The Experience of China-Educated Nurses Working in Australia: A Symbolic Interactionist Perspective

Background and Purpose

Transnational nurse migration is a growing phenomenon. This study explored the experiences of China-educated nurses working in Australia.

Design

Using a constructivist grounded theory method, 46 in-depth interviews were conducted with 28 China-educated nurses in two major cities in Australia.

Results

The core category emerged was “reconciling different realities”. Three phases of reconciling were conceptualised: realising, struggling, and reflecting. Realising refers to an awareness of the discrepancies between different realities. Struggling reflects the dilemma of the “middle position” and how being situated as “the other” is experienced. Reflecting is the process of making sense of the experience and rationalising the gains and losses associated with immigration.

Conclusions

This study produced a theoretical understanding of the experience of China-educated nurses working in Australia. The findings not only inform Chinese nurses who wish to migrate but contribute to the implementation of more effective support services for immigrant nurses.     

Development of a Composite Measure of Product Adherence,Protocol Compliance,and Semen Exposure Using DNA and Protein Biomarkers for Topical HIV Prevention Studies

Background

Poor and inconsistent use of study products has hindered clinical HIV prevention studies. It is important to be able to monitor product adherence and protocol compliance in order to determine microbicide efficacy and safety more accurately. Current methods for monitoring adherence are subjective, non-specific, or invasive. Herein, we present a composite, objective measure of product adherence and protocol compliance to assess vaginal insertion, semen exposure and drug expulsion utilizing DNA, protein, and drug isolated directly from returned, vaginally used gel applicators.

Methods

DNA, vaginal cells, and residual tenofovir were isolated from vaginally inserted applicators. Vaginal and semen biomarkers were amplified using a multiplex PCR to determine vaginal insertion. Vaginal cells were fixed followed by cytokeratin 4 immunocytochemistry to confirm DNA assessment of vaginal insertion. Tenofovir was extracted and quantitated through LC-MS/MS.

Results

DNA isolated from vaginally inserted applicators were positive for vaginal bacteria DNA and the control eukaryotic gene, amelogenin, while manually handled, “sham”, applicators were negative for both. Semen exposure was independently determined by simultaneous amplification of one or both Y-chromosomal genes, SRY and TSPY4. Vaginal insertion determination by DNA analysis was further confirmed by positive cytokeratin 4 (CK4) immunocytochemistry of vaginal cells remaining on the gel applicators. On the contrary, sham applicators provided very few cells when swabbed, and they were all negative for CK4. CK4 was not found in epidermal cells from the hand. Drug expulsion was detected through quantitation of residual gel present on the surface of returned applicators. Sham applicators had no detectable tenofovir.

Conclusion

Utilizing a composite, triple marker based panel of DNA, protein, and drug present on the surface of returned vaginal gel applicators, it is possible to determine, objectively and non-invasively, product adherence, protocol compliance, and semen exposure in microbicide trials.     

Acceptability of Carraguard vaginal microbicide gel among HIV-infected women in Chiang Rai, Thailand

Background

Few studies of microbicide acceptability among HIV-infected women have been done. We assessed Carraguard® vaginal gel acceptability among participants in a randomized, controlled, crossover safety trial in HIV-infected women in Thailand.

Methodology/Principal Findings

Participants used each of 3 treatments (Carraguard gel, methylcellulose placebo gel, and no product) for 7 days, were randomized to one of six treatment sequences, and were blinded to the type of gel they received in the two gel-use periods. After both gel-use periods, acceptability was assessed by face-to-face interview. Responses were compared to those of women participating in two previous Carraguard safety studies at the same study site. Sixty women enrolled with a median age of 34 years; 25% were sexually active. Self-reported adherence (98%) and overall satisfaction rating of the gels (87% liked “somewhat” or “very much”) were high, and most (77%) considered the volume of gel “just right.” For most characteristics, crossover trial participants evaluated the gels more favorably than women in the other two trials, but there were few differences in the desired characteristics of a hypothetical microbicide. Almost half (48%) of crossover trial participants noticed a difference between Carraguard and placebo gels; 33% preferred Carraguard while 12% preferred placebo (p = 0.01).

