Cognitive decrements in 1991 Gulf War veterans: associations with Gulf War illness and neurotoxicant exposures in the Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) cohorts.

BACKGROUND: During deployment, veterans of the 1991 Gulf War (GW) were exposed to multiple war-related toxicants. Roughly a third of these veterans continue to exhibit neurotoxicant induced symptoms of Gulf War Illness (GWI), a multi-faceted condition that includes fatigue, pain and cognitive decrements. When studied empirically, both deployed veterans with exposures and those who meet the criteria for GWI are more likely to show deficits in the area of neuropsychological functioning. Although studies have shown cognitive impairments in small sample sizes, it is necessary to revisit these findings with larger samples and newer cohorts to see if other areas of deficit emerge with more power to detect such differences. A group of researchers and clinicians with expertise in the area of GWI have identified common data elements (CDE) for use in research samples to compare data sets. At the same time, a subgroup of researchers created a new repository to share these cognitive data and biospecimens within the GWI research community. METHODS: The present study aimed to compare cognitive measures of attention, executive functioning, and verbal memory in a large sample of GWI cases and healthy GW veteran controls using neuropsychological tests recommended in the CDEs. We additionally subdivided samples based on the specific neurotoxicant exposures related to cognitive deficits and compared exposed versus non-exposed veterans regardless of case criteria status. The total sample utilized cognitive testing outcomes from the newly collated Boston, Biorepository, Recruitment, and Integrative Network (BBRAIN) for GWI. RESULTS: Participants included 411 GW veterans, 312 GWI (cases) and 99 healthy veterans (controls). Veterans with GWI showed significantly poorer attention, executive functioning, learning, and short-and-long term verbal memory than those without GWI. Further, GW veterans with exposures to acetylcholinesterase inhibiting pesticides and nerve gas agents, had worse performance on executive function tasks. Veterans with exposure to oil well fires had worse performance on verbal memory and those with pyridostigmine bromide anti-nerve gas pill exposures had better verbal memory and worse performance on an attention task compared to unexposed veterans. CONCLUSIONS: This study replicates prior results regarding the utility of the currently recommended CDEs in determining impairments in cognitive functioning in veterans with GWI in a new widely-available repository cohort and provides further evidence of cognitive decrements in GW veterans related to war-related neurotoxicant exposures.

Cannabis use frequency and pain interference among people with HIV.

Cannabis is often used by people with HIV (PWH) for pain, yet study results are inconsistent regarding whether and how it affects pain. This study examines whether greater cannabis use frequency is associated with lower pain interference and whether cannabis use modifies the association of pain severity and pain interference among 134 PWH with substance dependence or a lifetime history of injection drug use. Multi-variable linear regression models examined the association between past 30-day cannabis use frequency and pain interference. Additional models evaluated whether cannabis use modified the association between pain severity and pain interference. Cannabis use frequency was not significantly associated with pain interference. However, in a model with interaction between cannabis use frequency and pain severity, greater cannabis use frequency attenuated the strength of the association between pain severity and pain interference (p = 0.049). The adjusted mean difference (AMD) in pain interference was +1.13, + 0.81, and +0.05 points for each 1-point increase in pain severity for those with no cannabis use, 15 days of use, and daily use, respectively. These findings suggest that attenuating the impact of pain severity on pain-related functional impairment is a potential mechanism for a beneficial role of cannabis for PWH.

Boston biorepository, recruitment and integrative network (BBRAIN): A resource for the Gulf War Illness scientific community.

AIMS: Gulf War Illness (GWI), a chronic debilitating disorder characterized by fatigue, joint pain, cognitive, gastrointestinal, respiratory, and skin problems, is currently diagnosed by self-reported symptoms. The Boston Biorepository, Recruitment, and Integrative Network (BBRAIN) is the collaborative effort of expert Gulf War Illness (GWI) researchers who are creating objective diagnostic and pathobiological markers and recommend common data elements for GWI research. MAIN METHODS: BBRAIN is recruiting 300 GWI cases and 200 GW veteran controls for the prospective study. Key data and biological samples from prior GWI studies are being merged and combined into retrospective datasets. They will be made available for data mining by the BBRAIN network and the GWI research community. Prospective questionnaire data include general health and chronic symptoms, demographics, measures of pain, fatigue, medical conditions, deployment and exposure histories. Available repository biospecimens include blood, plasma, serum, saliva, stool, urine, human induced pluripotent stem cells and cerebrospinal fluid. KEY FINDINGS: To date, multiple datasets have been merged and combined from 15 participating study sites. These data and samples have been collated and an online request form for repository requests as well as recommended common data elements have been created. Data and biospecimen sample requests are reviewed by the BBRAIN steering committee members for approval as they are received. SIGNIFICANCE: The BBRAIN repository network serves as a much needed resource for GWI researchers to utilize for identification and validation of objective diagnostic and pathobiological markers of the illness.

