Oral corticosteroid dosage and taper duration at onset in myelin oligodendrocyte glycoprotein antibody-associated disease influences time to first relapse.

BACKGROUND: We sought to identify an optimal oral corticosteroid regimen at the onset of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), which would delay time to first relapse while minimising cumulative corticosteroid exposure. METHODS: In a retrospective multicentre cohort study, Cox proportional hazards models examined the relationship between corticosteroid course as a time-varying covariate and time to first relapse. Simon-Makuch and Kaplan-Meier plots identified an optimal dosing strategy. RESULTS: We evaluated 109 patients (62 female, 57%; 41 paediatric, 38%; median age at onset 26 years, (IQR 8-38); median follow-up 6.2 years (IQR 2.6-9.6)). 76/109 (70%) experienced a relapse (median time to first relapse 13.7 months; 95% CI 8.2 to 37.9). In a multivariable model, higher doses of oral prednisone delayed time to first relapse with an effect estimate of 3.7% (95% CI 0.8% to 6.6%; p=0.014) reduced hazard of relapse for every 1 mg/day dose increment. There was evidence of reduced hazard of relapse for patients dosed ≥12.5 mg/day (HR 0.21, 95% CI 0.07 to 0.6; p=0.0036), corresponding to a 79% reduction in relapse risk. There was evidence of reduced hazard of relapse for those dosed ≥12.5 mg/day for at least 3 months (HR 0.12, 95% CI 0.03 to 0.44; p=0.0012), corresponding to an 88% reduction in relapse risk compared with those never treated in this range. No patient with this recommended dosing at onset experienced a Common Terminology Criteria for Adverse Events grade >3 adverse effect. CONCLUSIONS: The optimal dose of 12.5 mg of prednisone daily in adults (0.16 mg/kg/day for children) for a minimum of 3 months at the onset of MOGAD delays time to first relapse.

The impact of wearing complete denture in one or both arches, on eating-related quality of life and patients' perceived need for advice to support eating well: Results from a qualitative study.

BACKGROUND: Wearing complete denture in one or both arches can impact enjoyment of eating and affect quality of life compared with being dentate. Clinicians focus on issuing technically sound dentures but ignore the impact of wearing dentures on the eating-related quality of life which affects the success of treatment. OBJECTIVES: The aim of this research was to qualitatively explore ERQoL in Australian adults wearing complete dentures using a validated questionnaire and through focus groups. METHODS: Complete denture wearers (n = 44) were recruited from dental clinics and invited to complete the self-administered Emotional and Social Issues Related to Eating questionnaire. Responses were categorised under the six questionnaire domains. A subsample of 20 participants who completed the questionnaire were invited to participate in focus groups to identify emerging themes. RESULTS: Twenty-three participants (52.3%) completed the questionnaire. Most participants expressed a decline in enjoyment of eating due to reduced ability to eat, longer chewing times and the need to frequently clean dentures while eating. Focus groups (n = 2 × 4 participants) indicated educational materials on eating with dentures would increase recognition of eating problems with dentures and reduce trial and error approaches to dealing with these. CONCLUSION: ERQoL is adversely affected by wearing complete dentures due to functional limitations, restricted food choices and adaptive eating behaviours. Patient support for eating well with a complete denture/s wearers is required.

Hepatitis B among immigrants from Myanmar: Genotypes and their clinical relevance.

Hepatitis B virus (HBV) from 76 adult immigrants in Australia from Myanmar was characterized to determine the prevalence of different HBV genotypes and subgenotypes. A mutational analysis was then performed to determine the presence of clinically significant mutations and correlate them to clinical outcomes. Initial genotyping revealed 68 patients with genotype C (89.5%) and eight patients with genotype B (10.5%). Phylogenetic analysis revealed the large majority of the genotype C infections were of subgenotype C1 (67/68). Sequencing of the HBV polymerase gene (and overlapping surface gene) revealed no mutations associated with antiviral resistance. HBV surface gene mutations were detected in 10 patients with subgenotype C1. HBV BCP/PC sequencing was obtained for 71/76 (93%) patients. BCP and/or PC mutations were identified in 57/71 (80%) of PCR positive patients. Treatment had been commenced for 15/76 (18%) patients, a further 26 untreated patients were in a stage of disease where HBV treatment would be considered standard of care. It was identified that genotype C1 is the predominant sub-genotype in this population. Genotype C is known to be associated with increased risk of development of HCC. This highlights the need for screening for HCC given the potential for the development of liver cancer. It was also identified that people with HBV were potentially not receiving optimal therapy in a timely fashion.

