query: The US health care system can save up to $5 billion if 7% of patients waiting for kidney transplants participate in the optimized national kidney paired donation program.

title: Kidney paired donation and optimizing the use of live donor organs.

text:
CONTEXT Blood type and crossmatch incompatibility will exclude at least one third of patients in need from receiving a live donor kidney transplant. Kidney paired donation (KPD) offers incompatible donor/recipient pairs the opportunity to match for compatible transplants. Despite its increasing popularity, very few transplants have resulted from KPD.
 OBJECTIVE To determine the potential impact of improved matching schemes on the number and quality of transplants achievable with KPD.
 DESIGN, SETTING, AND POPULATION We developed a model that simulates pools of incompatible donor/recipient pairs. We designed a mathematically verifiable optimized matching algorithm and compared it with the scheme currently used in some centers and regions. Simulated patients from the general community with characteristics drawn from distributions describing end-stage renal disease patients eligible for renal transplantation and their willing and eligible live donors.
 MAIN OUTCOME MEASURES Number of kidneys matched, HLA mismatch of matched kidneys, and number of grafts surviving 5 years after transplantation.
 RESULTS A national optimized matching algorithm would result in more transplants (47.7% vs 42.0%, P<.001), better HLA concordance (3.0 vs 4.5 mismatched antigens; P<.001), more grafts surviving at 5 years (34.9% vs 28.7%; P<.001), and a reduction in the number of pairs required to travel (2.9% vs 18.4%; P<.001) when compared with an extension of the currently used first-accept scheme to a national level. Furthermore, highly sensitized patients would benefit 6-fold from a national optimized scheme (2.3% vs 14.1% successfully matched; P<.001). Even if only 7% of patients awaiting kidney transplantation participated in an optimized national KPD program, the health care system could save as much as $750 million.
 CONCLUSIONS The combination of a national KPD program and a mathematically optimized matching algorithm yields more matches with lower HLA disparity. Optimized matching affords patients the flexibility of customizing their matching priorities and the security of knowing that the greatest number of high-quality matches will be found and distributed equitably.

title: Successful three-way kidney paired donation with cross-country live donor allograft transport.

text: Providing transplantation opportunities for patients with incompatible live donors through kidney paired donation (KPD) is seen as one of the important strategies for easing the crisis in organ availability. It has been estimated that an additional 1000-2000 transplants per year could be accomplished if a national KPD program were implemented in the United States. While most of these transplants could be arranged within the participants' local or regional area, patients with hard-to-match blood types or broad HLA sensitization would benefit from matching across larger geographic areas. In this case, either patients or organs would need to travel in order to obtain maximum benefit from a national program. In this study, we describe how a triple KPD enabled a highly sensitized patient (PRA 96%) to receive a well-matched kidney from a live donor on the opposite coast. The kidney was removed in San Francisco and transported to Baltimore where it was reperfused 8 h later. The patient had prompt function and 1 year later has a serum creatinine of 1.1 mg/dl. This case provides a blueprint for solving some of the complexities that are inherent in the implementation of a national KPD program in a large country like the United States.

title: Call to Develop a Standard Acquisition Charge Model for Kidney Paired Donation

text: We propose a Medicare Demonstration Project to develop a standard acquisition charge for kidney paired donation. A new payment strategy is required because Medicare and commercial insurance companies may not directly pay living donor costs intended to lead to transplantation of a beneficiary of a different insurance provider. Until the 1970s, when organ procurement organizations were empowered to serve as financial intermediaries to pay the upfront recovery expenses for deceased donor kidneys before knowing the identity of the recipient, there existed similar limitations in the recovery and placement of deceased donor organs. Analogous to the recovery of deceased donor kidneys, kidney paired donation requires the evaluation of living donors before identifying their recipient. Tissue typing, crossmatching and transportation of living donors or their kidneys represent additional financial barriers. Finally, the administrative expenses of the organizations that identify and coordinate kidney paired donation transplantation require reimbursement akin to that necessary for organ procurement organizations. To expand access to kidney paired donation for more patients, we propose a model to reimburse paired donation expenses analogous to the proven strategy used for over 30 years to pay for deceased donor solid organ transplantation in America.

title: Outcome of multipair donor kidney exchange by a web-based algorithm.

text: Donor kidney exchange is an established method to overcome incompatibility of donor-recipient pairs (DRP). A computerized algorithm was devised to exchange donor kidney and was tested in a multicenter setting. The algorithm was made according to the consensus of participating centers. It makes all possible exchange combinations not only between two incompatible DRP but also circularly among three DRP and selects an optimum set of exchange combinations, considering several factors that can affect the outcome of the exchanged transplant. The algorithm was implemented as a web-based program, and matching was performed five times. Fifty-three DRP were enrolled from five transplant centers. The numbers of DRP that were enrolled in each matching were 38 (25:13), 39 (34:5), 33 (31:2), 32 (28:4), and 34 (30:4) (carryover:newcomer). The numbers of generated exchange combinations were 4:11, 3:17, 2:12, 2:3, and 2:3 (two-pair exchange:three-pair exchange), and the numbers of DRP in selected exchange combinations were six, 12, six, five, and four in each matching. The numbers of DRP with blood type O recipient or AB donor were five and one, respectively, in selected exchange combinations. Six DRP of two-pair exchange combinations and six DRP of three-pair exchange combinations underwent transplantation successfully. Computerized algorithm of donor kidney exchange was tried not only between two incompatible DRP but also circularly among three DRP. It showed that the algorithm has potential to improve the outcome of donor kidney exchange, especially for disadvantaged DRP with blood type O recipients or AB donors.

title: Managing finances of shipping living donor kidneys for donor exchanges.

text: Kidney donor exchanges enable recipients with immunologically incompatible donors to receive compatible living donor grafts; however, the financial management of these exchanges, especially when an organ is shipped, is complex and thus has the potential to impede the broader implementation of donor exchange programs. Representatives from transplant centers that utilize the National Kidney Registry database to facilitate donor exchange transplants developed a financial model applicable to paired donor exchanges and donor chain transplants. The first tenet of the model is to eliminate financial liability to the donor. Thereafter, it accounts for the donor evaluation, donor nephrectomy hospital costs, donor nephrectomy physician fees, organ transport, donor complications and recipient inpatient services. Billing between hospitals is based on Medicare cost report defined costs rather than charges. We believe that this model complies with current federal regulations and effectively captures costs of the donor and recipient services. It could be considered as a financial paradigm for the United Network for Organ Sharing managed donor exchange program.

title: Towards an improved investment approach for an effective response to HIV/AIDS.

text: Substantial changes are needed to achieve a more targeted and strategic approach to investment in the response to the HIV/AIDS epidemic that will yield long-term dividends. Until now, advocacy for resources has been done on the basis of a commodity approach that encouraged scaling up of numerous strategies in parallel, irrespective of their relative effects. We propose a strategic investment framework that is intended to support better management of national and international HIV/AIDS responses than exists with the present system. Our framework incorporates major efficiency gains through community mobilisation, synergies between programme elements, and benefits of the extension of antiretroviral therapy for prevention of HIV transmission. It proposes three categories of investment, consisting of six basic programmatic activities, interventions that create an enabling environment to achieve maximum effectiveness, and programmatic efforts in other health and development sectors related to HIV/AIDS. The yearly cost of achievement of universal access to HIV prevention, treatment, care, and support by 2015 is estimated at no less than US$22 billion. Implementation of the new investment framework would avert 12·2 million new HIV infections and 7·4 million deaths from AIDS between 2011 and 2020 compared with continuation of present approaches, and result in 29·4 million life-years gained. The framework is cost effective at $1060 per life-year gained, and the additional investment proposed would be largely offset from savings in treatment costs alone.