Medication for addiction treatment and acute care utilization in HIV-positive adults with substance use disorders.

Medication for addiction treatment (MAT) could reduce acute care utilization in HIV-positive individuals with substance use disorders. The study objective was to determine if HIV-positive people with substance use disorders treated with MAT report less acute care utilization than those not receiving MAT. We assessed the association between MAT and acute care utilization among HIV-positive individuals with alcohol or opioid use disorder. Acute care utilization 6 months later was defined as any past 3-month self-reported (1) emergency department (ED) visit and (2) hospitalization. Of 153 participants, 88% had alcohol use disorder, 41% had opioid use disorder, and 48 (31%) were treated with MAT. Fifty-five (36%) participants had an ED visit and 38 (25%) participants had a hospitalization. MAT was not associated with an ED visit (AOR 1.12, 95% CI 0.46-2.75) or hospitalization (AOR 1.09, 95% CI 0.39-3.04). MAT was not associated with acute care utilization. These results highlight the need to increase MAT prescribing in HIV-positive individuals with substance use disorders, and to address the many factors that influence acute care utilization.

Caffeine decreases intermittent hypoxia in preterm infants nearing term-equivalent age.

OBJECTIVE: To determine whether intermittent hypoxia (IH) persisting after 36 weeks postmenstrual age (PMA) can be attenuated using caffeine doses sufficient to maintain caffeine concentrations >20 µg ml-1. STUDY DESIGN: Twenty-seven infants born <32 weeks were started on caffeine citrate at 10 mg kg-1 day-1 when clinical caffeine was discontinued. At 36 weeks PMA, the dose was increased to 14 or 20 mg kg-1 day-1 divided twice a day (BID) to compensate for progressively increasing caffeine metabolism. Caffeine concentrations were measured weekly. The extent of IH derived from continuous pulse oximetry was compared to data from 53 control infants. RESULT: The mean (s.d.) gestational age of enrolled infants was 27.9±2 weeks. Median caffeine levels were >20 µg ml-1 on study caffeine doses. IH was significantly attenuated through 38 weeks PMA compared with the control group. CONCLUSION: Caffeine doses of 14 to 20 mg kg-1 day-1 were sufficient to maintain caffeine concentrations >20 µg ml-1 and reduce IH in preterm infants at 36 to 38 weeks PMA.

[Morphological characteristics in macular telangiectasia type 2]. / Morphologische Charakteristika bei makulären Teleangiektasien Typ 2.

Macular telangiectasia type 2 is characterized by atrophic alterations of the central retina which is accompanied by a defined vascular phenotype. The disease manifests within an oval central retinal area the size of approximately two disc diameters, with a topographic predisposition temporal to the foveal center. Funduscopy reveals reduced retinal transparency, crystalline deposits, mildly ectatic capillaries, thickened venules and retinal pigment plaques. Secondary neovascularization and macular holes may occur during the disease course. Fluorescein angiography usually shows a diffuse leakage and often ectatic capillaries. On optical coherence tomography (OCT) examination, hyporeflective cavities and focal atrophy of the photoreceptor layer represent a frequent finding. A characteristic sign is an increased (para) central signal on fundus autofluorescence imaging due to a reduced density of macular pigment.

[Functional characteristics of macular telangiectasia type 2]. / Funktionelle Charakteristika bei makulären Teleangiektasien Typ 2.

