Medication-assisted treatment and self-help group participation among military veterans with opioid or alcohol use disorder.

INTRODUCTION: Medication-assisted treatment (MAT) is a combination of behavioural therapy and medications to assist with recovery and has been administered to individuals with alcohol and opioid withdrawal symptoms. Military veterans seeking MAT could have barriers preventing them from receiving the care they desire. The present study sought to compare outcomes in individuals who received MAT or those who participated in self-help groups for opioid or alcohol use disorder. In addition, the present study sought to compare outcomes between veterans and non-military-connected individuals. METHODS: We used the 2015-2017 United States Treatment Episode Data Set Discharges data from the Substance Abuse and Mental Health Services Administration. The data set included 138 594 unique discharges. A multinomial logistic regression model was used to examine differences in substance use outcomes for veterans/non-veterans in MAT and a self-help group. RESULTS: Fewer veterans (2.58%) than non-veterans (4.28%) reported usage of MAT. Fewer veterans (38.94%) than non-veterans (40.17%) reported signing up for a self-help group. Finally, those who participated in MAT and a self-help group had a better outcome (66.64%)-defined as no substance use at discharge-than those who only received MAT (43.02%) and those who did not participate in MAT or self-help groups (34.84%). CONCLUSIONS: Recommendations for future research on MAT and implementation for the veteran population would benefit the literature base.

Sex steroid hormones in depressive disorders as a basis for new potential treatment strategies.

The sex steroid hormones (SSHs) such as testosterone, estradiol, progesterone, and their metabolites have important organizational and activational impacts on the brain during critical periods of brain development and in adulthood. A variety of slow and rapid mechanisms mediate both organizational and activational processes via intracellular or membrane receptors for SSHs. Physiological concentrations and distribution of SSHs in the brain result in normal brain development. Nevertheless, dysregulation of hormonal equilibrium may result in several mood disorders, including depressive disorders, later in adolescence or adulthood. Gender differences in cognitive abilities, emotions as well as the 2-3 times higher prevalence of depressive disorders in females, were already described. This implies that SSHs may play a role in the development of depressive disorders. In this review, we discuss preclinical and clinical studies linked to SSHs and development of depressive disorders. Our secondary aim includes a review of up-to-date knowledge about molecular mechanisms in the pathogenesis of depressive disorders. Understanding these molecular mechanisms might lead to significant treatment adjustments for patients with depressive disorders and to an amelioration of clinical outcomes for these patients. Nevertheless, the impact of SSHs on the brain in the context of the development of depressive disorders, progression, and treatment responsiveness is complex in nature, and depends upon several factors in concert such as gender, age, comorbidities, and general health conditions.

Rapid actions of oestrogens and their receptors on memory acquisition and consolidation in females.

Increased attention has been paid in recent years to the ways in which oestrogens and oestrogen receptors rapidly affect learning and memory. These rapid effects occur within a timeframe that is too narrow for the classical genomic mode of action of oestrogen, thus suggesting nonclassical effects as underlying mechanisms. The present review examines recent developments in the study of the rapid effects of 17ß-oestradiol and oestrogen receptor (ER) agonists on learning and memory tasks in female rodents, including social recognition, object recognition, object placement (spatial memory) and social learning. By comparing studies utilising systemic or intracranial treatments, as well as pre- and post-acquisition administration of oestradiol or ER agonists, the respective contributions of individual ERs within specific brain regions to various forms of learning and memory can be determined. The first part of this review explores the effects of systemic administration of 17ß-oestradiol and ER agonists on memory when administered either pre- or post-acquisition. The second part not only focuses on the effects of pre- and post-acquisition infusions of 17ß-oestradiol or ER agonists into the dorsal hippocampus on memory, but also discusses the contributions of other brain regions, including the medial amygdala, medial prefrontal cortex and paraventricular nucleus of the hypothalamus. The cellular mechanisms mediating the rapid effects of 17ß-oestradiol on memory, including activation of intracellular signalling cascades and epigenetic processes, are discussed. Finally, the review concludes by comparing pre- and post-acquisition findings and effects of 17ß-oestradiol and ER agonists in different brain regions.

