Inconsistencies in Quality of Life Data Collection in Clinical Trials: A Potential Source of Bias? Interviews with Research Nurses and Trialists

Background

Patient-reported outcomes (PROs), such as health-related quality of life (HRQL) are increasingly used to evaluate treatment effectiveness in clinical trials, are valued by patients, and may inform important decisions in the clinical setting. It is of concern, therefore, that preliminary evidence, gained from group discussions at UK-wide Medical Research Council (MRC) quality of life training days, suggests there are inconsistent standards of HRQL data collection in trials and appropriate training and education is often lacking. Our objective was to investigate these reports, to determine if they represented isolated experiences, or were indicative of a potentially wider problem.

Methods And Findings

We undertook a qualitative study, conducting 26 semi-structured interviews with research nurses, data managers, trial coordinators and research facilitators involved in the collection and entry of HRQL data in clinical trials, across one primary care NHS trust, two secondary care NHS trusts and two clinical trials units in the UK. We used conventional content analysis to analyze and interpret our data. Our study participants reported (1) inconsistent standards in HRQL measurement, both between, and within, trials, which appeared to risk the introduction of bias; (2), difficulties in dealing with HRQL data that raised concern for the well-being of the trial participant, which in some instances led to the delivery of non-protocol driven co-interventions, (3), a frequent lack of HRQL protocol content and appropriate training and education of trial staff, and (4) that HRQL data collection could be associated with emotional and/or ethical burden.

Conclusions

Our findings suggest there are inconsistencies in the standards of HRQL data collection in some trials resulting from a general lack of HRQL-specific protocol content, training and education. These inconsistencies could lead to biased HRQL trial results. Future research should aim to develop HRQL guidelines and training programmes aimed at supporting researchers to carry out high quality data collection.     

Lifetime Victimization and Physical Health Outcomes among Lesbian and Heterosexual Women

Background

Lifetime victimization experiences, including child sexual abuse (CSA), child physical abuse (CPA), adult sexual assault (ASA), and adult physical assault (APA), are associated with health problems.

Purpose

To examine relationships between cumulative victimization and physical health among heterosexual and lesbian women and determine whether these relationships differ by sexual identity.

Methods

Large samples of heterosexual (n = 482) and lesbian women (n = 394) were interviewed. Questions included lifetime victimization experiences and physical health problems.

Results

Compared to women who reported no childhood victimization, those who reported experiencing both CSA and CPA were 44% more likely to report health problems and women who experienced all four types of victimization (CSA, CPA, APA, ASA) were nearly 240% as likely to report physical health problems. Interaction analyses revealed the association between victimization and physical health did not differ by sexual identity.

Conclusions

Although lesbians were more likely to report all types of victimization, results suggest that victimization conferred increased physical health risks regardless of sexual identity.     

Does Obesity Modify the Relationship between Exposure to Occupational Factors and Musculoskeletal Pain in Men? Results from the GAZEL Cohort Study

Objective

To analyze relationships between physical occupational exposures, post-retirement shoulder/knee pain, and obesity.

Methods

9 415 male participants (aged 63–73 in 2012) from the French GAZEL cohort answered self-administered questionnaires in 2006 and 2012. Occupational exposures retrospectively assessed in 2006 included arm elevation and squatting (never, <10 years, ≥10 years). “Severe” shoulder and knee pain were defined as ≥5 on an 8-point scale. BMI was self-reported.

Results

Mean BMI was 26.59 kg/m² +/−3.5 in 2012. Long-term occupational exposure to arm elevation and squatting predicted severe shoulder and knee pain after retirement. Obesity (BMI≥30 kg/m²) was a risk factor for severe shoulder pain (adjusted OR 1.28; 95% CI 1.03, 1.90). Overweight (adjusted OR 1.71; 1.28,2.29) and obesity (adjusted OR 3.21; 1.90,5.41) were risk factors for severe knee pain. In stratified models, associations between long-term squatting and severe knee pain varied by BMI.

Conclusion

Obesity plays a role in relationships between occupational exposures and musculoskeletal pain. Further prospective studies should use BMI in analyses of musculoskeletal pain and occupational factors, and continue to clarify this relationship.     

