 in control arm. One drug-related serious adverse event of hypersensitivity occurred in the combination arm, whereas 2 gastrointestinal serious adverse events in the sorafenib arm., Conclusion: AEG35156 in combination with sorafenib showed additional activity in terms of ORR and was well tolerated. The benefit on PFS is moderate but more apparent in the dose-reduced subgroups.

Background: Arabic women have been consistently reported as having remarkably low participation rates in breast cancer screening measures in their home countries and after migration to Western countries. Little is known about the screening behaviors of Arabic women in Australia., Objectives: This study aimed to report breast cancer screening practices among Arabic women in Australia and to examine the relationship between (1) demographic factors and (2) the Arabic version of the Breast Cancer Screening Beliefs Questionnaire (BCSBQ) score and women's breast screening behaviors., Methods: A descriptive cross-sectional method was used. Both English and Arabic versions of the BCSBQ were administered to the 251 Arabic Australian women 18 years or older who participated in the study., Results: The majority of participants (62.9%-92%) had heard of breast awareness, clinical breast examination, and mammography. However, only 7.6% practiced breast awareness monthly, 21.4% had undergone clinical breast examination annually, and 40.3% had biannual mammography. Length of stay in Australia, being retired, and being unemployed were positively associated with the recommended performance of breast awareness and mammography. In terms of BCSBQ scores, women who engaged in the 3 screening practices had significantly higher scores on the attitudes to health check-ups and barriers to mammography subscales., Conclusion: Attitudes toward health check-ups and perceived barriers to mammography were important determinants of breast cancer screening practices among Arabic Australian women., Implications for Practice: To fully understand barriers discouraging Arabic Australian women from participating in breast cancer screening practices, efforts should be focused on specific subgroup (ie, working group) of Arabic Australian women.

Background: Indian women have been consistently reported as having low participation in breast cancer screening practices. A valid and reliable instrument to explore their breast cancer beliefs is essential for development of interventions to promote breast cancer screening practices., Objective: The aim of this study was to report the psychometric properties of the Breast Cancer Screening Beliefs Questionnaire (BCSBQ) in an Indian community in Australia., Methods: A convenience sample of 242 Indian Australian women was recruited from Indian community organizations and personal networking. Explanatory factor analysis was conducted to study the factor structure. Clinical validity was examined by Cuzick's nonparametric test, and Cronbach's α was used to assess internal consistency reliability., Results: Exploratory factor analysis showed a similar fit to the hypothesized 3-factor structure. The frequency of breast cancer screening practices was significantly associated with attitudes toward general health check-up. Knowledge and perceptions about the breast cancer scale were not significantly associated with clinical breast examinations and mammography. Perceived barriers to mammography were much less evident among women who engaged in breast awareness and clinical breast examination. Results indicated that the BCSBQ had satisfactory validity and internal consistency. Cronbach's α of the 3 subscales ranged from .81 to .91., Conclusions: The BCSBQ is a culturally appropriate, valid, and reliable instrument for assessing the beliefs, knowledge, and attitudes about breast cancer and breast cancer screening practices among women of Indian ethnic extraction living in Australia., Implication for Practice: The BCSBQ can be used to provide nurses with information relevant for the development of culturally sensitive breast health education programs.

The rostroventral medial medulla (RVM) is part of a rapidly acting spino-bulbo-spinal loop that is activated by ascending nociceptive inputs and drives descending feedback modulation of spinal nociception. In the adult rat, the RVM can facilitate or inhibit dorsal horn neuron inputs but in young animals descending facilitation dominates. It is not known whether this early life facilitation is part of a feedback loop. We hypothesized that the newborn RVM functions independently of sensory input, before the maturation of feedback control. We show here that noxious hind paw pinch evokes no fos activation in the RVM or the periaqueductal gray at postnatal day (P) 4 or P8, indicating a lack of nociceptive input at these ages. Significant fos activation was evident at P12, P21, and in adults. Furthermore, direct excitation of RVM neurons with microinjection of DL-homocysteic acid did not alter the net activity of dorsal horn neurons at P10, suggesting an absence of glutamatergic drive, whereas the same injections caused significant facilitation at P21. In contrast, silencing RVM neurons at P8 with microinjection of lidocaine inhibited dorsal horn neuron activity, indicating a tonic descending spinal facilitation from the RVM at this age. The results support the hypothesis that early life descending facilitation of spinal nociception is independent of sensory input. Since it is not altered by RVM glutamatergic receptor activation, it is likely generated by spontaneous brainstem activity. Only later in postnatal life can this descending activity be modulated by ascending nociceptive inputs in a functional spinal-bulbo-spinal loop.

