We investigate conditions sufficient for identification of average treatment effects using instrumental variables. First we show that the existence of valid instruments is not sufficient to identify any meaningful average treatment effect. We then establish that the combination of an instrument and a condition on the relation between the instrument and the participation status is sufficient for identification of a local average treatment effect for those who can be induced to change their participation status by changing the value of the instrument. Finally we derive the probability limit of the standard IV estimator under these conditions. It is seen to be a weighted average of local average treatment effects.

Evolution and Rationality Some Recent Game-Theoretic Results. Identification and Estimation of Local Average Treatment Effects

Scholars in management and economics widely share the assumption that business firms focus on profits only, while it is the task of the state system to provide public goods. In this view business firms are conceived of as economic actors, and governments and their state agencies are considered the only political actors. We suggest that, under the conditions of globalization, the strict division of labour between private business and nation-state governance does not hold any more. Many business firms have started to assume social and political responsibilities that go beyond legal requirements and fill the regulatory vacuum in global governance. Our review of the literature shows that there are a growing number of publications from various disciplines that propose a politicized concept of corporate social responsibility. We consider the implications of this new perspective for theorizing about the business firm, governance, and democracy.

https://www.springer.com/cda/content/document/cda_downloaddocument/9783834931795-c1.pdf?SGWID=0-0-45-1347110-p174325274

The New Political Role of Business in a Globalized World: A Review of a New Perspective on CSR and its Implications for the Firm, Governance, and Democracy

Background
Accurate, rapid detection of tuberculosis (TB) and TB drug resistance is critical for improving patient care and decreasing TB transmission. Xpert® MTB/RIF assay is an automated test that can detect both TB and rifampicin resistance, generally within two hours after starting the test, with minimal hands-on technical time. The World Health Organization (WHO) issued initial recommendations on Xpert® MTB/RIF in early 2011. A Cochrane Review on the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB and rifampicin resistance was published January 2013. We performed this updated Cochrane Review as part of a WHO process to develop updated guidelines on the use of the test.

Objectives
To assess the diagnostic accuracy of Xpert® MTB/RIF for pulmonary TB (TB detection), where Xpert® MTB/RIF was used as both an initial test replacing microscopy and an add-on test following a negative smear microscopy result.

To assess the diagnostic accuracy of Xpert® MTB/RIF for rifampicin resistance detection, where Xpert® MTB/RIF was used as the initial test replacing culture-based drug susceptibility testing (DST).

The populations of interest were adults presumed to have pulmonary, rifampicin-resistant or multidrug-resistant TB (MDR-TB), with or without HIV infection. The settings of interest were intermediate- and peripheral-level laboratories. The latter may be associated with primary health care facilities.

Search methods
We searched for publications in any language up to 7 February 2013 in the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials.

Selection criteria
We included randomized controlled trials, cross-sectional studies, and cohort studies using respiratory specimens that allowed for extraction of data evaluating Xpert® MTB/RIF against the reference standard. We excluded gastric fluid specimens. The reference standard for TB was culture and for rifampicin resistance was phenotypic culture-based DST.

Data collection and analysis
For each study, two review authors independently extracted data using a standardized form. When possible, we extracted data for subgroups by smear and HIV status. We assessed the quality of studies using QUADAS-2 and carried out meta-analyses to estimate pooled sensitivity and specificity of Xpert® MTB/RIF separately for TB detection and rifampicin resistance detection. For TB detection, we performed the majority of analyses using a bivariate random-effects model and compared the sensitivity of Xpert® MTB/RIF and smear microscopy against culture as reference standard. For rifampicin resistance detection, we undertook univariate meta-analyses for sensitivity and specificity separately to include studies in which no rifampicin resistance was detected.

Main results
We included 27 unique studies (integrating nine new studies) involving 9557 participants. Sixteen studies (59%) were performed in low- or middle-income countries. For all QUADAS-2 domains, most studies were at low risk of bias and low concern regarding applicability.

As an initial test replacing smear microscopy, Xpert® MTB/RIF pooled sensitivity was 89% [95% Credible Interval (CrI) 85% to 92%] and pooled specificity 99% (95% CrI 98% to 99%), (22 studies, 8998 participants: 2953 confirmed TB, 6045 non-TB).
As an add-on test following a negative smear microscopy result, Xpert®MTB/RIF pooled sensitivity was 67% (95% CrI 60% to 74%) and pooled specificity 99% (95% CrI 98% to 99%; 21 studies, 6950 participants).

