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1.  Financial incentives and coverage of child health interventions: a systematic review and meta-analysis 
BMC Public Health  2013;13(Suppl 3):S30.
Background
Financial incentives are widely used strategies to alleviate poverty, foster development, and improve health. Cash transfer programs, microcredit, user fee removal policies and voucher schemes that provide direct or indirect monetary incentives to households have been used for decades in Latin America, Sub-Saharan Africa, and more recently in Southeast Asia. Until now, no systematic review of the impact of financial incentives on coverage and uptake of health interventions targeting children under 5 years of age has been conducted. The objective of this review is to provide estimates on the effect of six types of financial incentive programs: (i) Unconditional cash transfers (CT), (ii) Conditional cash transfers (CCT), (iii) Microcredit (MC), (iv) Conditional Microcredit (CMC), (v) Voucher schemes (VS) and (vi) User fee removal (UFR) on the uptake and coverage of health interventions targeting children under the age of five years.
Methods
We conducted systematic searches of a series of databases until September 1st, 2012, to identify relevant studies reporting on the impact of financial incentives on coverage of health interventions and behaviors targeting children under 5 years of age. The quality of the studies was assessed using the CHERG criteria. Meta-analyses were undertaken to estimate the effect when multiple studies meeting our inclusion criteria were available.
Results
Our searches resulted in 1671 titles identified 25 studies reporting on the impact of financial incentive programs on 5 groups of coverage indicators: breastfeeding practices (breastfeeding incidence, proportion of children receiving colostrum and early initiation of breastfeeding, exclusive breastfeeding for six months and duration of breastfeeding); vaccination (coverage of full immunization, partial immunization and specific antigens); health care use (seeking healthcare when child was ill, visits to health facilities for preventive reasons, visits to health facilities for any reason, visits for health check-up including growth control); management of diarrhoeal disease (ORS use during diarrhea episode, continued feeding during diarrhea, healthcare during diarrhea episode) and other preventive health interventions (iron supplementation, vitamin A, zinc supplementation, preventive deworming). The quality of evidence on the effect of financial incentives on breastfeeding practices was low but seems to indicate a potential positive impact on receiving colostrum, early initiation of breastfeeding, exclusive breastfeeding and mean duration of exclusive breastfeeding. There is no effect of financial incentives on immunization coverage although there was moderate quality evidence of conditional cash transfers leading to a small but non-significant increase in coverage of age-appropriate immunization. There was low quality evidence of impact of CCT on healthcare use by children under age 5 (Risk difference: 0.14 [95%CI: 0.03; 0.26]) as well as low quality evidence of an effect of user fee removal on use of curative health services (RD=0.62 [0.41; 0.82]).
Conclusions
Financial incentives may have potential to promote increased coverage of several important child health interventions, but the quality of evidence available is low. The more pronounced effects seem to be achieved by programs that directly removed user fees for access to health services. Some indication of effect were also observed for programs that conditioned financial incentives on participation in health education and attendance to health care visits. This finding suggest that the measured effect may be less a consequence of the financial incentive and more due to conditionalities addressing important informational barriers.
doi:10.1186/1471-2458-13-S3-S30
PMCID: PMC3847540  PMID: 24564520
2.  Effects of unconditional and conditional cash transfers on child health and development in Zimbabwe: a cluster-randomised trial 
Lancet  2013;381(9874):1283-1292.
Summary
Background
Cash-transfer programmes can improve the wellbeing of vulnerable children, but few studies have rigorously assessed their effectiveness in sub-Saharan Africa. We investigated the effects of unconditional cash transfers (UCTs) and conditional cash transfers (CCTs) on birth registration, vaccination uptake, and school attendance in children in Zimbabwe.
Methods
We did a matched, cluster-randomised controlled trial in ten sites in Manicaland, Zimbabwe. We divided each study site into three clusters. After a baseline survey between July, and September, 2009, clusters in each site were randomly assigned to UCT, CCT, or control, by drawing of lots from a hat. Eligible households contained children younger than 18 years and satisfied at least one other criteria: head of household was younger than 18 years; household cared for at least one orphan younger than 18 years, a disabled person, or an individual who was chronically ill; or household was in poorest wealth quintile. Between January, 2010, and January, 2011, households in UCT clusters collected payments every 2 months. Households in CCT clusters could receive the same amount but were monitored for compliance with several conditions related to child wellbeing. Eligible households in all clusters, including control clusters, had access to parenting skills classes and received maize seed and fertiliser in December, 2009, and August, 2010. Households and individuals delivering the intervention were not masked, but data analysts were. The primary endpoints were proportion of children younger than 5 years with a birth certificate, proportion younger than 5 years with up-to-date vaccinations, and proportion aged 6–12 years attending school at least 80% of the time. This trial is registered with ClinicalTrials.gov, number NCT00966849.
Findings
1199 eligible households were allocated to the control group, 1525 to the UCT group, and 1319 to the CCT group. Compared with control clusters, the proportion of children aged 0–4 years with birth certificates had increased by 1·5% (95% CI −7·1 to 10·1) in the UCT group and by 16·4% (7·8–25·0) in the CCT group by the end of the intervention period. The proportions of children aged 0–4 years with complete vaccination records was 3·1% (−3·8 to 9·9) greater in the UCT group and 1·8% (−5·0 to 8·7) greater in the CCT group than in the control group. The proportions of children aged 6–12 years who attended school at least 80% of the time was 7·2% (0·8–13·7) higher in the UCT group and 7·6% (1·2–14·1) in the CCT group than in the control group.
Interpretation
Our results support strategies to integrate cash transfers into social welfare programming in sub-Saharan Africa, but further evidence is needed for the comparative effectiveness of UCT and CCT programmes in this region.
Funding
Wellcome Trust, the World Bank through the Partnership for Child Development, and the Programme of Support for the Zimbabwe National Action Plan for Orphans and Vulnerable Children.
doi:10.1016/S0140-6736(12)62168-0
PMCID: PMC3627205  PMID: 23453283
3.  Conditional Cash Transfers and HIV/AIDS Prevention: Unconditionally Promising? 
The World Bank economic review  2012;26(2):165-190.
Conditional cash transfers (CCT) have recently received considerable attention as a potentially innovative and effective approach to the prevention of HIV/AIDS. We evaluate a conditional cash transfer program in rural Malawi which offered financial incentives to men and women to maintain their HIV status for approximately one year. The amounts of the reward ranged from zero to approximately 3–4 months wage. We find no effect of the offered incentives on HIV status or on reported sexual behavior. However, shortly after receiving the reward, men who received the cash transfer were 9 percentage points more likely and women were 6.7 percentage points less likely to engage in risky sex. Our analyses therefore question the “unconditional effectiveness” of CCT program for HIV prevention: CCT Programs that aim to motivate safe sexual behavior in Africa should take into account that money given in the present may have much stronger effects than rewards offered in the future, and any effect of these programs may be fairly sensitive to the specific design of the program, the local and/or cultural context, and the degree of agency an individual has with respect to sexual behaviors.
PMCID: PMC3849819  PMID: 24319306
4.  The Importance of Cash in Conditional Cash Transfer Programs for Child Health, Growth and Development: 
Lancet  2008;371(9615):828-837.
Background
Many governments around the world have implemented conditional cash transfer (CCT) programs with the goal of improving options for poor families through interventions in health, nutrition and education. Families enrolled in CCT programs receive cash in exchange for complying with “conditionalities” – preventive health requirements and nutrition supplementation, education and monitoring designed to improve health outcomes and promote positive behavior change. A great challenge in evaluating the effectiveness of CCT programs has been disaggregating the effects of the cash transfer component from that of the conditionalities.
Methods
In an intervention that began in 1998 in Mexico, low-income communities (n=506) were randomly assigned to be enrolled in a CCT program (Oportunidades, formerly Progresa) immediately or 18 months later. In 2003, children (n=3793), aged 24–72 months who had been enrolled in the program their entire lives, were assessed for a wide variety of outcomes. The analyses reported here separated out the association of the cash transfer component of Oportunidades with several outcomes in children from the program conditionalities, while controlling for a wide range of covariates including many measures of household socio-economic status.