Background: Providing quality care and support to cancer patients from minority cultures can challenge community nurses when language barriers and cultural complexities intersect with the need for complex care., Objectives: This article reports on a qualitative study that explores interactions between community nurses and Chinese-Australian cancer patients., Methods: The research method focused on particular nurse-patient encounters and involved preencounter and postencounter interviews with the nurse, postencounter interviews with the patient, and observation of the encounters. Participants included community nurses, Chinese cancer patients being cared for at home, and their carers if present., Results: Four themes were conceptualized: (1) the impact of language barriers on nurse-patient interactions, (2) patient understandings of the scope and objectives of healthcare services, (3) cultural complexities and sensitivities, and (4) valued care and support. The study demonstrates that, although many nurses do provide comprehensive, culturally competent care, language barriers can lead to task-oriented rather than comprehensive approaches, and other cultural complexities do have an impact on patient experiences and on the quality of nurse-patient interactions. Nevertheless, most patient participants experienced a feeling of security as a result of regular contact with a community nursing service., Conclusion: Cancer patients with complex care needs but limited English proficiency require support to negotiate complicated community services networks. Culturally competent community nurses can provide this support., Implications for Practice: The study highlights the need for continuing cultural competence education for community nurses and the importance of careful discharge planning to ensure continuity of care for this vulnerable patient group.

Objective: To estimate whether continuous combined oral contraceptive pill (OCP) use leads to higher continuation and lower pregnancy rates over 12 months than cyclic use in a developing country setting., Methods: We enrolled healthy women aged 18 to 30 years, in Santo Domingo, Dominican Republic. We randomly assigned women to cyclic or continuous use of OCPs. Participants made quarterly clinic visits for 12 months. During follow-up, we reviewed OCP adherence and continuation, side effects, and bleeding, and we tested for pregnancy., Results: We enrolled 358 women (mean age, 22.7 years) and 335 (93.6%) completed the study. In intent-to-treat analyses, 77.6% of the continuous use group and 71.7% of the cyclic group continued OCPs at 12 months (P=.21). The main reason for OCP discontinuation in both groups was running out of OCPs or forgetting. Across all visits, 26.1% of women in the continuous use group and 22.3% of women in the cyclic group ever reported missing three or more OCPs in the past month (P=.43). In multivariable analyses, regimen was not associated with discontinuation, but both previous birth and perceived ease of use of OCPs decreased risk of discontinuation, whereas desire for reduced menstruation increased risk of discontinuation. Although more women reported amenorrhea or infrequent bleeding in the continuous use group, more women in the cyclic group found their bleeding patterns acceptable. Bleeding was not associated with discontinuation in multivariable analyses. Pregnancy rates at 12 months were similar (16.2% continuous and 17.4% cyclic)., Conclusions: Continuous and cyclic OCP regimens were associated with similar 12-month continuation and pregnancy rates. Few factors predicted OCP discontinuation or pregnancy., Clinical Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00570440., Level of Evidence: I.

Background: Although the incidence rates of breast cancer have been increasing remarkably in Hong Kong over the last 2 decades, little is known on breast cancer screening practices among this group of women., Objectives: This study aimed to report breast cancer screening practices among Hong Kong Chinese women and to examine the relationship between (1) demographic factors and (2) the modified Chinese Breast Cancer Screening Beliefs Questionnaire (CBCSB) score and women's breast screening behaviors., Methods: A descriptive and cross-sectional method was used. Both English and Chinese versions of the modified CBCSB were administered. Of 946 Hong Kong Chinese women older than 18 years and invited to participate in the study, 753 (79.6%) completed and returned the questionnaire., Results: The majority of participants (70%-90%) had heard of breast self-examination (BSE), clinical breast examination (CBE), and mammograms. Only 33.3% performed a BSE monthly; 37.8% and 32.7% of women within the targeted age group had a CBE annually and had a mammogram every 2 years, respectively. Being married and part-time employment were positively associated with women who performed BSE as recommended. In terms of modified CBCSB score, women who had BSE, CBE, and mammogram as recommended had significantly higher scores on the subscale attitudes to health check-up., Conclusion: Attitudes toward health check-up was influential in compliance with breast cancer screening practices among Chinese-Australian women., Implications for Practice: Effort should be focused on specific subgroups of Hong Kong Chinese women, to fully understand the barriers involved in participating in breast cancer screening practices.

