Use of healthcare services 8 years after the war in Kosovo: role of post-traumatic stress disorder and depression

Background: The aim of the present study was to examine the use of health-care services and medication, as well as health risk behaviours such as smoking, in relation with post-traumatic stress disorder (PTSD) and major depressive episode (MDE) in post-war Kosovo. Methods: A sample of 864 adults was interviewed in 2007 of which 551 took part in a 2001 survey. They were assessed using the PTSD and MDE sections of the Mini International Neuropsychiatric Interview (MINI) and the Medical Outcomes Study 36-item Short Form Health Survey (SF-36). Use of health-care services, alcohol and tobacco were also recorded. Results: Respondents were predominantly female (56.6%) with a median age of 36 years and a primary educational level (44.6%). While 11.9% of participants met diagnostic criteria for PTSD, MDE prevalence was 30.6%. Both PTSD and MDE were significantly associated with lower scores on the SF-36 physical component summary. After adjustment for sex, age, education, unemployment, municipality and SF-36 perceived physical health, no significant association was observed between PTSD and medical visits in the past 12 months, hospitalizations in the past 12 months and use of medication in the past 7 days. Results were similar for MDE, except for a significantly higher frequency of medication use that included psychotropic and other drug classes. Conclusion: Eight years after the war in Kosovo, poor perceived physical health displayed a long-lasting association with PTSD and MDE and was a major determinant of increased use of health-care services without additional contribution of PTSD per s

Multivariate Analysis of Dietary Patterns in 939 Swiss Adults: Sociodemographic Parameters and Alcohol Consumption Profiles

A dietary survey of 939 Swiss adults, randomly selected from the population of Geneva and its surrounding communities, was performed according to the history method. A factor analysis, using average weekly intakes for 33 food variables, reveals three principal components of the diet: satiating capacity, healthfulness and culinary complexity. These characteristics, together with the energy content of the diet, were analysed for differences according to sex, age, relative weight index, birthplace, marital status and occupation. All of these sociodemographic variables influence some dimension of dietary habits. Alcohol consumption is positively associated with satiating, protein rich diets, but energy intake from foods does not significatively differ between various groups of abstainers and drinkers. Although the energy contribution of alcoholic beverages is globally additive, we suggest that cultural and societal norms may modulate the relationship of alcohol and die

Mental and physical health in Rwanda 14years after the genocide

Purpose: To examine the socio-demographic determinants of post-traumatic stress disorder (PTSD) and its association with major depressive episode and self-perceived physical and mental health in a large random sample of the Rwandan population 14years after the 1994 genocide. Methods: Using the Mini International Neuropsychiatric Interview and Medical Outcomes Study 36-Item Short-Form (SF-36) translated in Kinyarwanda, we interviewed 1,000 adult residents from the five provinces of Rwanda. Socio-demographic data and specific somatic symptoms were also recorded. Data analysis included 962 questionnaires. Results: Participants were predominantly female (58.9%), aged between 16 and 34years (53.2%), with a low level of education (79.7% below secondary school). Prevalence of PTSD was estimated to be 26.1%. In multivariable analysis, factors associated with PTSD were being aged between 25 and 34years, living in extreme poverty, having endured the murder of a close relative in 1994, being widowed or remarried, having lost both parents and living in the South Province. Participants who fulfilled diagnostic criteria for PTSD were significantly more often affected with major depression (68.4 vs. 6.6%, P<0.001) and substance dependence (7.6 vs. 3.5%, P=0.013) than respondents without PTSD. They scored significantly lower on all SF-36 subscales. Somatic symptoms such as hiccups, fainting and loss of speech or hearing delineated a specific pattern of post-traumatic stress syndrome. Conclusions: PTSD remains a significant public health problem in Rwanda 14years after the genocide. Facilitating access to appropriate care for all those who need it should be a national priorit

Attitudes toward psychopharmacology among hospitalized patients from diverse ethno-cultural backgrounds