Findings
An increase in the cash transfer to the household was associated with higher height-for-age z-score and hemoglobin concentration, lower prevalence of stunting, and lower prevalence of overweight. Children in families whose households received a greater quantity of cash also performed better on a scale of motor development (McCarthy Test of Children’s Abilities), three scales of cognitive development (sub-scales of the Woodcock-Muñoz, including working memory), and receptive language (Test de Vocabulario en Imágenes Peabody).
Interpretation
The results suggest that the cash transfer component of Oportunidades is associated with better outcomes in child health and development.
doi:10.1016/S0140-6736(08)60382-7
PMCID: PMC2779574  PMID: 18328930
child development; child health; stunting; conditional cash transfer programs; randomized experiment; income; poverty alleviation; parental investment; human capital
5.  Incentivising safe sex: a randomised trial of conditional cash transfers for HIV and sexually transmitted infection prevention in rural Tanzania 
BMJ Open  2012;2(1):e000747.
Objective
The authors evaluated the use of conditional cash transfers as an HIV and sexually transmitted infection prevention strategy to incentivise safe sex.
Design
An unblinded, individually randomised and controlled trial.
Setting
10 villages within the Kilombero/Ulanga districts of the Ifakara Health and Demographic Surveillance System in rural south-west Tanzania.
Participants
The authors enrolled 2399 participants, aged 18–30 years, including adult spouses.
Interventions
Participants were randomly assigned to either a control arm (n=1124) or one of two intervention arms: low-value conditional cash transfer (eligible for $10 per testing round, n=660) and high-value conditional cash transfer (eligible for $20 per testing round, n=615). The authors tested participants every 4 months over a 12-month period for the presence of common sexually transmitted infections. In the intervention arms, conditional cash transfer payments were tied to negative sexually transmitted infection test results. Anyone testing positive for a sexually transmitted infection was offered free treatment, and all received counselling.
Main outcome measures
The primary study end point was combined prevalence of the four sexually transmitted infections, which were tested and reported to subjects every 4 months: Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and Mycoplasma genitalium. The authors also tested for HIV, herpes simplex virus 2 and syphilis at baseline and month 12.
Results
At the end of the 12-month period, for the combined prevalence of any of the four sexually transmitted infections, which were tested and reported every 4 months (C trachomatis, N gonorrhoeae, T vaginalis and M genitalium), unadjusted RR for the high-value conditional cash transfer arm compared to controls was 0.80 (95% CI 0.54 to 1.06) and the adjusted RR was 0.73 (95% CI 0.47 to 0.99). Unadjusted RR for the high-value conditional cash transfer arm compared to the low-value conditional cash transfer arm was 0.76 (95% CI 0.49 to 1.03) and the adjusted RR was 0.69 (95% CI 0.45 to 0.92). No harm was reported.
Conclusions
Conditional cash transfers used to incentivise safer sexual practices are a potentially promising new tool in HIV and sexually transmitted infections prevention. Additional larger study would be useful to clarify the effect size, to calibrate the size of the incentive and to determine whether the intervention can be delivered cost effectively.
Trial registration number
NCT00922038 ClinicalTrials.gov.
Article summary
Article focus
Existing prevention strategies have had a limited impact on the trajectory of the HIV/AIDS epidemic.
Conditional cash transfers have been used successfully in a variety of settings to promote activities that are beneficial to the participants, such as school participation or health check-ups for children.
This trial asks whether conditional cash transfers can be used to prevent people from engaging in activities that are harmful to themselves and others, such as unsafe sex.
Key messages
We designed and evaluated a novel intervention that tests for risky sexual behaviour repeatedly over short time intervals, reinforcing learning about safer behaviour with cash transfer incentives conditional on testing negative for a set of curable sexually transmitted infections (STIs).
After 12 months, the results from the adjusted model showed a significant reduction in the combined point prevalence of the four curable STIs tested every 4 months by nucleic acid amplification tests in the group that was eligible for the $20 payments, but no such reduction was found for the group receiving the $10 payments.
The results suggest that conditional cash transfers used to incentivise safer sexual practices are a potentially promising new tool in HIV and STIs prevention. Additional larger study would be useful to clarify the effect size, to calibrate the size of the incentive and to determine whether the intervention can be delivered cost effectively.
Strengths and limitations of this study
This paper reports the results of a novel approach for HIV and STI prevention.
Our study methodology is rigorous, and the results are likely to advance a global conversation about economic approaches to HIV/STI prevention.
Our main outcome measure is the combined point prevalence of four STIs repeatedly tested by nucleic acid amplification tests over the course of the year and which have been incontrovertibly linked to risky sexual activity. These biological outcomes, however, cannot be used to infer the relative importance of STI treatment seeking behaviour versus other behaviour changes, such as increased condom use or reducing riskiness of partners.
The results reported in this study are limited to a 12-month experiment and cannot address the sustainability of improvements in STI outcomes over a longer period, particularly after the conditional cash transfers have been discontinued.
doi:10.1136/bmjopen-2011-000747
PMCID: PMC3330254  PMID: 22318666
6.  Conditional cash transfer schemes in Nigeria: potential gains for maternal and child health service uptake in a national pilot programme 
Background
This paper describes use of a Conditional Cash Transfer (CCT) programme to encourage use of critical MNCH services among rural women in Nigeria.
Methods
The CCT programme was first implemented as a pilot in 37 primary health care facilities (PHCs), in nine Nigerian states. The programme entitles women using these facilities up to N5,000 (approximately US$30) if they attend antenatal care (ANC), skilled delivery, and postnatal care. There are 88 other PHCs from these nine states included in this study, which implemented a standard package of supply upgrades without the CCT. Data on monthly service uptake throughout the continuum of care was collected at 124 facilities during quarterly monitoring visits. An interrupted time series using segmented linear regression was applied to estimate separately the effects of the CCT programme and supply package on service uptake.
Results
From April 2013-March 2014, 20,133 women enrolled in the CCT. Sixty-four percent of beneficiaries returned at least once after registration, and 80% of women delivering with skilled attendance returned after delivery. The CCT intervention is associated with a statistically significant increase in the monthly number of women attending four or more ANC visits (increase of 15.12 visits per 100,000 catchment population, p < 0.01; 95% confidence interval 7.38 to 22.85), despite a negative level effect immediately after the intervention began (-45.53/100,000 catchment population; p < 0.05; 95% CI −82.71 to −8.36). A statistically significant increase was also observed in the monthly number of women receiving two or more Tetanus toxoid doses during pregnancy (21.65/100,000 catchment population; p < 0.01; 95% CI 9.23 to 34.08). Changes for other outcomes with the CCT intervention (number of women attending first ANC visit; number of deliveries with skilled attendance; number of neonates receiving OPV at birth) were not found to be statistically significant.
Conclusions
The results show that the CCT intervention is capable of significant effects on service uptake, although results for several outcomes of interest were inconclusive. Key lessons learnt from the pilot phase of implementation include a need to track beneficiary retention throughout the continuum of care as closely as possible, and avert loss to follow-up.
doi:10.1186/s12884-014-0408-9
PMCID: PMC4273319  PMID: 25495258
Antenatal care; Conditional cash transfer; Demand creation; Health services; Maternal health; Maternal newborn and child health; Nigeria; Rural areas; Skilled birth attendance; Social protection
7.  India’s Conditional Cash Transfer Programme (the JSY) to Promote Institutional Birth: Is There an Association between Institutional Birth Proportion and Maternal Mortality? 
PLoS ONE  2013;8(6):e67452.
Background
India accounts for 19% of global maternal deaths, three-quarters of which come from nine states. In 2005, India launched a conditional cash transfer (CCT) programme, Janani Suraksha Yojana (JSY), to reduce maternal mortality ratio (MMR) through promotion of institutional births. JSY is the largest CCT in the world. In the nine states with relatively lower socioeconomic levels, JSY provides a cash incentive to all women on birthing in health institution. The cash incentive is intended to reduce financial barriers to accessing institutional care for delivery. Increased institutional births are expected to reduce MMR. Thus, JSY is expected to (a) increase institutional births and (b) reduce MMR in states with high proportions of institutional births. We examine the association between (a) service uptake, i.e., institutional birth proportions and (b) health outcome, i.e., MMR.