Objective: To evaluate the effect of nevirapine-containing antiretroviral therapy (ART) on combined oral contraceptive (COC) effectiveness., Design: Nonrandomized prospective clinical trial., Methods: We enrolled HIV-infected women aged 18-35 years in South Africa and Uganda who had regular menses, were sexually active, and had no medical contraindications to COC use. We enrolled 196 women taking nevirapine-containing ART and 206 women not yet eligible for ART as a control group. We treated all participants with low-dose COCs. Our main outcomes were ovulation and pregnancy rates. We estimated ovulation in the first two cycles using weekly serum progesterone and tested for pregnancy monthly for 24 weeks., Results: The median age of participants was 29 and their median CD4 cell count was 486. In the ART group, 43 of 168 (26%) ovulated in cycle 1, 30 of 163 (18%) in cycle 2, and 18 of 163 (11%) in both cycles. In the non-ART group, 26 of 168 (16%) ovulated in cycle 1, 31 of 165 (19%) in cycle 2, and 20 of 165 (12%) in both cycles. We found no significant difference in ovulation rates between groups: unadjusted odds ratio 1.36 (95% confidence interval 0.85-2.18). Pregnancy rates also did not differ: 10.0 per 100-women-years in the ART group and 10.1 per 100-women-years in the non-ART group. Self-reported COC adherence, condom use, vaginal bleeding, and adverse events were similar. Five serious adverse events were reported, all in the non-ART group., Conclusion: ART use did not affect risk of ovulation or pregnancy in women taking COCs, suggesting that nevirapine-containing ART does not interfere with COC contraceptive effectiveness.

Background: Chinese women have been consistently reported as having low breast cancer screening practices. The Chinese Breast Cancer Screening Beliefs Questionnaire (CBCSB) was designed to assess Chinese Australian women's beliefs, knowledge, and attitudes toward breast cancer and screening practices., Objectives: The objectives of the study were to confirm the factor structure of the CBCSB with a new, larger sample of immigrant Chinese Australian women and to report its clinical validity., Methods: A convenience sample of 785 Chinese Australian women was recruited from Chinese community organizations and shopping malls. Cronbach α was used to assess internal consistency reliability, and Amos v18 was used for confirmatory factor analysis. Clinical validity was assessed through linear regression using SPSS v18., Results: The 3-factor structure of the CBCSB was confirmed, although the model required respecification to arrive at a suitable model fit as measured by the goodness-of-fit index (0.98), adjusted goodness-of-fit index (0.97), normed fit index (0.95), and root mean square error of approximation (0.031). Internal consistency reliability coefficients were satisfactory (>.6). Women who engaged in all 3 types of screening had more proactive attitudes to health checkups and perceived less barriers to mammographic screening., Conclusion: The CBCSB is a valid and reliable tool for assessing Chinese women's beliefs, knowledge, and attitudes about breast cancer and breast cancer screening practices., Implication for Practice: The CBCSB can be used for providing practicing nurses with insights into the provision of culturally sensitive breast health education.

Objective: Mycoplasma genitalium is an emerging sexually transmitted infection (STI) and has been associated with reproductive tract infections and HIV in cross-sectional studies. In this longitudinal study, we assess whether M. genitalium is associated with risk of acquiring HIV-1 infection., Design: Nested case-control study within a large prospective study in Zimbabwe and Uganda, Methods: A total of 190 women who seroconverted to HIV-1 during follow-up (cases) were matched with up to two HIV-negative controls. Mycoplasma genitalium testing was performed by PCR-ELISA, using archived cervical samples from the HIV-1 detection visit and the last HIV-negative visit for cases, and equivalent visits in follow-up time for controls. Risk factors for HIV-1 acquisition were analyzed using conditional logistic regression, with M. genitalium as the primary exposure., Results: Mycoplasma genitalium was a common infection in these populations (14.8 and 6.5% prevalence among cases and controls, respectively, at the visit prior to HIV-1 detection), and more prevalent than other nonviral STIs. We found a greater than two-fold independent increased risk of HIV-1 acquisition among women infected with M. genitalium at the visit prior to HIV-1 acquisition [adjusted odds ratio (AOR) = 2.42; 95% confidence interval (CI) 1.01-5.80), and at time of HIV-1 acquisition (AOR = 2.18; 95% CI 0.98-4.85). An estimated 8.7% (95% CI 0.1-12.2%) of incident HIV-1 infections were attributable to M. genitalium., Conclusion: This is the first longitudinal study to assess the relationship between M. genitalium and HIV-1 acquisition. If findings from this research are confirmed, M. genitalium screening and treatment among women at high risk for HIV-1 infection may be warranted as part of an HIV-1 prevention strategy.