Conclusions/Significance

Daily Carraguard vaginal gel use was highly acceptable in this population of HIV-infected women, who assessed the gels more positively than women in two other trials at the site. This may be attributable to higher perceived need for protection among HIV-infected women, as well as to study design differences. This trial was registered in the U.S. National Institutes of Health clinical trials registry under registration number {"type":"clinical-trial","attrs":{"text":"NCT00213044","term_id":"NCT00213044"}}NCT00213044.     

Fertility Desires among Men and Women Living with HIV/AIDS in Nairobi Slums: A Mixed Methods Study

Objectives

Fertility desires require new understanding in a context of expanding access to antiretroviral therapy for people living with HIV/AIDS in Sub-Saharan Africa. This paper studies the fertility desires and their rationales, of slum-dwelling Kenyan men and women living with HIV/AIDS who know their serostatus, but have different antiretroviral therapy treatment statuses. It addresses two research questions: How do people living with HIV/AIDS consider their future fertility? What factors contribute to an explanation of fertility desires among people living with HIV/AIDS.

Methods

A mixed methods study (survey [n = 513] and in-depth interviews [n = 41]) with adults living with HIV/AIDS living in Nairobi slums was conducted in 2010. Regression analyses assess independent relationships between fertility desires and socio-demographic factors. Analyses of in-depth interviews are used to interpret the statistical analyses of fertility desires.

Results

Our analyses show that fertility desires are complex and ambivalent, reflecting tensions between familial and societal pressures to have children versus pressures for HIV (re-)infection prevention. More than a third (34%) of men and women living with HIV expressed future fertility desires; however, this is significantly lower than in the general population. Factors independently associated with desiring a child among people living with HIV/AIDS were age, sex, number of surviving children, social support and household wealth of the respondent.

Discussion

Increasing access to ART is changing the context of future childbearing for people living with HIV/AIDS. Prevailing values mean that, for many people living with HIV/AIDS, having children is seen as necessary for a “normal” and healthy adult life. However, the social rewards of childbearing conflict with moral imperatives of HIV prevention, presenting dilemmas about the “proper” reproductive behaviour of people living with HIV/AIDS. The health policy and service delivery implications of these findings are explored.     

Gatekeepers or Intermediaries? The Role of Clinicians in Commercial Genomic Testing

Background

Many commentators on “direct-to-consumer” genetic risk information have raised concerns that giving results to individuals with insufficient knowledge and training in genomics may harm consumers, the health care system, and society. In response, several commercial laboratories offering genomic risk profiling have shifted to more traditional “direct-to-provider” (DTP) marketing strategies, repositioning clinicians as the intended recipients of advertising of laboratory services and as gatekeepers to personal genomic information. Increasing popularity of next generation sequencing puts a premium on ensuring that those who are charged with interpreting, translating, communicating and managing commercial genomic risk information are appropriately equipped for the job. To shed light on their gatekeeping role, we conducted a study to assess how and why early clinical users of genomic risk assessment incorporate these tools in their clinical practices and how they interpret genomic information for their patients.

Methods and Findings

We conducted qualitative in-depth interviews with 18 clinicians providing genomic risk assessment services to their patients in partnership with DNA Direct and Navigenics. Our findings suggest that clinicians learned most of what they knew about genomics directly from the commercial laboratories. Clinicians rely on the expertise of the commercial laboratories without the ability to critically evaluate the knowledge or assess risks.

Conclusions

DTP service delivery model cannot guarantee that providers will have adequate expertise or sound clinical judgment. Even if clinicians want greater genomic knowledge, the current market structure is unlikely to build the independent substantive expertise of clinicians, but rather promote its continued outsourcing. Because commercial laboratories have the most “skin in the game” financially, genetics professionals and policymakers should scrutinize the scientific validity and clinical soundness of the process by which these laboratories interpret their findings to assess whether self-interested commercial sources are the most appropriate entities for gate-keeping genomic interpretation.     