Method
Data from Sample Registration Survey of India were analysed to describe trends in proportion of institutional births before (2005) and during (2006–2010) the implementation of the JSY. Data from Annual Health Survey (2010–2011) for all 284 districts in above- mentioned nine states were analysed to assess relationship between MMR and institutional births.
Results
Proportion of institutional births increased from a pre-programme average of 20% to 49% in 5 years (p<0.05). In bivariate analysis, proportion of institutional births had a small negative correlation with district MMR (r = −0.11).The multivariate regression model did not establish significant association between institutional birth proportions and MMR [CI: −0.10, 0.68].
Conclusions
Our analysis confirmed that JSY succeeded in raising institutional births significantly. However, we were unable to detect a significant association between institutional birth proportion and MMR. This indicates that high institutional birth proportions that JSY has achieved are of themselves inadequate to reduce MMR. Other factors including improved quality of care at institutions are required for intended effect.
doi:10.1371/journal.pone.0067452
PMCID: PMC3694862  PMID: 23826302
8.  Are Conditional Cash Transfers Effective in Urban Areas? Evidence from Mexico1 
Education economics  2012;20(3):233-259.
Conditional cash transfer (CCT) programs have spread worldwide as a new form of social assistance for the poor. Previous evaluations of CCT programs focus mainly on rural settings, and little is known about their effects in urban areas. This paper studies the short-term (one- and two-year) effects of the Mexican Oportunidades CCT program on urban children/youth. The program provides financial incentives for children/youth to attend school and for family members to visit health clinics. To participate, families had to sign up for the program and be deemed eligible. Difference-in-difference propensity score matching estimates indicate that the program is successful in increasing school enrollment, schooling attainment and time devoted to homework for girls and boys and in decreasing working rates of boys.
doi:10.1080/09645292.2012.672792
PMCID: PMC4334159
9.  Contingency Management in Cocaine Abusers: A Dose–Effect Comparison of Goods-Based Versus Cash-Based Incentives 
Goods-based contingency management interventions (e.g., those using vouchers or prizes as incentives) have demonstrated efficacy in reducing cocaine use, but cost has limited dissemination to community clinics. Recent research suggests that development of a cash-based contingency management approach may improve treatment outcomes while reducing operational costs of the intervention. However, the clinical safety of providing cash-based incentives to substance abusers has been a concern. The present 16-week study compared the effects of goods-based versus cash-based incentives worth $0, $25, $50, and $100 on short-term cocaine abstinence in a small sample of cocaine-dependent methadone patients (N=12). A within-subject design was used; a 9-day washout period separated each of 8 incentive conditions. Higher magnitude ($50 and $100) cash-based incentives (checks) produced greater cocaine abstinence compared with the control ($0) condition, but a magnitude effect was not seen for goods-based incentives (vouchers). A trend was observed for greater rates of abstinence in the cash-based versus goods-based incentives at the $50 and $100 magnitudes. Receipt of $100 checks did not increase subsequent rates of cocaine use above those seen in control conditions. The efficacy and safety data provided in this and other recent studies suggest that use of cash-based incentives deserves consideration for clinical applications of contingency management, but additional confirmation in research using larger samples and more prolonged periods of incentive delivery is needed.
doi:10.1037/1064-1297.15.4.338
PMCID: PMC2043576  PMID: 17696680
contingency management; abstinence incentives; contingent reinforcement; cocaine dependence
10.  Preventing Acute Malnutrition among Young Children in Crises: A Prospective Intervention Study in Niger 
PLoS Medicine  2014;11(9):e1001714.
Céline Langendorf and colleagues conducted a pragmatic intervention study in Niger to assess whether distributions of supplementary foods in addition to household support by cash transfer effectively reduced malnutrition in children aged 6 to 23 months.
Please see later in the article for the Editors' Summary
Background
Finding the most appropriate strategy for the prevention of moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in young children is essential in countries like Niger with annual “hunger gaps.” Options for large-scale prevention include distribution of supplementary foods, such as fortified-blended foods or lipid-based nutrient supplements (LNSs) with or without household support (cash or food transfer). To date, there has been no direct controlled comparison between these strategies leading to debate concerning their effectiveness. We compared the effectiveness of seven preventive strategies—including distribution of nutritious supplementary foods, with or without additional household support (family food ration or cash transfer), and cash transfer only—on the incidence of SAM and MAM among children aged 6–23 months over a 5-month period, partly overlapping the hunger gap, in Maradi region, Niger. We hypothesized that distributions of supplementary foods would more effectively reduce the incidence of acute malnutrition than distributions of household support by cash transfer.
Methods and Findings
We conducted a prospective intervention study in 48 rural villages located within 15 km of a health center supported by Forum Santé Niger (FORSANI)/Médecins Sans Frontières in Madarounfa. Seven groups of villages (five to 11 villages) were allocated to different strategies of monthly distributions targeting households including at least one child measuring 60 cm–80 cm (at any time during the study period whatever their nutritional status): three groups received high-quantity LNS (HQ-LNS) or medium-quantity LNS (MQ-LNS) or Super Cereal Plus (SC+) with cash (€38/month [US$52/month]); one group received SC+ and family food ration; two groups received HQ-LNS or SC+ only; one group received cash only (€43/month [US$59/month]). Children 60 cm–80 cm of participating households were assessed at each monthly distribution from August to December 2011. Primary endpoints were SAM (weight-for-length Z-score [WLZ]<−3 and/or mid-upper arm circumference [MUAC]<11.5 cm and/or bipedal edema) and MAM (−3≤WLZ<−2 and/or 11.5≤MUAC<12.5 cm). A total of 5,395 children were included in the analysis (615 to 1,054 per group). Incidence of MAM was twice lower in the strategies receiving a food supplement combined with cash compared with the cash-only strategy (cash versus HQ-LNS/cash adjusted hazard ratio [HR] = 2.30, 95% CI 1.60–3.29; cash versus SC+/cash HR = 2.42, 95% CI 1.39–4.21; cash versus MQ-LNS/cash HR = 2.07, 95% CI 1.52–2.83) or with the supplementary food only groups (HQ-LNS versus HQ-LNS/cash HR = 1.84, 95% CI 1.35–2.51; SC+ versus SC+/cash HR = 2.53, 95% CI 1.47–4.35). In addition, the incidence of SAM was three times lower in the SC+/cash group compared with the SC+ only group (SC+ only versus SC+/cash HR = 3.13, 95% CI 1.65–5.94). However, non-quantified differences between groups, may limit the interpretation of the impact of the strategies.
Conclusions
Preventive distributions combining a supplementary food and cash transfer had a better preventive effect on MAM and SAM than strategies relying on cash transfer or supplementary food alone. As a result, distribution of nutritious supplementary foods to young children in conjunction with household support should remain a pillar of emergency nutritional interventions. Additional rigorous research is vital to evaluate the effectiveness of these and other nutritional interventions in diverse settings.
Trial registration
ClinicalTrials.gov NCT01828814
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Good nutrition during childhood is essential for health and survival. Undernourished children are more susceptible to infection and are more likely to die from common ailments such as diarrhoea than well-nourished children. Malnutrition can be chronic or acute. Chronic (long-term) malnutrition causes stunting. A stunted child has a low height for his or her age when compared to the World Health Organization Child Growth Standards, which chart the growth of a reference population. By contrast, acute malnutrition causes wasting. A wasted child has a low weight for his or her height. Acute malnutrition, which is responsible for more than 800,000 deaths among children under 5 years old every year (12.6% of all deaths in this age group), often follows earthquakes or other emergencies but also occurs in countries such as Niger that regularly experience a “hunger gap,” a shortage of food in the months before the annual harvest. Interventions designed to prevent acute malnutrition include distributions of supplementary food such as lipid-based nutrient supplements (LNS) and fortified cereal products (for example, super cereal plus [SC+]) targeting children and household support in the form of food or cash transfers, which allow households to buy their own food.
Why Was This Study Done?