Healthcare utilisation among cancer survivors over 50 years of age.

There are now over 104,000 people living in Ireland with a cancer diagnosis. Using The Irish Longitudinal Study on Ageing (TILDA), healthcare utilisation of cancer survivors (aged 50 +) was compared with those without a history of cancer across service providers. Our cancer variable was stratified by time since diagnosis (2-5, 6-10, 11+ years) and type (breast, prostate, colorectal and a miscellaneous group of other cancers). While the probability of cancer survivors accessing GP services was not significant different to respondents without a history of cancer, the probability of an outpatient specialist office visit was 19.5, 11.8 and 14.0 percentage points higher, respectively for those 2-5years, 6-10 years and 11 years or more after their cancer diagnosis and was statistically significant. In Ireland, the pattern of GP and specialist use appears less well defined compared to other European countries. This suggests an overarching policy response is required for cancer survivorship care.

Home-Telemonitoring Lung Cancer Intervention in Appalachia: A Pilot Study.

Benefits of home-telemonitoring for rural dwelling cancer patients are largely unknown. This study examined the effectiveness of home-telemonitoring surveillance with nurse coaching for self-management to improve lung cancer outcomes in mountainous Appalachia where health care access/ service is limited. This randomized clinical trial pilot study compared patient outcomes for telemonitoring versus routine care. A convenience sample (N = 47) was enrolled/ randomized (Telemonitored: 26/ Control: 21) from a university hospital and cancer center. Physiologic parameters and symptoms were collected in the telemonitored group for two weeks; all participants were studied for 60 days after the index treatment/ discharge. The telemonitored group showed greater improvement for both functional status (Wald X2 = 3.78, p = .05) and quality of life (QOL) (Wald X2 = 7.25, p = .007) from baseline to 60 days post-discharge. Compared to controls, telemonitored patients survived longer; had more scheduled medical visits (96% vs. 75%); made more unplanned calls to doctors/ nurses (32% vs. 30% & 64% vs. 50%); had fewer rehospitalizations (28% vs. 40%); and had more ER utilization (36% vs. 30%). The telemonitored group had relative improvements for health utility (.09 on a scale where 0 = death/ 1= perfect health) and QOL (15 on 0-100 VAS). Differences in health care utilization and cost were not significantly different (p > .05), likely due to the sample size. Telemonitoring group satisfaction with care was high and recommended by patients and caregivers. Results suggest that it is possible to improve patient outcomes with home-telemonitoring for self-management in rural areas. Short-term, telemonitoring-based coaching is feasible and offers a promising option to develop patient self-management knowledge and skills.

Epigenetics, oestradiol and hippocampal memory consolidation.

Epigenetic alterations of histone proteins and DNA are essential for hippocampal synaptic plasticity and cognitive function, and contribute to the aetiology of psychiatric disorders and neurodegenerative diseases. Hippocampal memory formation depends on histone alterations and DNA methylation, and increasing evidence suggests that the regulation of these epigenetic processes by modulatory factors, such as environmental enrichment, stress and hormones, substantially influences memory function. Recent work from our laboratory suggests that the ability of the sex-steroid hormone 17ß-oestradiol (E2 ) to enhance novel object recognition memory consolidation in young adult female mice is dependent on histone H3 acetylation and DNA methylation in the dorsal hippocampus. Our data also suggest that enzymes mediating DNA methylation and histone acetylation work in concert to regulate the effects of E2 on memory consolidation. These findings shed light on the epigenetic mechanisms that influence hormonal modulation of cognitive function, and may have important implications for understanding how hormones influence cognition in adulthood and ageing. The present review provides a brief overview of the literature on epigenetics and memory, describes in detail our findings demonstrating that epigenetic alterations regulate E2 -induced memory enhancement in female mice, and discusses future directions for research on the epigenetic regulation of E2 -induced memory enhancement.

Global cost of correcting vision impairment from uncorrected refractive error.

