Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580

Different genes interact with particulate matter and tobacco smoke exposure in affecting lung function decline in the general population

BACKGROUND: Oxidative stress related genes modify the effects of ambient air pollution or tobacco smoking on lung function decline. The impact of interactions might be substantial, but previous studies mostly focused on main effects of single genes. OBJECTIVES: We studied the interaction of both exposures with a broad set of oxidative-stress related candidate genes and pathways on lung function decline and contrasted interactions between exposures. METHODS: For 12679 single nucleotide polymorphisms (SNPs), change in forced expiratory volume in one second (FEV(1)), FEV(1) over forced vital capacity (FEV(1)/FVC), and mean forced expiratory flow between 25 and 75% of the FVC (FEF(25-75)) was regressed on interval exposure to particulate matter >10 microm in diameter (PM10) or packyears smoked (a), additive SNP effects (b), and interaction terms between (a) and (b) in 669 adults with GWAS data. Interaction p-values for 152 genes and 14 pathways were calculated by the adaptive rank truncation product (ARTP) method, and compared between exposures. Interaction effect sizes were contrasted for the strongest SNPs of nominally significant genes (p(interaction)>0.05). Replication was attempted for SNPs with MAF<10% in 3320 SAPALDIA participants without GWAS. RESULTS: On the SNP-level, rs2035268 in gene SNCA accelerated FEV(1)/FVC decline by 3.8% (p(interaction) = 2.5x10(-6)), and rs12190800 in PARK2 attenuated FEV1 decline by 95.1 ml p(interaction) = 9.7x10(-8)) over 11 years, while interacting with PM10. Genes and pathways nominally interacting with PM10 and packyears exposure differed substantially. Gene CRISP2 presented a significant interaction with PM10 (p(interaction) = 3.0x10(-4)) on FEV(1)/FVC decline. Pathway interactions were weak. Replications for the strongest SNPs in PARK2 and CRISP2 were not successful. CONCLUSIONS: Consistent with a stratified response to increasing oxidative stress, different genes and pathways potentially mediate PM10 and tobac smoke effects on lung function decline. Ignoring environmental exposures would miss these patterns, but achieving sufficient sample size and comparability across study samples is challengin

Reliability and validity of the ESRD Symptom Checklist – Transplantation Module in Norwegian kidney transplant recipients

BACKGROUND: The aim of the study was to validate the Norwegian version of a self-administered 43-item questionnaire designed to assess quality of life in kidney transplant recipients, the End-Stage Renal Disease Symptom Checklist – Transplantation Module (ESRD-SCL). METHODS: In total, 53 kidney transplant recipients from one university-affiliated hospital responded to a questionnaire including the ESRD-SCL and the Short Form 36 (SF-36). We assessed internal consistency reliability and test-retest reliability with 2 weeks between assessments. Construct validity was assessed by correlations of the ESRD-SCL subscales with related and unrelated SF-36 scales, demographic, and clinical characteristics. RESULTS: Subscales of the ESRD-SCL showed good internal consistency reliability (Cronbach's = 0.72–0.81) and for the aggregate total scale α was 0.94. Test-retest reliability median 14 days apart was excellent with intraclass coefficients ranging from 0.87 to 0.95. The pattern of correlations of the ESRD-SCL scales with related and unrelated scales SF-36 scales and demographic and clinical characteristics gave support to the construct validity of the ESRD-SCL. CONCLUSION: The Norwegian translation of the ESRD-SCL showed satisfactory internal consistency reliability, test-retest reliability and construct validity, at the level of the original German version

Coping style and quality of life in patients with epilepsy: a cross-sectional study