Governments and donor agencies need to know which preventative strategy is most effective, particularly among children under 2 years old who are most vulnerable to acute malnutrition. Here, the researchers compare the effectiveness of seven preventative strategies—including the distribution of nutritious supplementary foods with and without additional household support (food or cash transfer) and cash transfer alone—on the incidence (occurrence) of moderate and severe acute malnutrition among children aged 6–23 months living in 48 villages in the Madarounfa district of Niger between August and December, 2011. Niger regularly experiences a hunger gap between June and October; 12.9% of the population of the Madarounfa district was at risk of severe food insecurity at the time of the study.
What Did the Researchers Do and Find?
The researchers allocated the villages to receive high or medium quantity LNS plus cash, SC+ plus cash or a family food ration, high quantity LNS only, SC+ only, or cash only; the cash transfer was sufficient to meet the energy needs of an average household. The interventions were distributed once a month to households that included at least one child measuring 60–80 cm in length at any time during the study period (length is used as a proxy for age when the precise age of children is unknown). Eligible children in each participating household were assessed for moderate and severe acute malnutrition as defined by the World Health Organization by measuring their weight, length, and mid-upper arm circumference at each distribution. The incidence of moderate acute malnutrition was about twice as high among children who received the cash-only intervention as among those who received any of the food supplement plus cash. For example, the incidence of moderate acute malnutrition was 3.33 cases per 100 child-months among children who received the SC+ plus cash intervention but 7.97 cases per 100 child-months among those who received the cash-only intervention. Moreover, the incidence of severe acute malnutrition was about three times higher among the children who received the SC+ only intervention than among those who received the SC+ plus cash intervention.
What Do These Findings Mean?
These findings suggest that, in this region of Niger, interventions that combined the distribution of supplementary food and a cash transfer prevented acute malnutrition more effectively than strategies that relied on cash transfer or supplementary food distribution alone. Unmeasured differences between the groups that affect the incidence of malnutrition may be responsible for some of the differences between intervention groups, and the incidences of malnutrition may have been different if the study period had covered the whole hunger gap. Moreover, these findings may not be generalizable to other regions of Niger or to other countries that experience an annual hunger gap. Despite these limitations, which highlight the need for further research into the effectiveness of nutritional interventions, these findings suggest that the distribution of supplementary foods to young children in conjunction with household support should remain an important part of nutritional interventions during the hunger gap and other emergencies.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001714.
This study is further discussed in a PLOS Medicine Perspective by Marco Kerac and Andrew Seal
More information about this prospective intervention study is available from ClinicalTrials.gov
The charity UNICEF, which protects the rights of children and young people around the world, provides detailed statistics on child undernutrition; it has detailed information about malnutrition and the humanitarian situation in Niger; a 2012 article on malnutrition among children in Niger includes a personal story about a child with severe acute malnutrition in Maradi
The World Health Organization Child Growth Standards are available (in several languages)
The United Nations Millennium Development Goals provides information on ongoing world efforts to reduce hunger and child mortality
The World Food Programme is the world's largest humanitarian agency fighting hunger worldwide; its website provides information about malnutrition in Niger, including a visual presentation on wide-scale targeted food distribution in the country
“Starved for Attention” is an international multimedia campaign launched in 2010 by Médecins Sans Frontiéres (MSF) and the VII Photo agency to rewrite the story of childhood malnutrition; information about MSF's work in Niger to tackle malnutrition is available
doi:10.1371/journal.pmed.1001714
PMCID: PMC4152259  PMID: 25180584
11.  Functional Subunits of Eukaryotic Chaperonin CCT/TRiC in Protein Folding 
Journal of Amino Acids  2011;2011:843206.
Molecular chaperones are a class of proteins responsible for proper folding of a large number of polypeptides in both prokaryotic and eukaryotic cells. Newly synthesized polypeptides are prone to nonspecific interactions, and many of them make toxic aggregates in absence of chaperones. The eukaryotic chaperonin CCT is a large, multisubunit, cylindrical structure having two identical rings stacked back to back. Each ring is composed of eight different but similar subunits and each subunit has three distinct domains. CCT assists folding of actin, tubulin, and numerous other cellular proteins in an ATP-dependent manner. The catalytic cooperativity of ATP binding/hydrolysis in CCT occurs in a sequential manner different from concerted cooperativity as shown for GroEL. Unlike GroEL, CCT does not have GroES-like cofactor, rather it has a built-in lid structure responsible for closing the central cavity. The CCT complex recognizes its substrates through diverse mechanisms involving hydrophobic or electrostatic interactions. Upstream factors like Hsp70 and Hsp90 also work in a concerted manner to transfer the substrate to CCT. Moreover, prefoldin, phosducin-like proteins, and Bag3 protein interact with CCT and modulate its function for the fine-tuning of protein folding process. Any misregulation of protein folding process leads to the formation of misfolded proteins or toxic aggregates which are linked to multiple pathological disorders.
doi:10.4061/2011/843206
PMCID: PMC3268035  PMID: 22312474
12.  Computerized Cognitive Training in Cognitively Healthy Older Adults: A Systematic Review and Meta-Analysis of Effect Modifiers 
PLoS Medicine  2014;11(11):e1001756.
Michael Valenzuela and colleagues systematically review and meta-analyze the evidence that computerized cognitive training improves cognitive skills in older adults with normal cognition.
Please see later in the article for the Editors' Summary
Background
New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors.
Methods and Findings
We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I2 = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects.
Conclusions
CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
As we get older, we notice many bodily changes. Our hair goes grey, we develop new aches and pains, and getting out of bed in the morning takes longer than it did when we were young. Our brain may also show signs of aging. It may take us longer to learn new information, we may lose our keys more frequently, and we may forget people's names. Cognitive decline—developing worsened thinking, language, memory, understanding, and judgment—can be a normal part of aging, but it can also be an early sign of dementia, a group of brain disorders characterized by a severe, irreversible decline in cognitive functions. We know that age-related physical decline can be attenuated by keeping physically active; similarly, engaging in activities that stimulate the brain throughout life is thought to enhance cognition in later life and reduce the risk of age-related cognitive decline and dementia. Thus, having an active social life and doing challenging activities that stimulate both the brain and the body may help to stave off cognitive decline.
Why Was This Study Done?
“Brain training” may be another way of keeping mentally fit. The sale of computerized cognitive training (CCT) packages, which provide standardized, cognitively challenging tasks designed to “exercise” various cognitive functions, is a lucrative and expanding business. But does CCT work? Given the rising global incidence of dementia, effective interventions that attenuate age-related cognitive decline are urgently needed. However, the impact of CCT on cognitive performance in older adults is unclear, and little is known about what makes a good CCT package. In this systematic review and meta-analysis, the researchers assess whether CCT programs improve cognitive test performance in cognitively healthy older adults and identify the aspects of cognition (cognitive domains) that are responsive to CCT, and the CCT design features that are most important in improving cognitive performance. A systematic review uses pre-defined criteria to identify all the research on a given topic; meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 51 trials that investigated the effects of more than four hours of CCT on nearly 5,000 cognitively healthy older adults by measuring several cognitive functions before and after CCT. Meta-analysis of these studies indicated that the overall effect size for CCT (compared to control individuals who did not participate in CCT) was small but statistically significant. An effect size quantifies the difference between two groups; a statistically significant result is a result that is unlikely to have occurred by chance. So, the meta-analysis suggests that CCT slightly increased overall cognitive function. Notably, CCT also had small to moderate significant effects on individual cognitive functions. For example, some CCT slightly improved nonverbal memory (the ability to remember visual images) and working memory (the ability to remember recent events; short-term memory). However, CCT had no significant effect on executive functions (cognitive processes involved in planning and judgment) or attention (selective concentration on one aspect of the environment). The design of CCT used in the different studies varied considerably, and “moderator” analyses revealed that home-based CCT was not effective, whereas center-based CCT was effective, and that training sessions undertaken more than three times a week were not effective. There was also some weak evidence suggesting that CCT sessions lasting less than 30 minutes may be ineffective. Finally, there was no evidence for the effectiveness of working memory training by itself (for example, programs that ask individuals to recall series of letters).
