Irbesartan in Marfan syndrome (AIMS): a double-blind, placebo-controlled randomised trial.

BACKGROUND: Irbesartan, a long acting selective angiotensin-1 receptor inhibitor, in Marfan syndrome might reduce aortic dilatation, which is associated with dissection and rupture. We aimed to determine the effects of irbesartan on the rate of aortic dilatation in children and adults with Marfan syndrome. METHODS: We did a placebo-controlled, double-blind randomised trial at 22 centres in the UK. Individuals aged 6-40 years with clinically confirmed Marfan syndrome were eligible for inclusion. Study participants were all given 75 mg open label irbesartan once daily, then randomly assigned to 150 mg of irbesartan (increased to 300 mg as tolerated) or matching placebo. Aortic diameter was measured by echocardiography at baseline and then annually. All images were analysed by a core laboratory blinded to treatment allocation. The primary endpoint was the rate of aortic root dilatation. This trial is registered with ISRCTN, number ISRCTN90011794. FINDINGS: Between March 14, 2012, and May 1, 2015, 192 participants were recruited and randomly assigned to irbesartan (n=104) or placebo (n=88), and all were followed for up to 5 years. Median age at recruitment was 18 years (IQR 12-28), 99 (52%) were female, mean blood pressure was 110/65 mm Hg (SDs 16 and 12), and 108 (56%) were taking ß blockers. Mean baseline aortic root diameter was 34·4 mm in the irbesartan group (SD 5·8) and placebo group (5·5). The mean rate of aortic root dilatation was 0·53 mm per year (95% CI 0·39 to 0·67) in the irbesartan group compared with 0·74 mm per year (0·60 to 0·89) in the placebo group, with a difference in means of -0·22 mm per year (-0·41 to -0·02, p=0·030). The rate of change in aortic Z score was also reduced by irbesartan (difference in means -0·10 per year, 95% CI -0·19 to -0·01, p=0·035). Irbesartan was well tolerated with no observed differences in rates of serious adverse events. INTERPRETATION: Irbesartan is associated with a reduction in the rate of aortic dilatation in children and young adults with Marfan syndrome and could reduce the incidence of aortic complications. FUNDING: British Heart Foundation, the UK Marfan Trust, the UK Marfan Association.

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden.

Early remote ischaemic preconditioning leads to sustained improvement in allograft function after live donor kidney transplantation: long-term outcomes in the REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) randomised trial.

BACKGROUND: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation. METHODS: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss. RESULTS: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]). CONCLUSIONS: RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia. CLINICAL TRIAL REGISTRATION: ISRCTN30083294.

Remote Ischemic Preconditioning and Outcomes of Cardiac Surgery.

BACKGROUND: Whether remote ischemic preconditioning (transient ischemia and reperfusion of the arm) can improve clinical outcomes in patients undergoing coronary-artery bypass graft (CABG) surgery is not known. We investigated this question in a randomized trial. METHODS: We conducted a multicenter, sham-controlled trial involving adults at increased surgical risk who were undergoing on-pump CABG (with or without valve surgery) with blood cardioplegia. After anesthesia induction and before surgical incision, patients were randomly assigned to remote ischemic preconditioning (four 5-minute inflations and deflations of a standard blood-pressure cuff on the upper arm) or sham conditioning (control group). Anesthetic management and perioperative care were not standardized. The combined primary end point was death from cardiovascular causes, nonfatal myocardial infarction, coronary revascularization, or stroke, assessed 12 months after randomization. RESULTS: We enrolled a total of 1612 patients (811 in the control group and 801 in the ischemic-preconditioning group) at 30 cardiac surgery centers in the United Kingdom. There was no significant difference in the cumulative incidence of the primary end point at 12 months between the patients in the remote ischemic preconditioning group and those in the control group (212 patients [26.5%] and 225 patients [27.7%], respectively; hazard ratio with ischemic preconditioning, 0.95; 95% confidence interval, 0.79 to 1.15; P=0.58). Furthermore, there were no significant between-group differences in either adverse events or the secondary end points of perioperative myocardial injury (assessed on the basis of the area under the curve for the high-sensitivity assay of serum troponin T at 72 hours), inotrope score (calculated from the maximum dose of the individual inotropic agents administered in the first 3 days after surgery), acute kidney injury, duration of stay in the intensive care unit and hospital, distance on the 6-minute walk test, and quality of life. CONCLUSIONS: Remote ischemic preconditioning did not improve clinical outcomes in patients undergoing elective on-pump CABG with or without valve surgery. (Funded by the Efficacy and Mechanism Evaluation Program [a Medical Research Council and National Institute of Health Research partnership] and the British Heart Foundation; ERICCA ClinicalTrials.gov number, NCT01247545.).