OBJECTIVE: To estimate the global cost of establishing and operating the educational and refractive care facilities required to provide care to all individuals who currently have vision impairment resulting from uncorrected refractive error (URE). METHODS: The global cost of correcting URE was estimated using data on the population, the prevalence of URE and the number of existing refractive care practitioners in individual countries, the cost of establishing and operating educational programmes for practitioners and the cost of establishing and operating refractive care facilities. The assumptions made ensured that costs were not underestimated and an upper limit to the costs was derived using the most expensive extreme for each assumption. FINDINGS: There were an estimated 158 million cases of distance vision impairment and 544 million cases of near vision impairment caused by URE worldwide in 2007. Approximately 47 000 additional full-time functional clinical refractionists and 18 000 ophthalmic dispensers would be required to provide refractive care services for these individuals. The global cost of educating the additional personnel and of establishing, maintaining and operating the refractive care facilities needed was estimated to be around 20 000 million United States dollars (US$) and the upper-limit cost was US$ 28 000 million. The estimated loss in global gross domestic product due to distance vision impairment caused by URE was US$ 202 000 million annually. CONCLUSION: The cost of establishing and operating the educational and refractive care facilities required to deal with vision impairment resulting from URE was a small proportion of the global loss in productivity associated with that vision impairment.

Cost-effectiveness analysis of targeted and sequential screening strategies for latent tuberculosis.

SETTING: No cost-effectiveness studies of testing for latent tuberculosis infection have incorporated both targeted testing and the use of interferon-gamma release assays (IGRAs) in heterogeneous populations. OBJECTIVE: To examine the cost-effectiveness of universal vs. targeted and sequential testing strategies and the use of tuberculin skin testing (TST) vs. IGRAs. DESIGN: Using a decision-analytic model, incremental cost-effectiveness ratios were calculated in 2009 among nine potential strategies for screening recruits. A societal perspective was taken over a 20-year analytic horizon, discounting future costs at 3% annually. Sensitivity analyses were conducted to determine how changes in assumptions affected the estimates. RESULTS: Targeted strategies cost over US$250 000 per case prevented, whereas universal testing strategies cost over US$700 000 per incremental case prevented in base case and most sensitivity analyses. CONCLUSION: Targeted testing offered the best value in this population, although it was still relatively expensive compared to no testing. Sequential testing with both TST and IGRAs provided a poor incremental value compared to targeted and universal testing strategies. Targeted testing using TST was slightly more cost-effective than targeted testing using either QuantiFERON®-TB Gold In-Tube or T-SPOT®.TB, but these estimates were very sensitive to changes in model assumptions.

Potential lost productivity resulting from the global burden of uncorrected refractive error.

OBJECTIVE: To estimate the potential global economic productivity loss associated with the existing burden of visual impairment from uncorrected refractive error (URE). METHODS: Conservative assumptions and national population, epidemiological and economic data were used to estimate the purchasing power parity-adjusted gross domestic product (PPP-adjusted GDP) loss for all individuals with impaired vision and blindness, and for individuals with normal sight who provide them with informal care. FINDINGS: An estimated 158.1 million cases of visual impairment resulted from uncorrected or undercorrected refractive error in 2007; of these, 8.7 million were blind. We estimated the global economic productivity loss in international dollars (I$) associated with this burden at I$ 427.7 billion before, and I$ 268.8 billion after, adjustment for country-specific labour force participation and employment rates. With the same adjustment, but assuming no economic productivity for individuals aged > 50 years, we estimated the potential productivity loss at I$ 121.4 billion. CONCLUSION: Even under the most conservative assumptions, the total estimated productivity loss, in $I, associated with visual impairment from URE is approximately a thousand times greater than the global number of cases. The cost of scaling up existing refractive services to meet this burden is unknown, but if each affected individual were to be provided with appropriate eyeglasses for less than I$ 1000, a net economic gain may be attainable.

Dose-dependent effects of post-training estradiol plus progesterone treatment on object memory consolidation and hippocampal extracellular signal-regulated kinase activation in young ovariectomized mice.