Mother to Mother (M2M) Peer Support for Women in Prevention of Mother to Child Transmission (PMTCT) Programmes: A Qualitative Study

Introduction

Mother-to-Mother (M2M) or “Mentor Mother” programmes utilise HIV positive mothers to provide support and advice to HIV positive pregnant women and mothers of HIV exposed babies. Médecins Sans Frontières (MSF) supported a Mentor Mother programme in Bulawayo, Zimbabwe from 2009 to 2012; with programme beneficiaries observed to have far higher retention at 6–8 weeks (99% vs 50%, p<0.0005) and to have higher adherence to Prevention of Mother to Child Transmission (PMTCT) guidelines, compared to those not opting in. In this study we explore how the M2M progamme may have contributed to these findings.

Methods

In this qualitative study we used thematic analysis of in-depth interviews (n = 79). This study was conducted in 2 urban districts of Bulawayo, Zimbabwe’s second largest city.

Results

Interviews were completed by 14 mentor mothers, 10 mentor mother family members, 30 beneficiaries (women enrolled both in PMTCT and M2M), 10 beneficiary family members, 5 women enrolled in PMTCT but who had declined to take part in the M2M programme and 10 health care staff members. All beneficiaries and health care staff reported that the programme had improved retention and provided rich information on how this was achieved. Additionally respondents described how the programme had helped bring about beneficial behaviour change.

Conclusions

M2M programmes offer great potential to empower communities affected by HIV to catalyse positive behaviour change. Our results illustrate how M2M involvement may increase retention in PMTCT programmes. Non-disclosure to one’s partner, as well as some cultural practices prevalent in Zimbabwe appear to be major barriers to participation in M2M programmes.     

Patent and Exclusivity Status of Essential Medicines for Non-Communicable Disease

Objective

The threat of non-communicable diseases (“NCDs”) is increasingly becoming a global health crisis and are pervasive in high, middle, and low-income populations resulting in an estimated 36 million deaths per year. There is a need to assess intellectual property rights (“IPRs”) that may impede generic production and availability and affordability to essential NCD medicines.

Methods

Using the data sources listed below, the study design systematically eliminated NCD drugs that had no patent/exclusivity provisions on API, dosage, or administration route. The first step identified essential medicines that treat certain high disease burden NCDs. A second step examined the patent and exclusivity status of active ingredient, dosage and listed route of administration using exclusion criteria outlined in this study.

Materials

We examined the patent and exclusivity status of medicines listed in the World Health Organization’s (“WHO”) Model List of Essential Drugs (Medicines) (“MLEM”) and other WHO sources for drugs treating certain NCDs. i.e., cardiovascular and respiratory disease, cancers, and diabetes. We utilized the USA Food and Drug Administration Orange Book and the USA Patent and Trademark Office databases as references given the predominant number of medicines registered in the USA.

Results

Of the 359 MLEM medicines identified, 22% (79/359) address targeted NCDs. Of these 79, only eight required in-depth patent or exclusivity assessment. Upon further review, no NCD MLEM medicines had study patent or exclusivity protection for reviewed criteria.

Conclusions

We find that ensuring availability and affordability of potential generic formulations of NCD MLEM medicines appears to be more complex than the presence of IPRs with API, dosage, or administration patent or exclusivity protection. Hence, more sophisticated analysis of NCD barriers to generic availability and affordability should be conducted in order to ensure equitable access to global populations for these essential medicines.     

In-Depth Analysis of Patient-Clinician Cell Phone Communication during the WelTel Kenya1 Antiretroviral Adherence Trial

Background

The WelTel Kenya1 trial demonstrated that text message support improved adherence to antiretroviral therapy (ART) and suppression of HIV-1 RNA load. The intervention involved sending weekly messages to patients inquiring how they were doing; participants were required to respond either that they were well or that there was a problem.

Objectives

1) Describe problems participants identified through mobile phone support and reasons why participants did not respond to the messages; 2) investigate factors associated with indicating a problem and not responding; and 3) examine participant perceptions of the intervention.