Corruption practices in drug prescribing in Vietnam - an analysis based on qualitative interviews.

BACKGROUND: Results from a previous study showed that 40 to 60% of the price of off-patent medicines in Vietnam was typically spent to induce prescribers to use the medicines, and to persuade procurement officers within hospitals to buy them. In this article we examine how and why inducements were paid by the pharmaceutical industry to health care providers in Vietnam. METHODS: We use a theoretically informed analysis to understand pharmaceutical companies' account of giving inducements and prescribers' account of taking them, elicited through in-depth interviews. RESULTS: Analysis of the emergent concepts derived from our qualitative data led to viewing the constructs from the theoretical framework of opportunities; pressures; and rationalization within a hierarchy of systemic factors and individual factors. Economic survival pressures in an imperfectly competitive market reportedly encouraged pharmaceutical companies and prescribers to be linked financially. Although individual factors such as professional ethics and personal values influenced doctors' responses to corrupt practices, entrenched systemic issues, including lack of transparency, accountability, poor enforcement of legislation and prevalence of corruption emerged as important factors supporting corrupt practice or even making it very difficult for individuals to opt out of corrupt practices. CONCLUSIONS: Our theoretically informed analysis of inducements provides an in-depth understanding of an angle of corruption in Vietnam's health sector, showing the need for multifaceted strategies in the fight against corruption in the health sector. Remedial strategies need to address both systemic and individual factors including interventions to relieve dependencies for survival of health care services on the corrupt system.

Effect of remote ischaemic conditioning on clinical outcomes in patients presenting with an ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

The rationale and study design for the multicentre, randomized, controlled CONDI2/ERIC-PPCI study are discussed.

Evaluation of Models for Estimating Hydraulic Conductivity in Glacial Aquifers with NMR Logging.

Nuclear magnetic resonance (NMR) logging is a promising method for estimating hydraulic conductivity (K). During the past ∼60 years, NMR logging has been used for petroleum applications, and different models have been developed for deriving estimates of permeability. These models involve calibration parameters whose values were determined through decades of research on sandstones and carbonates. We assessed the use of five models to derive estimates of K in glacial aquifers from NMR logging data acquired in two wells at each of two field sites in central Wisconsin, USA. Measurements of K, obtained with a direct push permeameter (DPP), KDPP , were used to obtain the calibration parameters in the Schlumberger-Doll Research, Seevers, Timur-Coates, Kozeny-Godefroy, and sum-of-echoes (SOE) models so as to predict K from the NMR data; and were also used to assess the ability of the models to predict KDPP . We obtained four well-scale calibration parameter values for each model using the NMR and DPP measurements in each well; and one study-scale parameter value for each model by using all data. The SOE model achieved an agreement with KDPP that matched or exceeded that of the other models. The Timur-Coates estimates of K were found to be substantially different from KDPP . Although the well-scale parameter values for the Schlumberger-Doll, Seevers, and SOE models were found to vary by less than a factor of 2, more research is needed to confirm their general applicability so that site-specific calibration is not required to obtain accurate estimates of K from NMR logging data.

Smoking cessation support delivered via mobile phone text messaging (txt2stop): a single-blind, randomised trial.