Objectives: To evaluate the effect of hormonal contraception including combined oral contraceptives (COCs), and the injectable progestins depo-medroxyprogesterone acetate (DMPA) and norethisterone enanthate (Net-En) on the risk of HIV acquisition among women in South Africa., Design/methods: We analyzed data from 5567 women aged 16-49 years participating in the Carraguard Phase 3 Efficacy Trial. Participants were interviewed about contraceptive use and sexual behaviors and underwent pelvic examinations and HIV testing quarterly. We used marginal structural Cox regression models to estimate the effect of hormonal contraception exposure on HIV acquisition risk among women overall and among young women (16-24 years) in particular., Results: Two hundred and seventy participants became HIV-infected (3.7 per 100 woman-years); HIV incidence was 2.8, 4.6, 3.5 and 3.4 per 100 woman-years in the COC, DMPA, Net-En and nonhormonal contraceptive groups, respectively (P = 0.09). The adjusted hazard ratios (AHRs) were 0.84 [95% confidence interval (CI) 0.51-1.39], 1.28 (95% CI 0.92-1.78) and 0.92 (95% CI 0.64-1.32) among COC, DMPA and Net-En users, respectively, compared with the nonhormonal group controlling for covariates. Age modified the effect of hormonal contraception on HIV acquisition risk; among young women, the AHRs were 1.02 (95% CI 0.46-2.28) for COCs, 1.68 (95% CI 0.96-2.94) for DMPA and 1.36 (95% CI0.78-2.35) for Net-En users., Conclusions: In this study conducted among South African women, hormonal contraception did not significantly increase the risk of HIV acquisition. However, the effect estimate does not rule out a moderate increase in HIV risk associated with DMPA use found in some other recent studies.

Background: Previous systematic reviews that examined whether atrial fibrillation (AF) is associated with dementia have relied on different study designs (including retrospective ones) and did not evaluate risk using meta-analysis., Methods: We searched Medline, Embase, and PsychINFO in September 2010 for published prospective studies reporting on the association between baseline AF and incident dementia. Pooled odds ratios for AF and dementia were calculated using the random effects model, with heterogeneity assessed using I(2)., Results: We identified 15 relevant studies covering 46,637 participants, mean age 71.7 years. One study that reported no significant difference in Mini-Mental State Examination scores between patients with or without AF could not be pooled. Meta-analysis of the remaining 14 studies showed that AF was associated with a significant increase in dementia overall (odds ratio [OR] 2.0, 95% confidence interval [CI] 1.4 to 2.7, p < 0.0001), with substantial heterogeneity (I(2) = 75%). When stratified by participants, the association was significant (with little heterogeneity) in studies focusing solely on patients with stroke (7 studies, OR 2.4, 95% CI 1.7 to 3.5, p < 0.001, I(2) = 10%), and of borderline significance (with substantial heterogeneity) for studies in broader populations (7 studies, OR 1.6, 95% CI 1.0 to 2.7, p = 0.05, I(2) = 87%). For conversion of mild cognitive impairment to dementia, one study showed a significant association with AF (OR 4.6, 95% CI 1.7 to 12.5)., Conclusion: There is consistent evidence supporting an association between AF and increased incidence of dementia in patients with stroke whereas there remains considerable uncertainty about any link in the broader population. The potential association between AF and incident dementia in mild cognitive impairment merits further investigation.

Hormonal contraceptives are used widely worldwide; their effect on HIV acquisition remains unresolved. We reanalyzed data from the Hormonal Contraception and HIV Study using marginal structural modeling to reduce selection bias due to time-dependent confounding. Replicating our original analysis closely, we found that depo-medroxyprogesterone acetate (DMPA) but not combined oral contraceptive (COC) was associated with increased HIV acquisition. Also, young (18-24 years) but not older women who used DMPA and COCs were at increased HIV risk.