The Effect of PPE-Induced Emphysema and Chronic LPS-Induced Pulmonary Inflammation on Atherosclerosis Development in APOE*3-LEIDEN Mice

Background

Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the contribution of emphysema in the presence or absence of pulmonary inflammation to the increased risk of CVD, using a mouse model for atherosclerosis. Because smoke is a known risk factor for both COPD and CVD, emphysema was induced by intratracheal instillation of porcine pancreatic elastase (PPE).

Methods

Hyperlipidemic APOE*3-Leiden mice were intratracheally instilled with vehicle, 15 or 30 µg PPE and after 4 weeks, mice received a Western-type diet (WTD). To study the effect of emphysema combined with pulmonary inflammation on atherosclerosis, mice received 30 µg PPE and during WTD feeding, mice were intranasally instilled with vehicle or low-dose lipopolysaccharide (LPS; 1 µg/mouse, twice weekly). After 20 weeks WTD, mice were sacrificed and emphysema, pulmonary inflammation and atherosclerosis were analysed.

Results

Intratracheal PPE administration resulted in a dose-dependent increase in emphysema, whereas atherosclerotic lesion area was not affected by PPE treatment. Additional low-dose intranasal LPS administration induced a low-grade systemic IL-6 response, as compared to vehicle. Combining intratracheal PPE with intranasal LPS instillation significantly increased the number of pulmonary macrophages and neutrophils. Plasma lipids during the study were not different. LPS instillation caused a limited, but significant increase in the atherosclerotic lesion area. This increase was not further enhanced by PPE.

Conclusion

This study shows for the first time that PPE-induced emphysema both in the presence and absence of pulmonary inflammation does not affect atherosclerotic lesion development.     

Healthcare Workers' Challenges in the Implementation of Tuberculosis Infection Prevention and Control Measures in Mozambique

Objective

Healthcare Workers (HCWs) have a higher frequency of TB exposure than the general population and have therefore an occupational TB risk that infection prevention and control (IPC) measures aim to reduce. HCWs are crucial in the implementation of these measures. The objective of the study was to investigate Mozambican HCWs'' perceptions of their occupational TB risk and the measures they report using to reduce this risk. In addition, we explored the challenges HCWs encounter while using these TBIPC measures.

Methods

Focus group discussion. Analysis according content method.

Participants

Four categories of HCWs: auxiliary workers, medical (doctors and clinical officers), nurses and TB program staff.

Results

HCWs are aware of their occupational TB risk and use various measures to reduce their risk of infection. HCWs find it challenging to employ measures that minimize such risks and a lack of clear guidelines contributes to these challenges. HCWs'' and patient behavior further complicate the use of TBIPC measures.

Conclusion

HCWs in Mozambique perceive a high occupational risk of TB infection. They report several challenges using measures to reduce this risk such as shortage of material, lack of clear guidelines, insufficient motivation and inadequate training. Robust training with motivational approaches, alongside supervision and support for HCWs could improve implementation of TBIPC measures. Healthcare management should address the areas for improvement that are beyond the individual HCW''s control.     

Work,Diabetes and Obesity: A Seven Year Follow-Up Study among Danish Health Care Workers

Objectives

The rise in prevalence of diabetes is alarming and research ascribes most of the increase to lifestyle. However, little knowledge exists about the influence of occupational factors on the risk for developing diabetes. This study estimates the importance of work and lifestyle as risk factors for developing diabetes mellitus among healthcare workers and explores the association of work factors and obesity, which is a risk factor for diabetes.

Methods

Questionnaire-based prospective cohort study among 7,305 health care workers followed for seven years in the Danish National Diabetes Register. We used bivariate comparisons to give an unadjusted estimate of associations, followed by adjusted survival analysis and logistic regression models to estimate the influences of potential risk factors related to job, health and lifestyle on diabetes and obesity.

Results

During seven years of follow up, 3.5% of participants developed diabetes, associated with obesity (HR  =  6.53; 95% CI 4.68–9.10), overweight (HR  =  2.89; CI 2.11–3.96) age 50–69 y (HR  =  2.27; 95% CI 1.57–3.43) and high quality of leadership (HR  =  1.60; CI 1.19–2.16). Obesity at baseline was most common among the youngest employees, and was mainly associated with developing diabetes (OR  =  3.84; CI 2.85–5.17), impaired physical capacity and physical inactivity. In the occupational setting, obesity was associated with shift work, severe musculoskeletal pain, low influence, but also by good management, fewer role conflicts and a positive work-life balance. Looking only at non-smokers, removed the influence of age and pain. However, non-smokers also had higher depression scores and more role conflicts.