Design

Secondary analysis of WelTel Kenya1 trial data.

Methods

Reasons participants indicated a problem or did not respond were extracted from the study log. Negative binomial regression was used to determine participant characteristics associated with indicating a problem and non-response. Data from follow-up questionnaires were used to describe participant perceptions of the intervention.

Results

Between 2007 and 2009, 271 participants generated 11,873 responses; 377 of which indicated a problem. Health issues were the primary reason for problem responses (72%). Rural residence (adjusted incidence rate ratio [IRR] 1.96; 95%CI 1.19–3.25; p = 0.009 and age were associated with indicating a problem (adjusted IRR 0.63 per increase in age group category; 95%CI 0.50–0.80; p<0.001). Higher educational level was associated with a decreased rate of non-response (adjusted IRR 0.81; 95%CI 0.69–0.94; p = 0.005). Of participants interviewed, 62% (n = 129) stated there were no barriers to the intervention; cell phone issues were the most common barrier. Benefits included reminding patients to take medication and promoting a feeling that “someone cares”.

Conclusions

The WelTel intervention enabled frequent communication between clinicians and patients during the WelTel Kenya1 trial. Many patients valued the service for the support it provided, with health-related concerns comprising the majority of problems identified by participants. Few sociodemographic characteristics were associated with participant engagement in the intervention.     

A randomized trial to assess anti-HIV activity in female genital tract secretions and soluble mucosal immunity following application of 1% tenofovir gel

Background

Preclinical and early phase clinical microbicide studies have not consistently predicted the outcome of efficacy trials. To address this gap, candidate biomarkers of microbicide pharmacodynamics and safety were evaluated in a double-blind, placebo-controlled trial of tenofovir gel, the first microbicide to demonstrate significant protection against HIV acquisition.

Methods

30 women were randomized to apply a single daily dose of tenofovir or placebo gel for 14 consecutive days. Anti-HIV activity was measured in cervicovaginal lavage (CVL) on Days 0, 3, 7, 14 and 21 by luciferase assay as a surrogate marker of pharmacodynamics. Endogenous activity against E. coli and HSV-2 and concentrations of immune mediators were quantified in CVL as candidate biomarkers of safety. Tenofovir levels were measured in CVL and blood.

Results

A significant increase in anti-HIV activity was detected in CVL from women who applied tenofovir gel compared to their endogenous anti-HIV activity in genital tract secretions on Day 0 and compared to activity in CVL from women in the placebo group. The activity correlated significantly with CVL concentration of tenofovir (r = 0.6, p<0.001) and fit a sigmoid E_max pharmacodynamic model. Anti-HIV activity in CVL from women who applied tenofovir persisted when virus was introduced in semen, whereas endogenous anti-HIV activity decreased. Tenofovir did not trigger an inflammatory response or induce sustained loss in endogenous antimicrobial activity or immune mediators.

Conclusions

Tenofovir gel had no deleterious impact on soluble mucosal immunity. The increased anti-HIV activity in CVL, which persisted in the presence of semen and correlated with tenofovir concentration, is consistent with the efficacy observed in a recent clinical trial. These results promote quantified CVL anti-HIV activity as a surrogate of tissue pharmacodynamics and as a potential biomarker of adherence to product. This simple, feasible and inexpensive bioassay may promote the development of models more predictive of microbicide efficacy.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00594373","term_id":"NCT00594373"}}NCT00594373     

Adherence to Pharmacotherapy and Medication-Related Beliefs in Patients with Hypertension in Lima,Peru

Objective

To characterize adherence to pharmacological medication and beliefs towards medication in a group of patients with hypertension in a large national hospital.

Materials and Methods

Cross-sectional survey among patients with hypertension attending the outpatient clinic of a large national hospital. Exposure of interest was the patient''s beliefs towards general medication and antihypertensive drugs, i.e. beliefs of harm, overuse, necessity and concern, measured using the Beliefs about Medication questionnaire. Main outcome was adherence measured using the Morisky Medication Adherence Scale-8. Multivariate analysis was conducted using Poisson distribution logistic regression, prevalence ratios and 95% confidence intervals were calculated.