Genotypic profiles of hepatitis B in African immigrants and their clinical relevance.

Hepatitis B virus (HBV) from 40 adult African immigrants in Australia was characterized to determine the prevalence of different HBV genotypes and subgenotypes. A mutational analysis was then performed to determine the presence of clinically significant mutations and correlate them to clinical outcomes. Initial sequencing analysis revealed 13 with genotype A (32.5%), 13 with genotype D (32.5%), and 14 with genotype E (35%). Serology showed that 37 were HBeAg negative. Phylogenetic analysis identified a high prevalence (25%) of HBV subgenotype A1 in our cohort, a subgenotype which has been associated with more aggressive clinical disease. BCP/PC sequencing was obtained for 38 patients. BCP and/or PC mutations were identified in 36/38 (95%). The median viral load of all patients was 2995 IU/mL and most of the pathology results were within the normal range. Only one patient had an increased APRI score of 1.1 suggestive of cirrhosis. We present novel information on the HBV genotypes amongst the African population in Australia along with clinical correlates. The high prevalence of A1 subgenotype in this population supports the current Australian recommendation to commence hepatocellular carcinoma screening in Africans with chronic HBV from 20 years old.

Impact of cinacalcet pre-transplantation on mineral metabolism in renal transplant recipients.

AIM: Cinacalcet is effective in reducing parathyroid hormone (PTH) in patients on dialysis. Reports of biochemical profiles and other clinical outcomes in patients discontinuing cinacalcet at time of renal transplantation are limited. METHODS: A retrospective study assessing markers of mineral metabolism, graft and patient outcomes in renal transplant recipients to determine differences in patients discontinuing cinacalcet (C+) compared with patients not treated with cinacalcet (C-) at time of transplantation. To allow for differences between groups in pre-transplant biochemical parameters, we also analysed a matched cohort of C- with C+ recipients (2:1), matched for age, calcium and PTH levels at transplantation. RESULTS: Five hundred thirty-two recipients (460 C-, 72 C+), transplanted January 2006-December 2012, were analysed, mean age 48.0 ± 12.7 years and 64.3% were men. At a median 42.9 months follow up, there were 10 deaths (1.9%), 56 allograft loss (10.6%) and 5 parathyroidectomies post-transplant (0.8%). Median PTH immediately pre-transplant was higher in C+ versus C- (50.7(25.4-75.2) versus 28.3(13.9-49.7) pmol/L, P < 0.001). Twelve-month post-transplant PTH was reduced but higher in C+ (11.7(6.9-21.2) vs 7.2(4.6-11.2) pmol/L, P < 0.001). Mean calcium was higher for C+ versus C- at 12 months (2.50 ± 0.19 vs 2.43 ± 0.17 mmol/L, P < 0.001), with differences to 4 years post-transplant. No difference was seen in renal function, graft loss, post-transplant parathyroidectomy rate and mortality. In the matched cohort (144 C- vs 72 C+), similar findings were also seen. CONCLUSION: Differences in mineral metabolism post-transplant are seen with cinacalcet pre-transplant compared with no cinacalcet. Transplant recipients discontinuing cinacalcet had higher post-transplant PTH and calcium although the clinical significance is unclear.

Water-Holding and Transport Properties of Skin Stratum Corneum of Infants and Toddlers Are Different from Those of Adults: Studies in Three Geographical Regions and Four Ethnic Groups.