Previous work from our laboratory has shown that the ability of estradiol to enhance object memory consolidation in young ovariectomized mice is dependent on dorsal hippocampal activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway [Fernandez SM, Lewis MC, Pechenino AS, Harburger LL, Orr PT, Gresack JE, Schafe GE, Frick KM (2008) Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors. J Neurosci 28:8660-8667]. However, it is unclear if estradiol modulates memory or ERK activation similarly in the presence of progesterone. Therefore, the present study investigated effects of combined estradiol and progesterone treatment on object memory consolidation and dorsal hippocampal ERK activation in young ovariectomized C57BL/6 mice. Object memory was tested in a novel object recognition task. Immediately after training, mice received intraperiotoneal (i.p.) injections of vehicle, 17beta-estradiol (E(2); 0.2 mg/kg), or E(2) plus 5, 10, or 20 mg/kg progesterone (P). Forty-eight hours later, mice receiving E(2) alone or E(2) plus 10 or 20 mg/kg P exhibited significantly enhanced memory for the novel object relative to chance, whereas those receiving vehicle or E(2) plus 5 mg/kg P spent no more time than chance with the novel object. Two weeks later, ERK phosphorylation was measured in the dorsal hippocampus 1 h after i.p. injection of vehicle, E(2), or E(2) plus P. Consistent with our previous work [Fernandez SM, Lewis MC, Pechenino AS, Harburger LL, Orr PT, Gresack JE, Schafe GE, Frick KM (2008) Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors. J Neurosci 28:8660-8667], E(2) alone significantly increased phospho-p42 ERK protein levels in the dorsal hippocampus relative to vehicle controls. In contrast, no combination of E(2) and P affected dorsal hippocampal phospho-ERK levels. These data indicate that, unlike E(2) alone, the beneficial effects of combined E(2) plus P treatment on memory are not associated with ERK activation in the dorsal hippocampus 1 h after treatment, and suggest that E(2) alone and combined E(2) plus P may influence ERK activation in different time frames or enhance memory through different mechanisms.

Sex differences in contextual fear conditioning are associated with differential ventral hippocampal extracellular signal-regulated kinase activation.

Although sex differences have been reported in hippocampal-dependent learning and memory, including contextual fear memories, the underlying molecular mechanisms contributing to such differences are not well understood. The present study examined the extent to which sex differences in contextual fear conditioning are related to differential activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK), a protein kinase critically involved in memory formation. We first show that male rats exhibit more long-term retention of contextual fear conditioning than female rats. During a tone test, females spent more time freezing than males, although both sexes exhibited robust retention of auditory fear learning. Using Western blot analysis, we then show that phosphorylated ERK levels in ventral, but not dorsal, hippocampus are higher in males than females, relative to same-sex controls, 60 minutes after fear conditioning. Post-conditioning increases in ERK activation were observed in the amygdala in both males and females, suggesting a selective effect of sex on hippocampal ERK activation. Together, these findings suggest that differential activation of the ERK signal transduction pathway in male and female rats, particularly in the ventral hippocampus, is associated with sex differences in contextual fear.

Finding the ideal place for a psychotherapeutic intervention in a stepped care approach--a brief overview of the literature and preliminary results from the Project PREDICT.

AIMS: To provide an overview over empirical evidence regarding stepped care approaches that include psychotherapies. To present own preliminary study results in alcohol dependent patients. METHODS: Publications were searched in the databases Medline, PsycINFO and the internet search engine Google Scholar. Inclusion criteria were psychosocial treatment and psychiatric disorders. Our own study consists of two steps. In step 1 patients receive anti-craving medication or placebo and Medical Management (MM). After a relapse to heavy drinking patients can step up and after randomization they either continue with the same treatment or they receive additional alcoholism specific psychotherapy (ASP). RESULTS: Evidence suggests that stepped care might be efficacious in patients with obsessive-compulsive behavior and depression. There is no evidence for efficacy in problem drinkers. Results of our own study show that the completer rate in MM alone is higher than in ASP with MM, but there are no significant differences concerning age, sex and disease severity between completer and non-completer in both study arms. CONCLUSIONS: Further research with regard to stepped care in alcohol dependent patients is needed. An introduction of the psychotherapy at earlier stages might be sensible.

Assessment of health state utilities of controlled and uncontrolled psoriasis and atopic eczema: a population-based study.