Conclusions

Confirming obesity as the strongest risk factor for developing diabetes, the present study identified few occupational risk factors. However, obesity, the key risk factor for diabetes, had a more variable relation with work than did diabetes.     

Arterial Stiffness and Pulse Wave Reflection Are Increased in Patients Suffering from Severe Periodontitis

Aim

This single blind cross-sectional study compared the vascular health of subjects suffering from severe chronic periodontitis, severe aggressive periodontitis and periodontal healthy controls by evaluating pulse wave velocity (PWV), augmentation index (AIx) and pulse pressure amplification (PPA).

Material and Methods

In a total of 158 subjects, 92 suffering from severe periodontitis and 66 matched periodontal healthy controls, PWV, AIx, central and peripheral blood pressure were recorded using an oscillometric device (Arteriograph).

Results

Subjects suffering from severe chronic or aggressive periodontitis exhibited significantly higher PWV (p = 0.00004), higher AIx (p = 0.0049) and lower PPA (p = 0.028) than matched periodontal healthy controls.

Conclusions

The results of this study confirm the association between periodontal inflammation and increased cardiovascular risk shown by impaired vascular health in case of severe periodontitis. As impaired vascular health is a common finding in patients suffering from severe periodontal disease a concomitant routine cardiovascular evaluation may be advised.     

A Cross-Sectional Randomised Study of Fracture Risk in People with HIV Infection in the Probono 1 Study

Objective

To determine comparative fracture risk in HIV patients compared with uninfected controls.

Design

A randomised cross-sectional study assessing bone mineral density (BMD), fracture history and risk factors in the 2 groups.

Setting

Hospital Outpatients.

Subbbjects

222 HIV infected patients and an equal number of age-matched controls. Assessments: Fracture risk factors were assessed and biochemical, endocrine and bone markers measured. BMD was assessed at hip and spine. 10-year fracture probability (FRAX) and remaining lifetime fracture probability (RFLP) were calculated.

Main Outcome Measures

BMD, and history of fractures.

Results

Reported fractures occurred more frequently in HIV than controls, (45 vs. 16; 20.3 vs. 7%; OR=3.27; p=0.0001), and unsurprisingly in this age range, non-fragility fractures in men substantially contributed to this increase. Osteoporosis was more prevalent in patients with HIV (17.6% vs. 3.6%, p<0.0001). BMD was most reduced, and predicted fracture rates most increased, at the spine. Low BMD was associated with antiretroviral therapy (ART), low body mass index and PTH. 10-year FRAX risk was <5% for all groups. RLFP was greater in patients with HIV (OR=1.22; p=0.003) and increased with ART (2.4 vs. 1.50; OR= 1.50; p=0.03).

Conclusions

The increased fracture rate in HIV patients in our relatively youthful population is partly driven by fractures, including non-fragility fractures, in men. Nonetheless, these findings may herald a rise in osteoporotic fractures in HIV patients. An appropriate screening and management response is required to assess these risks and identify associated lifestyle factors that are also associated with other conditions such as cardiovascular disease and diabetes.     

Pathway Evidence of How Musical Perception Predicts Word-Level Reading Ability in Children with Reading Difficulties

Objective

To investigate whether specific domains of musical perception (temporal and melodic domains) predict the word-level reading skills of eight- to ten-year-old children (n = 235) with reading difficulties, normal quotient of intelligence, and no previous exposure to music education classes.

Method

A general-specific solution of the Montreal Battery of Evaluation of Amusia (MBEA), which underlies a musical perception construct and is constituted by three latent factors (the general, temporal, and the melodic domain), was regressed on word-level reading skills (rate of correct isolated words/non-words read per minute).

Results

General and melodic latent domains predicted word-level reading skills.     