Objectives: High levels of HIV-1 viremia exist in peripheral blood during acute and early infection; however, data on HIV-1 viral loads in female genital secretions during this period are sparse., Design: Prospective cohort of 188 African women with primary HIV-1 infection., Methods: HIV-uninfected and infected women were followed quarterly; we tested serial plasma specimens by HIV PCR to estimate infection dates. We used the Loess procedure to estimate the magnitude and timing of viral setpoints in plasma and cervical secretions and generalized estimating equations (GEE) to identify predictors of plasma and cervical viral setpoints., Results: We estimated the mean HIV-1 plasma setpoint to be 4.20 log10 HIV-1 RNA copies/ml [95% confidence interval (CI) 4.04-4.35] at 121 days (95% CI 91-137) from infection; an analogous mean cervical viral setpoint was 1.64 log10 HIV-1 RNA copies/swab (95% CI 1.46-1.82) at 174 days (95% CI 145-194) from infection. Cervical loads were significantly higher (0.7-1.1 log10 copies/swab) during acute infection than subsequently. Subtype D infection, pregnancy, breastfeeding, and older age at the time of infection were associated with higher plasma viral setpoint. Subtype C infection, nonviral sexually transmitted infections, having a partner spending nights away from home, recent unprotected sex, and shorter time since infection were associated with higher cervical HIV-1 loads. Hormonal contraception was not associated with either the HIV-1 plasma setpoint or cervical loads during early infection., Conclusion: Cervical HIV-1 viral loads were highest during acute infection and then declined up to 6 months following infection, when a 'setpoint' was attained. The prognostic value of a cervical 'setpoint' on future transmission risk remains unclear.

Ethnicity and culture play significant roles in determining how an individual is likely to understand and explain cancer, which, in turn, is posited to have an impact on cancer screening behavior. Chinese women in Western countries are consistently reported to have low participation rates in mammographic screening. This may be related to the fact that women of Chinese ancestry have different images and beliefs about cancer, which can have implications for participation in health promotion programs regarding cancer prevention and early detection. To investigate this issue, a qualitative study involving in-depth interviews with 20 Chinese-Australian women was conducted. Embedded in the women's images of cancer were notions associated with fear, mystery, contagion, and stigma. Based on information provided by the women who participated in this study, 6 domains of folk explanations about the causes of cancer were identified: lifestyle, stress, environment, genes, unknown causes, and destiny. These beliefs should be considered in the design of breast health promotion programs because they are likely to have a bearing on Chinese-Australian women's attitudes regarding the value they perceive of cancer screening.

Background: Use of remifentanil during general anesthesia for cesarean delivery has been described, but its maternal and neonatal effects have not been investigated by a controlled study., Methods: In a randomized, double-blind, controlled study, patients undergoing elective cesarean delivery received an intravenous bolus of 1 microg/kg remifentanil (n = 20) or saline (n = 20) immediately before induction of general anesthesia. The authors compared maternal hemodynamic changes and neonatal condition and measured plasma concentrations of remifentanil., Results: The maximum increase in systolic arterial pressure from baseline after induction was smaller in the remifentanil group (median, 9 [range, -17 to 31] mmHg) compared with the control group (42 [6-73] mmHg, median difference, 33 mmHg; 95% confidence interval of difference, 23-45 mmHg; P < 0.0001). Maximum recorded values were smaller in the remifentanil group compared with the control group for systolic and mean arterial pressure and maternal heart rate. Apgar scores and time to sustained respiration were similar between groups. Two neonates in the remifentanil group were considered clinically depressed at birth and were given a single dose of naloxone. Remifentanil crossed the placenta with an umbilical venous/maternal arterial concentration ratio of 0.73 (SD, 0.17) and an umbilical arterial/umbilical venous concentration ratio of 0.60 (0.23)., Conclusions: A single bolus of 1 microg/kg remifentanil effectively attenuated hemodynamic changes after induction and tracheal intubation. However, remifentanil crosses the placenta and may cause mild neonatal depression and thus should be used for clear maternal indications when adequate facilities for neonatal resuscitation are available.

