The cascade of HIV care among refugees and nationals in Nakivale Refugee Settlement in Uganda.

OBJECTIVES: Refugees living in Uganda come from HIV-endemic countries, and many remain in refugee settlements for over a decade. Our objective was to evaluate the HIV care cascade in Nakivale Refugee Settlement and to assess correlates of linkage to care. METHODS: We prospectively enrolled individuals accessing clinic-based HIV testing in Nakivale Refugee Settlement from March 2013 to July 2014. Newly HIV-diagnosed clients were followed for 3 months post-diagnosis. Clients underwent a baseline survey. The following outcomes were obtained from HIV clinic registers in Nakivale: clinic attendance ('linkage to HIV care'), CD4 testing, antiretroviral therapy (ART) eligibility, and ART initiation within 90 days of testing. Descriptive data were reported as frequency with 95% confidence interval (CI) or median with interquartile range (IQR). The impact of baseline variables on linkage to care was assessed with logistic regression models. RESULTS: Of 6850 adult clients tested for HIV, 276 (4%; CI: 3-5%) were diagnosed with HIV infection, 148 (54%; CI: 47-60%) of those were linked to HIV care, 54 (20%; CI: 15-25%) had a CD4 test, 22 (8%; CI: 5-12%) were eligible for ART, and 17 (6%; CI: 3-10%) initiated ART. The proportions of refugees and nationals at each step of the cascade were similar. We identified no significant predictors of linkage to care. CONCLUSIONS: Less than a quarter of newly HIV-diagnosed clients completed ART assessment, considerably lower than in other reports from sub-Saharan Africa. Understanding which factors hinder linkage to and engagement in care in the settlement will be important to inform interventions specific for this environment.

Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

OBJECTIVE: Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. METHOD: The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. RESULTS: At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. CONCLUSION: Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment.

Medication adherence in a comparative effectiveness trial for bipolar disorder.

OBJECTIVE: Psychopharmacology remains the foundation of treatment for bipolar disorder, but medication adherence in this population is low (range 20-64%). We examined medication adherence in a multisite, comparative effectiveness study of lithium. METHOD: The Lithium Moderate Dose Use Study (LiTMUS) was a 6-month, six-site, randomized effectiveness trial of adjunctive moderate dose lithium therapy compared with optimized treatment in adult out-patients with bipolar I or II disorder (N=283). Medication adherence was measured at each study visit with the Tablet Routine Questionnaire. RESULTS: We found that 4.50% of participants reported missing at least 30% of their medications in the past week at baseline and non-adherence remained low throughout the trial (<7%). Poor medication adherence was associated with more manic symptoms and side-effects as well as lower lithium serum levels at mid- and post-treatment, but not with poor quality of life, overall severity of illness, or depressive symptoms. CONCLUSION: Participants in LiTMUS were highly adherent with taking their medications. The lack of association with possible predictors of adherence, such as depression and quality of life, could be explained by the limited variance or other factors as well as by not using an objective measure of adherence.

General medical burden in bipolar disorder: findings from the LiTMUS comparative effectiveness trial.

OBJECTIVE: This study examined general medical illnesses and their association with clinical features of bipolar disorder. METHOD: Data were cross-sectional and derived from the Lithium Treatment - Moderate Dose Use Study (LiTMUS), which randomized symptomatic adults (n = 264 with available medical comorbidity scores) with bipolar disorder to moderate doses of lithium plus optimized treatment (OPT) or to OPT alone. Clinically significant high and low medical comorbidity burden were defined as a Cumulative Illness Rating Scale (CIRS) score ≥4 and <4 respectively. RESULTS: The baseline prevalence of significant medical comorbidity was 53% (n = 139). Patients with high medical burden were more likely to present in a major depressive episode (P = .04), meet criteria for obsessive-compulsive disorder (P = .02), and experience a greater number of lifetime mood episodes (P = 0.02). They were also more likely to be prescribed a greater number of psychotropic medications (P = .002). Sixty-nine per cent of the sample was overweight or obese as defined by body mass index (BMI), with African Americans representing the racial group with the highest proportion of stage II obesity (BMI ≥35; 31%, n = 14). CONCLUSION: The burden of comorbid medical illnesses was high in this generalizable sample of treatment-seeking patients and appears associated with worsened course of illness and psychotropic medication patterns.

Characterization of purified avian 90,000-Da heat shock protein.

The so-called 90,000-Da heat shock protein (hsp90) from chicken liver has been purified and physically characterized in the presence of high levels of the serine phosphatase inhibitor fluoride. The protein is an elongated dimer with a molecular weight of 160,000 and a frictional ratio of 1.6. On two-dimensional electrophoresis it exhibits several isoelectric forms lying between pH 5.1 and 5.8. It contains an average of 5.8 mol of covalently bound phosphate per dimer and is thus extensively phosphorylated. Analysis of the ultraviolet spectrum showed the purified protein to be free of nucleotide-containing components. Molybdate has been shown to stabilize complexes between the 90,000-Da heat shock protein and steroid receptors. However, molybdate has no effect on the sedimentation of the purified heat shock protein. Proteins structurally related to hsp90 have been reported to penetrate the endoplasmic reticulum. However, when purified hsp90 was tested using the partition method of Bordier, which distinguishes hydrophilic and lipophilic proteins, it partitioned totally into the aqueous phase.