title: Systemic arterial hypertension in children following renal transplantation: prevalence and risk factors.

text:
BACKGROUND Control of blood pressure (BP) following renal transplantation may improve allograft and patient survival. Our aims were (i) to describe the distribution of BP and the prevalence of systolic and/or diastolic hypertension in children over the first 5 years following renal transplantation and (ii) to evaluate clinical risk factors and centre-specific factors associated with hypertension in this population.
 METHODS We conducted a retrospective case note review of all current paediatric kidney transplant patients in the UK, with data collected at 6 months, 1, 2 and 5 years following transplantation in subjects with hypertension (systolic and/or diastolic BP > 95th > ) and non-hypertensive subjects BP ≤ 95th > .
 RESULTS In total, 27.3% (117/428), 27.6% (118/428), 26.0% (95/365) and 25.6% (50/195) of the patients were hypertensive (systolic and/or diastolic BP > 95th > ) at 6 months, 1, 2 and 5 years following transplantation, respectively. A total of 58.4% of the patients at 6 months, 52.8% at 1 year, 48.2% at 2 years and 48.2% at 5 years were receiving anti-hypertensive therapy, of whom 31.6-36.6% remained hypertensive. When subjects were identified as being hypertensive, on anti-hypertensive medication or had untreated hypertension (systolic and/or diastolic BP > 95th > ), 66.4, 61.0, 56.4 and 55.9% of patients were hypertensive at 6 months, 1, 2 and 5 years, respectively. In a multivariate model, odds ratios for systolic hypertension were 4.16 (deceased versus living donor), 2.65 (lowest versus highest quartile of height z-score) and 2.07 (if on anti-hypertensive; yes versus no). There was significant variation in prevalent rates of hypertension between centres (P < 0.0001) that remained significant (P = 0.003) after adjustment for all the factors in the multivariate model.
 CONCLUSIONS Control of BP after kidney transplantation remains sub-optimal in paediatric centres in the UK. Just over 25% of patients remain hypertensive 5 years following transplantation. Significant differences between centres remain unexplained and may reflect differences in assessment and management of hypertension.

title: The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

text:
OBJECTIVE To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system.
 DESIGN Systematic review and meta-analysis of randomised controlled trials.
 DATA SOURCES Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011.    STUDY SELECTION Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes.
 RESULTS 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89).
 CONCLUSION Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.

title: Renal Disease and Pregnancy

text: Pregnancy in women with different renal diseases has important consequences for the developing fetus and maternal health. Kidneys and the urinary tract have to adapt to the pregnancy status and therefore suffer significant anatomical, hemodynamic and endocrine changes. Failure to adapt can aggravate the preexisting maternal disease and can also create suboptimal environment for fetal development and increase the risk of obstetric complications. Knowledge and correct interpretation of the renal functional tests is necessary for the modern obstetrician, avoiding an incorrect diagnosis for renal disease where only specific renal changes during pregnancy are present, but meanwhile a correct evaluation of the renal function and changes can detect a pathology that can aggravate both the mother’s and the baby’s condition. Improvement and better understanding of the renal pathophysiology in pregnancy made possible that pregnant woman look forward for a good outcome, including here also the women with renal transplant. Nowadays is underlined the concept of multidisciplinary teamwork, a very important concept of modern medicine. The obstetrician should consider nephrologists as key players in the team and in our opinion should refer to them the pregnant women for a routine check-up of the renal status in the 2nd or beginning of 3rd trimester by ultrasound, beside the usual blood and urine analysis. The nephrologists and urologists should be involved in the management of severe medical conditions, such as preeclampsia, acute and chronic renal failure and never the less in the complex management of dialysis or renal transplant patients. In pregnancy it can be encountered several renal diseases, some of them preexisting the pregnancy and other developed or being direct influenced by pregnancy. This chapter will discuss briefly the basic evaluation of renal status in order to present and better understand the acute and chronic renal disorders in pregnancy. The chapter will focus on the most common preexisting diseases in pregnancy such as: chronic glomerulonephritis, secondary glomerular nephropathies, interstitial nephropathies (chronic pyelonephritis, renal tuberculosis), diabetes nephropathy, unique surgical kidney, chronic renal failure. From the renal diseases directly influenced by pregnancy it will be discussed: asymptomatic bacteriuria, symptomatic urinary infection, urolithiasis and acute renal failure in pregnancy. It will be presented also the management of dialysis in pregnancy and pregnant women with renal transplant.

title: Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost?

text: Maternal undernutrition contributes to 800,000 neonatal deaths annually through small for gestational age births; stunting, wasting, and micronutrient deficiencies are estimated to underlie nearly 3·1 million child deaths annually. Progress has been made with many interventions implemented at scale and the evidence for effectiveness of nutrition interventions and delivery strategies has grown since The Lancet Series on Maternal and Child Undernutrition in 2008. We did a comprehensive update of interventions to address undernutrition and micronutrient deficiencies in women and children and used standard methods to assess emerging new evidence for delivery platforms. We modelled the effect on lives saved and cost of these interventions in the 34 countries that have 90% of the world's children with stunted growth. We also examined the effect of various delivery platforms and delivery options using community health workers to engage poor populations and promote behaviour change, access and uptake of interventions. Our analysis suggests the current total of deaths in children younger than 5 years can be reduced by 15% if populations can access ten evidence-based nutrition interventions at 90% coverage. Additionally, access to and uptake of iodised salt can alleviate iodine deficiency and improve health outcomes. Accelerated gains are possible and about a fifth of the existing burden of stunting can be averted using these approaches, if access is improved in this way. The estimated total additional annual cost involved for scaling up access to these ten direct nutrition interventions in the 34 focus countries is Int$9·6 billion per year. Continued investments in nutrition-specific interventions to avert maternal and child undernutrition and micronutrient deficiencies through community engagement and delivery strategies that can reach poor segments of the population at greatest risk can make a great difference. If this improved access is linked to nutrition-sensitive approaches--ie, women's empowerment, agriculture, food systems, education, employment, social protection, and safety nets--they can greatly accelerate progress in countries with the highest burden of maternal and child undernutrition and mortality.

title: Liver transplantation and opioid dependence.

text: ContextChronic hepatitis C is the leading cause for liver transplantation in the United States. Intravenous drug use, the major risk factor, accounts for approximately 60% of hepatitis C virus transmission. Information from the United Network of Organ Sharing (UNOS) does not address substance use among liver transplantation patients. ObjectiveTo identify addiction-related criteria for admission to the UNOS liver transplantation waiting list and posttransplantation problems experienced by patients who are prescribed maintenance methadone. Design, Setting, and ParticipantsMail survey of all 97 adult US liver transplantation programs (belonging to UNOS) in March 2000 with telephone follow-up conducted in May and June 2000.Main Outcome MeasuresPrograms' acceptance and management of patients with past or present substance use disorder. ResultsOf the 97 programs surveyed, 87 (90%) responded. All accept applicants with a history of alcoholism or other addictions, including heroin dependence. Eighty-eight percent of the responding programs require at least 6 months of abstinence from alcohol; 83% from illicit drugs. Ninety-four percent have addiction treatment requirements. Consultations from substance abuse specialists are obtained by 86%. Patients receiving methadone maintenance are accepted by 56% of the responding programs. Approximately 180 patients receiving methadone maintenance are reported to have undergone liver transplantation. ConclusionsMost liver transplantation programs have established policies for patients with substance use disorders. Opiate-dependent patients receiving opiate replacement therapy seem underrepresented in transplantation programs. Little anecdotal evidence for negative impact of opiate replacement therapy on liver transplantation outcome was found. Policies requiring discontinuation of methadone in 32% of all programs contradict the evidence base for efficacy of long-term replacement therapies and potentially result in relapse of previously stable patients.

title: Malaria eradication back on the table.