BACKGROUND/OBJECTIVE: Epidermal structure, function, and composition are different in white infants and adults. We investigated whether ethnicity and location contribute to differences in functional and clinical measurements of skin barrier function during the first years of life and in adults. METHODS: Children (n = 397, ages 3-49 mos) and women (n = 117, mean age 31 yrs) were enrolled at independent centers in Beijing, China (ethnic Chinese), Skillman, New Jersey (white, African American), and Mumbai, India (ethnic South Asian). Water barrier properties of the stratum corneum were assessed using high-frequency conductance and transepidermal water loss (TEWL) on the dorsal forearm and upper inner arm. Digital imaging was used to evaluate facial erythema and scaling. RESULTS: Despite differences in local climate, TEWL was similar in adults. In children, conductance and TEWL decreased monotonically from age 3 months to 4 years. In children from Beijing, TEWL values were higher in both arm locations than in children in Mumbai and Skillman. No significant differences were observed in TEWL or conductance between the white and African American groups. CONCLUSION: In general, TEWL and conductance were greater on the upper inner arm than the dorsal forearm. Erythema and scaling were observed most often in subjects from Beijing and most infrequently in subjects from Mumbai. Stratum corneum water barrier properties were different in children and adults. Although there may be differences in these properties between ethnic groups in childhood, TEWL values were similar in adults across the three geographic locations and four ethnicities.

Developmental Changes in Skin Barrier and Structure during the First 5 Years of Life.

The structure of the stratum corneum (SC) and the corresponding skin barrier develops from before birth up to about 4 years of age. Large subject-to-subject variability within an age group requires a large population to observe trends in skin barrier properties over time. Barrier function, quantified by transepidermal water loss (TEWL) and SC thickness, was measured on the upper inner arm and dorsal forearm in subjects aged 3 months to 4 years (n = 171) and a subset of mothers (n = 44). The rate of skin surface area expansion as a function of age peaked before birth (∼90 cm2/week) and declined to a steady plateau (∼10 cm2/week) by 1 year of age. SC thickness increased and TEWL decreased, but did not reach adult values until 3-4 years of age. A better understanding of how skin hydration changes after birth suggests that barrier function may be related mechanistically to skin surface area expansion.

Non-invasive assessment of tryptophan fluorescence and confocal microscopy provide information on skin barrier repair dynamics beyond TEWL.

The stratum corneum (SC) serves a primary function of skin barrier and understanding the kinetics of SC formation may provide great insight for skin diagnosis and evaluation of therapies. Besides trans-epidermal water loss (TEWL), few methods have been characterized to assess skin barrier non-invasively in vivo, particularly for dynamic measurements on the same specimen over time. The objective of this study was to characterize alternative non-invasive methods to evaluate the dynamic processes involved in the recovery of normal human SC after total removal. TEWL, tryptophan fluorescence and reflectance confocal microscopy (RCM) were used to determine skin barrier function, cell turnover and epidermal morphology over a period of 10 days after total removal of the SC by tape stripping. The results show a biphasic recovery of TEWL over time, which contrasted with a linear increase of 2.3 µm/day in SC thickness. Tryptophan assessment of cell turnover also demonstrated a biphasic pattern attaining a maximum three to four times the levels of the control site 3 days after injury that slowly returned to baseline and displayed great correlation (R(2)  > 0.95) to viable epidermis thickness that also achieved a maximum about 3 days after injury with an approximate increase of 55%. When plotting the change of TEWL versus SC thickness, a single exponential function is observed [Δ-TEWL = 55 exp (-0.157×)] which contrasts with other proposed models. These methods were able to present rates for SC recovery processes beyond skin barrier (TEWL) that may provide new insights on kinetics of barrier formation for evaluation of skin conditions and treatments.

Syphilitic meningitis presenting with multiple cranial neuropathies.

Syphilis is increasingly prevalent in the community. The protean manifestations of neurosyphilis make the recognition, diagnosis and early initiation of treatment challenging. We report a case of early syphilitic meningitis presenting with multiple cranial neuropathies. Cerebrospinal fluid (CSF) examination was inflammatory with predominant lymphocytosis. The patient was diagnosed with neurosyphilis based on serum as well as CSF testing. Intravenous benzylpenicillin treatment resulted in rapid improvement of neurological symptoms. Neurosyphilis should be considered in immunocompetent patients presenting with multiple cranial neuropathies, or isolated cranial neuropathies without vascular risk factors.