Purpose: Although the mainstay of treatment of patients with nasopharyngeal carcinoma (NPC) had been radiotherapy, chemotherapy has increasingly been adopted in conjunction with radiation and in advanced disease. In parts of Asia where NPC is prevalent, it is also known that around 10% of the population has chronic hepatitis B virus (HBV) infection. Cancer patients who are HBV carriers are frequently complicated by HBV reactivation during chemotherapy. This may result in liver damage, which disrupts anticancer therapy and compromises the patients' prognosis. In its most severe form, fatal hepatic failure may occur. With the increasing use of chemotherapy in NPC, the occurrence of HBV reactivation is likely to increase further. Although recent reports have suggested that the antiviral agent lamivudine may reduce HBV reactivation and its associated morbidity, there has been no data on this aspect in NPC patients. This study assessed the role of lamivudine in preventing HBV reactivation and its associated morbidity in NPC patients who have chronic HBV infection and are undergoing chemotherapy., Materials and Methods: Two groups were studied. One group consisted of 16 patients who received prophylactic lamivudine prior to and until 8 weeks after discontinuing chemotherapy. The other comprised 21 historical control subjects who underwent chemotherapy without prophylactic lamivudine. The outcomes were compared., Results: With prophylactic lamivudine, there were significantly fewer incidences of hepatitis (6.7% vs 33.3%, P = 0.047) and HBV reactivation (0% vs 28.6%, P = 0.027), and less disruption of chemotherapy (18.8% vs 67.7%, P = 0.045)., Conclusion: Prophylactic lamivudine significantly reduces the incidence and morbidity of HBV reactivation in NPC patients undergoing chemotherapy.

The efficacy and safety of docetaxel-epirubicin chemotherapy in the treatment of metastatic breast cancer was investigated in Chinese women. Three-weekly cycles comprised epirubicin 75 mg/m2 i.v. followed 1 h later by docetaxel 75 mg/m2 i.v. After 3 cycles, responding patients received a further 3 cycles, followed by 3 cycles of docetaxel alone. Forty-six patients entered the study, of whom 37% had received prior adjuvant chemotherapy. Three patients withdrew due to toxicity and were not evaluable for response. There were five complete responses and 31 partial responses, giving an overall response rate of 83.7% (95% CI 72.7-94.8%). The median time to progression was 10.96 months (95% CI 7.76-12.86) and median survival was 24.2 months (95% CI 16.6-). The most common grade 3/4 adverse events were neutropenia (96% of patients) and neutropenia with fever (39%). Hepatotoxicity occurred in six patients, two being attributable to hepatitis B virus reactivation. No patients suffered grade 3/4 cardiac toxicity and there were no treatment-related mortalities. Quality of life aspects deteriorated after 3 cycles, but there was a trend towards improved emotional aspects after 9 cycles. We conclude that docetaxel-epirubicin chemotherapy is highly effective for recurrent metastatic/locoregional breast cancer, with myelosuppression being the main toxicity.

The purpose of this study was to compare the antiemetic efficacy of three 5-HT3 antagonists (granisetron, ondansetron, tropisetron) plus dexamethasone for the prevention of acute emesis induced by high-dose cisplatin chemotherapy. This was a randomized, open label, crossover study. Recruited into the study were 94 chemotherapy-naive patients of whom five were excluded because chemotherapy was not given, noncisplatin regimen was used instead, or presence of anticipatory vomiting. The remaining 89 evaluable patients were mostly (86.5%) male, and were all treated for head and neck cancers. The antiemetic regimens consisted of 1) granisetron 3 mg i.v. and dexamethasone 20 mg i.v. on day 1 (GRADEX); 2) tropisetron 5 mg i.v. and dexamethasone 20 mg i.v. on day 1 (TRODEX); and 3) ondansetron 8 mg i.v. and dexamethasone 20 mg i.v. to be followed by ondansetron 8 mg p.o. x 2 on day 1 (ONDEX). Patients were randomized to receive one of the three regimens in the first cycle, and treatment was crossed over to the other two regimens in subsequent cycles. Antiemetic efficacy was assessed using self-report diaries recording the number of vomiting episodes as well as duration and severity of nausea within the first 24 hours. Complete response was defined as no vomiting with or without mild nausea, and major response was defined as one vomiting episode and/or moderate to severe nausea. Major efficacy refers to either complete or major response. A total of 219 cycles was given to 89 patients: 16 received one cycle only, 16 received two cycles, and 57 received three cycles. No carryover effects were observed between cycles. Using pooled data from all cycles, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 68%, and 71%, respectively (p = 0.11); the corresponding major efficacy rates were 91%, 93%, and 86%, respectively (p = 0.36). When only the first cycle was considered, the complete response rates to GRADEX, TRODEX, and ONDEX were 81%, 75%, and 74%, respectively (p = 0.58); the corresponding major efficacy rates were 92%, 94%, and 84%, respectively (p = 0.38). Analysis of the crossover data showed that the majority of patients achieved complete response or major efficacy with the different pairs of regimens, and there were no significant differences between different regimens in terms of complete response or major efficacy. The only exception was GRADEX versus TRODEX, in which 15.5% of patient achieved complete response with GRADEX as compared with 1.7% with TRODEX (p = 0.025). The majority of patients (53%) did not report any preference, whereas 14% preferred GRADEX, 15% preferred TRODEX, and 18% preferred ONDEX. The three 5-HT3 antagonists, when used in combination with steroids, had similar major efficacy for prophylaxis against cisplatin-induced acute emesis. Although GRADEX was superior to TRODEX in terms of complete response, this may not be of clinical significance. The choice of antiemetic regimens should therefore depend on patient preference and drug cost.