For smear-positive, culture-positive TB, Xpert® MTB/RIF pooled sensitivity was 98% (95% CrI 97% to 99%; 21 studies, 1936 participants).

For people with HIV infection, Xpert® MTB/RIF pooled sensitivity was 79% (95% CrI 70% to 86%; seven studies, 1789 participants), and for people without HIV infection, it was 86% (95% CrI 76% to 92%; seven studies, 1470 participants).

Among 180 specimens with nontuberculous mycobacteria (NTM), Xpert® MTB/RIF was positive in only one specimen that grew NTM (14 studies, 2626 participants).

Comparison with smear microscopy

In comparison with smear microscopy, Xpert® MTB/RIF increased TB detection among culture-confirmed cases by 23% (95% CrI 15% to 32%; 21 studies, 8880 participants).

For TB detection, if pooled sensitivity estimates for Xpert® MTB/RIF and smear microscopy are applied to a hypothetical cohort of 1000 patients where 10% of those with symptoms have TB, Xpert® MTB/RIF will diagnose 88 cases and miss 12 cases, whereas sputum microscopy will diagnose 65 cases and miss 35 cases.

Rifampicin resistance

For rifampicin resistance detection, Xpert® MTB/RIF pooled sensitivity was 95% (95% CrI 90% to 97%; 17 studies, 555 rifampicin resistance positives) and pooled specificity was 98% (95% CrI 97% to 99%; 24 studies, 2411 rifampicin resistance negatives).

For rifampicin resistance detection, if the pooled accuracy estimates for Xpert® MTB/RIF are applied to a hypothetical cohort of 1000 individuals where 15% of those with symptoms are rifampicin resistant, Xpert® MTB/RIF would correctly identify 143 individuals as rifampicin resistant and miss eight cases, and correctly identify 833 individuals as rifampicin susceptible and misclassify 17 individuals as resistant. Where 5% of those with symptoms are rifampicin resistant, Xpert® MTB/RIF would correctly identify 48 individuals as rifampicin resistant and miss three cases and correctly identify 931 individuals as rifampicin susceptible and misclassify 19 individuals as resistant.

Authors' conclusions
In adults thought to have TB, with or without HIV infection, Xpert® MTB/RIF is sensitive and specific. Compared with smear microscopy, Xpert® MTB/RIF substantially increases TB detection among culture-confirmed cases. Xpert® MTB/RIF has higher sensitivity for TB detection in smear-positive than smear-negative patients. Nonetheless, this test may be valuable as an add-on test following smear microscopy in patients previously found to be smear-negative. For rifampicin resistance detection, Xpert® MTB/RIF provides accurate results and can allow rapid initiation of MDR-TB treatment, pending results from conventional culture and DST. The tests are expensive, so current research evaluating the use of Xpert® MTB/RIF in TB programmes in high TB burden settings will help evaluate how this investment may help start treatment promptly and improve outcomes.

/pdf/xpert-mtb-rif-assay-for-pulmonary-tuberculosis-and-1ruthojy6l.pdf

Xpert® MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(10)61997-6.pdf

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya (R T Lester MD, A Kariri BSc, S Karanja BSc, E Ngugi PhD, L J Gelmon MD, J Kimani, MBChB); Department of Medical Microbiology, University of Manitoba, Health Sciences Centre, Winnipeg, MB, Canada (R T Lester, T B Ball PhD, L J Gelmon, J Kimani, Prof F A Plummer MD); Division of Infectious Diseases, Department of Medicine, University of British Columbia, Vancouver, BC, Canada (R T Lester); School of Kinesiology and Health Sciences, Department of Psychology, York University, York, ON, Canada (P Ritvo PhD); Faculty of Health Sciences, University of Ottawa, Ottawa, ON, Canada (E J Mills PhD); Department of Global Health, University of Washington, Seattle, WA, USA (M H Chung MD); Department of Economics (W Jack DPhil) and Georgetown Public Policy Institute (J Habyarimana PhD), Georgetown University, Washington, DC, USA; Collaboration for Outcome Research and Evaluation, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada (M Sadatsafavi MD, M Najafzadeh MSc, C A Marra PharmD); University of Nairobi Institute of Tropical and Infectious Diseases, Nairobi, Kenya (B Estambale MBChB); Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Eff ects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