Diffuse reflectance spectroscopy for ultraviolet A protection factor measurement: correlation studies between in vitro and in vivo measurements.

BACKGROUND/PURPOSE: Assessing the ultraviolet (UVA) protection factor of sunscreen formulations has been discussed for the past 20 years. The purpose of this study is to correlate the measurements of the UVA protection factor value (PFA value) via in vivo diffuse reflectance spectroscopy (DRS) and to compare this method with the in vitro method of measuring the PFA value, as well as with the in vivo persistent pigment darkening (PPD) and PFA methodologies. METHODS: The UVA protection factor via DRS technique was assessed in two clinical studies. The first study was performed in 12 subjects and the second one consisting of 10 subjects. All subjects in these studies had Fitzpatrick skin phototypes II-IV. DRS measurements were performed using a SkinScan spectrofluorimeter (Spex SkinScan, Yvon Horiba). The in vitro PFA measurements were performed using Labsphere UV-1000s UV Transmission Analyzer. RESULTS: The results obtained from the non-invasive DRS studies were used to correlate with the in vitro testing and with the in vivo PFA/PPD multicenter study. A positive relationship (regression coefficient r(2)=0.90) of PFA values was found between in vitro PFA testing and the in vivo DRS testing. There was also a very good correlation (regression coefficient r(2)=0.99) between the in vivo PFA/PPD values and UVA protection factor obtained from the DRS method. CONCLUSION: This paper presents studies using the DRS technique to assess the UVA protection factor in different sunscreen formulae correlating with in vitro and in vivo PFA/PPD values. It is a fast method, non-invasive and does not involve any subject irradiation. The technique is a good estimator for the in vivo UVA protection factor as well as a way to assess, in vivo, the photostability of sunscreen formulation in the UVA.

High-intensity physical exercise increases serum α-klotho levels in healthy volunteers.

The recently discovered klotho proteins have roles in a diverse range of metabolic processes with the oldest protein, α-klotho, implicated in various cellular pathways in energy, glucose, and phosphate metabolism. Circulating soluble klotho (sKl), derived from membrane α-klotho cleavage, not only has effects on ion channels and insulin signaling pathways, but is inversely associated with mortality. Effects of physical exercise on sKl have not been well studied. The effect of a single high-intensity standardized exercise on sKl and serum phosphate (sPi) levels in healthy adults was investigated. A standard Bruce protocol treadmill exercise was undertaken by 10 fasting healthy volunteers. sKl, sPi, and blood glucose levels were measured in samples collected 1-week prior, immediately pre (Tpre), 0 (Tpost), 30 (T30), 240 (T240) min, and 1-week after exercise. Median (interquartile range) age of participants was 47.5 (44-51) years; five (50%) were male. All study participants achieved at least 90% predicted maximum heart rate (MHR). sKl increased acutely after exercise (Tpre median 448 pg/mL vs. Tpost median 576 pg/mL; p < 0.01). There was a nonsignificant sPi decline at T30 (Tpre 0.94 ± 0.12 mmol/L vs. T30 0.83 ± 0.22 mmol/L). Exercise led to a reduction in blood glucose by T240 with median glucose levels at Tpre, Tpost, T30, and T240 of 6.0, 6.5, 6.3, and 5.7 mmol/L, respectively. In conclusion, a single high-intensity exercise session is associated with a transient increase in sKl, a delayed reduction in blood glucose, and a nonsignificant decrease in sPi levels in healthy adults. The evaluation of long-term effects of cardiovascular fitness programs on sKl and sPi in healthy individuals and disease cohorts are required to identify potential lifestyle modifications to help improve chronic disease management and long-term outcomes.

Lithium administration to preadolescent rats causes long-lasting increases in anxiety-like behavior and has molecular consequences.