Increased Basal and Alum-Induced Interleukin-6 Levels in Geriatric Patients Are Associated with Cardiovascular Morbidity

Background/Aim of the study

Low-grade systemic inflammation was suggested to participate to the decline of physiological functions and increased vulnerability encountered in older patients. Geriatric syndromes encompass various features such as functional dependence, polymorbidity, depression and malnutrition. There is a strong prevalence of cardiovascular diseases and related risk factors and chronic cytomegalovirus infections in the geriatric population. As these underlying conditions were proposed to influence the inflammatory state, the aim of this study was to assess their potential contribution to the association of geriatric syndromes with inflammatory parameters.

Methodology

We recruited 100 subjects in the general population or hospitalized for chronic medical conditions (age, 23-96 years). We collected information on clinical status (medical history, ongoing comorbidities, treatments and geriatric scales), biological parameters (hematological tests, cytomegalovirus serology) and cytokines production (basal and alum-induced interleukin (IL)-1β and IL-6 levels). Using stepwise backward multivariate analyses, we defined which set of clinical and biological variables could be predictive for increased inflammatory markers.

Principal Findings

We confirmed the age-associated increase of circulating IL-6 levels. In contrast to geriatric scales, we found history of cardiovascular diseases to be strongly associated for this parameter as for high IL-6 production upon ex vivo stimulation with alum.

Conclusions

Association between low-grade inflammation and geriatric conditions could be linked to underlying cardiovascular diseases.     

Multiple Chronic Health Conditions and Their Link with Labour Force Participation and Economic Status

Aims

To assess the labour force participation and quantify the economic status of older Australian workers with multiple health conditions.

Background

Many older people suffer from multiple health conditions. While multiple morbidities have been highlighted as an important research topic, there has been limited research in this area to date, particularly on the economic status of those with multiple morbidities.

Methods

Cross sectional analysis of Health&WealthMOD, a microsimulation model of Australians aged 45 to 64 years.

Results

People with one chronic health condition had 0.59 times the odds of being employed compared to those with no condition (OR 0.59, 95% CI: 0.49, 0.71), and those with four or more conditions had 0.14 times the odds of being employed compared to those with no condition (OR 0.14, 95% CI: 0.11, 0.18). People with one condition received a weekly income 32% lower than those with no health condition, paid 49 % less tax, and received 37% more in government transfer payments; those with four or more conditions received a weekly income 94% lower, paid 97% less in tax and received over 2,000% more in government transfer payments per week than those with no condition.

Conclusion

While having a chronic health condition is associated with lower labour force participation and poorer economic status, having multiple conditions compounds the affect – with these people being far less likely to be employed and having drastically lower incomes.     

WHO Antiretroviral Therapy Guidelines 2010 and Impact of Tenofovir on Chronic Kidney Disease in Vietnamese HIV-Infected Patients

Objective

The 2010 WHO antiretroviral therapy (ART) guidelines have resulted in increased tenofovir use. Little is known about tenofovir-induced chronic kidney disease (CKD) in HIV-infected Vietnamese with mean body weight of 55 kg. We evaluated the prevalence and risk factors of CKD in this country.

Design

Cross-sectional study was performed.

Methods

Clinical data on HIV-infected Vietnamese cohort were collected twice a year. To evaluate the prevalence of CKD, serum creatinine was measured in 771 patients in October 2011 and April 2012. CKD was defined as creatinine clearance less than 60 ml/min at both time points. Multivariate logistic regression was used to determine the factors associated with CKD

Results

Tenofovir use increased in Vietnam from 11.9% in April 2011 to 40.3% in April 2012. CKD was diagnosed in 7.3%, of which 7% was considered moderate and 0.3% was severe. Multivariate analysis of October-2011 data identified age per year-increase (OR: 1.229, 95%CI, 1.170-1.291), body weight per 1 kg-decrement (1.286, 1.193-1.386), and tenofovir use (2.715, 1.028-7.168) as risk factors for CKD.

Conclusions

Older age, low body weight and tenofovir use were independent risk factors for CKD in Vietnam. Further longitudinal study is required to evaluate the impact of TDF on renal function in Vietnam and other countries with small-body weight patients.     

The Development of a Preference for Cocaine over Food Identifies Individual Rats with Addiction-Like Behaviors

Rationale

Cocaine dependence is characterized by compulsive drug taking that supercedes other recreational, occupational or social pursuits. We hypothesized that rats vulnerable to addiction could be identified within the larger population based on their preference for cocaine over palatable food rewards.

