Control of complement-induced inflammatory responses to SARS-CoV-2 infection by anti-SARS-CoV-2 antibodies.

Dysregulated immune responses contribute to the excessive and uncontrolled inflammation observed in severe COVID-19. However, how immunity to SARS-CoV-2 is induced and regulated remains unclear. Here, we uncover the role of the complement system in the induction of innate and adaptive immunity to SARS-CoV-2. Complement rapidly opsonizes SARS-CoV-2 particles via the lectin pathway. Complement-opsonized SARS-CoV-2 efficiently induces type-I interferon and pro-inflammatory cytokine responses via activation of dendritic cells, which are inhibited by antibodies against the complement receptors (CR) 3 and 4. Serum from COVID-19 patients, or monoclonal antibodies against SARS-CoV-2, attenuate innate and adaptive immunity induced by complement-opsonized SARS-CoV-2. Blocking of CD32, the FcγRII antibody receptor of dendritic cells, restores complement-induced immunity. These results suggest that opsonization of SARS-CoV-2 by complement is involved in the induction of innate and adaptive immunity to SARS-CoV-2 in the acute phase of infection. Subsequent antibody responses limit inflammation and restore immune homeostasis. These findings suggest that dysregulation of the complement system and FcγRII signaling may contribute to severe COVID-19.

Aberrant neutrophil degranulation in hospitalized patients with COVID-19 partially remains for 6 months.

Neutrophils are important players in COVID-19, contributing to tissue damage by release of inflammatory mediators, including ROS and neutrophil elastase. Longitudinal studies on the effects of COVID-19 on neutrophil phenotype and function are scarce. Here, we longitudinally investigated the phenotype and degranulation of neutrophils in COVID-19 patients (28 nonhospitalized and 35 hospitalized patients) compared with 17 healthy donors (HDs). We assessed phenotype, degranulation, CXCL8 (IL-8) release, and ROS generation within 8 days, at one or 6 month(s) after COVID-19 diagnosis. For degranulation and ROS production, we stimulated neutrophils, either with ssRNA and TNF or granulocyte-macrophage colony-stimulating factor and N-Formylmethionyl-leucyl-phenylalanine. During active COVID-19, neutrophils from hospitalized patients were more immature than from HDs and were impaired in degranulation and ROS generation, while neutrophils from nonhospitalized patients only demonstrated reduced CD66b+ granule release and ROS production. Baseline CD63 expression, indicative of primary granule release, and CXCL8 production by neutrophils from hospitalized patients were elevated for up to 6 months. These findings show that patients hospitalized due to COVID-19, but not nonhospitalized patients, demonstrated an aberrant neutrophil phenotype, degranulation, CXCL8 release, and ROS generation that partially persists up to 6 months after infection.

Between delivering chronic care and answering patients' burdens: Understanding HIV specialist nurses' experiences in the age of treatment.

AIM(S): To understand the experiences of HIV nurses in the context of ambivalence between biomedical treatment advancements and the continuing burden for people living with HIV and negative representations of HIV. DESIGN: An interpretative phenomenological study was conducted using in-depth interviews. METHODS: Twenty-one interviews with nurses were conducted between November 2021 and March 2022. A thematic analysis was performed. RESULTS: Six themes related to the nurses' experiences emerged. Despite effective treatment for most people with HIV, nurses identify patient populations that require additional care. Nurses are flexible in making extra appointments to accommodate complex issues in these patients. Nurses develop a unique relationship with their patients based on trust and empathy, linked to patient's experiences with stigma and discrimination for people with HIV. Nurses perceive their tasks as becoming increasingly complex. There is explicit awareness about the changes in HIV care from acute to chronic care and how this affects nurses' tasks. Nurses continue to differentiate HIV from other chronic conditions. CONCLUSION: Biomedical advancements change the organization of HIV care while public health concerns remain and patient population has particular needs due to negative social representations of HIV. Nurses navigate these issues in their everyday care. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: A potential re-evaluation of the role of nurses in providing chronic HIV care. IMPACT: Our study addresses the roles of HIV nurses as care is shifting towards chronic care models. The unique relationship between nurses and patients is key in understanding the importance of nurses in the care trajectory. These findings impact the institutional role of nurses in HIV treatment centres and the institutional organization of HIV care. REPORT METHOD: The COREQ guideline was used. PATIENT OR PUBLIC CONTRIBUTION: Amsterdam UMC (AMC) staff, the national organization of HIV Nurses and patient organizations contributed to the study design.