Lithium (Li) is frequently used in the treatment of bipolar disorder (BPD), a debilitating condition that is increasingly diagnosed in children and adolescents. Because the symptoms of BPD in children are different from the typical symptoms in adulthood and have significant overlap with other childhood psychiatric disorders, this disorder is notoriously difficult to diagnose. This raises the possibility that some children not affected by BPD are treated with Li during key periods of brain development. The objective of this investigation was to examine the long-term effects of Li on the developing brain via a series of behavioral and molecular studies in rats. Rat pups were reared on Li chow for 3 weeks. Parallel groups were tested while on Li chow or 2 and 6 weeks after discontinuation of treatment. We found increased measures of anxiety-like behavior at all times tested. Gene microarray studies of the amygdala revealed that Li affected the expression of gene transcripts of the synapse and the cytoskeleton, suggesting that the treatment induced synaptic adjustments. Our study indicates that Li can alter the trajectory of brain development. Although the effects of Li on the normal brain seems unfavorable, effects on the abnormal brain cannot be determined from these studies alone and may well be therapeutic. Our results indicate that Li administration to the normal brain has the potential for lasting adverse effects.

A feasibility study of a web-based performance improvement system for substance abuse treatment providers.

We report here on the feasibility of implementing a semiautomated performance improvement system-Patient Feedback (PF)-that enables real-time monitoring of patient ratings of therapeutic alliance, treatment satisfaction, and drug/alcohol use in outpatient substance abuse treatment clinics. The study was conducted in six clinics within the National Institute on Drug Abuse Clinical Trials Network. It involved a total of 39 clinicians and 6 clinic supervisors. Throughout the course of the study (consisting of five phases: training period [4 weeks], baseline [4 weeks], intervention [12 weeks], postintervention assessment [4 weeks], sustainability [1 year]), there was an overall collection rate of 75.5% of the clinic patient census. In general, the clinicians in these clinics had very positive treatment satisfaction and alliance ratings throughout the study. However, one clinic had worse drug use scores at baseline than other participating clinics and showed a decrease in self-reported drug use at postintervention. Although the implementation of the PF system proved to be feasible in actual clinical settings, further modifications of the PF system are needed to enhance any potential clinical usefulness.

Safety, efficacy, and tolerability of nelfinavir-containing antiretroviral therapy for patients coinfected with HIV and hepatitis C undergoing methadone maintenance.

The safety, efficacy, and tolerability of nelfinavir (NFV)-containing antiretroviral therapy were evaluated in patients coinfected with HIV and hepatitis C undergoing methadone maintenance at an urban outpatient opioid treatment program serving a minority adult population. Eligibility covered methadone-maintained patients coinfected with HIV and hepatitis C who had received or were currently receiving NFV. The yield was 51 case patients. Parameters examined looked into safety, efficacy, and tolerability. Nelfinavir was discontinued in 2 patients for liver function abnormalities but resumed in 1 patient. One patient developed laboratory abnormalities during NFV therapy that were not present before NFV therapy; in 12 case patients, pre-NFV therapy liver function abnormalities resolved completely during NFV therapy. There was a statistically significant increase in CD4 count during NFV therapy. Viral load decreased or was unchanged in 10 case patients and increased in 8, of whom 5 had a CD4 count increase during NFV therapy. Three patients had diarrhea and 4 patients had constipation. Nelfinavir was not discontinued -- neither was dose adjusted -- in any of these patients. Patients who had received NFV > or =36 months had a smaller increase in mean methadone dose as compared with patients who had received NFV <36 months. The results show that NFV is safe, efficacious, and well tolerated.

Exposure to interpersonal violence as a predictor of PTSD symptomatology in domestic violence survivors.

This study examines the interrelationships between childhood abuse, exposure to maternal domestic violence, and posttraumatic stress disorder (PTSD) symptomatology in a multiethnic sample of 111 adult female residents of a domestic violence (DV) shelter. Participants completed structured interviews about the DV and their prior violence exposure, as well as the Impact of Event Scale-Revised. As hypothesized, there was high co-occurrence between exposure to maternal DV and childhood physical and sexual abuse, and the frequency of lifetime violence exposure predicted PTSD symptomatology. A series of multiple regressions indicated a more complex pattern of relationships, in which specific forms of prior violence exposure predicted different PTSD symptom dimensions. A history of witnessing maternal DV predicted intrusion symptoms, and a history of childhood sexual abuse predicted hyperarousal symptoms. Ethnicity was not related to levels of violence exposure or to PTSD symptoms. Clinical implications of the findings are discussed.