The first symptoms of macular telangiectasia type 2 usually occur between 50 and 70 years of age. Functional alterations topographically correspond to the morphological changes. Characteristic paracentral scotomata due to focal photoreceptor atrophy can be detected using microperimetry. The predominant paracentral functional loss may cause reading difficulties despite visual acuity in the range between 20/20 and 20/50. Visual acuity around 20/200 may occur once the paracentral photoreceptor atrophy extends centrally, or due to the development of a macular hole or a secondary neovascular membrane. Progression of functional loss can often only be detected by mapping scotoma size or occurrence using microperimetry, while visual acuity may remain unchanged.

[Therapeutic approaches for macular telangiectasia type 2: status quo and perspectives]. / Therapeutische Ansätze bei makulären Teleangiektasien Typ 2: Status quo und Perspektiven.

Macular telangiectasia type 2 is characterized by neurodegenerative as well as vascular and retinal alterations. Previous therapeutic approaches mainly targeted the vascular changes; however, this did not prove to be beneficial except for secondary neovascularization which may be successfully treated with intravitreal vascular endothelial growth factor inhibitors. As the natural history of the disease is primarily characterized by the neurodegenerative processes, new therapeutic strategies, such as neuroprotective agents are already being explored in clinical trials.

Alcohol-related problems among younger drinkers who misuse prescription drugs: results from the national epidemiologic survey of alcohol and related conditions (NESARC).

The authors determined whether lifetime prescription drug misuse (PDM) associated with increased risks for alcohol-related problems among 18- to 34-year-old, NESARC respondents. Among 8222 "ever-drinkers," 15.4% reported ever "misusing sedatives, tranquilizers, painkillers or stimulants ... as prescriptions or from indirect sources." Outcomes were within two alcohol-related problem domains, "risk-taking behaviors," including driving while drinking, fights, injuries, and arrests, and "interpersonal troubles," including problems with jobs, family, or friends. Among all drinkers and among alcohol-dependent and cannabis-using subsamples, those reporting PDM were significantly more likely to report alcohol-related "risk-taking behaviors" or "interpersonal troubles" than were those without PDM. In adjusted analysis, young age drinking onsets, and heavy and dependent drinking independently increased these risks. Results of this cross-sectional analysis support the need for longitudinal data to more clearly define the association between drinking problems and PDM, and which can support prevention, treatment, and harm-reduction efforts for younger, multisubstance users.

Outcome of late-life depression after 3 years of sequential treatment.

OBJECTIVE: To study the outcome of a sequential treatment protocol in elderly, severely depressed in-patients. METHOD: All 81 patients from a 12-week double-blind randomized controlled trial (RCT) comparing venlafaxine with nortriptyline were asked to participate in a 3 year follow-up study. Thirty-two patients who did not achieve remission during the RCT, entered an open sequential treatment protocol and were treated with augmentation with lithium, switch to a monoamine oxidase inhibitor or ECT. RESULTS: Seventy-eight of the 81 patients (96.3%) achieved a response [> or = 50% reduction in Montgomery Asberg Depression Rating Scale score) and 68 patients (84%) a complete remission (final MADRS score < or = 10) within 3 years of treatment. Greater severity and longer duration of the depressive episode at baseline predicted poor recovery. Augmentation with lithium may be the best treatment option in treatment resistant depressed elderly. Only few patients dropped-out due to side-effects. CONCLUSION: Our study demonstrates the importance of persisting with antidepressant treatment in elderly patients who do not respond to the first or second treatment.

The relationship between characteristics of supported housing and the quality of life of older adults with severe mental illness.

This study examined whether group living (as opposed to single living), staff availability and degree of personal freedom are associated with the quality of life of older adults with severe mental illness. A cross-sectional study was carried out in 18 supported living programmes in residential homes for the elderly that differed in terms of these three characteristics. The study included 35 patients with a psychotic disorder and 38 with an anxiety or mood disorder. Quality of life was assessed with the Philadelphia Geriatric Centre Morale Scale (PGCMS) and the Manchester Short Assessment of Quality of Life (MANSA). No association was found between group living and quality of life. Availability of psychiatrically trained staff was associated with life quality only for patients with a psychotic disorder, and perceived amount of personal freedom was associated with life quality only for patients with a non-psychotic disorder. Both differences were seen only on the PGCMS Agitation subscale. Older people with psychotic disorders appear to have relatively high needs for professional psychiatric support, and those with non-psychotic disorders for control over their daily lives. Further research is needed in other settings for older people with severe mental illness, preferably using longitudinal designs.