text: After a lapse of almost 40 years, malaria eradication is back on the global health agenda. Inspired by the Gates Malaria Forum in October 2007,1,2 key organizations are starting to debate the pros and cons of redefining eradication as an explicit goal of malaria control efforts. Attempts to eliminate malaria in southern Africa3 and Pacific Island states,4 and WHO’s Global Malaria Programme agenda and field manual for malaria elimination,5,6 foreshadow this movement towards another global attempt at eradication.     When marking 60 years of WHO’s commitment to fighting malaria, we must ask what has been achieved, but also what can we learn from the past. We now know so much more about the biology of parasite-host responses, the determinants of endemicity and transmission dynamics, the social, economic and cultural implications of malaria at household, community and national levels, and the demands made upon health systems in endemic countries. We do not yet know how to synthesize and integrate this knowledge to achieve elimination in different settings.     Regional malaria elimination campaigns were first conducted in the late 1940s, preparing the ground for the Global Malaria Eradication Program in 1955. This campaign succeeded in eliminating malaria from Europe, North America, the Caribbean and parts of Asia and South-Central America.7 But no major success occurred in sub-Saharan Africa, which accounts for 80% of today’s burden of malaria.8 When the aspiration of global eradication was abandoned in 1969, the main reasons for failure were technical challenges of executing the strategy especially in Africa.     The post-eradication era from 1969 to 1991 focused on technical issues, and research and development for new tools, leading to advances in drug and vaccine development, vector control and insecticide-treated nets. These decades also brought a better understanding of the social, economic and cultural dimensions of malaria. There was little global support provided specifically for malaria control in the newly independent states of Africa that were struggling to establish broad-based health systems and primary health care. By 1992, the combination of a worsening malaria situation and promising technical developments led to renewed global focus on malaria control.     The Roll Back Malaria initiative, launched by WHO in 1998, led to the Abuja Declaration in 2000, which defined progressive intervention coverage targets for control designed to eliminate malaria as a public health problem, while emphasizing that this could only be achieved through vastly strengthened local health systems.9 Increased resources through the Global Fund to Fight AIDS, Tuberculosis and Malaria, the World Bank’s Booster Program, the US President’s Malaria Initiative and many others has meant that this page is finally beginning to turn as intervention coverage is rising.10    It is against this background that we hear this call for elimination/eradication. The challenges remain formidable. We all know that elimination in Africa is not possible with current tools. But efforts must focus beyond simply developing better tools, to include how existing and future tools can be strategically combined for maximum synergistic effectiveness when integrated into different health and social systems prevailing in endemic areas. Aiming at elimination and eradication further implies the need for effective surveillance strategies to monitor progress (again a challenge for health systems). This in turn requires a better understanding of malaria transmission heterogeneity in a globalized world with rapidly changing dynamics in environment, climate, migration and transnational cooperation.     Maintaining long-term momentum in the face of success in regional elimination while waiting to achieve final eradication will be a major challenge. Shrinking the map by starting on the malaria margins with the “easy-to-eliminate” settings will boost morale initially but may bring marginal benefits to such areas at the expense of those where the burden of malaria is highest. Any strategic plan – and here we learn again from the past – needs to be a synchronous global effort, locally adapted in all endemic areas.     Although we lack sufficient knowledge, systems and tools to eradicate malaria today, we do have a window of political will and financial resources to refocus on the goal of effective control through universal coverage of appropriate interventions. The prerequisites for a successful start are: (i) a process of inclusive discourse to agree on global vision, goals and strategy; and (ii) a global plan for all endemic areas describing how, where and when we move from control towards elimination. What must distinguish the new era, especially in Africa, is a real rather than rhetorical emphasis on health systems. ■

title: Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study

text: Objectives To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design Prospective open cohort study. Setting General practices in England providing data for the QResearch database. Participants 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell's C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke.

title: Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care

text:
OBJECTIVE To assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones).
 DESIGN Open cohort study in primary care.
 SETTING 1243 practices contributing data to the QResearch database in England.
 PARTICIPANTS 469,688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015.    EXPOSURES Hypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination.
 MAIN OUTCOME MEASURES First recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders.
 RESULTS 21,308 (4.5%) and 32,533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10,000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94).
 CONCLUSIONS We have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs.

title: Prevalence, risk factors, and uptake of interventions for sexually transmitted infections in Britain: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal)

text:
BACKGROUND Population-based estimates of prevalence, risk distribution, and intervention uptake inform delivery of control programmes for sexually transmitted infections (STIs). We undertook the third National Survey of Sexual Attitudes and Lifestyles (Natsal-3) after implementation of national sexual health strategies, and describe the epidemiology of four STIs in Britain (England, Scotland, and Wales) and the uptake of interventions.
 METHODS Between Sept 6, 2010 and Aug 31, 2012 , we did a probability sample survey of 15,162 women and men aged 16-74 years in Britain. Participants were interviewed with computer-assisted face-to-face and self-completion questionnaires. Urine from a sample of participants aged 16-44 years who reported at least one sexual partner over the lifetime was tested for the presence of Chlamydia trachomatis, type-specific human papillomavirus (HPV), Neisseria gonorrhoeae, and HIV antibody. We describe age-specific and sex-specific prevalences of infection and intervention uptake, in relation to demographic and behavioural factors, and explore changes since Natsal-1 (1990-91) and Natsal-2 (1999-2001).
 FINDINGS Of 8047 eligible participants invited to provide a urine sample, 4828 (60%) agreed. We excluded 278 samples, leaving 4550 (94%) participants with STI test results. Chlamydia prevalence was 1·5% (95% CI 1·1-2·0) in women and 1·1% (0·7-1·6) in men. Prevalences in individuals aged 16-24 years were 3·1% (2·2-4·3) in women and 2·3% (1·5-3·4) in men. Area-level deprivation and higher numbers of partners, especially without use of condoms, were risk factors. However, 60·4% (45·5-73·7) of chlamydia in women and 43·3% (25·9-62·5) in men was in individuals who had had one partner in the past year. Among sexually active 16-24-year-olds, 54·2% (51·4-56·9) of women and 34·6% (31·8-37·4) of men reported testing for chlamydia in the past year, with testing higher in those with more partners. High-risk HPV was detected in 15·9% (14·4-17·5) of women, similar to in Natsal-2. Coverage of HPV catch-up vaccination was 61·5% (58·2-64·7). Prevalence of HPV types 16 and 18 in women aged 18-20 years was lower in Natsal-3 than Natsal-2 (5·8% [3·9-8·6] vs 11·3% [6·8-18·2]; age-adjusted odds ratio 0·44 [0·21-0·94]). Gonorrhoea (<0·1% prevalence in women and men) and HIV (0·1% prevalence in women and 0·2% in men) were uncommon and restricted to participants with recognised high-risk factors. Since Natsal-2, substantial increases were noted in attendance at sexual health clinics (from 6·7% to 21·4% in women and from 7·7% to 19·6% in men) and HIV testing (from 8·7% to 27·6% in women and from 9·2% to 16·9% in men) in the past 5 years.
 INTERPRETATION STIs were distributed heterogeneously, requiring general and infection-specific interventions. Increases in testing and attendance at sexual health clinics, especially in people at highest risk, are encouraging. However, STIs persist both in individuals accessing and those not accessing services. Our findings provide empirical evidence to inform future sexual health interventions and services.
 FUNDING Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.