Objectives

To validate the choice self-administration paradigm as a preclinical model of addiction, we examined changes in motivation for cocaine and recidivism to drug seeking in cocaine-preferring and pellet-preferring rats. We also examined behavior in males and females to identify sex differences in this “addicted” phenotype.

Methods

Preferences were identified during self-administration on a fixed-ratio schedule with cocaine-only, pellet-only and choice sessions. Motivation for each reward was probed early and late during self-administration using a progressive-ratio schedule. Reinstatement of cocaine- and pellet-seeking was examined following exposure to their cues and non-contingent delivery of each reward.

Results

Cocaine preferring rats increased their drug intake at the expense of pellets, displayed increased motivation for cocaine, attenuated motivation for pellets and greater cocaine and cue-induced reinstatement of drug seeking. Females were more likely to develop cocaine preferences and recidivism of cocaine- and pellet-seeking was sexually dimorphic.

Conclusions

The choice self-administration paradigm is a valid preclinical model of addiction. The unbiased selection criteria also revealed sex-specific vulnerability factors that could be differentiated from generalized sex differences in behavior, which has implications for the neurobiology of addiction and effective treatments in each sex.     

Biopersistent Granular Dust and Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Objective

Applying a systematic review to identify studies eligible for meta-analysis of the association between occupational exposure to inorganic dust and the development of chronic obstructive pulmonary disease (COPD), and conducting a meta-analysis.

Data Sources

Searches of PubMed and Embase for the time period 1970–2010 yielded 257 cross-sectional and longitudinal studies on people exposed to inorganic dust at the workplace with data on lung function. These studies were independently abstracted and evaluated by two authors; any disagreement was resolved by a third reviewer. Of 55 publications accepted for meta-analysis, 27 investigated the effects of occupational exposure to biopersistent granular dust (bg-dust).

Methods

A random effects meta-analysis allowed us to provide an estimate of the average exposure effect on spirometric parameters presented in forest plots. Between-study heterogeneity was assessed by using I² statistics, with I²>25% indicating significant heterogeneity. Publication bias was investigated by visual inspection of funnel plots. The influence of individual studies was assessed by dropping the respective study before pooling study-specific estimates.

Results

The mean FEV1 of workers exposed to bg-dust was 160 ml lower or 5.7% less than predicted compared to workers with no/low exposure. The risk of an obstructive airway disease—defined as FEV1/FVC < 70%—increased by 7% per 1 mg· m^-3 respirable bg-dust.

Conclusion

Occupational inhalative exposure to bg-dust was associated with a statistically significant decreased FEV1 and FEV1/FVC revealing airway obstruction consistent with COPD.     

Practice and Attitude of Cigarette Smoking: A Community-Based Study

Background

In Saudi Arabia many studies have addressed cigarette smoking from various perspectives. Most of these studies, however, were conducted among males and confined to Riyadh, the capital city. Such limitations have enhanced the need for community-based epidemiological studies that include both genders and various age groups and socio-demographic features, as well as different regions.

Objective

This cross-sectional study aims to assess the prevalence of cigarette smoking and to discuss the association between cigarette smoking habits and socio-demographic factors among community members of the Jazan area in southwest Saudi Arabia.

Methods

A pre-coded questionnaire was designed and tested for data consistency. A well-trained health team was assigned to gather the data from the 30 primary healthcare centers distributed across eight provinces. The response rate was 92.8% (4,326 respondents ≥13 years old). The associations among the subjects'' socio-demographic characteristics were examined by the chi-square test. A multiple logistic regression and odds ratios were calculated as well.

Results

A total of 1,017 (23.5%), 1,042 (24.1%), and 3,284 (75.9%) respondents were, respectively, current smokers (TCS), ever-smokers (TES), and non-smokers (TNS). Though current smokers seem to be more prevalent in urban populations (13.8%) than in rural populations (9.7%), the association of urbanization with a current smoking habit is insignificant.

Conclusion

Having fun, relieving stress, and the influence of parents, particularly of mothers, were the main motives that encouraged participants'' cigarette-smoking habits. This situation was worsened by the fact that accessing cigarettes was either very easy or easy for over 90% of the respondents.     