BACKGROUND: Smoking cessation programmes delivered via mobile phone text messaging show increases in self-reported quitting in the short term. We assessed the effect of an automated smoking cessation programme delivered via mobile phone text messaging on continuous abstinence, which was biochemically verified at 6 months. METHODS: In this single-blind, randomised trial, undertaken in the UK, smokers willing to make a quit attempt were randomly allocated, using an independent telephone randomisation system, to a mobile phone text messaging smoking cessation programme (txt2stop), comprising motivational messages and behavioural-change support, or to a control group that received text messages unrelated to quitting. The system automatically generated intervention or control group texts according to the allocation. Outcome assessors were masked to treatment allocation. The primary outcome was self-reported continuous smoking abstinence, biochemically verified at 6 months. All analyses were by intention to treat. This study is registered, number ISRCTN 80978588. FINDINGS: We assessed 11,914 participants for eligibility. 5800 participants were randomised, of whom 2915 smokers were allocated to the txt2stop intervention and 2885 were allocated to the control group; eight were excluded because they were randomised more than once. Primary outcome data were available for 5524 (95%) participants. Biochemically verified continuous abstinence at 6 months was significantly increased in the txt2stop group (10·7% txt2stop vs 4·9% control, relative risk [RR] 2·20, 95% CI 1·80-2·68; p<0·0001). Similar results were obtained when participants that were lost to follow-up were treated as smokers (268 [9%] of 2911 txt2stop vs 124 [4%] of 2881 control [RR 2·14, 95% CI 1·74-2·63; p<0·0001]), and when they were excluded (268 [10%] of 2735 txt2stop vs 124 [4%] of 2789 control [2·20, 1·79-2·71; p<0·0001]). No significant heterogeneity was shown in any of the prespecified subgroups. INTERPRETATION: The txt2stop smoking cessation programme significantly improved smoking cessation rates at 6 months and should be considered for inclusion in smoking cessation services. FUNDING: UK Medical Research Council, Primary Care Research Networks.

Assessing the utility of remote sensing data to accurately estimate changes in groundwater storage.

Accurate and timely estimates of groundwater storage changes are critical to the sustainable management of aquifers worldwide, but are hindered by the lack of in-situ groundwater measurements in most regions. Hydrologic remote sensing measurements provide a potential pathway to quantify groundwater storage changes by closing the water balance, but the degree to which remote sensing data can accurately estimate groundwater storage changes is unclear. In this study, we quantified groundwater storage changes in California's Central Valley at two spatial scales for the period 2002 through 2020 using remote sensing data and an ensemble water balance method. To evaluate performance, we compared estimates of groundwater storage changes to three independent estimates: GRACE satellite data, groundwater wells and a groundwater flow model. Results suggest evapotranspiration has the highest uncertainty among water balance components, while precipitation has the lowest. We found that remote sensing-based groundwater storage estimates correlated well with independent estimates; annual trends during droughts fall within 15% of trends calculated using wells and groundwater models within the Central Valley. Remote sensing-based estimates also reliably estimated the long-term trend, seasonality, and rate of groundwater depletion during major drought events. Additionally, our study suggests that the proposed method estimate changes in groundwater at sub-annual latencies, which is not currently possible using other methods. The findings have implications for improving the understanding of aquifer dynamics and can inform regional water managers about the status of groundwater systems during droughts.

Two controlled trials to increase participant retention in a randomized controlled trial of mobile phone-based smoking cessation support in the United Kingdom.