title: A feasibility study for a randomised controlled trial of the Positive Reappraisal Coping Intervention, a novel supportive technique for recurrent miscarriage

text:
INTRODUCTION Recurrent miscarriage (RM) is diagnosed when a woman has had three or more miscarriages. Increased levels of distress and anxiety are common during the waiting period of any subsequent pregnancies, posing a significant threat to psychological well-being. However, only limited support and therapy are available for these women, and many are left to cope alone. The Positive Reappraisal Coping Intervention (PRCI) is a novel self-administered supportive technique which has been shown to be effective in patients awaiting the outcome of in vitro fertilisation treatment. The primary objective of this study is to assess the feasibility and effectiveness of the PRCI in improving quality of life in the difficult waiting period which women with previous RM endure before an ongoing pregnancy can be confirmed.
 METHODS AND ANALYSIS A randomised controlled trial (RCT) feasibility study will establish the viability of conducting a multicentre RCT to definitively test the effects of the PRCI on the psychological well-being of women who have experienced RM during the initial waiting period of a subsequent pregnancy. A second component consists of a qualitative process evaluation exploring the initial experience of pregnancy following repeated miscarriages. Participants (n=50) will be randomised into one of two groups. The PRCI intervention group will receive the PRCI card and weekly questionnaires to assess their psychological well-being during the waiting period of their new pregnancy. The non-intervention group will be asked to complete the same weekly questionnaires. The qualitative process analysis will employ semistructured interviews (n=20) to address relevant aspects of the study objectives.    ETHICS AND DISSEMINATION Ethics approval has been obtained from the National Research Ethics Service Committee South Central-Hampshire A. Participating centres have given National Health Service R&D approval. Study findings will be disseminated through peer reviewed journals, national and international conferences and lay user groups.
 TRIAL REGISTRATION NUMBER ISRCTN43571276. This study was registered with the ISRCTN 18/02/2014 following adoption onto the United Kingdom Clinical Research Network (UKCRN) portfolio. Recruitment of the first participant occurred 04/02/2014.

title: Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial.

text:
CONTEXT Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease.
 OBJECTIVE To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor.
 DESIGN, SETTING, AND PATIENTS One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed.
 INTERVENTION Patients were inoculated with marrow-derived autologous MSC (1-2 x 10(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 51 patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs.
 MAIN OUTCOME MEASURES The primary measure was 1-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events.
 RESULTS Patient and graft survival at 13 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-14.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-14.9%; P = .046) compared with 11 of 51 controls (21.6%; 95% CI, 10.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-15.1%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per 1.73 m(2) (95% CI, 0.4-11.9; P=.04) and those in the low-dose CNI of 10.0 mL/min per 1.73 m(2) (95% CI, 3.8-16.2; P=.002). Also, during the 1-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group (hazard ratio, 0.42; 95% CI, 0.20-0.85, P=.02)   CONCLUSION Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at 1 year.
 TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00658073.

title: The state of US health, 1990-2010: burden of diseases, injuries, and risk factors.

text:
IMPORTANCE Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy.
 OBJECTIVES To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries.
 DESIGN We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages.
 RESULTS US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th.
 CONCLUSIONS AND RELEVANCE From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.

title: Renal outcomes with different fixed-dose combination therapies in patients with hypertension at high risk for cardiovascular events (ACCOMPLISH): a prespecified secondary analysis of a randomised controlled trial.

text:
BACKGROUND The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial showed that initial antihypertensive therapy with benazepril plus amlodipine was superior to benazepril plus hydrochlorothiazide in reducing cardiovascular morbidity and mortality. We assessed the effects of these drug combinations on progression of chronic kidney disease.
 METHODS ACCOMPLISH was a double-blind, randomised trial undertaken in five countries (USA, Sweden, Norway, Denmark, and Finland). 11 506 patients with hypertension who were at high risk for cardiovascular events were randomly assigned via a central, telephone-based interactive voice response system in a 1:1 ratio to receive benazepril (20 mg) plus amlodipine (5 mg; n=5744) or benazepril (20 mg) plus hydrochlorothiazide (12.5 mg; n=5762), orally once daily. Drug doses were force-titrated for patients to attain recommended blood pressure goals. Progression of chronic kidney disease, a prespecified endpoint, was defined as doubling of serum creatinine concentration or end-stage renal disease (estimated glomerular filtration rate <15 mL/min/1.73 m(2) or need for dialysis). Analysis was by intention to treat (ITT). This trial is registered with ClinicalTrials.gov, number NCT00170950.
 FINDINGS The trial was terminated early (mean follow-up 2.9 years [SD 0.4]) because of superior efficacy of benazepril plus amlodipine compared with benazepril plus hydrochlorothiazide. At trial completion, vital status was not known for 143 (1%) patients who were lost to follow-up (benazepril plus amlodipine, n=70; benazepril plus hydrochlorothiazide, n=73). All randomised patients were included in the ITT analysis. There were 113 (2.0%) events of chronic kidney disease progression in the benazepril plus amlodipine group compared with 215 (3.7%) in the benazepril plus hydrochlorothiazide group (HR 0.52, 0.41-0.65, p<0.0001). The most frequent adverse event in patients with chronic kidney disease was peripheral oedema (benazepril plus amlodipine, 189 of 561, 33.7%; benazepril plus hydrochlorothiazide, 85 of 532, 16.0%). In patients with chronic kidney disease, angio-oedema was more frequent in the benazepril plus amlodipine group than in the benazepril plus hydrochlorothiazide group. In patients without chronic kidney disease, dizziness, hypokalaemia, and hypotension were more frequent in the benazepril plus hydrochlorothiazide group than in the benazepril plus amlodipine group.
 INTERPRETATION Initial antihypertensive treatment with benazepril plus amlodipine should be considered in preference to benazepril plus hydrochlorothiazide since it slows progression of nephropathy to a greater extent.
 FUNDING Novartis.

title: Unmet need for mental health care among U.S. children: variation by ethnicity and insurance status.

text:
OBJECTIVE Policy discussions regarding the mental health needs of children and adolescents emphasize a lack of use of mental health services among youth, but few national estimates are available. The authors use three national data sets and examine ethnic disparities in unmet need (defined as having a need for mental health evaluation but not using any services in a 1-year period) to provide such estimates.
 METHOD The authors conducted secondary data analyses in three nationally representative household surveys fielded in 1996-1998: the National Health Interview Survey, the National Survey of American Families, and the Community Tracking Survey. They determined rates of mental health service use by children and adolescents 3-17 years of age and differences by ethnicity and insurance status. Among the children defined as in need of mental health services, defined by an estimator of mental health problems (selected items from the Child Behavior Checklist), they examined the association of unmet need with ethnicity and insurance status.
 RESULTS In a 12-month period, 2%-3% of children 3-5 years old and 6%-9% of children and adolescents 6-17 years old used mental health services. Of children and adolescents 6-17 years old who were defined as needing mental health services, nearly 80% did not receive mental health care. Controlling for other factors, the authors determined that the rate of unmet need was greater among Latino than white children and among uninsured than publicly insured children.
 CONCLUSIONS These findings reveal that most children who need a mental health evaluation do not receive services and that Latinos and the uninsured have especially high rates of unmet need relative to other children. Rates of use of mental health services are extremely low among preschool children. Research clarifying the reasons for high rates of unmet need in specific groups can help inform policy and clinical programs.


query: The World Health Organization's (WHO) data collection process is biased downward by unequal selection of larger outbreaks.