Implementation of 'IBD-Specific Cognitive Behavioural Therapy' for Patients with Inflammatory Bowel Diseases with Poor Mental Quality of Life, Anxiety and Depression.

This paper describes the implementation of inflammatory bowel disease (IBD)-specific cognitive behavioural therapy (CBT) for IBD patients with poor quality of life (QoL), anxiety and depression, in four hospitals in the Netherlands. Treatment outcomes were compared with those of a previously published randomized control trial (RCT) of 'IBD-specific CBT', following a benchmark strategy. Primary outcome was IBD-specific QoL (IBDQ) completed before and after CBT, secondary outcomes were anxiety and depressive symptoms (HADS, CES-D). Semi-structured interviews were conducted among a pilot of gastroenterologists, nurse specialists and psychologists to evaluate 'IBD-specific CBT'. 94 patients started treatment (280 screened). At follow-up, 63 participants (67% compared to 81% in the RCT benchmark) completed the IBDQ. Treatment effect sizes of the implementation study were comparable and slightly larger than those of RCT benchmark. Gastroenterologists, IBD nurses and psychologists found CBT necessary for IBD patients with poor QoL, depression and/or anxiety disorders. 'IBD-specific CBT' can be successfully implemented. Regular supervision of psychologists performing 'IBD-specific CBT' treatment is needed.

Efficacy of Cognitive-Behavioral Therapy Targeting Severe Fatigue Following Coronavirus Disease 2019: Results of a Randomized Controlled Trial.

BACKGROUND: Severe fatigue following coronavirus disease 2019 (COVID-19) is prevalent and debilitating. This study investigated the efficacy of cognitive-behavioral therapy (CBT) for severe fatigue following COVID-19. METHODS: A multicenter, 2-arm randomized controlled trial was conducted in the Netherlands with patients being severely fatigued 3-12 months following COVID-19. Patients (N = 114) were randomly assigned (1:1) to CBT or care as usual (CAU). CBT, targeting perpetuating factors of fatigue, was provided for 17 weeks. The primary outcome was the overall mean difference between CBT and CAU on the fatigue severity subscale of the Checklist Individual Strength, directly post-CBT or CAU (T1), and after 6 months (T2). Secondary outcomes were differences in proportions of patients meeting criteria for severe and/or chronic fatigue, differences in physical and social functioning, somatic symptoms, and problems concentrating between CBT and CAU. RESULTS: Patients were mainly nonhospitalized and self-referred. Patients who received CBT were significantly less severely fatigued across follow-up assessments than patients receiving CAU (-8.8 [95% confidence interval {CI}, -11.9 to -5.8]); P < .001), representing a medium Cohen's d effect size (0.69). The between-group difference in fatigue severity was present at T1 (-9.3 [95% CI, -13.3 to -5.3]) and T2 (-8.4 [95% CI, -13.1 to -3.7]). All secondary outcomes favored CBT. Eight adverse events were recorded during CBT, and 20 during CAU. No serious adverse events were recorded. CONCLUSIONS: Among patients, who were mainly nonhospitalized and self-referred, CBT was effective in reducing fatigue. The positive effect was sustained at 6-month follow-up. CLINICAL TRIALS REGISTRATION: Netherlands Trial Register NL8947.

Emotional distress in cancer survivors from various ethnic backgrounds: Analysis of the multi-ethnic HELIUS study.