What Do These Findings Mean?
These findings suggest that CCT produces small improvements in cognitive performance in cognitively healthy older adults but that the efficacy of CCT varies across cognitive domains and is largely determined by design aspects of CCT. The most important result was that “do-it-yourself” CCT at home did not produce improvements. Rather, the small improvements seen were in individuals supervised by a trainer in a center and undergoing sessions 1–3 times a week. Because only cognitively healthy older adults were enrolled in the studies considered in this systematic review and meta-analysis, these findings do not necessarily apply to cognitively impaired individuals. Moreover, because all the included studies measured cognitive function immediately after CCT, these findings provide no information about the durability of the effects of CCT or about how the effects of CCT on cognitive function translate into real-life outcomes for individuals such as independence and the long-term risk of dementia. The researchers call, therefore, for additional research into CCT, an intervention that might help to attenuate age-related cognitive decline and improve the quality of life for older individuals.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001756.
This study is further discussed in a PLOS Medicine Perspective by Druin Burch
The US National Institute on Aging provides information for patients and carers about age-related forgetfulness, about memory and cognitive health, and about dementia (in English and Spanish)
The UK National Health Service Choices website also provides information about dementia and about memory loss
MedlinePlus provides links to additional resources about memory, mild cognitive impairment, and dementia (in English and Spanish)
doi:10.1371/journal.pmed.1001756
PMCID: PMC4236015  PMID: 25405755
13.  Impact of Conditional Cash Transfers on Maternal and Newborn Health 
Journal of Health, Population, and Nutrition  2013;31(4 Suppl 2):S48-S66.
Maternal and newborn health (MNH) is a high priority for global health and is included among the Millennium Development Goals (MDGs). However, the slow decline in maternal and newborn mortality jeopardizes achievements of the targets of MDGs. According to UNICEF, 60 million women give birth outside of health facilities, and family planning needs are satisfied for only 50%. Further, skilled birth attendance and the use of antenatal care are most inequitably distributed in maternal and newborn health interventions in low- and middle-income countries. Conditional cash transfer (CCT) programmes have been shown to increase health service utilization among the poorest but little is written on the effects of such programmes on maternal and newborn health. We carried out a systematic review of studies on CCT that report maternal and newborn health outcomes, including studies from 8 countries. The CCT programmes have increased antenatal visits, skilled attendance at birth, delivery at a health facility, and tetanus toxoid vaccination for mothers and reduced the incidence of low birthweight. The programmes have not had a significant impact on fertility while the impact on maternal and newborn mortality has not been well-documented thus far. Given these positive effects, we make the case for further investment in CCT programmes for maternal and newborn health, noting gaps in knowledge and providing recommendations for better design and evaluation of such programmes. We recommend more rigorous impact evaluations that document impact pathways and take factors, such as cost-effectiveness, into account.
PMCID: PMC4021703
Conditional cash transfers; Global health; Incentives; Maternal health; Millennium Development Goals; Newborn health; Social protection
14.  Three CCT domain-containing genes were identified to regulate heading date by candidate gene-based association mapping and transformation in rice 
Scientific Reports  2015;5:7663.
CCT domain-containing genes generally control flowering in plants. Currently, only six of the 41 CCT family genes have been confirmed to control flowering in rice. To efficiently identify more heading date-related genes from the CCT family, we compared the positions of heading date QTLs and CCT genes and found that 25 CCT family genes were located in the QTL regions. Association mapping showed that a total of 19 CCT family genes were associated with the heading date. Five of the seven associated genes within QTL regions and two of four associated genes outside of the QTL regions were confirmed to regulate heading date by transformation. None of the seven non-associated genes outside of the QTL regions regulates heading date. Obviously, combination of candidate gene-based association mapping with linkage analysis could improve the identification of functional genes. Three novel CCT family genes, including one non-associated (OsCCT01) and two associated genes (OsCCT11 and OsCCT19) regulated the heading date. The overexpression of OsCCT01 delayed flowering through suppressing the expression of Ehd1, Hd3a and RFT1 under both long day and short day conditions. Potential functions in regulating heading date of some untested CCT family genes were discussed.
doi:10.1038/srep07663
PMCID: PMC4286927  PMID: 25563494
15.  Comparing thousands of circular genomes using the CGView Comparison Tool 
BMC Genomics  2012;13:202.
Background
Continued sequencing efforts coupled with advances in sequencing technology will lead to the completion of a vast number of small genomes. Whole-genome comparisons represent an important part of the analysis of any new genome sequence, as they can provide a better understanding of the biology and evolution of the source organism. Visualization of the results is important, as it allows information from a variety of sources to be integrated and interpreted. However, existing graphical comparison tools lack features needed for efficiently comparing a new genome to hundreds or thousands of existing sequences. Moreover, existing tools are limited in terms of the types of comparisons that can be performed, the extent to which the output can be customized, and the ease with which the entire process can be automated.
Results
The CGView Comparison Tool (CCT) is a package for visually comparing bacterial, plasmid, chloroplast, or mitochondrial sequences of interest to existing genomes or sequence collections. The comparisons are conducted using BLAST, and the BLAST results are presented in the form of graphical maps that can also show sequence features, gene and protein names, COG (Clusters of Orthologous Groups of proteins) category assignments, and sequence composition characteristics. CCT can generate maps in a variety of sizes, including 400 Megapixel maps suitable for posters. Comparisons can be conducted within a particular species or genus, or all available genomes can be used. The entire map creation process, from downloading sequences to redrawing zoomed maps, can be completed easily using scripts included with the CCT. User-defined features or analysis results can be included on maps, and maps can be extensively customized. To simplify program setup, a CCT virtual machine that includes all dependencies preinstalled is available. Detailed tutorials illustrating the use of CCT are included with the CCT documentation.
Conclusion
CCT can be used to visually compare a reference sequence to thousands of existing genomes or sequence collections (next-generation sequencing reads for example) on a standard desktop computer. It provides analysis and visualization functionality not available in any existing circular genome visualization tool. By visually presenting sequence conservation information along with functional classifications and sequence composition characteristics, CCT can be a useful tool for identifying rapidly evolving or novel sequences, horizontally transferred sequences, or unusual functional properties in newly sequenced genomes. CCT is freely available for download at http://stothard.afns.ualberta.ca/downloads/CCT/.
doi:10.1186/1471-2164-13-202
PMCID: PMC3469350  PMID: 22621371
16.  Contingency Management and Levodopa-Carbidopa for Cocaine Treatment: A Comparison of Three Behavioral Targets 
New data support use of levodopa pharmacotherapy with behavioral contingency management (CM) as one efficacious combination in cocaine dependence disorder treatment. A potential mechanism of the combined treatment effects may be related to dopamine-induced enhancement of the saliency of contingently delivered reinforcers. Evidence to support this mechanism was sought by evaluating levodopa-enhancing effects across distinct CM conditions that varied in behavioral targets. A total of 136 treatment-seeking, cocaine dependent subjects participated in this 12-week, randomized, placebo-controlled trial of levodopa (vs. placebo) administered in combination with one of three behavioral CM conditions. In the CM-URINE condition, subjects received cash-valued vouchers contingent on cocaine-negative urine toxicology results. In the CM-ATTEND condition, the same voucher schedule was contingent on attending thrice weekly clinic visits. In the CM-MEDICATION condition, the same voucher schedule was contingent on Medication Event Monitoring Systems- and riboflavin-based evidence of pill-taking behavior. Primary outcomes associated with each CM target behavior were analyzed using generalized linear mixed models for repeated outcomes. CM responding in the CM-ATTENDANCE and CM-MEDICATION conditions showed orderly effects, with each condition producing corresponding changes in targeted behaviors, regardless of medication condition. In contrast, CM responding in the CM-URINE condition was moderated by medication, with levodopa-treated subjects more likely to submit cocaine-negative urines. These findings specify the optimal target behavior for CM when used in combination with levodopa pharmacotherapy.
doi:10.1037/a0019195
PMCID: PMC3164487  PMID: 20545388
contingency management; levodopa; medication compliance; pharmacotherapy; behavior therapy
17.  The impact of Brazil’s Bolsa Família conditional cash transfer program on children’s health care utilization and health outcomes 
Background
Conditional cash transfer (CCT) programs provide poor families with cash conditional on investments in health and education. Brazil’s Bolsa Família program began in 2003 and is currently the largest CCT program in the world. This community-based study examines the impact of Bolsa Família on child health in a slum community in a large urban center.
