Pythia T. Nieuwkerk

Self-reported adherence to antiretroviral therapy for HIV-1 infection and virologic treatment response: a meta-analysis.

Background:Adherence to highly active antiretroviral therapy (HAART) for HIV-1 infection is essential for plasma HIV-1 RNA suppression. Self-report is the most frequently used measure of adherence to HAART, but its validity is controversial. Studies on the relation between self-reported adherence and virologic treatment response have shown inconsistent results. We investigated whether this variability between studies about the effect of self-reported adherence on virologic treatment response could be attributed to study design features. Methods:We searched for studies reporting on adult nonpregnant patients prescribed antiretroviral therapy for chronic HIV-1 infection using a self-reported adherence measure and providing information about the relation between adherence and plasma HIV-1 RNA concentrations. Meta-analysis with random effects modeling was used to pool data and to investigate sources of heterogeneity. Results:Sixty-five studies fulfilled inclusion criteria, containing data from 15,351 patients. The pooled odds ratio (95% confidence interval) of detectable plasma viral load in nonadherent patients was 2.31 (1.99-2.68). There was significant heterogeneity among studies (P < 0.001). Not ascertaining confidentiality of responses, use of actual viral load measurements, an adherence threshold lower than 95%, higher percentages of patients on their initial antiretroviral regimen, and higher percentages of patients with a history of intravenous drug use within a study were associated with higher point estimates. Conclusions:Overall, we observed that self-reported adherence measures can distinguish between clinically meaningful patterns of medication-taking behavior. Distinct study characteristics were significantly associated with the relation between adherence and virologic response. These characteristics should be taken into consideration when interpreting results from studies on self-reported adherence.

Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome

Pulmonary arterial hypertension associated with congenital heart disease caused by systemic-to-pulmonary shunting was associated with a high risk of morbidity and mortality. In this retrospective study, the longer term treatment effect of bosentan on exercise capacity and quality of life (QoL) were evaluated in 58 adult patients (>18 years) with pulmonary arterial hypertension associated with congenital heart disease, including patients with Downs syndrome. All patients were evaluated at baseline and during follow-up using laboratory tests, 6-minute walk test, QoL questionnaires, and Doppler echocardiography. Treatment efficacy was analyzed separately for patients without (n = 30) and with Downs syndrome (n = 28). Median follow-up of all patients treated with bosentan was 22 months (range 3 to 36). In patients without Downs syndrome, mean 6-minute walk distance increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment, followed by a gradual return to baseline and disease stabilization. QoL improved significantly during treatment and was maintained during 18 months of follow-up (p <0.05). In patients with Downs syndrome, 6-minute walk distance and QoL were stable during treatment. In conclusion, findings suggested that in patients without Downs syndrome, longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity.

Do Inflammatory Bowel Disease patients with anxiety and depressive symptoms receive the care they need

BACKGROUND AND AIMS Inflammatory Bowel Disease (IBD) patients with anxiety and/or depressive symptoms may not receive the care they need. Provision of care requires insight into the factors affecting these psychiatric symptoms. The study was designed to examine the extent to which: (1) IBD patients with anxiety and/or depressive symptoms receive mental treatment and (2) clinical and socio-demographic variables are associated with these symptoms. METHODS 231 adult IBD patients (79% response rate), attending a tertiary care center, completed standardized measures on anxiety and depressive symptoms (HADS), quality of life (SF-12) and mental health care use (TIC-P). Diagnosis and disease activity were determined by the gastroenterologist. RESULTS 43% had high levels of anxiety and/or depressive symptoms, indicative of a psychiatric disorder (HADS ≥ 8), of whom 18% received psychological treatment and 21% used psychotropic medication. In multivariate analysis, high disease activity was associated with anxiety (OR=2.72 | p<0.03) and depression (OR=3.36 | p<0.01), while Crohns disease was associated with anxiety (OR=2.60 | p<0.03). CONCLUSIONS Despite high levels of anxiety and depressive symptoms and poor quality of life, psychiatric complaints in IBD patients were undertreated. Screening for and treatment of psychiatric symptoms should become an integral part of IBD medical care.

Systemic methotrexate therapy versus laparoscopic salpingostomy in tubal pregnancy. Part II. Patient preferences for systemic methotrexate

OBJECTIVE To investigate patient preferences for systemic methotrexate therapy relative to laparoscopic salpingostomy in the treatment of tubal pregnancy. DESIGN Preference assessment in controlled clinical study. SETTING Four hospitals and one infertility clinic. PATIENT(S) Forty patients who had been treated for tubal pregnancy and 40 nonpregnant controls. INTERVENTION(S) Preference for methotrexate therapy relative to salpingostomy was established during an interview. Two scenarios were offered for methotrexate therapy: one with and one without preceding diagnostic laparoscopy. Hypothetical tubal patency rates after methotrexate therapy were varied in both scenarios until patients switched in their initial preference. MAIN OUTCOME MEASURE(S) Preference for systemic methotrexate therapy. RESULT(S) Only a few patients switched in their initial preference when the tubal patency rate after systemic methotrexate therapy was varied. Most preferred methotrexate therapy without an increase in the tubal patency rate in a scenario without preceding diagnostic laparoscopy. A small group never opted for methotrexate therapy even when it would guarantee a 100% tubal patency rate. CONCLUSION(S) Systemic methotrexate therapy would be preferred by most patients as part of a completely nonsurgical management strategy. Tubal patency was a decisive factor for treatment preference in a minority of patients only.