title: Using Routine Surveillance Data to Estimate the Epidemic Potential of Emerging Zoonoses: Application to the Emergence of US Swine Origin Influenza A H3N2v Virus

text:
BACKGROUND Prior to emergence in human populations, zoonoses such as SARS cause occasional infections in human populations exposed to reservoir species. The risk of widespread epidemics in humans can be assessed by monitoring the reproduction number R (average number of persons infected by a human case). However, until now, estimating R required detailed outbreak investigations of human clusters, for which resources and expertise are not always available. Additionally, existing methods do not correct for important selection and under-ascertainment biases. Here, we present simple estimation methods that overcome many of these limitations.
 METHODS AND FINDINGS Our approach is based on a parsimonious mathematical model of disease transmission and only requires data collected through routine surveillance and standard case investigations. We apply it to assess the transmissibility of swine-origin influenza A H3N2v-M virus in the US, Nipah virus in Malaysia and Bangladesh, and also present a non-zoonotic example (cholera in the Dominican Republic). Estimation is based on two simple summary statistics, the proportion infected by the natural reservoir among detected cases (G) and among the subset of the first detected cases in each cluster (F). If detection of a case does not affect detection of other cases from the same cluster, we find that R can be estimated by 1-G; otherwise R can be estimated by 1-F when the case detection rate is low. In more general cases, bounds on R can still be derived.
 CONCLUSIONS We have developed a simple approach with limited data requirements that enables robust assessment of the risks posed by emerging zoonoses. We illustrate this by deriving transmissibility estimates for the H3N2v-M virus, an important step in evaluating the possible pandemic threat posed by this virus. Please see later in the article for the Editors' Summary.

title: The World Health Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for use in the general population.

text:
BACKGROUND A self-report screening scale of adult attention-deficit/hyperactivity disorder (ADHD), the World Health Organization (WHO) Adult ADHD Self-Report Scale (ASRS) was developed in conjunction with revision of the WHO Composite International Diagnostic Interview (CIDI). The current report presents data on concordance of the ASRS and of a short-form ASRS screener with blind clinical diagnoses in a community sample.
 METHOD The ASRS includes 18 questions about frequency of recent DSM-IV Criterion A symptoms of adult ADHD. The ASRS screener consists of six out of these 18 questions that were selected based on stepwise logistic regression to optimize concordance with the clinical classification. ASRS responses were compared to blind clinical ratings of DSM-IV adult ADHD in a sample of 154 respondents who previously participated in the US National Comorbidity Survey Replication (NCS-R), oversampling those who reported childhood ADHD and adult persistence.
 RESULTS Each ASRS symptom measure was significantly related to the comparable clinical symptom rating, but varied substantially in concordance (Cohen's kappa in the range 0.16-0.81). Optimal scoring to predict clinical syndrome classifications was to sum unweighted dichotomous responses across all 18 ASRS questions. However, because of the wide variation in symptom-level concordance, the unweighted six-question ASRS screener outperformed the unweighted 18-question ASRS in sensitivity (68.7% v. 56.3%), specificity (99.5% v. 98.3%), total classification accuracy (97.9% v. 96.2%), and kappa (0.76 v. 0.58).
 CONCLUSIONS Clinical calibration in larger samples might show that a weighted version of the 18-question ASRS outperforms the six-question ASRS screener. Until that time, however, the unweighted screener should be preferred to the full ASRS, both in community surveys and in clinical outreach and case-finding initiatives.

title: Adapting the WHO package of essential noncommunicable disease interventions, Samoa

text: Problem Samoa has been struggling to address the burden of noncommunicable diseases at the health system, community and individual levels.    Approach The World Health Organization (WHO) package of essential noncommunicable disease interventions for primary health care in low-resource settings was adopted in seven villages throughout Samoa in 2015. The National Steering Committee Members designed and implemented a screening process, and local facilitators and health-care workers collected health and lifestyle data. The WHO/International Society of Hypertension risk assessment was used on villagers older than 40 years to identify people at high risk of noncommunicable disease.    Local setting Samoa is a small island developing state with increasing morbidity and mortality due to noncommunicable diseases. A national representative survey indicated that 50.1% (595/1188) of the Samoan adult population is at high risk of such diseases. High numbers of noncommunicable diseases are undiagnosed or untreated, because of shortage of health-care staff and lack of awareness of risk factors.    Relevant changes The teams collected data from 2234 adults. For people older than 40 years, 6.7% (54/804) were identified as being at high-risk and were encouraged to seek treatment or manage risk factors. Community members developed an awareness programme to improve understanding of lifestyle risk factors.    Lessons learnt Engaging community members was crucial in conducting a successful screening campaign. By identifying those villagers at high risk of developing noncommunicable diseases, early intervention was possible. Education improved awareness of the symptom-free nature of early-stage noncommunicable diseases.

title: Surveillance for foodborne-disease outbreaks--United States, 1993-1997.

text:
PROBLEM/CONDITION Since 1973, CDC has maintained a collaborative surveillance program for collection and periodic reporting of data on the occurrence and causes of foodborne-disease outbreaks (FBDOs) in the United States.    REPORTING PERIOD COVERED This summary reviews data from January 1993 through December 1997.    DESCRIPTION OF SYSTEM The Foodborne-Disease Outbreak Surveillance System reviews data concerning FBDOs, defined as the occurrence of two or more cases of a similar illness resulting from the ingestion of a common food. State and local public health departments have primary responsibility for identifying and investigating FBDOs. State, local, and territorial health departments use a standard form to report these outbreaks to CDC.
 RESULTS During 1993-1997, a total of 2,751 outbreaks of foodborne disease were reported (489 in 1993, 653 in 1994, 628 in 1995, 477 in 1996, and 504 in 1997). These outbreaks caused a reported 86,058 persons to become ill. Among outbreaks for which the etiology was determined, bacterial pathogens caused the largest percentage of outbreaks (75%) and the largest percentage of cases (86%). Salmonella serotype Enteritidis accounted for the largest number of outbreaks, cases, and deaths; most of these outbreaks were attributed to eating eggs. Chemical agents caused 17% of outbreaks and 1% of cases; viruses, 6% of outbreaks and 8% of cases; and parasites, 2% of outbreaks and 5% of cases.
 INTERPRETATION The annual number of FBDOs reported to CDC did not change substantially during this period or from previous years. During this reporting period, S. Enteritidis continued to be a major cause of illness and death. In addition, multistate outbreaks caused by contaminated produce and outbreaks caused by Escherichia coli O157:H7 remained prominent.    ACTIONS TAKEN Current methods to detect FBDOs are improving, and several changes to improve the ease and timeliness of reporting FBDO data are occurring (e.g., a revised form to simplify FBDO reporting by state health departments and electronic reporting methods). State and local health departments continue to investigate and report FBDOs as part of efforts to better understand and define the epidemiology of foodborne disease in the United States. At the regional and national levels, surveillance data provide an indication of the etiologic agents, vehicles of transmission, and contributing factors associated with FBDOs and help direct public health actions to reduce illness and death caused by FBDOs.

title: Home birth and barriers to referring women with obstetric complications to hospitals: a mixed-methods study in Zahedan, southeastern Iran

text:
BACKGROUND One factor that contributes to high maternal mortality in developing countries is the delayed use of Emergency Obstetric-Care (EmOC) facilities. The objective of this study was to determine the factors that hinder midwives and parturient women from using hospitals when complications occur during home birth in Sistan and Baluchestan province, Iran, where 23% of all deliveries take place in non- hospital settings.
 METHODS In the study and data management, a mixed-methods approach was used. In the quantitative phase, we compared the existing health-sector data with World Health Organization (WHO) standards for the availability and use of EmOC services. The qualitative phase included collection and analysis of interviews with midwives and traditional birth attendants and twenty-one in-depth interviews with mothers. The data collected in this phase were managed according to the principles of qualitative data analysis.
 RESULTS The findings demonstrate that three distinct factors lead to indecisiveness and delay in the use of EmOC by the midwives and mothers studied. Socio-cultural and familial reasons compel some women to choose to give birth at home and to hesitate seeking professional emergency care for delivery complications. Apprehension about being insulted by physicians, the necessity of protecting their professional integrity in front of patients and an inability to persuade their patients lead to an over-insistence by midwives on completing deliveries at the mothers' homes and a reluctance to refer their patients to hospitals. The low quality and expense of EmOC and the mothers' lack of health insurance also contribute to delays in referral.
 CONCLUSIONS Women who choose to give birth at home accept the risk that complications may arise. Training midwives and persuading mothers and significant others who make decisions about the value of referring women to hospitals at the onset of life-threatening complications are central factors to increasing the use of available hospitals. The hospitals must be safe, comfortable and attractive environments for parturition and should give appropriate consideration to the ethical and cultural concerns of the women. Appropriate management of financial and insurance-related issues can help midwives and mothers make a rational decision when complications arise.