[A primary care program in old age psychiatry: background, implementation and first experiences]. / Eerstelijns programma voor ouderenpsychiatrie (EPO): achtergrond, implementatie en eerste ervaring.

The specific characteristics of elderly people, who are likely to develop somatic and psychiatric co-morbidity, and cognitive deterioration, require tailored support in primary care. The first results of a support programme for the elderly in primary care are encouraging. Further research will show whether the EPO has sufficient added value for both the GP and the patient to justify large-scale introduction.

Effects on alcohol related fatal crashes of a community based initiative to increase substance abuse treatment and reduce alcohol availability.

OBJECTIVE: This analysis tested whether comprehensive community interventions that focus on reducing alcohol availability and increasing substance abuse treatment can reduce alcohol related fatal traffic crashes. INTERVENTION: Five of 14 communities awarded Fighting Back grants by The Robert Wood Johnson Foundation to reduce substance abuse and related problems attempted to reduce availability of alcohol and expand substance abuse treatment programs (FBAT communities). Program implementation began on 1 January 1992. DESIGN: A quasi-experimental design matched each program community to two or three other communities of similar demographic composition in the same state. MAIN OUTCOME MEASURES: The ratio of fatal crashes involving a driver or pedestrian with a blood alcohol concentration of 0.01% or higher, 0.08% or higher, or 0.15% or higher were examined relative to fatal crashes where no alcohol was involved for 10 years preceding and 10 years following program initiation. RESULTS: Relative to their comparison communities, the five FBAT communities experienced significant declines of 22% in alcohol related fatal crashes at 0.01% BAC or higher, 20% at 0.08% or higher, and 17% at 0.15% or higher relative to fatal crashes not involving alcohol. CONCLUSIONS: Community interventions to reduce alcohol availability and increase substance abuse treatment can reduce alcohol related fatal traffic crashes.

Eerstelijns Programma voor Ouderenpsychiatrie (EPO): Achtergrond, implementatie en eerste ervaring.

A Primary Care Program in old age psychiatry: Background, implementation and first experiences. Since 1999, the GP has been assigned the role of the "gatekeeper of mental health care". The aim of which is to treat as many mental problems as possible in primary health care. The generally complicated mental health problems in the elderly confront the GP with difficult diagnostic, treatment, and referral issues. Psychological problems are often masked by somatic complaints and rarely lead to referrals or adequate treatment. Many GPs use support programmes from second-line mental health care, yet nearly all these programs are executed by mental health care units for adults. In mid-western Utrecht, GPs have indicated a distinctive requirement for a support programme specifically aimed at elderly people with mental problems. The specific characteristics of elderly people, who are likely to develop somatic and psychiatric co-morbidity, and cognitive deterioration, require tailored support in primary care. The first results of a support programme for the elderly in primary care are encouraging. Further research will show whether the EPO has sufficient added value for both the GP and the patient to justify large-scale introduction.

Supported living in residential homes for the elderly: impact on patients and elder care workers.

To enable older people with severe and persistent mental illness to live in the community, the Dutch mental health sector has developed a program for supported living in residential homes for the elderly. It provides for the permanent stationing of mental health workers (MHWs) in elder care facilities to support both the resident patients and the elder care staff. The authors examined associations between the number of MHW staff and the degree to which (1) patients were integrated into the community and (2) elder care workers had developed effective working alliances with their patients. Participants included 110 patients participating in 18 supported living programs in the Netherlands. Community integration was assessed in face-to-face interviews with the patients about their perceived influence over daily life, involvement in social activities, and social network size. The quality of the worker-patient relationship was assessed using the Dutch Working Alliance Questionnaire for Community Care, completed by the elder care worker primarily responsible for each patient. After differentiation of the MHW staff into medically trained and nurse-trained professionals, associations with outcome measures were found only for the nurse-trained staff. The more hours of nurse-trained staff capacity per patient, the more influence perceived by the patients, and the more directiveness shown by the elder care workers in their contacts with patients. The impact of supported living programs in residential homes for the elderly appears to be determined in part by the caseloads of the on-site MHWs.