Coping and violence exposure as predictors of psychological functioning in domestic violence survivors.

This study examines the differential effects of adult and childhood physical and psychological abuse, abuse-specific coping, and psychological adjustment in battered women seeking emergency shelter. Multivariate regression analyses confirmed the devastating impact of psychological abuse (childhood and concurrent) on battered women's adjustment. The results corroborated prior research suggesting a cumulative vulnerability to psychological victimization in a substantial proportion of residents. Unexpectedly, frequency of physical violence was unrelated to women's distress. The study argues that modes of coping traditionally considered adaptive (e.g., engaged, proactive) may be unsafe for battered women and children. The multifaceted nature of survivors' coping choices is discussed.

Skin responses to micro scale field size of solar-simulated radiation--preliminary evaluation by reflectance confocal microscopy in vivo.

Erythema and pigment responses of human skin following an acute exposure to ultraviolet radiation (UVR) are frequently used to determine the photosensitivity of the skin. In this study we investigated the responses of the skin to a micro-scale area of UVR exposure (MiR) and compared the responses to a macro-scale area of exposure (MaR). Ten human volunteers were tested with solar-simulated radiation on their upper arm or back using a beam size of 8 mm and 0.2 mm in diameter. The fluence required to produce a minimally perceptible erythema (MED) using the MiR was found to be higher than that for the MaR. The erythema response extended beyond the exposed area and this became pronounced when the beam size was microscopic. Reflectance confocal microscopy in vivo revealed that MiR induced cellular alterations within a confined area of smaller dimensions than the area of exposure. Pigment responses were confined within the areas of cellular damage. The erythema expression of exposed skin recovered faster for the sites receiving MiR even when the applied fluence was higher than the MED for the MaR. Through the use of MiR we were able to visualize spatially dissimilar skin responses of erythema and pigmentation suggesting different cellular mechanisms.

Electronic health information system at an opioid treatment programme: roadblocks to implementation.

RATIONALE: Electronic health systems are commonly included in health care reform discussions. However, their embrace by the health care community has been slow. METHODS: At Addiction Research and Treatment Corporation, a methadone maintenance programme that also provides primary medical care, HIV medical care and case management, substance abuse counselling and vocational services, we describe our experience in implementing an electronic health information system that encompasses all of these areas. RESULTS: We describe the challenges and opportunities of this process in terms of change management, hierarchy of corporate objectives, process mastering, training issues, information technology governance, electronic security, and communication and collaboration. CONCLUSION: This description may provide practical insights to other institutions seeking to pursue this technology.

Electronic medical record system at an opioid agonist treatment programme: study design, pre-implementation results and post-implementation trends.

RATIONALE: Electronic medical record (EMR) systems are commonly included in health care reform discussions. However, their embrace by the health care community has been slow. METHODS: At Addiction Research and Treatment Corporation, an outpatient opioid agonist treatment programme that also provides primary medical care, HIV medical care and case management, substance abuse counselling and vocational services, we studied the implementation of an EMR in the domains of quality, productivity, satisfaction, risk management and financial performance utilizing a prospective pre- and post-implementation study design. RESULTS: This report details the research approach, pre-implementation findings for all five domains, analysis of the pre-implementation findings and some preliminary post-implementation results in the domains of quality and risk management. For quality, there was a highly statistically significant improvement in timely performance of annual medical assessments (P < 0.001) and annual multidiscipline assessments (P < 0.0001). For risk management, the number of events was not sufficient to perform valid statistical analysis. CONCLUSIONS: The preliminary findings in the domain of quality are very promising. Should the findings in the other domains prove to be positive, then the impetus to implement EMR in similar health care facilities will be advanced.