<p>Abstract</p> <p>Background</p> <p>Biological factors influencing individual response to drugs are being extensively studied in psychiatry. Strikingly, there are few studies addressing social and cultural differences in attitudes toward psychotropic medications. The objective of this study was to investigate ethno-culturally determined beliefs, expectations and attitudes toward medication among a sample of hospitalized psychiatric patients.</p> <p>Methods</p> <p>An ad hoc questionnaire was designed to assess patients' expectations, attitudes and prejudice toward medication. The study included 100 adult patients hospitalized in Geneva, Switzerland.</p> <p>Results</p> <p>Patients were in majority male (63%), originated from Switzerland (54%) and spoke the local language fluently (93%). They took on the average 3 different psychotropic drugs. Sixty-eight percent of patients expected side effects and 60% were ready to stop medication because of them. Thirty percent of patients expected negative personal changes with treatment and 34% thought that their mental disorder could have been treated without drugs. Thirty six percent of the sample used alternative or complementary medicines. 35% of immigrant patients believed that medication had different effects on them than on local patients. When compared with Swiss patients, they more often reported that significant others had an opinion about medication (p = 0.041) and more frequently valued information provided by other patients about treatment (p = 0.010).</p> <p>Conclusion</p> <p>Patients' attitudes toward medication should be investigated in clinical practice, as specific expectations and prejudice exist. Targeted interventions, especially for immigrant patients, might improve adherence.</p

A shared HLA-DRB1 epitope in the DR beta first domain is associated with Vogt-Koyanagi-Harada syndrome in Indian patients

PURPOSE: Vogt-Koyanagi-Harada (VKH) disease and sympathetic ophthalmia (SO) are two distinct entities that share common clinical and histopathological features; however, it remains unknown whether they have a common genetic susceptibility. Several studies have shown an association of human leukocyte antigen (HLA)-DR4 with VKH disease in patients of different ethnic backgrounds. We present in this paper the HLA-DRB1 genotyping analysis of a large cohort of VKH patients from southern India and compare these patients to patients with SO and to healthy individuals from the same geographic area. METHODS: VKH patients were diagnosed according to the revised criteria of the International Committee on VKH disease. Patients with granulomatous uveitis after ocular trauma or multiple eye surgeries were diagnosed as having SO. Genomic DNA was extracted from all patients and controls. Samples were analyzed for HLA-DRB1 alleles by reverse polymerase chain reaction (PCR) sequence-specific oligonucleotide (SSO) hybridization on microbeads, using the Luminex technology, and by PCR sequence-specific primers (SSP) typing for DRB1*04 allele determination. Strength of associations was estimated by odds ratios (OR) and 95% confidence intervals (CI) and frequencies were compared using the Fisher's exact test. RESULTS: HLA-DRB1 alleles were determined in 94 VKH patients, 39 SO patients, and 112 healthy controls. HLA-DRB1*04 frequency was higher in VKH patients (20.2% versus 10.3% in controls; OR=2.2, p=0.005, pc=0.067). This association was lower than the association of HLA-DRB1*04 frequency in cohorts of patients from different origins. No significant DR4 association with SO was detected. HLA-DRB1*0405 and HLA-DRB1*0410 alleles were significantly increased in VKH patients (8.5% versus 0.9% in controls; OR=10.3, 95% CI=2.34-45.5, p<0.001). These two alleles share the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DR molecule. None of the DRB1 alleles was significantly associated with SO. CONCLUSIONS: Based on the association of HLA-DRB1*0405 and HLA-DRB1*0410 alleles with VKH disease, we propose that the epitope S57-LLEQRRAA (67-74) in the third hypervariable region of the HLA-DRbeta1 molecule is the relevant susceptibility epitope. This genetic component seems specific to VKH disease since no correlation could be identified in SO patients. The weaker association with HLA-DR4 in this VKH patient cohort compared to VKH patients from northern India is probably related to the lower frequency of HLA-DRB1*0405 in our study group. The HLA-DRB1 association with susceptibility to VKH syndrome seems weaker in Indian patients compared to Japanese or Hispanic patients, suggesting a different non-HLA immunogenetic background in Indian VKH patients

Mental and physical health of Kosovar Albanians in their place of origin: a post-war 6-year follow-up study

Purpose: Long-term outcome of traumatic experiences among war-exposed civilians living in their home country has been seldom documented. The present study examined change in posttraumatic stress disorder (PTSD) frequency and perceived physical and mental health in a cohort of Kosovar Albanians over 6years (2001-2007). Methods: Of 996 Albanian Kosovar civilians included in the 2001 survey, 551 subjects (55.3%) were recalled and interviewed in 2007. Diagnoses of PTSD and major depressive episode were assessed using the Mini International Neuropsychiatric Interview. Subjective physical and mental health were investigated using the Medical Outcomes Study 36-Item Short-Form (SF-36). A list of traumatic events adapted from the Harvard Trauma Questionnaire and other stressful life events was also considered. Results: Posttraumatic stress disorder was significantly less frequent in 2007 than in 2001 (14.5% vs. 23.2%, p<0.001). For 18.0, 5.3 and 9.3% of participants, PTSD remitted, persisted and developed over the 6-year follow-up period, respectively. Ill health without having access to medical care and major changes in responsibilities at work were associated with both persistence and new occurrence of PTSD. While the SF-36 mental component summary score significantly improved (mean change +4.5, p<0.001), the physical component summary score did not change between 2001 and 2007, after adjustment for age (mean change −0.8, p=0.14). Conclusions: Results point at the importance of economic and health system reconstruction programs with respect to public health in post-conflict countrie