Eff ects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial

Background Long-term retention of patients in Africa’s rapidly expanding antiretroviral therapy (ART) programs for HIV/AIDS is essential for these programs’ success but has received relatively little attention. In this paper we present a systematic review of patient retention in ART programs in sub-Saharan Africa. Methods and Findings We searched Medline, other literature databases, conference abstracts, publications archives, and the ‘‘gray literature’’ (project reports available online) between 2000 and 2007 for reports on the proportion of adult patients retained (i.e., remaining in care and on ART) after 6 mo or longer in sub-Saharan African, non-research ART programs, with and without donor support. Estimated retention rates at 6, 12, and 24 mo were calculated and plotted for each program. Retention was also estimated using Kaplan-Meier curves. In sensitivity analyses we considered best-case, worst-case, and midpoint scenarios for retention at 2 y; the best-case scenario assumed no further attrition beyond that reported, while the worst-case scenario assumed that attrition would continue in a linear fashion. We reviewed 32 publications reporting on 33 patient cohorts (74,192 patients, 13 countries). For all studies, the weighted average follow-up period reported was 9.9 mo, after which 77.5% of patients were retained. Loss to follow-up and death accounted for 56% and 40% of attrition, respectively. Weighted mean retention rates as reported were 79.1%, 75.0% and 61.6 % at 6, 12, and 24 mo, respectively. Of those reporting 24 mo of follow-up, the best program retained 85% of patients and the worst retained 46%. Attrition was higher in studies with shorter reporting periods, leading to monthly weighted mean attrition rates of 3.3%/mo, 1.9%/mo, and 1.6%/month for studies reporting to 6, 12, and 24 months, respectively, and suggesting that overall patient retention may be overestimated in the published reports. In sensitivity analyses, estimated retention rates ranged from 24% in the worse case to 77% in the best case at the end of 2 y, with a plausible midpoint scenario of 50%.

/pdf/patient-retention-in-antiretroviral-therapy-programs-in-sub-4aor73di0s.pdf

Patient Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa: A Systematic Review

Background: Improving the outcomes of HIV/AIDS treatment programs in resource-limited settings requires successful linkage of patients testing positive for HIV to pre–antiretroviral therapy (ART) care and retention in pre-ART care until ART initiation. We conducted a systematic review of pre-ART retention in care in Africa. Methods and Findings: We searched PubMed, ISI Web of Knowledge, conference abstracts, and reference lists for reports on the proportion of adult patients retained between any two points between testing positive for HIV and initiating ART in sub-Saharan African HIV/AIDS care programs. Results were categorized as Stage 1 (from HIV testing to receipt of CD4 count results or clinical staging), Stage 2 (from staging to ART eligibility), or Stage 3 (from ART eligibility to ART initiation). Medians (ranges) were reported for the proportions of patients retained in each stage. We identified 28 eligible studies. The median proportion retained in Stage 1 was 59% (35%–88%); Stage 2, 46% (31%–95%); and Stage 3, 68% (14%–84%). Most studies reported on only one stage; none followed a cohort of patients through all three stages. Enrollment criteria, terminology, end points, follow-up, and outcomes varied widely and were often poorly defined, making aggregation of results difficult. Synthesis of findings from multiple studies suggests that fewer than one-third of patients testing positive for HIV and not yet eligible for ART when diagnosed are retained continuously in care, though this estimate should be regarded with caution because of review limitations. Conclusions: Studies of retention in pre-ART care report substantial loss of patients at every step, starting with patients who do not return for their initial CD4 count results and ending with those who do not initiate ART despite eligibility. Better health information systems that allow patients to be tracked between service delivery points are needed to properly evaluate pre-ART loss to care, and researchers should attempt to standardize the terminology, definitions, and time periods reported. Please see later in the article for the Editors’ Summary.

/pdf/retention-in-hiv-care-between-testing-and-treatment-in-sub-19vgfpy5sx.pdf

Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review

Many countries use the cost–effectiveness thresholds recommended by the World Health Organization’s Choosing Interventions that are Cost–Effective project (WHO-CHOICE) when evaluating health interventions. This project sets the threshold for cost–effectiveness as the cost of the intervention per disability-adjusted life-year (DALY) averted less than three times the country’s annual gross domestic product (GDP) per capita. Highly cost–effective interventions are defined as meeting a threshold per DALY averted of once the annual GDP per capita. We argue that reliance on these thresholds reduces the value of cost–effectiveness analyses and makes such analyses too blunt to be useful for most decision-making in the field of public health. Use of these thresholds has little theoretical justification, skirts the difficult but necessary ranking of the relative values of locally-applicable interventions and omits any consideration of what is truly affordable. The WHO-CHOICE thresholds set such a low bar for cost–effectiveness that very few interventions with evidence of efficacy can be ruled out. The thresholds have little value in assessing the trade-offs that decision-makers must confront. We present alternative approaches for applying cost–effectiveness criteria to choices in the allocation of health-care resources.