title: Anthropometric reference data for international use: recommendations from a World Health Organization Expert Committee.

text: The World Health Organization (WHO) convened an Expert Committee to reevaluate the use of anthropometry at different ages for assessing health, nutrition, and social wellbeing. The Committee's task included identifying reference data for anthropometric indexes when appropriate, and providing guidelines on how the data should be used. For fetal growth, the Committee recommended an existing sex-specific multiracial reference. In view of the significant technical drawbacks of the current National Center for Health Statistics (NCHS)/WHO reference and its inadequacy for assessing the growth of breast-fed infants, the Committee recommended the development of a new reference concerning weight and length/height for infants and children, which will be a complex and costly undertaking. Proper interpretation of midupper arm circumference for preschoolers requires age-specific reference data. To evaluate adolescent height-for-age, the Committee recommended the current NCHS/WHO reference. Use of the NCHS body mass index (BMI) data, with their upper percentile elevations and skewness, is undesirable for setting health goals; however, these data were provisionally recommended for defining obesity based on a combination of elevated BMI and high subcutaneous fat. The NCHS values were provisionally recommended as reference data for subscapular and triceps skinfold thicknesses. Guidelines were also provided for adjusting adolescent anthropometric comparisons for maturational status. Currently, there is no need for adult reference data for BMI; interpretation should be based on pragmatic BMI cutoffs. Finally, the Committee noted that few normative anthropometric data exist for the elderly, especially for those > 80 y of age. Proper definitions of health status, function, and biologic age remain to be developed for this group.

title: The impact of COPD on lung health worldwide: epidemiology and incidence.

text: Information on the prevalence of COPD was obtained from vital statistics, health interview surveys, hospital charge records, national publications, and the World Health Organization (WHO). These data indicate that COPD is a common disease with implications for global health. In the United States, morbidity caused by COPD is 4%, making COPD the fourth leading cause of death, exceeded only by heart attacks, cancer, and stroke. Internationally, there is substantial variation in death rates possibly reflecting smoking behavior, type and processing of tobacco, pollution, climate, respiratory management, and genetic factors. The Global Obstructive Lung Disease Initiative, initiated by the National Heart, Lung, and Blood Institute and the WHO, aims to raise awareness of the increasing burden of COPD, decrease morbidity and mortality, promote further study of the condition, and implement programs to prevent COPD.

title: Prevalence, severity, and unmet need for treatment of mental disorders in the World Health Organization World Mental Health Surveys.

text:
CONTEXT Little is known about the extent or severity of untreated mental disorders, especially in less-developed countries.
 OBJECTIVE To estimate prevalence, severity, and treatment of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders in 14 countries (6 less developed, 8 developed) in the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative.
 DESIGN, SETTING, AND PARTICIPANTS Face-to-face household surveys of 60 463 community adults conducted from 2001-2003 in 14 countries in the Americas, Europe, the Middle East, Africa, and Asia.
 MAIN OUTCOME MEASURES The DSM-IV disorders, severity, and treatment were assessed with the WMH version of the WHO Composite International Diagnostic Interview (WMH-CIDI), a fully structured, lay-administered psychiatric diagnostic interview.
 RESULTS The prevalence of having any WMH-CIDI/DSM-IV disorder in the prior year varied widely, from 4.3% in Shanghai to 26.4% in the United States, with an interquartile range (IQR) of 9.1%-16.9%. Between 33.1% (Colombia) and 80.9% (Nigeria) of 12-month cases were mild (IQR, 40.2%-53.3%). Serious disorders were associated with substantial role disability. Although disorder severity was correlated with probability of treatment in almost all countries, 35.5% to 50.3% of serious cases in developed countries and 76.3% to 85.4% in less-developed countries received no treatment in the 12 months before the interview. Due to the high prevalence of mild and subthreshold cases, the number of those who received treatment far exceeds the number of untreated serious cases in every country.
 CONCLUSIONS Reallocation of treatment resources could substantially decrease the problem of unmet need for treatment of mental disorders among serious cases. Structural barriers exist to this reallocation. Careful consideration needs to be given to the value of treating some mild cases, especially those at risk for progressing to more serious disorders.

title: Socioeconomic factors, material inequalities, and perceived control in self-rated health: cross-sectional data from seven post-communist countries.

text: This study examined the association between perceived control and several socioeconomic variables and self-rated health in seven post-communist countries (Russia, Estonia, Lithuania, Latvia, Hungary, Poland, Czech Republic). Questionnaire interviews were used to collect data on self-rated health in the last 12 months, education, marital status, perceived control based on nine questions, and material deprivation based on availability of food, clothing and heating. For each population, two ecological measures of material inequalities were available: an inequality score estimated from the survey data as the distance between the 90th and 10th percentiles of material deprivation, and Gini coefficient from published sources. Data on 5330 men and women aged 20-60 were analysed. Prevalence of poor health (worse than average) varied between 8% in Czechs and 19% in Hungarians. The age-sex-adjusted odds ratio for university vs primary education was 0.36 (0.26-0.49); odds ratios per 1 standard deviation increase in perceived control and in material deprivation were 0.58 (95% CI 0.48-0.69) and 1.51 (1.40-1.63), respectively. The odds ratio for an increase in inequality equivalent to the difference between the most and the least unequal populations was 1.49 (0.88-2.52) using the material inequality score and 1.41 (0.91-2.20) using the Gini coefficient. No indication of an effect of either inequality measure was seen after adjustment for individuals' deprivation or perceived control. The results suggest that, as in western populations, education and material deprivation are strongly related to self-rated health. Perceived control appeared statistically to mediate some of the effects of material deprivation. The non-significant effects of both ecological measures of inequality were eliminated by controlling for individuals' characteristics.

title: Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS).

text: The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative longitudinal survey of persons in China 45 years of age or older and their spouses, including assessments of social, economic, and health circumstances of community-residents. CHARLS examines health and economic adjustments to rapid ageing of the population in China. The national baseline survey for the study was conducted between June 2011 and March 2012 and involved 17 708 respondents. CHARLS respondents are followed every 2 years, using a face-to-face computer-assisted personal interview (CAPI). Physical measurements are made at every 2-year follow-up, and blood sample collection is done once in every two follow-up periods. A pilot survey for CHARLS was conducted in two provinces of China in 2008, on 2685 individuals, who were resurveyed in 2012. To ensure the adoption of best practices and international comparability of results, CHARLS was harmonized with leading international research studies in the Health and Retirement Study (HRS) model. Requests for collaborations should be directed to Dr Yaohui Zhao (yhzhao@nsd.edu.cn). All data in CHARLS are maintained at the National School of Development of Peking University and will be accessible to researchers around the world at the study website. The 2008 pilot data for CHARLS are available at: http://charls.ccer.edu.cn/charls/. National baseline data for the study are expected to be released in January 2013.

title: Reforming the health sector in developing countries: the central role of policy analysis.