PURPOSE: Insight into emotional distress of cancer survivors from ethnic minority groups in Europe is scarce. We aimed to compare distress levels of survivors from ethnic minorities to that of the majority population, determine whether the association between having cancer (yes vs. no) and distress differs among ethnic groups and investigate sociocultural correlates of distress. METHODS: Cross-sectional data were derived from HELIUS, a multi-ethnic cohort study conducted in the Netherlands. Of 19,147 participants, 351 were diagnosed with cancer (n = 130 Dutch, n = 75 African Surinamese, n = 53 South-Asian Surinamese, n = 43 Moroccan, n = 28 Turkish, n = 22 Ghanaian). Distress (PHQ-9, MCS-12) and correlates were assessed by self-report. Cancer-related variables were derived from the Netherlands Cancer Registry. RESULTS: Survivors were on average 7 years post-diagnosis. Survivors from South-Asian Surinamese, Moroccan, Turkish and Ghanaian origin reported more distress than survivors from Dutch origin (effect sizerange : 0.44-1.17; adjusted models). The association between having cancer or not with distress differed in direction between Dutch and the non-Dutch ethnic groups: Non-Dutch cancer patients tended to have more distress than their cancer-free peers, whereas Dutch cancer patients tended to have less distress than their cancer-free peers. For Moroccan and Turkish patients, the acculturation style of separation/marginalization, compared to integration/assimilation, was associated with higher depressive symptoms. In analyses pooling data from all ethnic minorities, lower health literacy, lower emotional support satisfaction and younger age at the time of migration were associated with higher depressive symptoms. Lower health literacy, fewer emotional support transactions, and more frequent attendance at religious services were associated with worse mental health. CONCLUSION: Cancer survivors from ethnic minorities experience more distress than those from the majority population. Culturally sensitive supportive care should be considered.

Intentional- but not Unintentional Medication Non-adherence was Related with Beliefs about Medicines Among a Multi-Ethnic Sample of People with HIV.

Medication non-adherence can be intentional or unintentional. We investigated the prevalence of unintentional and intentional non-adherence to antiretroviral therapy (ART) and the relationship with beliefs about medicines, sociodemographic- and HIV-related variables among people with HIV (PWH) attending the HIV clinic of the Amsterdam University Medical Centers. Participants completed the Medication Adherence Rating Scale (MARS) and the Beliefs about Medicines (BMQ) questionnaire. About half of 80 participants reported unintentional non-adherence and 20% reported intentional non-adherence. Both unintentional and intentional non-adherence were associated with younger age. Additionally, intentional non-adherence was associated with being a migrant from Suriname /Netherlands Antilles, having more concerns about negative effects of ART and stronger beliefs that medicines in general are overused/ overprescribed. In conclusion, intentional but not unintentional non-adherence was associated with beliefs about medicines. Eliciting and discussing beliefs about medicines may be a promising avenue to address patients' concerns and perceptions thereby potentially enhancing medication adherence.

Long-term fear of cancer recurrence in patients treated endoscopically for early Barrett's neoplasia.

Previous studies on fear of cancer recurrence after endoscopic treatment for early Barrett's neoplasia focused on fear during a relatively short period after the intervention. The aim of this study was to explore whether fear of cancer (recurrence) persists during long-term follow-up in patients treated endoscopically for Barrett's neoplasia compared to patients treated surgically for a more advanced stage of esophageal adenocarcinoma. Participants previously participated in a prospective longitudinal study investigating quality of life and fear of cancer recurrence and were treated endoscopically for early Barrett's neoplasia (high-grade dysplasia-T1sm1N0M0) or surgically for a more advanced esophageal adenocarcinoma (T1N0M0-T3N1M0). For the present study, participants were again invited to complete a set of questionnaires including the fear of cancer recurrence scale (FORS), worry for cancer scale (WOCS), and the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS Anxiety). Thirty-nine patients were eligible in the endoscopy group and 28 in the surgical group. The median time between the baseline measurement (original study) and the long-term follow-up assessment was 4 years (interquartile range 3-5 years). Fear and worry for cancer recurrence and general anxiety diminished over time in both treatment groups. However, at long-term follow-up, endoscopically treated patients had significantly higher levels of worry for cancer and general anxiety than surgically treated patients. Fear of cancer recurrence did not significantly differ between endoscopically and surgically treated patients. We found that worry and fear of cancer recurrence and general anxiety in endoscopically treated patients declined over time, but not as much as in surgically treated patients.

Health-related quality of life among persons with initial mild, moderate, and severe or critical COVID-19 at 1 and 12 months after infection: a prospective cohort study.