Time course of clinical response to venlafaxine: relevance of plasma level and chirality

Objective: Early clinical response to antidepressant treatment is an important therapeutic goal, considering the psychological, social and economic consequences of depression. The aim of the present study was to investigate the relationship between the time course of response and the concentration of venlafaxine (V), its active metabolite O-desmethylvenlafaxine (ODV) and enantiomeric ratios V(+)/V(−) and ODV(+)/ODV(−). Methods: Depressed inpatients (n=35) received V orally at a fixed 300mg daily dose. Accepted comedication included clorazepate (maximum 60mg/day), zopiclone (maximum 15mg/day) and low-dose trazodone (maximum 200mg/day). Severity of depression was assessed on days0, 4, 7, 11, 14, 21 and 28 (Montgomery and Åsberg Depression Rating Scale). Blood samples were taken on day14 and day28 and submitted to stereoselective determination. All measurements reflected trough steady-state values. First, pattern analysis was used to provide a categorical perspective of clinical response (50% improvement from baseline depression score). Patients displaying non-response, transient response, early persistent response and delayed persistent response were compared with respect to racemic concentrations and enantiomeric ratios. Second, in a dimensional perspective, mixed-effects modelling was used to analyse severity of depression versus time curves with respect to the possible influence of concentrations and enantiomeric ratios. Results: Comparison of patients with and without persistent response did not reveal any significant difference for V, ODV, V+ODV plasma levels or enantiomeric ratios. Persistent response was significantly associated with less frequent pre-study antidepressant medication and less frequent comedication with zopiclone (day14) and clorazepate (day28) during the study. Focus on patients with persistent response (n=19, 54.3%) indicated that early response, first observed before day14, was associated with significantly higher V+ODV concentration than delayed response (median 725ng/ml versus 554ng/ml, P=0.023). No difference was found for pre-study medication or comedication during the study. Shorter time to onset of response was significantly associated with lower V(+)/V(−) enantiomeric ratio (rs=0.48, P<0.05). Mixed-effects modelling of depression severity versus time curves in patients with persistent response confirmed that either higher V+ODV plasma level or lower V(+)/V(−) ratio were significantly associated with more rapid decrease of depression score (likelihood ratio tests, P=0.012 and P=0.046, respectively). Conclusion: Considering its modest sample size, naturalistic design and limited observation period, the present study provided preliminary indication that earlier clinical response may occur with higher V+ODV plasma level, extending previous dose-response studies. The hypothesis was also raised that exposure to a more potent noradrenergic therapeutic moiety, as reflected by a lower V(+)/V(−) ratio, may be relevant to early improvement of depressio

Intraocular penetration of penciclovir after oral administration of famciclovir: a population pharmacokinetic model

Objectives We developed a population model that describes the ocular penetration and pharmacokinetics of penciclovir in human aqueous humour and plasma after oral administration of famciclovir. Methods Fifty-three patients undergoing cataract surgery received a single oral dose of 500 mg of famciclovir prior to surgery. Concentrations of penciclovir in both plasma and aqueous humour were measured by HPLC with fluorescence detection. Concentrations in plasma and aqueous humour were fitted using a two-compartment model (NONMEM software). Inter-individual and intra-individual variabilities were quantified and the influence of demographics and physiopathological and environmental variables on penciclovir pharmacokinetics was explored. Results Drug concentrations were fitted using a two-compartment, open model with first-order transfer rates between plasma and aqueous humour compartments. Among tested covariates, creatinine clearance, co-intake of angiotensin-converting enzyme inhibitors and body weight significantly influenced penciclovir pharmacokinetics. Plasma clearance was 22.8 ± 9.1 L/h and clearance from the aqueous humour was 8.2 × 10−5 L/h. AUCs were 25.4 ± 10.2 and 6.6 ± 1.8 μg · h/mL in plasma and aqueous humour, respectively, yielding a penetration ratio of 0.28 ± 0.06. Simulated concentrations in the aqueous humour after administration of 500 mg of famciclovir three times daily were in the range of values required for 50% growth inhibition of non-resistant strains of the herpes zoster virus family. Conclusions Plasma and aqueous penciclovir concentrations showed significant variability that could only be partially explained by renal function, body weight and comedication. Concentrations in the aqueous humour were much lower than in plasma, suggesting that factors in the blood-aqueous humour barrier might prevent its ocular penetration or that redistribution occurs in other ocular compartment

