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Screening tools and neuropsychological testing: Neurocognitive function was screened for using Sacktor’s IHDS [8]. This test consists of three parts, each one analysing a specific cognitive domain –motor speed, psychomotor speed and memory– and scoring up to a maximum of four points. The final score is the sum of the three sub-scores with a range from 0 to 12 points. To measure functional decline we used a questionnaire developed by the German NeuroAIDS Association (DNAA) consisting of twenty-two yes-no questions intended to evaluate neurological abnormalities such as memory and motor impairment, depression and similar problems in HIV-positive patients. A copy of the questionnaire is available as an additional material (S1 File). Nine of these questions have been mentioned as potentially helpful in describing mild interference with everyday functioning, and therefore useful in discerning between ANI and MND. The questionnaire also gives an idea of the patient’s mood status, which is useful in identifying a current depressive episode. For the purpose of our study we put together a neuropsychological battery of tests with eleven different tests covering eight ability domains. Table 1 shows each test with its evaluated domain(s). Raw scores were normalised to Z-scores using demographic corrections for age and education. A more detailed description of the norms used can be found on the right column of the table under “references”. The time between screening and neuropsychological testing was three months or less. The patient’s general practitioner performed the IHDS as part of the regular visits to the health centre. A further physician trained in neuropsychology performed the neuropsychological evaluations.
Table data removed from full text. Table identifier and caption: 10.1371/journal.pone.0168225.t001 Content of the neuropsychological battery of tests. * This domain not included in the Frascati definition, but needed for evaluation of other tests;a: adjusted for age;e: adjusted for educational level;g: adjusted for gender.
Four hundred and eighty HIV-positive patients, aged 19–80, were screened for neurocognitive dysfunction and functional decline as described. They were then divided according to their IHDS score and distributed into three subsamples: The ‘poor performance’ subsample (n = 49, 10%) included participants with a score of 10 points or fewer, the ‘average performance’ subsample (n = 87, 18%) scored between 10.5 and 11 points, and the ‘high performance’ subsample (n = 344, 72%) scored either 11.5 or 12 points. Then, thirty members of each subsample were randomly selected to establish three study groups—with identical names as the subsamples—and to undergo neuropsychological examination. Participants had all been diagnosed with HIV for at least three months and spoke fluent German. Participants were excluded if they had a confounding neurological or psychiatric condition, cancer, an active opportunistic infection or were currently using mind-altering substances. A control group of thirty participants with a documented negative HIV test within the year preceding the evaluation and the same eligibility and exclusion criteria, was recruited in parallel. The ethics committee of the Charité School of Medicine approved the study. The general terms of data protection and the Charité ‘Good Medical and Scientific Practice’ statutes were applied. All the study procedures were conducted in accordance with the 1964 Declaration of Helsinki (fourth revision). Participants who met the eligibility criteria were given detailed information about the study and provided with a written consent form. Only after signing this form were they finally recruited.
Descriptive statistics were used to compare characteristics between groups of individuals. All normally distributed continuous variables were reported as means and standard deviation (SD). All non-normally distributed continuous variables were reported as medians with interquartile ranges (IQR). Associations of categorical variables between the different groups and analysed factors were assessed using the chi-square test. For normally distributed and non-normally distributed continuous variables with more than two samples, ANOVA and Kruskal–Wallis one-way analysis of variance tests were used, respectively. Mann-Whitney U Test was used for non-normally distributed variables with two samples. The relationship between two variables was evaluated by linear correlation analysis. The Pearson correlation coefficient was applied to samples with normal distribution. For nonparametric samples, Spearman’s rho coefficient was used. The intensity of the association between a categorical and a quantitative variable was assessed using Cohen’s d association index. All p-values were 2-tailed and considered significant at p < 0.05. The optimal cut-off point for the screening test was assessed by a Receiver Operating Characteristic (ROC) curve. The analyses were performed using IBM SPSS Statistics version 22.0. Sensitivity, specificity, predictive values and Youden’s J-Index were calculated using a Microsoft Excel spreadsheet provided by The Critical Appraisal Skills Programme (CASPe), which is available at redcaspe.org. All raw data used in this study has been made available for download as an additional material (S2 File).
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