Methods
In 2010, detailed household surveys were conducted with randomly selected Bolsa Família beneficiaries and non-beneficiaries in a Brazilian slum community of approximately 14,000 inhabitants in a large urban center. 567 families (with 1,266 children) were interviewed. Propensity score methods were used to control for differences between beneficiary and non-beneficiary children to estimate program impacts on health care utilization and health outcomes.
Results
Bolsa Família has increased the odds of children’s visits to the health post for preventive services. In children under age seven, Bolsa Família was associated with increased odds for growth monitoring (OR = 3.1; 95% CI 1.9-5.1), vaccinations (OR = 2.8; 95% CI 1.4-5.4), and checkups (OR = 1.6; 95% CI 0.98-2.5), and with the number of growth monitoring visits (β = 0.6; p = 0.049) and checkups (β = 0.2; p = 0.068). There were positive spillover effects on older siblings (ages 7-17) no longer required to meet the health conditionalities. Bolsa Família increased their odds for growth monitoring (OR = 2.5; 95% CI 1.3-4.9) and checkups (OR = 1.7; 95% CI 0.9-3.2) and improved psychosocial health (β = 2.6; p = 0.007).
Conclusions
Bolsa Família has improved health care utilization, especially for services related to the health conditionalites, and there were positive spillover effects on older siblings. The findings of this study are promising, but they also suggest that further improvements in health may depend on the quality of health care services provided, the scope of services linked to the health conditionalities, and coordination with other social safety net programs.
doi:10.1186/1472-698X-14-10
PMCID: PMC4021270  PMID: 24690131
18.  Interactions between the actin filament capping and severing protein gelsolin and the molecular chaperone CCT: evidence for nonclassical substrate interactions 
Cell Stress & Chaperones  2010;16(2):173-179.
CCT is a member of the chaperonin family of molecular chaperones and consists of eight distinct subunit species which occupy fixed positions within the chaperonin rings. The activity of CCT is closely linked to the integrity of the cytoskeleton as newly synthesized actin and tubulin monomers are dependent upon CCT to reach their native conformations. Furthermore, an additional role for CCT involving interactions with assembling/assembled microfilaments and microtubules is emerging. CCT is also known to interact with other proteins, only some of which will be genuine folding substrates. Here, we identify the actin filament remodeling protein gelsolin as a CCT-binding partner, and although it does not behave as a classical folding substrate, gelsolin binds to CCT with a degree of specificity. In cultured cells, the levels of CCT monomers affect levels of gelsolin, suggesting an additional link between CCT and the actin cytoskeleton that is mediated via the actin filament severing and capping protein gelsolin.
Electronic supplementary material
The online version of this article (doi:10.1007/s12192-010-0230-x) contains supplementary material, which is available to authorized users.
doi:10.1007/s12192-010-0230-x
PMCID: PMC3059788  PMID: 20890741
Molecular chaperone; CCT; Actin cytoskeleton; Gelsolin
19.  TOKEN REINFORCEMENT: A REVIEW AND ANALYSIS 
Token reinforcement procedures and concepts are reviewed and discussed in relation to general principles of behavior. The paper is divided into four main parts. Part I reviews and discusses previous research on token systems in relation to common behavioral functions—reinforcement, temporal organization, antecedent stimulus functions, and aversive control—emphasizing both the continuities with other contingencies and the distinctive features of token systems. Part II describes the role of token procedures in the symmetrical law of effect, the view that reinforcers (gains) and punishers (losses) can be measured in conceptually analogous terms. Part III considers the utility of token reinforcement procedures in cross-species analysis of behavior more generally, showing how token procedures can be used to bridge the methodological gulf separating research with humans from that with other animals. Part IV discusses the relevance of token systems to the field of behavioral economics. Token systems have the potential to significantly advance research and theory in behavioral economics, permitting both a more refined analysis of the costs and benefits underlying standard economic models, and a common currency more akin to human monetary systems. Some implications for applied research and for broader theoretical integration across disciplines will also be considered.
doi:10.1901/jeab.2009.91-257
PMCID: PMC2648534  PMID: 19794838
token reinforcement; conditioned reinforcement; symmetrical law of effect; cross-species analysis; behavioral economics
20.  Central Corneal Thickness in Children With Intellectual Disability: A Controlled Study 
Cornea  2010;29(2):159-161.
Purpose
To evaluate the central corneal thickness (CCT) in children with intellectual disability (ID) and to determine the association between ID-related variables and CCT.
Methods
A total of 77 subjects with ID and 38 healthy controls were included in the study. The subjects with ID were subdivided into mild (IQ 50–69; n = 34), moderate (IQ 35–49; n = 30), and severe (IQ <34; n = 13) groups and syndromic (n = 40) versus nonsyndromic (n = 37) distinctions. All children underwent CCT assessment by ultrasound pachymetry, in addition to complete ophthalmologic examination. Analysis of variance, χ2 test, and linear regression analysis were used for statistical analysis.
Results
CCT was significantly higher in the ID group (549.7 ± 21.4 μm) than that the control group (521.6 ± 16.9 μm; P < 0.0001). Linear regression analysis revealed that presence of syndromic etiology significantly predicted higher CCT among the individuals with ID (P < 0.0001).
Conclusions
Children with ID have an increased CCT compared with healthy controls. Syndromic etiology is the only variable that predicts higher CCT among the individuals with ID. Although the finding of an increased CCT in children with ID is statistically significant, it is not clinically significant.
doi:10.1097/ICO.0b013e3181af7610
PMCID: PMC3166639  PMID: 20023578
intellectual disability; central corneal thickness
21.  Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma 
Background
Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC.
Methods
We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes.
Results
We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality.
Conclusions
Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC.
doi:10.1186/1477-7819-11-143
PMCID: PMC3691597  PMID: 23782473
gallbladder cancer; adenocarcinoma; squamous cell carcinoma; adenosquamous carcinoma; CCT2; PDIA3
22.  Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this analysis was to conduct an evidence-based assessment of home telehealth technologies for patients with chronic obstructive pulmonary disease (COPD) in order to inform recommendations regarding the access and provision of these services in Ontario. This analysis was one of several analyses undertaken to evaluate interventions for COPD. The perspective of this assessment was that of the Ontario Ministry of Health and Long-Term Care, a provincial payer of medically necessary health care services.
Clinical Need: Condition and Target Population
Canada is facing an increase in chronic respiratory diseases due in part to its aging demographic. The projected increase in COPD will put a strain on health care payers and providers. There is therefore an increasing demand for telehealth services that improve access to health care services while maintaining or improving quality and equality of care. Many telehealth technologies however are in the early stages of development or diffusion and thus require study to define their application and potential harms or benefits. The Medical Advisory Secretariat (MAS) therefore sought to evaluate telehealth technologies for COPD.
Technology
Telemedicine (or telehealth) refers to using advanced information and communication technologies and electronic medical devices to support the delivery of clinical care, professional education, and health-related administrative services.
Generally there are 4 broad functions of home telehealth interventions for COPD:
to monitor vital signs or biological health data (e.g., oxygen saturation),
to monitor symptoms, medication, or other non-biologic endpoints (e.g., exercise adherence),
to provide information (education) and/or other support services (such as reminders to exercise or positive reinforcement), and
to establish a communication link between patient and provider.
These functions often require distinct technologies, although some devices can perform a number of these diverse functions. For the purposes of this review, MAS focused on home telemonitoring and telephone only support technologies.
Telemonitoring (or remote monitoring) refers to the use of medical devices to remotely collect a patient’s vital signs and/or other biologic health data and the transmission of those data to a monitoring station for interpretation by a health care provider.
Telephone only support refers to disease/disorder management support provided by a health care provider to a patient who is at home via telephone or videoconferencing technology in the absence of transmission of patient biologic data.