Results

Data from 115 participants, 67% females and mean age 62.7 years were analyzed. Low adherence was found in 57.4%. Highest scores were on the ideas of necessity and one of the most rated statements was “physicians would prescribe less medication if they spent more time with patients”. Beliefs of harm about medications and concerns about antihypertensive drugs were higher in the low adherence group (p<0.01). Those who scored higher on ideas of harm were 52% less likely of being high adherents (PR 0.48; 95% CI 0.25–0.93) and those with higher scores on concerns were 41% less likely of being high adherents (PR 0.59; 95% CI 0.39–0.91). Patients whose ideas of necessity outweighed their concerns were more likely to be adherent (PR 2.65; 95% CI 1.21–5.81).

Conclusions

Low adherence to antihypertensive medication is common. High scores on ideas of harm, concern and a high necessity-concern differential were predictors of medication adherence.     

The Meaning of Adherence When Behavioral Risk Patterns Vary: Obscured Use- and Method-Effectiveness in HIV-Prevention Trials

Background

Recently promising trials of innovative biomedical approaches to prevent HIV transmission have been reported. Participants'' non-adherence to the prevention methods complicates the analyses and interpretation of trial results. The influence of variable sexual behaviors within and between participants of trials further obscures matters. Current methodological and statistical approaches in HIV-prevention studies, as well as ongoing debates on contradictory trial results, may fail to accurately address these topics.

Methodology/Principal Findings

Through developing a cumulative probability model of infection within HIV prevention trials, we demonstrate how adherence and sexual behavior patterns impact the overall estimate of effectiveness, the effectiveness of prevention methods as a function of adherence, and conclusions about methods'' true effectiveness. Applying the model to summary-level data from the CAPRISA trial, we observe markedly different values for the true method effectiveness of the microbicide, and show that if the gel would have been tested among women with slightly different sexual behavior patterns, conclusions might well have been that the gel is not effective.

Conclusions/Significance

Relative risk and adherence analyses in HIV prevention trials overlook the complex interplay between adherence and sexual behavior patterns. Consequently, they may not provide accurate estimates of use- and method-effectiveness. Moreover, trial conclusions are contingent upon the predominant sexual behavior pattern of participants and cannot be directly generalized to other contexts. We recommend researchers to (re)examine their data and use the cumulative probability model to estimate the true method effectiveness, which might contribute to resolving current questions about contradictory trial results. Moreover, we suggest taking into account the issues raised in the design of future trials and in population models estimating the impact of large-scale dissemination of prevention methods. Comprehension of the topics described will help readers to better interpret (apparently contradictory) trial outcomes.     

Patients Are Paying Too Much for Tuberculosis: A Direct Cost-Burden Evaluation in Burkina Faso

Background

Paying for health care may exclude poor people. Burkina Faso adopted the DOTS strategy implementing “free care” for Tuberculosis (TB) diagnosis and treatment. This should increase universal health coverage and help to overcome social and economic barriers to health access.

Methods

Straddling 2007 and 2008, in-depth interviews were conducted over a year among smear-positive pulmonary tuberculosis patients in six rural districts of Burkina Faso. Out-of-pocket expenses (direct costs) associated with TB were collected according to the different stages of their healthcare pathway.

Results

Median direct cost associated with TB was US$101 (n = 229) (i.e. 2.8 months of household income). Respectively 72% of patients incurred direct costs during the pre-diagnosis stage (i.e. self-medication, travel, traditional healers'' services), 95% during the diagnosis process (i.e. user fees, travel costs to various providers, extra sputum smears microscopy and chest radiology), 68% during the intensive treatment (i.e. medical and travel costs) and 50% during the continuation treatment (i.e. medical and travel costs). For the diagnosis stage, median direct costs already amounted to 35% of overall direct costs.