Ubiquitin Fusion Degradation Protein 1 as a Blood Marker for The Early Diagnosis of Ischemic Stroke

Background: Efficacy of thrombolysis in acute ischemic stroke is strongly related to physician’s ability to make an accurate diagnosis and to intervene within 3–6 h after event onset. In this context, the discovery and validation of very early blood markers have recently become an urgent, yet unmet, goal of stroke research. Ubiquitin fusion degradation protein 1 is increased in human postmortem CSF, a model of global brain insult, suggesting that its measurement in blood may prove useful as a biomarker of stroke.Methods: Enzyme-linked immunosorbent assay (ELISA) was used to measure UFD1 in plasma and sera in three independent cohorts, European (Swiss and Spanish) and North-American retrospective analysis encompassing a total of 123 consecutive stroke and 90 control subjects.Results: Highly significant increase of ubiquitin fusion degradation protein 1 (UFD1) was found in Swiss stroke patients with 71% sensitivity (95% CI, 52–85.8%), and 90% specificity (95% CI, 74.2–98%) (N = 31, p < 0.0001). Significantly elevated concentration of this marker was then validated in Spanish (N = 39, p < 0.0001, 95% sensitivity (95% CI, 82.7–99.4%)), 76% specificity (95% CI, 56.5–89.7%)) and North-American stroke patients (N = 53, 62% sensitivity (95% CI, 47.9–75.2%), 90% specificity (95% CI, 73.5–97.9%), p < 0.0001). Its concentration was increased within 3 h of stroke onset, on both the Swiss (p < 0.0001) and Spanish (p = 0.0004) cohorts.Conclusions: UFD1 emerges as a reliable plasma biomarker for the early diagnosis of stroke, and in the future, might be used in conjunction with clinical assessments, neuroimaging and other blood markers.Abbreviations: AUC: area under curve; BBB: blood–brain barrier; CO: cut-off; CSF: cerebrospinal fluid; CT: computerized tomography; H-FABP: heart-fatty acid binding protein; MMP9: matrix metalloproteinase 9; MRI: magnetic resonance imaging; NDKA: nucleotide diphosphate kinase A; OR: odds ratio; RFU: relative fluorescence units; ROC: receiver operating characteristic; rtPA: recombinant tissue plasminogen activator; SE: sensitivity; SP: specificity; TIA: transient ischemic attack; UFD1: ubiquitin fusion degradation protein

A multiparameter panel method for outcome prediction following aneurysmal subarachnoid hemorrhage

Purpose: Accurate early anticipation of long-term irreversible brain damage during the acute phase of patients with aneurysmal subarachnoid hemorrhage (aSAH) remains difficult. Using a combination of clinical scores together with brain injury-related biomarkers (H-FABP, NDKA, UFD1 and S100β), this study aimed at developing a multiparameter prognostic panel to facilitate early outcome prediction following aSAH. Methods: Blood samples of 141 aSAH patients from two separated cohorts (sets of 28 and 113 patients) were prospectively enrolled and analyzed with 14months of delay. Patients were admitted within 48h following aSAH onset. A venous blood sample was withdrawn within 12h after admission. H-FABP, NDKA, UFD1, S100β and troponin I levels were determined using classical immunoassays. The World Federation of Neurological Surgeons (WFNS) at admission and the Glasgow Outcome Score (GOS) at 6months were evaluated. Results: In the two cohorts, blood concentration of H-FABP, S100β and troponin I at admission significantly predicted unfavorable outcome (GOS 1-2-3). A multivariate analysis identified a six-parameter panel, including WFNS, H-FABP, S100β, troponin I, NDKA and UFD-1; when at least three of these parameters were simultaneously above cutoff values, prediction of unfavorable outcome reached around 70% sensitivity in both cohorts for 100% specificity. Conclusion: The use of this panel, including four brain injury-related proteins, one cardiac marker and a clinical score, could be a valuable tool to identify aSAH patients at risk of poor outcom