/pdf/thresholds-for-the-cost-effectiveness-of-interventions-bqxxlxcgch.pdf

Thresholds for the cost-effectiveness of interventions: alternative approaches.

Summary objectives To estimate the proportion of all-cause adult patient attrition from antiretroviral therapy (ART) programs in service delivery settings in sub-Saharan Africa through 36 months on treatment. methods We identified cohorts within Ovid Medline, ISI Web of Knowledge, Cochrane Database of Systematic Reviews and four conference abstract archives. We summarized retention rates from studies describing observational cohorts from sub-Saharan Africa reporting on adult HIV 1- infected patients initiating first-line three-drug ART. We estimated all-cause attrition rates for 6, 12, 18, 24, or 36 months after ART initiation including patients who died or were lost to follow-up (as defined by the author), but excluding transferred patients. results We analysed 33 sources describing 39 cohorts and 226 307 patients. Patients were more likely to be female (median 65%) and had a median age at initiation of 37 (range 34‐40). Median starting CD4 count was 109 cells ⁄mm 3 . Loss to follow-up was the most common cause of attrition (59%), followed by death (41%). Median attrition at 12, 24 and 36 months was 22.6% (range 7%‐45%), 25% (range 11%‐32%) and 29.5% (range 13%‐36.1%) respectively. After pooling data in a random-effects metaanalysis, retention declined from 86.1% at 6 months to 80.2% at 12 months, 76.8% at 24 months and 72.3% at 36 months. Adjusting for variable follow-up time in a sensitivity analysis, 24 month retention was 70.0% (range: 66.7%‐73.3%), while 36 month retention was 64.6% (range: 57.5%‐72.1%). conclusions Our findings document the difficulties in retaining patients in care for lifelong treatment, and the progress being made in raising overall retention rates.

/pdf/patient-retention-in-antiretroviral-therapy-programs-up-to-1axdmn03td.pdf

Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007–2009: systematic review

BACKGROUND: We previously published systematic reviews of retention in care after antiretroviral therapy initiation among general adult populations in sub-Saharan Africa. We estimated 36-month retention at 73% for publications from 2007 to 2010. This report extends the review to cover 2008-2013 and expands it to all low- and middle-income countries. METHODS: We searched PubMed Embase Cochrane Register and ISI Web of Science from January 1 2008 to December 31 2013 and abstracts from AIDS and IAS from 2008-2013. We estimated retention across cohorts using simple averages and interpolated missing times through the last time reported. We estimated all-cause attrition (death loss to follow-up) for patients receiving first-line antiretroviral therapy in routine settings in low- and middle-income countries. RESULTS: We found 123 articles and abstracts reporting retention for 154 patient cohorts and 1554773 patients in 42 countries. Overall 43% of all patients not retained were known to have died. Unweighted averages of reported retention were 78% 71% and 69% at 12 24 and 36 months after treatment initiation respectively. We estimated 36-month retention at 65% in Africa 80% in Asia and 64% in Latin America and the Caribbean. From lifetable analysis we estimated retention at 12 24 36 48 and 60 months at 83% 74% 68% 64% and 60% respectively. CONCLUSIONS: Retention at 36 months on treatment averages 65%-70%. There are several important gaps in the evidence base which could be filled by further research especially in terms of geographic coverage and duration of follow-up.

Sydney Rosen

Papers

Patient Retention in Antiretroviral Therapy Programs in Sub-Saharan Africa: A Systematic Review

Retention in HIV Care between Testing and Treatment in Sub-Saharan Africa: A Systematic Review

Thresholds for the cost-effectiveness of interventions: alternative approaches.

Patient retention in antiretroviral therapy programs up to three years on treatment in sub-Saharan Africa, 2007–2009: systematic review

Retention of Adult Patients on Antiretroviral Therapy in Low- and Middle-Income Countries: Systematic Review and Meta-analysis 2008-2013.