We studied the mechanisms by which oral or intravenous administration of allogeneic splenocytes prevents sensitization by skin allografts and development of accelerated rejection of subsequent cardiac allografts. LEW rats were sensitized with BN skin allografts 7 days prior to receiving heterotopic (LEW x BN)F1 vascularized cardiac allografts. While unsensitized cardiac allografts are rejected on days 6-8, control sensitized grafts were rejected within 24 to 48 hr. Oral administration of BN splenocytes during the sensitization phase (between skin and heart grafting) has been found to prevent accelerated allograft rejection and prolong cardiac allograft survival to 7 days. An alternative route of antigen exposure, specifically intravenous administration of BN splenocytes (50 x 10(6) daily for 5 days starting on the day of skin grafting), also prevented accelerated cardiac allograft rejection and prolonged allograft survival to 9 +/- 1 days (n = 5). Immunoperoxidase studies of cardiac allografts harvested 24-48 hr posttransplant showed that, when compared with sensitized controls, animals that received oral splenocytes had reduced deposition of IgG (end-point titer of 1/1000 vs. 1/4000), IgM (1/1000 vs. 1/16000), C3 (1/4000 vs. 1/16000), and fibrin (1/4000 vs. 1/16000). There was also decreased infiltration by macrophages (18 +/- 8 vs. 37 +/- 8 cells/HPF, P < 0.01), T cells (5 +/- 3 vs. 19 +/- 7, P < 0.01), and IL-2R+ T cells (5 +/- 3 vs. 15 +/- 4, P < 0.01), and a significant reduction in the numbers and extent of intragraft mononuclear cells stained with antibodies to IL-1, IL-2, IL-6, IL-8, IFN-gamma, and TNF-alpha. In contrast, these grafts showed markedly increased IL-4 staining (including most mononuclear and all endothelial cells), as compared with control grafts (< 20% of mononuclear cells and only focal endothelial staining). Immunoperoxidase studies of cardiac allografts harvested from rats receiving intravenous splenocytes also showed markedly reduced humoral deposits and cellular infiltrates, comparable to that found in the oral splenocytes-treated group, but showed significantly different cytokine expression. In particular, some intragraft mononuclear cell labeling for IFN-gamma remained, and IL-4 staining was not increased relative to control grafts. Attempts were then made to abrogate spleen cell-induced prolongation of cardiac allograft survival by daily injections of CD4 monoclonal antibody (BWH-4 mAb, 700 micrograms) from the time of cardiac transplantation, therapy previously shown unable to prolong cardiac survival in this model when commenced after skin graft-induced sensitization has occurred.(ABSTRACT TRUNCATED AT 400 WORDS)

The effects of oral administration of major histocompatibility antigens on the alloimmune response have not been investigated. Lymphocytes from inbred LEW (RT1u) rats that were pre-fed allogeneic WF (RT1l) splenocytes exhibited significant antigen specific reduction of the mixed lymphocyte response in vitro and delayed-type hypersensitivity response in vivo, when compared with unfed controls. In an accelerated allograft rejection model, LEW rats were presensitized with BN (RT1n) skin allografts 7 days before challenging them with (LEW x BN)F1 or BN vascularized cardiac allografts. While sensitized control animals hyperacutely reject their cardiac allografts within 2 days, animals prefed with BN splenocytes maintained cardiac allograft survival to 7 days, a time similar to that observed in unsensitized control recipients. This phenomenon was antigen-specific, as third-party WF grafts were rejected within 2 days. Immunohistologic examination of cardiac allografts harvested on day 2 from the fed animals had markedly reduced deposition of IgG, IgM, C3, and fibrin. In addition, there were significantly fewer cellular infiltrates of total white blood cells, neutrophils, macrophages, T cells, IL-2 receptor-positive T cells, and mononuclear cells with positive staining for the activation cytokines IL-2 and IFN-g. On day 6 posttransplant, the grafts from fed animals showed immunohistologic changes typical of acute cellular rejection usually seen in unsensitized rejecting controls. Feeding allogeneic splenocytes prevents sensitization by skin grafts and transforms accelerated rejection of vascularized cardiac allografts to an acute form typical of unsensitized recipients. Oral administration of alloantigen provides a novel approach to down-regulate the specific systemic alloimmune response against histocompatibility antigens.