Therapeutic drug monitoring of HIV-protease inhibitors to assess noncompliance.

Objective To determine plasma concentration ratio limits (CORALS) for HIV-protease inhibitors outside of which random plasma concentrations reflect partial compliance or noncompliance. In the absence of a gold standard for measuring compliance and to avoid complex techniques, measuring plasma concentrations may be an objective and easy way to check noncompliance. Methods Pharmacokinetic curves after observed ingestion were recorded in patients on steady-state indinavir 800 mg TID (n = 22), ritonavir 400 mg/saquinavir 400 mg BID (n = 22, ritonavir; n = 17, saquinavir hard-gel capsules), or nelfinavir 750 mg TID (n = 4) or 1250 mg BID (n = 4). Concentration ratios were calculated by dividing the measured concentration by the median population value at the corresponding sampling time. Limits were based on the minimum P05 (5th percentile) and maximum P95 of these ratios found during the sampling interval. With these limits the authors determined (1) the proportion of patients falsely judged as noncompliers after observed ingestion, (2) discrimination between compliers and noncompliers, and (3) the absolute percentage of noncompliers. To judge the last two elements, two sets of random plasma samples were included: (1) samples sent in by the physician on suspicion of noncompliance (indinavir, n = 42; nelfinavir, n = 22;) or from a study population stating imperfect compliance in a questionnaire (ritonavir/saquinavir, n = 11); (2) control samples sent in routinely for monitoring therapeutic levels (indinavir, n = 41; nelfinavir, n = 201) or drawn from patients who stated perfect compliance in the questionnaire (ritonavir/saquinavir, n = 35). Results The following CORALS were found: indinavir <0.23 or >3.3; nelfinavir <0.36 or >2.1; ritonavir <0.18 or >1.9; saquinavir <0.28 or >2.3. In 31% to 55% of the patients suspected of noncompliance a plasma concentration ratio outside these limits was found. If a ratio was outside the limits, there was a 68% to 88% chance that that plasma sample belonged to a patient suspected of noncompliance, compared with the controls (all Chi-squared tests P < 0.05). Compared with observed ingestion, these chances ranged from 87% to 92%. Conclusion By using concentration ratio limits (CORALS), plasma samples of protease inhibitors with values outside these limits are highly indicative of partial or noncompliance.

Health-related quality of life and posttraumatic stress disorder among survivors of an outbreak of legionnaires disease

A follow-up study of 122 survivors of an outbreak of legionnaires disease (LD) in The Netherlands was conducted to determine persistence of symptoms, health-related quality of life (HRQL), and presence of posttraumatic stress disorder (PTSD). Seventeen months after diagnosis of LD, survivors completed a questionnaire assessing symptoms and HRQL and a questionnaire assessing PTSD. The most prevalent new symptoms were fatigue (in 75% of patients), neurologic symptoms (in 66%), and neuromuscular symptoms (in 63%). HRQL was impaired in 7 of the 8 dimensions assessed by the HRQL questionnaire, and 15% of patients experienced PTSD. Symptoms and impaired HRQL persisted for >1.5 years. As a result of the design of this study, it could not be inferred whether Legionella pneumophila infection, severe pneumonia in general, or the outbreak situation was responsible for impaired well-being. However, awareness of this problem by health care providers may improve the aftercare of patients.

Self-reported adherence is more predictive of virological treatment response among patients with a lower tendency towards socially desirable responding.

BACKGROUND Self-report is the most commonly used measure of adherence to highly active antiretroviral therapy, but typically shows weaker associations with virological treatment outcome than more objective adherence assessment methods. Socially desirable responding might hamper the validity of self-reported adherence. We investigated whether stratifying patients according to their socially desirable response set might improve the prediction of virological treatment response by self-reported adherence. METHODS Patients enrolled in the focus group of the Dutch national cohort ATHENA completed a social desirability scale, four self-report adherence questions, and had their plasma HIV type-1 (HIV-1) RNA concentrations measured. We calculated odds ratios and 95% confidence intervals for self-reported non-adherence to predict HIV-1 RNA>50 copies/ml among patients with a lower or a higher tendency towards socially desirable responding. RESULTS A total of 331 patients were included. Self-reported non-adherence was significantly predictive of HIV-1 RNA>50 copies/ml on three out of four questions among patients with lower socially desirable responding (n=198). Self-reported non-adherence did not predict HIV-1 RNA>50 copies/ml among patients with higher socially desirable responding (n=132). CONCLUSIONS Stratifying patients according to their socially desirable response set improved the prediction of virological treatment response by self-reported adherence. This finding emphasizes the importance of discussing medication adherence with patients in a non-threatening and non-judgemental way that normalizes non-adherence in order to reduce socially desirable responding.