Research Questions
What is the effectiveness, cost-effectiveness, and safety of home telemonitoring compared with usual care for patients with COPD?
What is the effectiveness, cost-effectiveness, and safety of telephone only support programs compared with usual care for patients with COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on November 3, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2000 until November 3, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low, or very low according to GRADE methodology.
Inclusion Criteria – Question #1
frequent transmission of a patient’s physiological data collected at home and without a health care professional physically present to health care professionals for routine monitoring through the use of a communication technology;
monitoring combined with a coordinated management and feedback system based on transmitted data;
telemonitoring as a key component of the intervention (subjective determination);
usual care as provided by the usual care provider for the control group;
randomized controlled trials (RCTs), controlled clinical trials (CCTs), systematic reviews, and/or meta-analyses;
published between January 1, 2000 and November 3, 2010.
Inclusion Criteria – Question #2
scheduled or frequent contact between patient and a health care professional via telephone or videoconferencing technology in the absence of transmission of patient physiological data;
monitoring combined with a coordinated management and feedback system based on transmitted data;
telephone support as a key component of the intervention (subjective determination);
usual care as provided by the usual care provider for the control group;
RCTs, CCTs, systematic reviews, and/or meta-analyses;
published between January 1, 2000 and November 3, 2010.
Exclusion Criteria
published in a language other than English;
intervention group (and not control) receiving some form of home visits by a medical professional, typically a nurse (i.e., telenursing) beyond initial technology set-up and education, to collect physiological data, or to somehow manage or treat the patient;
not recording patient or health system outcomes (e.g., technical reports testing accuracy, reliability or other development-related outcomes of a device, acceptability/feasibility studies, etc.);
not using an independent control group that received usual care (e.g., studies employing historical or periodic controls).
Outcomes of Interest
hospitalizations (primary outcome)
mortality
emergency department visits
length of stay
quality of life
other […]
Subgroup Analyses (a priori)
length of intervention (primary)
severity of COPD (primary)
Quality of Evidence
The quality of evidence assigned to individual studies was determined using a modified CONSORT Statement Checklist for Randomized Controlled Trials. (1) The CONSORT Statement was adapted to include 3 additional quality measures: the adequacy of control group description, significant differential loss to follow-up between groups, and greater than or equal to 30% study attrition. Individual study quality was defined based on total scores according to the CONSORT Statement checklist: very low (0 to < 40%), low (≥ 40 to < 60%), moderate (≥ 60 to < 80%), and high (≥ 80 to 100%).
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Six publications, representing 5 independent trials, met the eligibility criteria for Research Question #1. Three trials were RCTs reported across 4 publications, whereby patients were randomized to home telemonitoring or usual care, and 2 trials were CCTs, whereby patients or health care centers were nonrandomly assigned to intervention or usual care.
A total of 310 participants were studied across the 5 included trials. The mean age of study participants in the included trials ranged from 61.2 to 74.5 years for the intervention group and 61.1 to 74.5 years for the usual care group. The percentage of men ranged from 40% to 64% in the intervention group and 46% to 72% in the control group.
All 5 trials were performed in a moderate to severe COPD patient population. Three trials initiated the intervention following discharge from hospital. One trial initiated the intervention following a pulmonary rehabilitation program. The final trial initiated the intervention during management of patients at an outpatient clinic.
Four of the 5 trials included oxygen saturation (i.e., pulse oximetry) as one of the biological patient parameters being monitored. Additional parameters monitored included forced expiratory volume in one second, peak expiratory flow, and temperature.
There was considerable clinical heterogeneity between trials in study design, methods, and intervention/control. In relation to the telemonitoring intervention, 3 of the 5 included studies used an electronic health hub that performed multiple functions beyond the monitoring of biological parameters. One study used only a pulse oximeter device alone with modem capabilities. Finally, in 1 study, patients measured and then forwarded biological data to a nurse during a televideo consultation. Usual care varied considerably between studies.
Only one trial met the eligibility criteria for Research Question #2. The included trial was an RCT that randomized 60 patients to nurse telephone follow-up or usual care (no telephone follow-up). Participants were recruited from the medical department of an acute-care hospital in Hong Kong and began receiving follow-up after discharge from the hospital with a diagnosis of COPD (no severity restriction). The intervention itself consisted of only two 10-to 20-minute telephone calls, once between days 3 to 7 and once between days 14 to 20, involving a structured, individualized educational and supportive programme led by a nurse that focused on 3 components: assessment, management options, and evaluation.
Regarding Research Question #1:
Low to very low quality evidence (according to GRADE) finds non-significant effects or conflicting effects (of significant or non-significant benefit) for all outcomes examined when comparing home telemonitoring to usual care.
There is a trend towards significant increase in time free of hospitalization and use of other health care services with home telemonitoring, but these findings need to be confirmed further in randomized trials of high quality.
There is severe clinical heterogeneity between studies that limits summary conclusions.
The economic impact of home telemonitoring is uncertain and requires further study.
Home telemonitoring is largely dependent on local information technologies, infrastructure, and personnel, and thus the generalizability of external findings may be low. Jurisdictions wishing to replicate home telemonitoring interventions should likely test those interventions within their jurisdictional framework before adoption, or should focus on home-grown interventions that are subjected to appropriate evaluation and proven effective.
Regarding Research Question #2:
Low quality evidence finds significant benefit in favour of telephone-only support for self-efficacy and emergency department visits when compared to usual care, but non-significant results for hospitalizations and hospital length of stay.
There are very serious issues with the generalizability of the evidence and thus additional research is required.
PMCID: PMC3384362  PMID: 23074421
23.  Is Health of the Aging Improved by Conditional Cash Transfer Programs? Evidence From Mexico 
Demography  2013;50(4):10.1007/s13524-013-0199-z.
Conditional cash transfer (CCT) programs link public transfers to human capital investment in the hopes of alleviating current poverty and reducing its intergenerational transmission. Whereas nearly all studies of their effects have focused on youth, CCT programs may also have an impact on aging adults by increasing household resources or inducing changes in allocations of time of household members, which may be of substantial interest, particularly given the rapid aging of most populations. This article contributes to this underresearched area by examining health and work impacts on the aging for the best-known and most influential of these programs, the Mexican PROGRESA/Oportunidades program. For a number of health indicators, the program appears to significantly improve health, with larger effects for recipients with a greater time receiving benefits from the program. Most of these health effects are concentrated on women.
doi:10.1007/s13524-013-0199-z
PMCID: PMC3832425  PMID: 23494570
Health; Aging; Conditional cash transfers; Mexico
24.  Community-Based Care for Chronic Wound Management 
Executive Summary
In August 2008, the Medical Advisory Secretariat (MAS) presented a vignette to the Ontario Health Technology Advisory Committee (OHTAC) on a proposed targeted health care delivery model for chronic care. The proposed model was defined as multidisciplinary, ambulatory, community-based care that bridged the gap between primary and tertiary care, and was intended for individuals with a chronic disease who were at risk of a hospital admission or emergency department visit. The goals of this care model were thought to include: the prevention of emergency department visits, a reduction in hospital admissions and re-admissions, facilitation of earlier hospital discharge, a reduction or delay in long-term care admissions, and an improvement in mortality and other disease-specific patient outcomes.
OHTAC approved the development of an evidence-based assessment to determine the effectiveness of specialized community based care for the management of heart failure, Type 2 diabetes and chronic wounds.
Please visit the Medical Advisory Secretariat Web site at: www.health.gov.on.ca/ohtas to review the following reports associated with the Specialized Multidisciplinary Community-Based care series.
Specialized multidisciplinary community-based care series: a summary of evidence-based analyses
Community-based care for the specialized management of heart failure: an evidence-based analysis
Community-based care for chronic wound management: an evidence-based analysis
Please note that the evidence-based analysis of specialized community-based care for the management of diabetes titled: “Community-based care for the management of type 2 diabetes: an evidence-based analysis” has been published as part of the Diabetes Strategy Evidence Platform at this URL: http://www.health.gov.on.ca/english/providers/program/mas/tech/ohtas/tech_diabetes_20091020.html
Please visit the Toronto Health Economics and Technology Assessment Collaborative Web site at: http://theta.utoronto.ca/papers/MAS_CHF_Clinics_Report.pdf to review the following economic project associated with this series:
Community-based Care for the specialized management of heart failure: a cost-effectiveness and budget impact analysis.