text: Policy analysis is an established discipline in the industrialized world, yet its application to developing countries has been limited. The health sector in particular appears to have been neglected. This is surprising because there is a well recognized crisis in health systems, and prescriptions abound of what health policy reforms countries should introduce. However, little attention has been paid to how countries should carry out reforms, much less who is likely to favour or resist such policies. This paper argues that much health policy wrongly focuses attention on the content of reform, and neglects the actors involved in policy reform (at the international, national sub-national levels), the processes contingent on developing and implementing change and the context within which policy is developed. Focus on policy content diverts attention from understanding the processes which explain why desired policy outcomes fail to emerge. The paper is organized in 4 sections. The first sets the scene, demonstrating how the shift from consensus to conflict in health policy established the need for a greater emphasis on policy analysis. The second section explores what is meant by policy analysis. The third investigates what other disciplines have written that help to develop a framework of analysis. And the final section suggests how policy analysis can be used not only to analyze the policy process, but also to plan.

title: Estimates of global prevalence of childhood underweight in 1990 and 2015.

text:
CONTEXT One key target of the United Nations Millennium Development goals is to reduce the prevalence of underweight among children younger than 5 years by half between 1990 and 2015.
 OBJECTIVE To estimate trends in childhood underweight by geographic regions of the world.
 DESIGN, SETTING, AND PARTICIPANTS Time series study of prevalence of underweight, defined as weight 2 SDs below the mean weight for age of the National Center for Health Statistics and World Health Organization (WHO) reference population. National prevalence rates derived from the WHO Global Database on Child Growth and Malnutrition, which includes data on approximately 31 million children younger than 5 years who participated in 419 national nutritional surveys in 139 countries from 1965 through 2002.
 MAIN OUTCOME MEASURES Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight children by region in 1990 and 2015 and to calculate the changes (ie, increase or decrease) to these values between 1990 and 2015.
 RESULTS Worldwide, underweight prevalence was projected to decline from 26.5% in 1990 to 17.6% in 2015, a change of -34% (95% confidence interval [CI], -43% to -23%). In developed countries, the prevalence was estimated to decrease from 1.6% to 0.9%, a change of -41% (95% CI, -92% to 343%). In developing regions, the prevalence was forecasted to decline from 30.2% to 19.3%, a change of -36% (95% CI, -45% to -26%). In Africa, the prevalence of underweight was forecasted to increase from 24.0% to 26.8%, a change of 12% (95% CI, 8%-16%). In Asia, the prevalence was estimated to decrease from 35.1% to 18.5%, a change of -47% (95% CI, -58% to -34%). Worldwide, the number of underweight children was projected to decline from 163.8 million in 1990 to 113.4 million in 2015, a change of -31% (95% CI, -40% to -20%). Numbers are projected to decrease in all subregions except the subregions of sub-Saharan, Eastern, Middle, and Western Africa, which are expected to experience substantial increases in the number of underweight children.
 CONCLUSIONS An overall improvement in the global situation is anticipated; however, neither the world as a whole, nor the developing regions, are expected to achieve the Millennium Development goals. This is largely due to the deteriorating situation in Africa where all subregions, except Northern Africa, are expected to fail to meet the goal.

title: Integration of mental health into primary healthcare in low-income countries: avoiding medicalization.

text: Since 2008 the World Health Organization (WHO), through its mental health Gap Action Programme, has attempted to revitalize efforts to integrate mental health into non-specialized (e.g. primary) healthcare. While this has led to renewed interest in this potential method of mental health service delivery, it has also prompted criticism. Some concerns raised are that it would contribute to the medicalization of social and psychological problems, and narrowly focus on primary care without sufficient attention given to strengthening other levels of the healthcare system, notably community-based care and care on district levels. This paper discusses seven elements that may be critical to preventing inadvertently contributing to increasing a narrow biomedical approach to mental healthcare when integrating mental health into non-specialized healthcare: (1) using task shifting approaches within a system of stepped care, (2) ensuring primary mental healthcare also includes brief psychotherapeutic interventions, (3) promote community-based recovery-oriented interventions for people with disabling chronic mental disorders, (4) conceptualizing training as a continuous process of strengthening clinical competencies through supervision, (5) engaging communities as partners in psychosocial interventions, (6) embedding shifts to primary mental healthcare within wider health policy reforms, and (7) promoting inter-sectoral approaches to address social determinants of mental health.

title: [New guidelines to evaluate the response to treatment in solid tumors].

text: Anticancer agents go through a process by which their antitumor activity, on the basis of the amount of tumor shrinkage they could generate, has been investigated. In the late 1970s, the International Union Against Cancer and the World Health Organization (WHO) introduced specific criteria for the codification of tumor response evaluation. In 1994, several organizations involved in clinical cancer research joined together to undertake the review of these response evaluation criteria on the basis of their experience and knowledge. After several years of intensive discussions, new guidelines are ready and will replace the previous WHO criteria. In parallel to this initiative, one of the participating groups developed a model by which response rates could be derived from unidimensional measurement of tumor lesions instead of the usual bidimensional approach. This new concept has been largely validated by the Response Evaluation Criteria in Solid Tumors (Recist) Group and integrated into the present guidelines. This special article provides some philosophic background to clarify the various purposes of response evaluation. It proposes a model by which a combined assessment of all existing lesions, characterized by target lesion (to be measured) and nontarget lesions, is used to extrapolate an overall response to treatment. Methods of assessing tumor lesions are better codified. All other aspects of response evaluation have been discussed, reviewed, and amended whenever suitable.

title: The HIV Treatment Gap: Estimates of the Financial Resources Needed versus Available for Scale-Up of Antiretroviral Therapy in 97 Countries from 2015 to 2020

text:
BACKGROUND The World Health Organization (WHO) released revised guidelines in 2015 recommending that all people living with HIV, regardless of CD4 count, initiate antiretroviral therapy (ART) upon diagnosis. However, few studies have projected the global resources needed for rapid scale-up of ART. Under the Health Policy Project, we conducted modeling analyses for 97 countries to estimate eligibility for and numbers on ART from 2015 to 2020, along with the facility-level financial resources required. We compared the estimated financial requirements to estimated funding available.
 METHODS AND FINDINGS Current coverage levels and future need for treatment were based on country-specific epidemiological and demographic data. Simulated annual numbers of individuals on treatment were derived from three scenarios: (1) continuation of countries' current policies of eligibility for ART, (2) universal adoption of aspects of the WHO 2013 eligibility guidelines, and (3) expanded eligibility as per the WHO 2015 guidelines and meeting the Joint United Nations Programme on HIV/AIDS "90-90-90" ART targets. We modeled uncertainty in the annual resource requirements for antiretroviral drugs, laboratory tests, and facility-level personnel and overhead. We estimate that 25.7 (95% CI 25.5, 26.0) million adults and 1.57 (95% CI 1.55, 1.60) million children could receive ART by 2020 if countries maintain current eligibility plans and increase coverage based on historical rates, which may be ambitious. If countries uniformly adopt aspects of the WHO 2013 guidelines, 26.5 (95% CI 26.0 27.0) million adults and 1.53 (95% CI 1.52, 1.55) million children could be on ART by 2020. Under the 90-90-90 scenario, 30.4 (95% CI 30.1, 30.7) million adults and 1.68 (95% CI 1.63, 1.73) million children could receive treatment by 2020. The facility-level financial resources needed for scaling up ART in these countries from 2015 to 2020 are estimated to be US$45.8 (95% CI 45.4, 46.2) billion under the current scenario, US$48.7 (95% CI 47.8, 49.6) billion under the WHO 2013 scenario, and US$52.5 (95% CI 51.4, 53.6) billion under the 90-90-90 scenario. After projecting recent external and domestic funding trends, the estimated 6-y financing gap ranges from US$19.8 billion to US$25.0 billion, depending on the costing scenario and the U.S. President's Emergency Plan for AIDS Relief contribution level, with the gap for ART commodities alone ranging from US$14.0 to US$16.8 billion. The study is limited by excluding above-facility and other costs essential to ART service delivery and by the availability and quality of country- and region-specific data.
 CONCLUSIONS The projected number of people receiving ART across three scenarios suggests that countries are unlikely to meet the 90-90-90 treatment target (81% of people living with HIV on ART by 2020) unless they adopt a test-and-offer approach and increase ART coverage. Our results suggest that future resource needs for ART scale-up are smaller than stated elsewhere but still significantly threaten the sustainability of the global HIV response without additional resource mobilization from domestic or innovative financing sources or efficiency gains. As the world moves towards adopting the WHO 2015 guidelines, advances in technology, including the introduction of lower-cost, highly effective antiretroviral regimens, whose value are assessed here, may prove to be "game changers" that allow more people to be on ART with the resources available.