BACKGROUND: Currently, there is limited evidence about the long-term impact on physical, social and emotional functioning, i.e. health-related quality of life (HRQL) after mild or moderate COVID-19 not requiring hospitalization. We compared HRQL among persons with initial mild, moderate or severe/critical COVID-19 at 1 and 12 months following illness onset with Dutch population norms and investigated the impact of restrictive public health control measures on HRQL. METHODS: RECoVERED, a prospective cohort study in Amsterdam, the Netherlands, enrolled adult participants after confirmed SARS-CoV-2 diagnosis. HRQL was assessed with the Medical Outcomes Study Short Form 36-item health survey (SF-36). SF-36 scores were converted to standard scores based on an age- and sex-matched representative reference sample of the Dutch population. Differences in HRQL over time were compared among persons with initial mild, moderate or severe/critical COVID-19 using mixed linear models adjusted for potential confounders. RESULTS: By December 2021, 349 persons were enrolled of whom 269 completed at least one SF-36 form (77%). One month after illness onset, HRQL was significantly below population norms on all SF-36 domains except general health and bodily pain among persons with mild COVID-19. After 12 months, persons with mild COVID-19 had HRQL within population norms, whereas persons with moderate or severe/critical COVID-19 had HRQL below population norms on more than half of the SF-36 domains. Dutch-origin participants had significantly better HRQL than participants with a migration background. Participants with three or more COVID-19 high-risk comorbidities had worse HRQL than part participants with fewer comorbidities. Participants who completed the SF-36 when restrictive public health control measures applied reported less limitations in social and physical functioning and less impaired mental health than participants who completed the SF-36 when no restrictive measures applied. CONCLUSIONS: Twelve months after illness onset, persons with initial mild COVID-19 had HRQL within population norms, whereas persons with initial moderate or severe/critical COVID-19 still had impaired HRQL. Having a migration background and a higher number of COVID-19 high-risk comorbidities were associated with worse HRQL. Interestingly, HRQL was less impaired during periods when restrictive public health control measures were in place compared to periods without.

Response shift after coronary revascularization.

PURPOSE: The aims of this study were to investigate (1) the extent to which response shift occurs among patients with coronary artery disease (CAD) after coronary revascularization, (2) whether the assessment of changes in health-related quality of life (HRQoL), controlled for response shift, yield more valid estimates of changes in HRQoL, as indicated by stronger associations with criterion measures of change, than without controlling for response shift, and (3) if occurrences of response shift are related to patient characteristics. METHODS: Patients with CAD completed the SF-36 and the Seattle Angina Questionnaire (SAQ7) at baseline and 3 months after coronary revascularization. Sociodemographic, clinical and psychosocial variables were measured with the patient version of the New York Heart Association-class, Subjective Significance Questionnaire, Reconstruction of Life Events Questionnaire (RE-LIFE), and HEXACO personality inventory. Oort's Structural Equation Modeling (SEM) approach was used to investigate response shift. RESULTS: 191 patient completed questionnaires at baseline and at 3 months after treatment. The SF-36 showed recalibration and reprioritization response shift and the SAQ7 reconceptualization response shift. Controlling for these response shift effects did not result in more valid estimates of change. One significant association was found between reprioritization response shift and complete integration of having CAD into their life story, as indicated by the RE-LIFE. CONCLUSION: Results indicate response shift in HRQoL following coronary revascularization. While we did not find an impact of response shift on the estimates of change, the SEM approach provides a more comprehensive insight into the different types of change in HRQoL following coronary revascularization.

Predicting viral load suppression by self-reported adherence, pharmacy refill counts and real time medication monitoring among people living with HIV in Tanzania.