A Qualitative Exploration of Workarounds Related to the Implementation of National Electronic Health Records in Early Adopter Mental Health Hospitals

Aims

To investigate the perceptions and reported practices of mental health hospital staff using national hospital electronic health records (EHRs) in order to inform future implementations, particularly in acute mental health settings.

Methods

Thematic analysis of interviews with a wide range of clinical, information technology (IT), managerial and other staff at two early adopter mental health National Health Service (NHS) hospitals in London, UK, implementing national EHRs.

Results

We analysed 33 interviews. We first sought out examples of workarounds, such as delayed data entry, entering data in wrong places and individuals using the EHR while logged in as a colleague, then identified possible reasons for the reported workarounds. Our analysis identified four main categories of factors contributing to workarounds (i.e., operational, cultural, organisational and technical). Operational factors included poor system integration with existing workflows and the system not meeting users'' perceived needs. Cultural factors involved users'' competence with IT and resistance to change. Organisational factors referred to insufficient organisational resources and training, while technical factors included inadequate local technical infrastructure. Many of these factors, such as integrating the EHR system with day-to-day operational processes, staff training and adequate local IT infrastructure, were likely to apply to system implementations in various settings, but we also identified factors that related particularly to implementing EHRs in mental health hospitals, for example: EHR system incompatibility with IT systems used by mental health–related sectors, notably social services; the EHR system lacking specific, mental health functionalities and options; and clinicians feeling unable to use computers while attending to distressed psychiatric patients.

Conclusions

A better conceptual model of reasons for workarounds should help with designing, and supporting the implementation and adoption of, EHRs for use in hospital mental health settings.     

Family History as a Predictor for Disease Risk in Healthy Individuals: A Cross-Sectional Study in Slovenia

Background

Family history can be used as a genetic risk predictor for common non-communicable diseases. The aim of this study was to determine the prevalence of healthy individuals at risk of developing these diseases, based on their self-reported family history.

Methods and Findings

This was a cross-sectional observational study. Data were collected in the three largest occupational practices in primary health care centres in Slovenia, a Central European country. The study population consisted of consecutive individuals who came to occupational practices for their regular preventive check-up from November 2010 to June 2012. We included 1,696 individuals. Data were collected by a self-developed questionnaire. The main outcome was the number of participants at a moderate or high risk for the development of cardiovascular diseases, diabetes, and cancer.The final sample consisted of 1,340 respondents. Moderate or high risk for the development of cardiovascular diseases was present in 280 (20.9%) participants, for the development of diabetes in 154 (11.5%) participants and for cancer in 163 (12.1%) participants.

Conclusions

In this study, we found a significant proportion of healthy individuals with an increased genetic risk for common non-communicable diseases; consequently further genetic and clinical evaluation and preventive measures should be offered.     

Injections,Cocktails and Diviners: Therapeutic Flexibility in the Context of Malaria Elimination and Drug Resistance in Northeast Cambodia

Background

Adherence to effective malaria medication is extremely important in the context of Cambodia’s elimination targets and drug resistance containment. Although the public sector health facilities are accessible to the local ethnic minorities of Ratanakiri province (Northeast Cambodia), their illness itineraries often lead them to private pharmacies selling “cocktails” and artemether injections, or to local diviners prescribing animal sacrifices to appease the spirits.

Methods

The research design consisted of a mixed methods study, combining qualitative (in-depth interviews and participant observation) and quantitative methods (household and cross-sectional survey).

Results

Three broad options for malaria treatment were identified: i) the public sector; ii) the private sector; iii) traditional treatment based on divination and ceremonial sacrifice. Treatment choice was influenced by the availability of treatment and provider, perceived side effects and efficacy of treatments, perceived etiology of symptoms, and patient-health provider encounters. Moreover, treatment paths proved to be highly flexible, changing mostly in relation to the perceived efficacy of a chosen treatment.

Conclusions

Despite good availability of anti-malarial treatment in the public health sector, attendance remained low due to both structural and human behavioral factors. The common use and under-dosage of anti-malaria monotherapy in the private sector (single-dose injections, single-day drug cocktails) represents a threat not only for individual case management, but also for the regional plan of drug resistance containment and malaria elimination.