Having epilepsy has a large impact on one's well-being, but often seizure frequency and severity do not explain self-reported quality of life. We hypothesized that one's personal coping style is more important. In this study, 105 patients attending the outpatient neurological clinic at the University Medical Centre in Utrecht, the Netherlands, with a diagnosis of partial epilepsy, aged 17–80 years, completed questionnaires. Demographic information, disease characteristics, health-related quality of life (HRQoL), and coping styles were obtained by postal-validated HRQoL questionnaires: the EQ5D and RAND-36 and the Utrecht Coping List. A passive coping style explained 45% of the variance in the mental component of HRQoL and was more important than ‘objective’ seizure-related measures. Confounders such as employment, gender, and side-effects of treatment explained another 6%. Passive coping style also influenced the physical component of the HRQoL, but here seizure-related factors predominated. Overall, epilepsy patients showed a more avoiding coping style, and female patients a less active coping style and more reassuring thoughts, compared to the Dutch population. The personal coping style of patients appears to be more important than seizure-related measures in predicting mental aspects of quality of life. Coping style characteristics rather than disease characteristics should guide clinical decision-making in patients with epilepsy. Further studies should investigate the effect on HRQoL of behavioral interventions to improve coping

Health-related quality of life after myocardial infarction is associated with level of left ventricular ejection fraction

<p>Abstract</p> <p>Background</p> <p>The objective was to explore the relationship between left ventricular ejection fraction (LVEF) assessed during hospitalization for acute myocardial infarction (MI) and later health-related quality of life (HRQoL).</p> <p>Methods</p> <p>We used multivariable linear regression to assess the relationship between LVEF and HRQoL in 256 MI patients who responded to the Kansas City Cardiomyopathy Questionnaire (KCCQ), the EQ-5D Index, and the EuroQol Visual Analogue Scale (EQ-VAS) 2.5 years after the index MI.</p> <p>Results</p> <p>167 patients had normal LVEF (>50%), 56 intermediate (40%–50%), and 33 reduced (<40%). The mean (SD) KCCQ clinical summary scores were 85 (18), 75 (22), and 68 (21) (<it>p </it><0.001) in the three groups, respectively. The corresponding EQ-5D Index scores were 0.83 (0.18), 0.72 (0.27), and 0.76 (0.14) (<it>p </it>= 0.005) and EQ-VAS scores were 72 (18), 65 (21), and 57 (20) (<it>p </it>= 0.001). In multivariable linear regression analysis age ≥ 70 years, known chronic obstructive pulmonary disease (COPD), subsequent MI, intermediate LVEF, and reduced LVEF were independent determinants for reduced KCCQ clinical summary score. Female sex, medication for angina pectoris at discharge, and intermediate LVEF were independent determinants for reduced EQ-5D Index score. Age ≥ 70 years, COPD, and reduced LVEF were associated with reduced EQ-VAS score.</p> <p>Conclusion</p> <p>LVEF measured during hospitalization for MI was a determinant for HRQoL 2.5 years later.</p

Cutpoints for mild, moderate and severe pain in patients with osteoarthritis of the hip or knee ready for joint replacement surgery

<p>Abstract</p> <p>Background</p> <p>Cutpoints (CPs) for mild, moderate and severe pain are established and used primarily in cancer pain. In this study, we wanted to determine the optimal CPs for mild, moderate, and severe pain in joint replacement surgery candidates with osteoarthritis (OA) of the hip or knee, and to validate the different CPs.</p> <p>Methods</p> <p>Patients (n = 353) completed the Brief Pain Inventory (BPI), the WOMAC Arthritis Index, and the SF-36 health status measure. Optimal CPs for categorizing average pain with three severity levels were derived using multivariate analysis of variance, using different CP sets for average pain as the independent variable and seven interference items from the BPI as the dependent variable. To validate the CPs, we assessed if patients in the three pain severity groups differed in pain as assessed with WOMAC and SF-36, and if BPI average pain with the optimal CPs resulted in higher correlation with pain dimensions of the WOMAC and SF-36 than other CPs.</p> <p>Results</p> <p>The optimal CPs on the 0–10 point BPI scale were CP (4,6) among hip patients and CP (4,7) among knee patients. The resulting pain severity groups differed in pain, as assessed with other scales than those used to derive the CPs. The optimal CPs had the highest association of average pain with WOMAC pain scores.</p> <p>Conclusion</p> <p>CPs for pain severity differed somewhat for patients with OA of the hip and knee. The association of BPI average pain scores categorized according to the optimal CPs with WOMAC pain scores supports the validity of the derived optimal CPs.</p

What causes increasing and unnecessary use of radiological investigations? a survey of radiologists' perceptions