BACKGROUND: Loss to follow-up of trial participants represents a threat to research validity. To date, interventions designed to increase participants' awareness of benefits to society of completing follow-up, and the impact of a telephone call from a senior female clinician and researcher requesting follow-up have not been evaluated robustly. PURPOSE: Trial 1 aimed to evaluate the effect on trial follow-up of written information regarding the benefits of participation to society. Trial 2 aimed to evaluate the effect on trial follow-up of a telephone call from a senior female clinician and researcher. METHODS: Two single-blind randomized controlled trials were nested within a larger trial, Txt2stop. In Trial 1, participants were allocated using minimization to receive a refrigerator magnet and a text message emphasizing the benefits to society of completing follow-up, or to a control group receiving a simple reminder regarding follow-up. In Trial 2, participants were randomly allocated to receive a telephone call from a senior female clinician and researcher, or to a control group receiving standard Txt2stop follow-up procedures. RESULTS: Trial 1: 33.5% (327 of 976) of the intervention group and 33.8% (329 of 974) of the control group returned the questionnaire within 26 weeks of randomization, risk ratio (RR) 0.99; 95% confidence interval (CI) 0.88-1.12. In all, 83.3% (813 of 976) of the intervention group and 82.2% (801 of/974) of the control group sent back the questionnaire within 30 weeks of randomization, RR 1.01; 95% CI 0.97, 1.05. Trial 2: 31% (20 of 65) of the intervention group and 32% (20 of 62) of the control group completed trial follow-up, RR 0.93; 95%CI 0.44, 1.98. CONCLUSIONS: In presence of other methods to increase follow-up neither experimental method (refrigerator magnet and text message emphasizing participation's benefits to society nor a telephone call from study's principal investigator) increased participant follow-up in the Txt2stop trial.

Assessment of NMR Logging for Estimating Hydraulic Conductivity in Glacial Aquifers.

Glacial aquifers are an important source of groundwater in the United States and require accurate characterization to make informed management decisions. One parameter that is crucial for understanding the movement of groundwater is hydraulic conductivity, K. Nuclear magnetic resonance (NMR) logging measures the NMR response associated with the water in geological materials. By utilizing an external magnetic field to manipulate the nuclear spins associated with 1 H, the time-varying decay of the nuclear magnetization is measured. This logging method could provide an effective way to estimate K at submeter vertical resolution, but the models that relate NMR measurements to K require calibration. At two field sites in a glacial aquifer in central Wisconsin, we collected a total of four NMR logs and obtained measurements of K in their immediate vicinity with a direct-push permeameter (DPP). Using a bootstrap algorithm to calibrate the Schlumberger-Doll Research (SDR) NMR-K model, we estimated K to within a factor of 5 of the DPP measurements. The lowest levels of accuracy occurred in the lower-K (K < 10-4  m/s) intervals. We also evaluated the applicability of prior SDR model calibrations. We found the NMR calibration parameters varied with K, suggesting the SDR model does not incorporate all the properties of the pore space that control K. Thus, the expected range of K in an aquifer may need to be considered during calibration of NMR-K models. This study is the first step toward establishing NMR logging as an effective method for estimating K in glacial aquifers.

Three controlled trials of interventions to increase recruitment to a randomized controlled trial of mobile phone based smoking cessation support.

BACKGROUND: Recruitment is a major challenge for trials but there is little evidence regarding interventions to increase trial recruitment. We report three controlled trials of interventions to increase recruitment to the Txt2stop trial. PURPOSE: To evaluate: Trial 1. The impact on registrations of a text message regarding an online registration facility; Trial 2. The impact on randomizations of sending pound5 with a covering letter to those eligible to join the trial; Trial 3. The impact on randomizations of text messages containing quotes from existing participants. METHODS: Single blind controlled trials with allocation concealment. INTERVENTIONS: Trial 1: A text message regarding our new online registration facility; Trial 2: A letter with pound5 enclosed; Trial 3: A series of four text messages containing quotes from participants. The control group in each trial received standard Txt2stop procedures. RESULTS: Trial 1: 3.6% (17/470) of the intervention group and 1.1% (5/467) of the control group registered for the trial, risk difference 2.5% (95% CI 0.6-4.5). 0% (0/ 470) of the intervention group and 0.2% (1/467) of the control group registered successfully online, risk difference -0.2 (95% CI -0.6-0.2); Trial 2: 4.5% (11/246) of the intervention group and 0.4% (1/245) of the control group were randomized into the Txt2stop trial, risk difference 4.0% (95% CI 1.4-6.7); Trial 3: 3.5% (14/405) of the intervention group and 0% (0/406) of the control group were randomized into the Txt2stop trial, risk difference 3.5 (95% CI 1.7-5.2). LIMITATIONS: There were no baseline data available for trial 1. Allocation of participant IDs in trials 2 and 3 were systematic. CONCLUSION: Sending a text message about an online registration facility increased registrations to Txt2stop, but did not increase online registrations. Sending a pound5 reimbursement for participants' time and sending text messages containing quotes from existing participants increased randomizations into the Txt2stop trial. Clinical Trials 2010; 7: 265-273. http://ctj.sagepub.com.