BACKGROUND: Health utilities are used to express relevant trade-offs for resource allocation. The absence of valid and generalizable utilities for atopic eczema (AE) and psoriasis limits the validity of previous cost-utility analyses. OBJECTIVES: (i) To assess health utilities of standardized scenarios of controlled and uncontrolled AE and psoriasis in participants from the general population and in patients using the time trade-off (TTO) method; (ii) to test the association of the utilities obtained with demographic and patient characteristics; and (iii) to compare these utilities with other health economic outcomes [utilities assessed on visual analogue scale (VAS), willingness to pay (WTP)]. METHODS: A single-centre study conducted in 2006 at the Department of Dermatology, Dresden, Germany. Standardized interactive computer-assisted interviews in a random sample from the general population (n=139), and patients with AE (n=58) and psoriasis (n=62). Information on health states included characteristic clinical pictures and a short text explaining aetiology, signs, symptoms and quality of life impact. RESULTS: In participants from the general population median utilities (TTO) of controlled and uncontrolled AE were 0.97 and 0.64, respectively. For psoriasis the corresponding utilities were 0.93 and 0.56. Utilities were independent of sex and socioeconomic position, and tended to be lower in patients with psoriasis. Correlations between TTO, VAS and WTP responses were weak. CONCLUSIONS: To avoid uncontrolled psoriasis or eczema participants chose an approximately 40% shorter life expectancy. This indicates that severe chronic inflammatory skin diseases may be considered as severe as angina pectoris, chronic anxiety, rheumatoid arthritis, multiple sclerosis or regional oesophageal cancer. The different economic outcomes assessed are not interchangeable.

Environmental enrichment reduces the mnemonic and neural benefits of estrogen.

The degree to which memory is enhanced by estrogen replacement in postmenopausal women may depend on environmental factors such as education. The present study utilized an animal model of environmental enrichment to determine whether environmental factors influence the mnemonic and neural response to estrogen. Female mice were raised in standard (SC) or enriched (EC) conditions from weaning until adulthood (7 months). All mice were ovariectomized at 10 weeks, and tested in object recognition and water-escape motivated radial arm maze (WRAM) tasks at 6 months. Each day at the completion of training, mice received injections of 0.1 mg/kg cyclodextrin-encapsulated 17-beta-estradiol (E2), 0.2 mg/kg E2, or cyclodextrin vehicle (VEH). At the completion of behavioral testing, hippocampal levels of the presynaptic protein synaptophysin and of brain-derived neurotrophic factor (BDNF) were measured. Enrichment effects were evident in VEH-treated mice; relative to SC-VEH females, EC-VEH females committed fewer working memory errors in the WRAM and exhibited increased hippocampal synaptophysin levels. Estrogen effects depended on environmental conditions. E2 (0.2 mg/kg) improved object memory only in SC females. The same dose improved working memory in SC females, but somewhat impaired working memory in EC females. Furthermore, both doses reduced hippocampal synaptophysin levels in EC, but not SC, females. In contrast, E2 reduced hippocampal BDNF levels in SC, but not EC, females. This study is the first to compare the effects of estrogen on memory and hippocampal function in enriched and non-enriched female mice. The results suggest that: (1) estrogen benefits object and working memory more in mice raised in non-enriched environments than in those raised in enriched environments, and (2) the changes induced by estrogen and/or enrichment may be associated with alterations in hippocampal synaptic plasticity.

Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice.

Estrogen deficiency during menopause is often associated with memory dysfunction. However, inconsistencies regarding the ability of estrogen to improve memory in menopausal women highlight the need to evaluate, in a controlled animal model, the potential for estrogen to alleviate age-related mnemonic decline. The current study tested whether estrogen could ameliorate spatial reference memory decline in aged female mice. At the conclusion of testing, levels of the presynaptic protein synaptophysin, and activities of the synthetic enzymes for acetylcholine and GABA, were measured in the hippocampus and neocortex. Aged (27-28-month-old) female C57BL/6 mice were given daily subcutaneous injections of 1 microg or 5 microg of beta-estradiol-3-benzoate dissolved in sesame oil. Control mice received daily injections of sesame oil or no injections. Estradiol treatment began 5 days prior to behavioral testing and continued throughout testing. Spatial and non-spatial memory were assessed in the Morris water maze. The 5 microg dose of estradiol significantly improved spatial learning and memory in aged females. The performance of 5 microg females improved significantly more rapidly than that of control females; estradiol-treated females performed at asymptotic levels by session 2. Furthermore, 5 microg females exhibited a more robust spatial bias than controls during probe trials. In contrast, 1 microg of estradiol did not improve spatial task performance. Neither dose affected performance of the non-spatial task. In the hippocampus, synaptophysin was increased in 5 microg females relative to controls. Estrogen did not affect enzyme activities in either brain region. This study is the first to examine the effects of estrogen replacement on spatial reference memory and synaptophysin expression in aged post-estropausal female rodents. The results suggest that: (1) estrogen can profoundly improve spatial reference memory in aged females, and (2) this improvement may be related to increased hippocampal synaptic plasticity, but not modulation of the synthetic enzymes for acetylcholine and GABA.