Objective
The objective of this evidence-based review is to determine the effectiveness of a multidisciplinary wound care team for the management of chronic wounds.
Clinical Need: Condition and Target Population
Chronic wounds develop from various aetiologies including pressure, diabetes, venous pathology, and surgery. A pressure ulcer is defined as a localized injury to the skin/and or underlying tissue occurring most often over a bony prominence and caused, alone or in combination, by pressure, shear, or friction. Up to three fifths of venous leg ulcers are due to venous aetiology.
Approximately 1.5 million Ontarians will sustain a pressure ulcer, 111,000 will develop a diabetic foot ulcer, and between 80,000 and 130,000 will develop a venous leg ulcer. Up to 65% of those afflicted by chronic leg ulcers report experiencing decreased quality of life, restricted mobility, anxiety, depression, and/or severe or continuous pain.
Multidisciplinary Wound Care Teams
The term ‘multidisciplinary’ refers to multiple disciplines on a team and ‘interdisciplinary’ to such a team functioning in a coordinated and collaborative manner. There is general consensus that a group of multidisciplinary professionals is necessary for optimum specialist management of chronic wounds stemming from all aetiologies. However, there is little evidence to guide the decision of which professionals might be needed form an optimal wound care team.
Evidence-Based Analysis Methods
Literature Search
A literature search was performed on July 7, 2009 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, Wiley Cochrane, Centre for Reviews and Dissemination/International Agency for Health Technology Assessment, and on July 13, 2009 using the Cumulative Index to Nursing & Allied Health Literature (CINAHL), and the International Agency for Health Technology Assessment (INAHTA) for studies pertaining to leg and foot ulcers. A similar literature search was conducted on July 29’ 2009 for studies pertaining to pressure ulcers. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Randomized controlled trials and Controlled clinical Trials (CCT)
Systematic review with meta analysis
Population includes persons with pressure ulcers (anywhere) and/or leg and foot ulcers
The intervention includes a multidisciplinary (two or more disciplines) wound care team.
The control group does not receive care by a wound care team
Studies published in the English language between 2004 and 2009
Exclusion Criteria
Single centre retrospective observational studies
Outcomes of Interest
Proportion of persons and/or wounds completely healed
Time to complete healing
Quality of Life
Pain assessment
Summary of Findings
Two studies met the inclusion and exclusion criteria, one a randomized controlled trial (RCT), the other a CCT using a before and after study design. There was variation in the setting, composition of the wound care team, outcome measures, and follow up periods between the studies. In both studies, however, the wound care team members received training in wound care management and followed a wound care management protocol.
In the RCT, Vu et al. reported a non-significant difference between the proportion of wounds healed in 6 months using a univariate analysis (61.7% for treatment vs. 52.5% for control; p=0.074, RR=1.19) There was also a non-significant difference in the mean time to healing in days (82 for treatment vs. 101 for control; p=0.095). More persons in the intervention group had a Brief Pain Inventory (BPI) score equal to zero (better pain control) at 6 months when compared with the control group (38.6% for intervention vs. 24.4% for control; p=0.017, RR=1.58). By multivariate analysis a statistically significant hazard ratio was reported in the intervention group (1.73, 95% CI 1.20-1.50; p=0.003).
In the CCT, Harrison et al. reported a statistically significant difference in healing rates between the pre (control) and post (intervention) phases of the study. Of patients in the pre phase, 23% had healed ulcers 3 months after study enrolment, whereas 56% were healed in the post phase (P<0.001, OR=4.17) (Figure 3). Furthermore, 27% of patients were treated daily or more often in the pre phase whereas only 6% were treated at this frequency in the post phase (P<0.001), equal to a 34% relative risk reduction in frequency of daily treatments. The authors did not report the results of pain relief assessment.
The body of evidence was assessed using the GRADE methodology for 4 outcomes: proportion of wounds healed, proportion of persons with healed wounds, wound associated pain relief, and proportion of persons needing daily wound treatments. In general, the evidence was found to be low to very low quality.
Conclusion
The evidence supports that managing chronic wounds with a multidisciplinary wound care team significantly increases wound healing and reduces the severity of wound-associated pain and the required daily wound treatments compared to persons not managed by a wound care team. The quality of evidence supporting these outcomes is low to very low meaning that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
PMCID: PMC3377537  PMID: 23074522
25.  The effectiveness of interventions in workplace health promotion as to maintain the working capacity of health care personal 
Background
The increasing proportion of elderly people with respective care requirements and within the total population stands against aging personnel and staff reduction in the field of health care where employees are exposed to high load factors. Health promotion interventions may be a possibility to improve work situations and behavior.
Methods
A systematic literature search is conducted in 32 databases limited to English and German publications since 1990. Moreover, internet-searches are performed and the reference lists of identified articles are scanned. The selection of literature was done by two reviewers independently according to inclusion and exclusion criteria. Data extraction and tables of evidence are verified by a second expert just like the assessment of risk of bias by means of the Cochrane Collaboration’s tool.
Results
We identified eleven intervention studies and two systematic reviews. There were three randomized controlled trials (RCT) and one controlled trial without randomization (CCT) on the improvement of physical health, four RCT and two CCT on the improvement of psychological health and one RCT on both. Study duration ranged from four weeks to two years and the number of participants included from 20 to 345, with a median of 56. Interventions and populations were predominantly heterogeneous. In three studies intervention for the improvement of physical health resulted in less complaints and increased strength and flexibility with statistically significant differences between groups. Regarding psychological health interventions lead to significantly decreased intake of analgesics, better stress management, coping with workload, communication skills and advanced training.
Discussion
Taking into consideration the small to very small sample sizes, other methodological flaws like a high potential of bias and poor quality of reporting the validity of the results has to be considered as limited. Due to the heterogeneity of health interventions, study populations with differing job specializations and different lengths of study durations and follow-up periods, the comparison of results would not make sense.
Conclusions
Further research is necessary with larger sample sizes, with a sufficient study duration and follow-up, with a lower risk of bias, by considering of relevant quality criteria and with better reporting in publications.
doi:10.3205/hta000097
PMCID: PMC3198117  PMID: 22031811
ability to work; absenteeism; academic review; accident; aged; behaviour-oriented; biomedical technology assessment; blinded; blinding; care; CCT; CT; clinical trial; condition-oriented; controlled clinical trials as topic; cost analysis; cost control; cost-effectiveness; cost reduction; cost-benefit analysis; cost-cutting; costs; costs and cost analysis; decision making; demographic development; demography; diagnosis; EBM; economic aspect; economics; economics, medical; effectiveness; efficacy; efficiency; ethics; evidence-based medicine; fitness for employment; fitness for work; Germany; health economic studies; health economics; health education; health policy; health promotion/*; Health Technology Assessment; HTA; HTA report; HTA-report; humans; judgment; juricical; medical assessment; medical costs; medical evaluation; mental health; meta analysis; meta analysis as topic; meta-analysis; methods; models, economic; nursing; nursing staff/*; nursing staff/psychology; nursing staff/standards; occupational health services; occupational health/*; orderlies; pathogenesis; peer review; pharmaeconomics; physical health; placebo; placebo effect; placebos; population development; prevention; primary prevention; random; random allocation; randomisation; randomised clinical study; randomised clinical trial; randomised controlled study; randomised controlled trial; randomised study; randomised trial; randomization; randomized clinical study; randomized clinical trial; randomized controlled study; randomized controlled trials as topic; randomized study; randomized trial; RCT; rehabilitation; report; research article; review; review literature; review literature as topic; rigths; risk assessment; risk of bias tool; salutogenesis; sensitivity; sickness costs; social economic factors; socioeconomic factors; socioeconomics; specifity; systematic review; technical report; technology; technology assessment; technology assessment, biomedical; technology evaluation; technology, medical; terms and condition of employment; therapy; treatment; Work Schedule Tolerance; workableness; working conditions; workload; workplace health promotion

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