INTRODUCTION: Monitoring of adherence to antiretroviral treatment (ART) is of utmost importance to prevent treatment failure. Several measures to monitor adherence have been applied in low-resource settings and they all have pros and cons. Our objective was to examine whether any of the following adherence measures is a better predictor of participants' viral load suppression: (1) self-report, (2) pharmacy refill count, (3) Real Time Medication Monitoring (RTMM), (4) a combination of self-report and pharmacy refill count or (5) all three adherence assessment methods combined. METHODOLOGY: This was a post-hoc analysis of data from our 48-week REMIND-HIV randomized controlled trial in which adherence to ART was measured using self-report, pharmacy refill counts and RTMM among ART-experienced adults living with HIV subjectively judged to be nonadherent to ART. For each adherence measure, we calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting virological failure defined as a viral load (VL) of > 20 copies/mL. To determine at which percentage of adherence the prediction was strongest, we evaluated adherence cut-offs of 80%, 85%, 90%, 95% and 100% using receiver operating characteristic (ROC) curves. VL data were obtained after 48 weeks of follow-up in the trial. RESULTS: A total of 233 people living with HIV (PLHIV) were included in this analysis. When comparing the ability of self-reported adherence with pharmacy refill count and RTMM adherence to predict viral load > 20 copies/ml, self-reported adherence had the lowest sensitivity, ranging from 6 to 17%, but the highest specificity, ranging from 100 to 86%, depending on cut-off values from 80 to 100%. Area under the ROC curves (AUC) were 0.54 for RTMM, 0.56 for pharmacy refill count and 0.52 for self-report, indicating low discriminatory capacity for each of the adherence measures. When we combined the self-report and pharmacy refill count measures, sensitivity increased, ranging from 28 to 57% but specificity decreased, ranging from 83 to 53%. When all three measures were combined, we observed the highest value of sensitivity, ranging from 46 to 92%, and PPV, ranging from 32 to 36%, at high cut-offs ranging from 80 to 100%. Upon combination of three adherence measures, the AUC increased to 0.59. CONCLUSION: Our results show that adherence assessed exclusively by self-report, pharmacy refill count or RTMM were insufficiently sensitive to predict virologic failure. Sensitivity markedly improved by combining all three measures, but the practical feasibility of such an approach would need to be studied.

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.

BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 µm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 µm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

Patients knowledge and experience with urinary and peripheral intravenous catheters.

PURPOSE: Inappropriate use of urinary and intravenous catheters is still frequent. The use of catheters is associated with some serious complications, such as health care associated infections (HAIs). An efficient way to reduce HAIs is to avoid inappropriate use of catheters, but the role for patients in quality improvement initiatives is unclear. The aim of this study is to investigate patients knowledge and experience with catheters, to design patient interventions to reduce inappropriate catheter use. METHODS: We assessed patient's knowledge and experience with catheters using a self report questionnaire, and included patients with a urinary and/or peripheral intravenous catheter (PIVC) during the baseline measurements of a quality improvement project to reduce inappropriate catheters use. RESULTS: A total number of 82 patients completed the questionnaire, of which 49 had a urinary catheter and 72 a PIVC. Patients were unaware about the indication for their urinary catheter in 20.9% and PIVC in 19.5%. Nevertheless, 65.3% reported symptoms due to urinary catheters and 37.5% for PIVCs. Interestingly, only 25.5% and 22.4% reported that they would ask their doctor if the catheter could be removed. CONCLUSIONS: There is a lack of knowledge about the indication for having a urinary and peripheral intravenous catheter in a substantial part of patients. Although catheters cause symptoms, patients in general do not ask if the catheter could be removed. Doctors should give more information and ask more questions about catheters to their patients. Quality improvement initiatives stimulating patients to actively participate in their treatment are needed.

The Prospective Studies of Atherosclerosis (Proof-ATHERO) Consortium: Design and Rationale.

Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, -ankle-brachial index, pulse wave velocity, and coronary -artery calcium. The Prospective Studies of Atherosclerosis -(Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. In summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. The consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences.

Returning of antiretroviral medication dispensed over a period of 8 months suggests non-adherence despite full adherence according to real time medication monitoring.

Real-time medication monitoring (RTMM) may potentially enhance adherence to antiretroviral treatment (ART). We describe a participant in an ongoing trial who, shortly after completing trial participation, died of cryptococcal meningitis despite high levels of adherence according to self-report, pill-counts and RTMM (> 99%). However, she evidenced consistently high HIV viral load throughout the 48-week study follow-up. Subsequently, her relatives unsolicitedly returned eight months' dispensed ART medication that she was supposed to have taken. This brief report illustrates the challenges of adherence measurements including RTMM, and reinforces the need to combine adherence assessments with viral load monitoring in HIV care.

Influence of response shift and disposition on patient-reported outcomes may lead to suboptimal medical decisions: a medical ethics perspective.