Validity and responsiveness of the euroqol as a measure of health-related quality of life in people enrolled in an AIDS clinical trial.

OBJECTIVE: Brief utility measures are needed in clinical trials in addition to existing descriptive measures of health-related quality of life (HRQOL). We examined the reliability and validity of the EuroQol (EQ-SD) and MOS-HIV and their responsiveness to HIV-related clinical events. METHODS: Subjects with advanced HIV disease (CD4 < 100) were enrolled in a randomized trial for CMV prophylaxis (n = 990). The EQ-5D includes a weighted sum of five domains (EQ-5D Index) and a visual analog scale (EQ-VAS). The MOS-HIV has 10 subscales and physical (PHS) and mental health summary scores (MHS). Construct validity of the EQ-5D was tested based on hypothesized relationships to subscales of the MOS-HIV. Relative precision and responsiveness to adverse experiences and opportunistic infections (Ols) were compared for the two instruments. RESULTS: Mean age of the patients was 38, 94% were male, 80% white, and 7% had injected drugs. Mean baseline scores for EQ-5D Index and EQ-VAS were 0.80 and 76.0, respectively, 28 and 4% reported maximum scores. Mean MOS-HIV subscales score ranged from 55 (role) to 84 (cognitive); mean PHS and MHS were 47.4 and 49.5, respectively. Correlations between MOS-HIV subscales and EQ-5D Index ranged from 0.45 (role) to 0.63 (pain); correlations with EQ-VAS ranged from 0.33 (cognitive) to 0.66 (health perceptions). Correlations between MOS-HIV PHS and MHS with EQ-5D Index were 0.61 and 0.58; and with EQ-VAS, 0.57 and 0.60, respectively. Responsiveness to adverse experiences was highest for MOS-HIV pain and PHS (effect sizes = 0.9 and 0.4); pain had the highest relative precision (2.4) for adverse experiences: EQ-VAS had the greatest relative precision (1.6) for developing an OI. CONCLUSION: In these patients with advanced HIV disease. EQ-5D showed good construct validity, but there may be a ceiling effect for its EQ-5D Index component. EQ-5D was less responsive to adverse events than the MOS-HIV. However, the EQ-VAS was most sensitive to developing an OI and is likely to be a useful measure of HRQOL for generating QALYs in cost-utility studies involving patients with advanced HIV disease.

Azithromycin for the treatment and control of trachoma.

Trachoma, a recurrent follicular conjunctivitis caused by Chlamydia trachomatis, is the leading cause of preventable blindness worldwide. Efforts to control this disease have met with limited success. This failure is due in part to the limitations of conventional antibiotic treatment, a prolonged course of topical tetracycline. Azithromycin, an azalide antibiotic, is effective against chlamydial infections when given as a single oral dose. Recent research from Africa has shown azithromycin to be as effective as tetracycline in the treatment of trachoma. Under operational conditions azithromycin proved to be more effective. This success is attributed to a much-improved compliance with treatment. Community-wide mass treatment with azithromycin is advocated as a means of controlling trachoma in endemic countries. Questions still remain over the use of azithromycin for this purpose. The frequency and target population of mass distribution campaigns need to be defined. A few countries are beneficiaries of a philanthropic donation by the manufacturer of azithromycin, Pfizer Inc. However, in the absence of a drug donation programme the cost-effectiveness of this measure is unclear.