Identification of the 90 kDa substrate of rat liver type II casein kinase with the heat shock protein which binds steroid receptors.

It was recently reported that the type II casein kinase of rat liver cytosol co-purified with a major 90 kDa substrate when subjected to gel filtration at low ionic strength. The identity of the 90 kDa substrate was unknown. We have verified this report and have shown that the 90 kDa substrate is recognized by a monoclonal antibody prepared against the 90 kDa heat shock protein. This ubiquitous phosphoprotein is known to increase in abundance in cells subjected to heat stress and has been shown to complex steroid receptors and certain retrovirus tyrosine kinases.

Characterization of the glomerular antibody in acute poststreptococcal glomerulonephritis.

Glomerular-fixed antibody was eluted from the kidney of a 17-year-old patient who died 2 weeks after the onset of acute poststreptococcal glomerulonephritis. Elevated titers of antibodies to streptococcal enzymes were found in the serum but not in the glomerular eluate. Streptococcal M protein and anti-M protein reactivity were not detected in the eluate. Immunoglobulin G was the only serum protein demonstrated in the eluate, and it was found to have anti-IgG activity highly concentrated with respect to the serum. These studies appear to indicate that anti-IgG is involved in the immune pathogenesis of acute poststreptococcal glomerulonephritis. Native IgG may be rendered autoimmunogenic by the streptococcus with subsequent antibody production to the neoautoimmunogen. Alernatively, anti-IgG may be produced to the IgG incorporated in an exogenous streptococcal antigen-antibody complex.

Circulating immune complexes and serum immunoglobulins in acute poststreptococcal glomerulonephritis.

Acute poststreptococcal glomerulonephritis (APSGN) is a disease thought to be induced by the renal deposition of circulating immune complexes. In order to test this possibility, serum samples from 119 patients with APSGN were studied for Clq binding activity (ClqBA), levels of IgG, IgM, IgA, C3 and antibody titers to streptococcal enzymes. These parameters were analyzed in relation to the clinical and laboratory data of the acute nephritic syndrome and with respect to the time elapsed from streptococcal infection and from the onset of nephritis. Elevated ClqBA was found in 66.7% of the patients in the first week of the disease and this frequency decreased progressively to 17.6% after the second week. Normal ClqBA was found in patients after the third week of nephritis. Serum levels of IgG and IgM were elevated in over 95% of the patients. Levels of IgG in excess of 2400 mg/dl were detected in 71.1% of the cases. No correlation could be found between the ClqBA and the clinical or immunoserological findings of the disease. The data support the hypothesis that circulating immune complexes are responsible for the nephritis that follows streptococcal infection.

Acute poststreptococcal glomerulonephritis in Maracaibo. II: Studies on the incidence, nature, and significance of circulating anti-immunoglobulins.

Antiglobulins were measured in the sera of 82 patients with acute poststreptococcal glomerulonephritis and correlated with C1q binding activity, serum levels of immunoglobulins and C3, site of infection, antibody titres to streptococcal enzymes, and the duration of the nephritis and interval from infection. Raised serum antiglobulins were found in 89.2% of the patients. In addition, raised titres were detected at any time during the course of the disease and very early after streptococcal infection. The finding of antiglobulins soon after the infection suggests the possibility that they appear as a primary event in the disease.

Evidence of an autologous immune complex pathogenic mechanism in acute poststreptococcal glomerulonephritis.

Clinical and experimental studies have suggested a role for antiimmunoglobulins in the pathogenesis of glomerulonephritis associated with streptococcal infection. We attempted to localize anti-IgG in the kidneys of 22 patients who had renal biopsies performed 7 to 66 days after the onset of acute poststreptococcal glomerulonephritis (APSGN). In addition to routine localization of immunoglobulins and C3, specimens were stained with neuraminidase-treated, heat-aggregated, and unmodified IgG. Twelve biopsies showed staining with fluorescein-labeled human neuraminidase-treated IgG. A lesser number gave positive staining with the other IgG preparations. Following treatment of slides with 0.01 M citrate buffer, seven previously negative biopsies showed positive staining with neuraminidase-treated IgG. The demonstration of anti-IgG by these methods was possible in 19 out of 22 biopsies. It correlated best with the presence of C3 and IgG, and to a lesser extent with IgM, in the renal glomerulus. These results and our previous finding of elevated levels of serum anti-IgG early in the course of APSGN, and as early as 8 days following the antecedent streptococcal infection, support a role for anti-IgG in the immune pathogenesis of APSGN. Although our series of studies support the hypothesis that anti-IgG is formed to an IgG modified enzymatically by streptococcal product, the formation of this autoantibody to IgG incorporated in an exogenous (streptococcal antigen-antibody) complex can not be ruled out.