Health-Related Quality of Life and Survival among HIV-Infected Patients Receiving Highly Active Antiretroviral Therapy: A Study of Patients in the AIDS Therapy Evaluation in the Netherlands (ATHENA) Cohort

BACKGROUND Previous studies have shown that health-related quality of life (HRQL) predicts survival in patients infected with human immunodeficiency virus (HIV). However, these studies predated the highly active antiretroviral therapy (HAART) era, included only a few patients receiving HAART, or had a limited duration of follow-up. This study investigates whether HRQL predicts survival among HIV-infected patients receiving HAART. METHODS HIV-infected patients participating in the focus group of the AIDS Therapy Evaluation in the Netherlands (ATHENA) study and starting or already receiving HAART completed the Medical Outcomes Study HIV Health Survey at study entry (1 May 1998 through 31 December 2000). The physical health summary (PHS) and mental health summary (MHS) scores were calculated. All-cause mortality was established at 31 March 2008. Kaplan-Meier analysis and Cox regression models were performed to predict survival. RESULTS The median follow-up was 8.4 years. Sixty-six patients (11.8%) died during follow-up. We found a significant relation between quartiles of PHS and survival (P < .001, log-rank test). Of patients with a PHS, 26 (20%) died in quartile 1 (indicating worst HRQL), 17 (13%) died in quartile 2, 10 (8%) died in quartile 3, and 5 (4%) died in quartile 4 (indicating best HRQL) (P< .001). The prediction of PHS on survival was independent of other (clinical) parameters (P< .001). No relation was found between MHS and survival (P= .13). CONCLUSION Patient-reported HRQL predicted survival among HIV-infected patients receiving HAART. This information could be highly useful for physicians in determining the prognosis of their patients.

Effects of active treatment discontinuation in patients with a CD4+ T-cell nadir greater than 350 cells/mm3 : 48-week treatment interruption in early starters netherlands study (TRIESTAN)

Objective:To evaluate the safety and efficacy of discontinuing highly active antiretroviral therapy (HAART) in HIV-1-positive patients who initiated HAART at a CD4+ T-cell count >350 cells/mm3. Methods:Eligible patients were identified from the Dutch AIDS Therapy Evaluation, The Netherlands (ATHENA) national observational cohort. Interruption or continuation of HAART was offered to all. Results:Of 71 patients enrolled, 46 (64%) interrupted HAART (STOP group) and 25 (36%) continued HAART (control group). The median CD4+ T-cell nadirs at the start of HAART were 469 (interquartile range [IQR]: 430-720) cells/mm3 and 510 (IQR: 440-637) cells/mm3, respectively. At week 48, the median plasma HIV RNA level in the STOP group had stabilized at approximately pre-HAART values (4.55 log10, IQR: 4.2-4.9 copies/mL), but the CD4+ T-cell count still exceeded the pre-HAART count (563 cells/mm3, IQR: 450-710 cells/mm3). Only 5 patients (11%) had reinitiated HAART after 48 weeks, all for personal reasons. No Centers for Disease Control and Prevention category events or death occurred after interruption. In 6 (13%) of 46 patients, mild symptoms of acute retroviral rebound syndrome (ARVS) were identified. No improvement was observed in mental or physical health scores. In 37% of patients, nonnucleoside reverse transcriptase inhibitor drug concentrations were still detectable 1 week after stopping. Conclusions:Although HAART can safely be interrupted in patients with a high CD4 T-cell nadir, no improvement in quality of life was established. Patients can experience ARVS, the risk for development of resistance after treatment interruption is realistic, and there is a potential hazard of HIV transmission to sexual partners. We would not actively advise stopping treatment in patients who started treatment too early according to current guidelines.

Are retrospective measures of change in quality of life more valid than prospective measures

Background:Adaptation to changing health presents a challenge to measuring change in quality of life (QoL). Previous studies have shown that different methods for measuring change yield different results, but it is unclear which method provides a more valid measurement of change. We investigated which of 3 commonly used methods for measuring change in QoL yielded the strongest associations with clinical measures of change in health status. Methods:A total of 268 human immunodeficiency virus (HIV)-1-infected patients starting highly active antiretroviral therapy completed QoL measures at baseline and after 36 weeks. We calculated Pearson correlation coefficients between change in QoL according to a prospective baseline and prospective follow-up measurement, a retrospective baseline and prospective follow-up measurement, or retrospective transition questions and change in CD4-cell count, plasma viral-load, body mass index, and hemoglobin concentration. Results:Patients evaluated their QoL significantly worse on the retrospective than on the prospective baseline measurement (P < 0.01). These results may indicate that patients’ reference value by which they evaluate their QoL changed over time, which would invalidate prospective serial QoL measurements. The retrospective baseline measurement method yielded strongest associations with clinical measures of change (P = 0.02 to P < 0.01). Distinguishing between the change inferred from the conventional prospective and the retrospective baseline measurement method was meaningful because the prospective method did not lead to changes that would be considered clinically significant, whereas the retrospective baseline measurement method did. Conclusions:A method for measuring change in QoL incorporating a retrospective baseline-measurement showed strongest associations with change in clinical indicators of health status, suggesting a more valid measurement of change in QoL than a conventional prospective method.