We studied the effects and mechanism of action of BWH-4, an IgG2a mouse antirat CD4 monoclonal antibody that recognizes a distinct epitope on the CD4 molecule, in LEW recipients of (LEW x BN)F1 vascularized heterotopic cardiac allografts. Ten animals received daily injections of 700 micrograms BWH-4 for ten days after engraftment. Median actuarial allograft survival was 37 days for the treated animals compared with 7.5 days for controls (n = 6). There was depletion of peripheral blood CD4+ lymphocytes to 4 +/- 1% one week posttransplant (normal = 48 +/- 4%, n = 6). Six additional animals were treated with a lower dose (100 micrograms) of BWH-4 daily for ten days. Median actuarial allograft survival was 10 days and the circulating CD4+ cells decreased to 30 +/- 6% at one week posttransplant. All six low-dose-treated animals mounted an anti-BN alloantibody response by 3 weeks, while only one of the ten high-dose-treated animals had positive alloantibodies two weeks posttransplant. Lymphocyte-mediated cytotoxicity against donor lymphoblasts was completely abolished in the high-dose-treated animals when compared with acutely rejecting controls. We also used low-dose (100 micrograms) BWH-4 to pretreat eleven experimental animals for 7 days prior to engraftment. The circulating CD4+ cells decreased to only 12 +/- 2% on the day of transplantation and 26 +/- 9% one week posttransplant. However, six (55%) pretreated animals survived more than 55 days. There was a 66% decrease in lymphocyte-mediated cytotoxicity against donor lymphoblasts when compared with acutely rejecting controls. We conclude that the anti-CD4 mAb, BWH-4, prevents acute rejection of vascularized heterotopic rat cardiac allografts; this effect is mediated by depletion of the CD4+ T cell subset, suppression of alloantibody production, and inhibition of lymphocyte-mediated cytotoxicity.

Although CD4-targeted therapy markedly prolongs survival of organ allografts in naive rodents, its effects in primed hosts have not been studied. In our model of accelerated rejection (ACCR) of cardiac Tx in rats, treatment with BWH-4, a CD4 mAb (IgG2a), in the sensitization (between skin and heart Tx) but not in the effector (after cardiac Tx) phase, abrogated fulminant less than 36 hr rejection response and prolonged Tx survival to ca. 11 days. This effect correlated with decreased frequency of circulating CD4+ cells, but it did not depend upon their total depletion. It was also related to BWH-4 mAb-mediated elimination/depression of strong anti-donor humoral responses and cellular responses as determined by lymphocyte-mediated cytotoxicity and mixed lymphocyte reaction and mounted otherwise at the time of engraftment by untreated sensitized hosts. Immunoperoxidase studies of cardiac Tx from BWH-4-conditioned recipients revealed reduced T and B cell activities, reflected in abolition/reduction in deposition of humoral mediators, infiltrating cells, intra-Tx elaboration of interleukin-2 and interferon-gamma, and cell activation. This first report of the successful use of CD4 mAb in sensitized recipients of vascularized organ Tx, stresses the role of CD4+ cells as potential targets for immunosuppression in the sensitization phase of accelerated Tx injury. The beneficial therapeutic effect, probably due to both depletion and functional inhibition of CD4+ T cells, has been achieved by using relatively low doses of BWH-4 mAb.

Cochlear implant surgery was performed in four Cantonese-speaking postlingually deaf Chinese adults, using the House/3M single channel device. This article outlines the methodology, including preoperative assessment and postoperative rehabilitation; and explains the necessary modifications in speech and audiologic work-up in Cantonese-speaking patients. Salient features of Cantonese phonetics, especially its tonal characteristics, are described. The findings of the study are presented. The results of the cochlear implant would suggest a performance superior to that of the hearing aid. Furthermore, the cochlear implant is able to detect tonal cues. This quality of the cochlear implant may prove to be a valuable asset to a tonal language-speaking cochlear implantee.