title: A culture-independent sequence-based metagenomics approach to the investigation of an outbreak of Shiga-toxigenic Escherichia coli O104:H4.

text:
IMPORTANCE Identification of the bacterium responsible for an outbreak can aid in disease management. However, traditional culture-based diagnosis can be difficult, particularly if no specific diagnostic test is available for an outbreak strain.
 OBJECTIVE To explore the potential of metagenomics, which is the direct sequencing of DNA extracted from microbiologically complex samples, as an open-ended clinical discovery platform capable of identifying and characterizing bacterial strains from an outbreak without laboratory culture.
 DESIGN, SETTING, AND PATIENTS In a retrospective investigation, 45 samples were selected from fecal specimens obtained from patients with diarrhea during the 2011 outbreak of Shiga-toxigenic Escherichia coli (STEC) O104:H4 in Germany. Samples were subjected to high-throughput sequencing (August-September 2012), followed by a 3-phase analysis (November 2012-February 2013). In phase 1, a de novo assembly approach was developed to obtain a draft genome of the outbreak strain. In phase 2, the depth of coverage of the outbreak strain genome was determined in each sample. In phase 3, sequences from each sample were compared with sequences from known bacteria to identify pathogens other than the outbreak strain.
 MAIN OUTCOMES AND MEASURES The recovery of genome sequence data for the purposes of identification and characterization of the outbreak strain and other pathogens from fecal samples.
 RESULTS During phase 1, a draft genome of the STEC outbreak strain was obtained. During phase 2, the outbreak strain genome was recovered from 10 samples at greater than 10-fold coverage and from 26 samples at greater than 1-fold coverage. Sequences from the Shiga-toxin genes were detected in 27 of 40 STEC-positive samples (67%). In phase 3, sequences from Clostridium difficile, Campylobacter jejuni, Campylobacter concisus, and Salmonella enterica were recovered.
 CONCLUSIONS AND RELEVANCE These results suggest the potential of metagenomics as a culture-independent approach for the identification of bacterial pathogens during an outbreak of diarrheal disease. Challenges include improving diagnostic sensitivity, speeding up and simplifying workflows, and reducing costs.

title: The feasibility of malaria elimination in South Africa

text:
BACKGROUND Following the last major malaria epidemic in 2000, malaria incidence in South Africa has declined markedly. The decrease has been so emphatic that South Africa now meets the World Health Organization (WHO) threshold for malaria elimination. Given the Millennium Development Goal of reversing the spread of malaria by 2015, South Africa is being urged to adopt an elimination agenda. This study aimed to determine the appropriateness of implementing a malaria elimination programme in present day South Africa.
 METHODS An assessment of the progress made by South Africa in terms of implementing an integrated malaria control programme across the three malaria-endemic provinces was undertaken. Vector control and case management data were analysed from the period of 2000 until 2011.
 RESULTS Both malaria-related morbidity and mortality have decreased significantly across all three malaria-endemic provinces since 2000. The greatest decline was seen in KwaZulu-Natal where cases decreased from 42,276 in 2000 to 380 in 2010 and deaths dropped from 122 in 2000 to six in 2010. Although there has been a 49.2 % (8,553 vs 4,214) decrease in the malaria cases reported in Limpopo Province, currently it is the largest contributor to the malaria incidence in South Africa. Despite all three provinces reporting average insecticide spray coverage of over 80%, malaria incidence in both Mpumalanga and Limpopo remains above the elimination threshold. Locally transmitted case numbers have declined in all three malaria provinces but imported case numbers have been increasing. Knowledge gaps in vector distribution, insecticide resistance status and drug usage were also identified.
 CONCLUSIONS Malaria elimination in South Africa is a realistic possibility if certain criteria are met. Firstly, there must be continued support for the existing malaria control programmes to ensure the gains made are sustained. Secondly, cross border malaria control initiatives with neighbouring countries must be strongly encouraged and supported to reduce malaria in the region and the importation of malaria into South Africa. Thirdly, operational research, particularly on vector distribution and insecticide resistance status must be conducted as a matter of urgency, and finally, the surveillance systems must be refined to ensure the information required to inform an elimination agenda are routinely collected.

title: Malaria eradication back on the table.

title: The Burden of Trachoma in Ayod County of Southern Sudan

text:
BACKGROUND Blindness due to trachoma is avoidable through Surgery, Antibiotics, Facial hygiene and Environmental improvements (SAFE). Recent surveys have shown trachoma to be a serious cause of blindness in Southern Sudan. We conducted this survey in Ayod County of Jonglei State to estimate the need for intervention activities to eliminate blinding trachoma.
 METHODOLOGY AND FINDINGS A cross-sectional two-stage cluster random survey was conducted in November 2006. All residents of selected households were clinically assessed for trachoma using the World Health Organization (WHO) simplified grading scheme. A total of 2,335 people from 392 households were examined, of whom 1,107 were over 14 years of age. Prevalence of signs of active trachoma in children 1-9 years of age was: trachomatous inflammation follicular (TF) = 80.1% (95% confidence interval [CI], 73.9-86.3); trachomatous inflammation intense (TI) = 60.7% (95% CI, 54.6-66.8); and TF and/or TI (active trachoma) = 88.3% (95% CI, 83.7-92.9). Prevalence of trachomatous trichiasis (TT) was 14.6% (95% CI, 10.9-18.3) in adults over 14 years of age; 2.9% (95% CI, 0.4-5.3) in children 1-14 years of age; and 8.4% (95% CI, 5.5-11.3) overall. The prevalence of corneal opacity in persons over 14 years of age with TT was 6.4% (95% CI, 4.5-8.3). No statistically significant difference was observed in the prevalence of trachoma signs between genders. Trachoma affected almost all households surveyed: 384/392 (98.0%) had at least one person with active trachoma and 130 (33.2%) had at least one person with trichiasis.
 CONCLUSIONS Trachoma is an unnecessary public health problem in Ayod. The high prevalence of active trachoma and trichiasis confirms the severe burden of blinding trachoma found in other post-conflict areas of Southern Sudan. Based on WHO recommended thresholds, all aspects of the SAFE strategy are indicated to eliminate blinding trachoma in Ayod.

title: Validity of the World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener in a representative sample of health plan members.

text: The validity of the six-question World Health Organization Adult ADHD Self-Report Scale (ASRS) Screener was assessed in a sample of subscribers to a large health plan in the US. A convenience subsample of 668 subscribers was administered the ASRS Screener twice to assess test-retest reliability and then a third time in conjunction with a clinical interviewer for DSM-IV adult ADHD. The data were weighted to adjust for discrepancies between the sample and the population on socio-demographics and past medical claims. Internal consistency reliability of the continuous ASRS Screener was in the range 0.63-0.72 and test-retest reliability (Pearson correlations) in the range 0.58-0.77. A four-category version The ASRS Screener had strong concordance with clinician diagnoses, with an area under the receiver operating characteristic curve (AUC) of 0.90. The brevity and ability to discriminate DSM-IV cases from non-cases make the six-question ASRS Screener attractive for use both in community epidemiological surveys and in clinical outreach and case-finding initiatives.