<p>Abstract</p> <p>Background</p> <p>Growth in use and overuse of diagnostic imaging significantly impacts the quality and costs of health care services. What are the modifiable factors for increasing and unnecessary use of radiological services? Various factors have been indentified, but little is known about their relative impact. Radiologists hold key positions for providing such knowledge. Therefore the purpose of this study was to obtain radiologists' perspective on the causes of increasing and unnecessary use of radiological investigations.</p> <p>Methods</p> <p>In a mailed questionnaire radiologist members of the Norwegian Medical Association were asked to rate potential causes of increased investigation volume (fifteen items) and unnecessary investigations (six items), using five-point-scales. Responses were analysed by using summary statistics and Factor Analysis. Associations between variables were determined using Students' t-test, Spearman rank correlation and Chi-Square tests.</p> <p>Results</p> <p>The response rate was 70% (374/537). The highest rated causes of increasing use of radiological investigations were: a) new radiological technology, b) peoples' demands, c) clinicians' intolerance for uncertainty, d) expanded clinical indications, and e) availability. 'Over-investigation' and 'insufficient referral information' were reported the most frequent causes of unnecessary investigations. Correlations between causes of increasing and unnecessary radiology use were identified.</p> <p>Conclusion</p> <p>In order to manage the growth in radiological imaging and curtail inappropriate investigations, the study findings point to measures that influence the supply and demand of services, specifically to support the decision-making process of physicians.</p

Interferon-γ-producing immature myeloid cells confer protection against severe invasive group A Streptococcus infections

Cytokine-activated neutrophils are known to be essential for protection against group A Streptococcus infections. However, during severe invasive group A Streptococcus infections that are accompanied by neutropenia, it remains unclear which factors are protective against such infections, and which cell population is the source of them. Here we show that mice infected with severe invasive group A Streptococcus isolates, but not with non-invasive group A Streptococcus isolates, exhibit high concentrations of plasma interferon-γ during the early stage of infection. Interferon-γ is necessary to protect mice, and is produced by a novel population of granulocyte–macrophage colony-stimulating factor-dependent immature myeloid cells with ring-shaped nuclei. These interferon-γ-producing immature myeloid cells express monocyte and granulocyte markers, and also produce nitric oxide. The adoptive transfer of interferon-γ-producing immature myeloid cells ameliorates infection in wild-type and interferon-γ-deficient mice. Our results indicate that interferon-γ-producing immature myeloid cells have a protective role during the early stage of severe invasive group A Streptococcus infections

Raising positive expectations helps patients with minor ailments: A cross-sectional study

Background: Consultations for minor ailments constitute a large part of the workload of general practitioners (GPs). As medical interventions are not always available, specific communication strategies, such as active listening and positive communication, might help GPs to handle these problems adequately. This study examines to what extent GPs display both strategies during consultations for minor ailments and investigates how each of these relate to the patients' perceived health, consultation frequency and medication adherence. Methods: 524 videotaped consultations between Dutch GPs and patients aged 18 years or older were selected. All patients presented a minor ailment, and none of them suffered from a diagnosed chronic illness. The observation protocol included the validated Active Listening Observation Scale (ALOS-global), as well as three domains of positive communication, i.e. providing reassurance, a clear explanation, and a favourable prognosis. Patients completed several questionnaires before, immediately after, and two weeks after the consultation. These included measures for state anxiety (STAI), functional health status (COOP/ WONCA charts) and medication adherence (MAQ). Consultation frequency was available from an ongoing patient registration. Data were analysed using multivariate regression analyses. Results: Reassurance was related to patients' better overall health. Providing a favourable prognosis was linked to patients feeling better, but only when accompanied by a clear explanation of the complaints. A clear explanation was also related to patients feeling better and less anxious, except when patients reported a low mood pre-visit. Active listening alone was positively associated with patients feeling worse. Among patients in a good mood state, active listening was associated with less adherence. Conclusion: To some extent, it seems helpful when GPs are at the same time clear and optimistic about the nature and course of minor ailments. Yet, it does not seem helpful always and in all cases, e.g. when patients feel low upon entering the consulting room. Although communication strategies might to some extent contribute to the management of minor ailments, the results of this observational study also indicate that it is important for a physician to pay attention to the mood of the patient who enters the consulting room. (aut. ref.