BACKGROUND: Patient-reported outcomes (PROs) are frequently used for medical decision making, at the levels of both individual patient care and healthcare policy. Evidence increasingly shows that PROs may be influenced by patients' response shifts (changes in interpretation) and dispositions (stable characteristics). MAIN TEXT: We identify how response shifts and dispositions may influence medical decisions on both the levels of individual patient care and health policy. We provide examples of these influences and analyse the consequences from the perspectives of ethical principles and theories of just distribution. CONCLUSION: If influences of response shift and disposition on PROs and consequently medical decision making are not considered, patients may not receive optimal treatment and health insurance packages may include treatments that are not the most effective or cost-effective. We call on healthcare practitioners, researchers, policy makers, health insurers, and other stakeholders to critically reflect on why and how such patient reports are used.

Sub-optimal adherence to combination anti-retroviral therapy and its associated factors according to self-report, clinician-recorded and pharmacy-refill assessment methods among HIV-infected adults in Addis Ababa.

Adherence to combination antiretroviral therapy (cART) is generally high in most resource-limited settings. However, sub-optimal adherence occurs in a sizable proportion of patients, and is independently predictive of detectable viremia. We investigated sub-optimal adherence according to self-report, clinician-recorded, and pharmacy-refill assessment methods, and their associated factors among HIV-infected adults receiving cART in Addis Ababa, Ethiopia. Eight-hundred seventy patients who initiated cART between May 2009 and April 2012 were randomly selected, and 664 patients who were alive, had remained in clinical care and were receiving cART for at least six-months were included. Sub-optimal adherence was defined as patients' response of less than "all-of the time" to the self-report adherence question, or any clinician-recorded poor adherence during the six most recent clinic visits, or a pharmacy-refill of <95% medication possession ratio (MPR). Logistic regression models were fitted to identify factors associated with sub-optimal adherence. The average adherence level to cART, expressed as MPR, was nearly 97%. However, sub-optimal adherence occurred in 12%, 4%, and 27% of patients according to self-report, clinician-recorded, and pharmacy-refill measures, respectively. More satisfaction with social support was significantly associated with less sub-optimal adherence according to self-report and clinician-record. Younger age, lower educational level, and lower CD4 cell count at cART initiation were significantly associated with sub-optimal refill-based adherence. Findings from our large multi-center study suggest that sub-optimal adherence was present in up to a quarter of the patients, despite a high degree of average adherence to cART. Interventions aimed at preventing sub-optimal adherence should focus on improving social support, on younger patients, on patients with lower educational level, and on those who started cART at a lower CD4 cell count.

Quality of life and fear of cancer recurrence after endoscopic treatment for early Barrett's neoplasia: a prospective study.

Endoscopic therapy is the treatment of choice for high grade intraepithelial neoplasia (HGIN) or early cancer (≤T1sm1) in Barrett's esophagus (BE). We prospectively evaluated the effect of endoscopic treatment on quality of life (QOL) and fear of cancer (recurrence) and compared this with the effect of Barrett's surveillance or surgery. Patients treated endoscopically for early Barrett's neoplasia (n = 42, HGIN - T1sm1N0M0) were compared with three groups: patients with non-dysplastic BE undergoing surveillance (n = 44); patients treated surgically for early BE neoplasia (HGIN - T2N0M0, n = 21); patients treated surgically for advanced BE cancer (T1N1M0 - T3N1M0, n = 19). QOL (SF-36; EORTC-QLQ-C30; EORTC-QLQ-OES18) and fear of cancer recurrence (Worry of Cancer Scale [WOCS] and the Hospital Anxiety and Depression Scale [HADS]) were measured at baseline, 2 and 6 months after treatment. The endoscopic treatment group reported significantly better QOL in both physical and mental scales of SF-36 and EORTC-QLQ-C30 and less esophageal cancer related symptoms compared to both surgical groups. The endoscopic treatment group reported significant more worry for cancer recurrence (WOCS) compared to the early surgical group. Their scores on the WOCS were comparable with the scores of the advanced surgical group. Endoscopic treatment of early esophageal cancer has less negative impact on QOL and esophageal cancer symptoms than surgery. However, endoscopically treated patients worry as much about cancer recurrence as patients treated surgically for advanced cancer.