Conclusions

The patient care pathway analysis in rural Burkina Faso showed substantial direct costs and healthcare system delay within a “free care” policy for TB diagnosis and treatment. Whether in terms of redefining the free TB package or rationalizing the care pathway, serious efforts must be undertaken to make “free” health care more affordable for the patients. Locally relevant for TB, this case-study in Burkina Faso has a real potential to document how health programs'' weaknesses can be identified and solved.     

Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis

Background:

It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did (“insiders”) and did not (“outsiders”) enter RCTs, without regard to the specific therapies received for their respective diagnoses.

Methods:

By searching the MEDLINE (1966–2010), Embase (1980–2010), CENTRAL (1960–2010) and PsycINFO (1880–2010) databases, we identified 147 studies that reported the health outcomes of “insiders” and a group of parallel or consecutive “outsiders” within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients’ outcomes.

Results:

We found no clinically or statistically significant differences in outcomes between “insiders” and “outsiders” in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes −0.03, 95% confidence interval [CI] −0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both “insiders” and “outsiders” (mean difference 0.04, 95% CI −0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by “insiders,” the “outsiders” experienced significantly worse health outcomes (mean difference −0.36, 95% CI −0.61 to −0.12).

Interpretation:

We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.When people are asked to participate in a randomized controlled trial (RCT), it is natural for them to ask several questions in return. How safe are these treatments? How many extra visits and tests must I undergo? Will the researchers keep my family doctor informed about what’s going on? What outcomes are to be measured, and do they include ones that are of interest to me as a patient?These multiple questions can be summarized as follows: Would I fare better being treated within the trial (as an “insider”) or in routine clinical care outside it (as an “outsider”)? Patients may ask this question in 1 of 2 ways. The first is highly specific: “Am I better off receiving this specific treatment as an insider or as an outsider?” Alternatively, they might ask a more general question: “Am I better off having my illness managed, regardless of the specific treatment I would receive, as an insider or as an outsider?” These questions are highly appropriate, and both deserve to be asked and answered,^1,2 especially given that nonsystematic reviews have suggested a possible “inclusion benefit” from participating in trials.³These 2 specific patient questions are analogous to those posed by researchers asking whether treatments do more good than harm when applied under “ideal” circumstances (in explanatory trials) or in the “real world” of routine health care (in pragmatic trials). Vist and colleagues answered the explanatory question when their earlier review⁴ found no advantage or disadvantage from receiving the same treatment inside or outside an RCT. Left unanswered, however, was the broader, more pragmatic question. In our experience, trial participants are often offered new, as-yet-untested treatments that would not be available to them outside the trial. This review looks at the dilemma faced by these patients, which needs to be addressed before general conclusions can be drawn about trial safety.     

Activation of Midbrain and Ventral Striatal Regions Implicates Salience Processing during a Modified Beads Task

Introduction

Metacognition, i.e. critically reflecting on and monitoring one’s own reasoning, has been linked behaviorally to the emergence of delusions and is a focus of cognitive therapy in patients with schizophrenia. However, little is known about the neural processing underlying metacognitive function. To address this issue, we studied brain activity during a modified beads task which has been used to measure a “Jumping to Conclusions” (JTC) bias in schizophrenia patients.

Methods

We used functional magnetic resonance imaging to identify neural systems active in twenty-five healthy subjects when solving a modified version of the “beads task”, which requires a probabilistic decision after a variable amount of data has been requested by the participants. We assessed brain activation over the duration of a trial and at the time point of decision making.

Results

Analysis of activation during the whole process of probabilistic reasoning showed an extended network including the prefronto-parietal executive functioning network as well as medial parieto-occipital regions. During the decision process alone, activity in midbrain and ventral striatum was detected, as well as in thalamus, medial occipital cortex and anterior insula.

Conclusions

Our data show that probabilistic reasoning shares neural substrates with executive functions. In addition, our finding that brain regions commonly associated with salience processing are active during probabilistic reasoning identifies a candidate mechanism that could underlie the behavioral link between dopamine-dependent aberrant salience and JTC in schizophrenia. Further studies with delusional schizophrenia patients will have to be performed to substantiate this link.