Safetxt: a safer sex intervention delivered by mobile phone messaging on sexually transmitted infections (STI) among young people in the UK - protocol for a randomised controlled trial.

INTRODUCTION: Young people aged 16 to 24 have the highest prevalence of genital chlamydia and gonorrhoea compared with other age groups and re-infection rates following treatment are high. Long-term adverse health effects include subfertility and ectopic pregnancy, particularly among those with repeated infections. We developed the safetxt intervention delivered by text message to reduce sexually transmitted infection (STI) by increasing partner notification, condom use and (STI) testing among young people in the UK. METHODS AND ANALYSIS: A single-blind randomised trial to reliably establish the effect of the safetxt intervention on chlamydia and gonorrhoea infection at 1 year. We will recruit 6250 people aged 16 to 24 years who have recently been diagnosed with chlamydia, gonorrhoea or non-specific urethritis from health services in the UK. Participants will be allocated to receive the safetxt intervention (text messages designed to promote safer sexual health behaviours) or to receive the control text messages (monthly messages asking participants about changes in contact details) by an automated remote online randomisation system. The primary outcome will be the cumulative incidence of chlamydia and gonorrhoea infection at 1 year assessed by nucleic acid amplification tests. Secondary outcomes include partner notification, correct treatment of infection, condom use and STI testing prior to sex with new partners. ETHICS AND DISSEMINATION: Ethics approval was obtained from NHS Health Research Authority - London - Riverside Research Ethics Committee (REC reference: 15/LO/1665) and the London School of Hygiene & Tropical Medicine. We will submit the results of the trial for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: International Standard Randomised Controlled Trials Number: ISRCTN64390461. Registered on 17th March 2016. WHO trial registration data set available at: http://apps.who.int/trialsearch/Trial2.aspx?TrialID=ISRCTN64390461. TRIAL PROTOCOL VERSION: 12, 19th July 2018.

Overpumping leads to California groundwater arsenic threat.

Water resources are being challenged to meet domestic, agricultural, and industrial needs. To complement finite surface water supplies that are being stressed by changes in precipitation and increased demand, groundwater is increasingly being used. Sustaining groundwater use requires considering both water quantity and quality. A unique challenge for groundwater use, as compared with surface water, is the presence of naturally occurring contaminants within aquifer sediments, which can enter the water supply. Here we find that recent groundwater pumping, observed through land subsidence, results in an increase in aquifer arsenic concentrations in the San Joaquin Valley of California. By comparison, historic groundwater pumping shows no link to current groundwater arsenic concentrations. Our results support the premise that arsenic can reside within pore water of clay strata within aquifers and is released due to overpumping. We provide a quantitative model for using subsidence as an indicator of arsenic concentrations correlated with groundwater pumping.

Mapping Aquifer Systems with Airborne Electromagnetics in the Central Valley of California.

The passage of the Sustainable Groundwater Management Act in California has highlighted a need for cost-effective ways to acquire the data used in building conceptual models of the aquifer systems in the Central Valley of California. One approach would be the regional implementation of the airborne electromagnetic (AEM) method. We acquired 104 line-kilometers of data in the Tulare Irrigation District, in the Central Valley, to determine the depth of investigation (DOI) of the AEM method, given the abundance of electrically conductive clays, and to assess the usefulness of the method for mapping the hydrostratigraphy. The data were high quality providing, through inversion of the data, models displaying the variation in electrical resistivity to a depth of approximately 500 m. In order to transform the resistivity models to interpreted sections displaying lithology, we established the relationship between resistivity and lithology using collocated lithology logs (from drillers' logs) and AEM data. We modeled the AEM response and employed a bootstrapping approach to solve for the range of values in the resistivity model corresponding to sand and gravel, mixed coarse and fine, and clay in the unsaturated and saturated regions. The comparison between the resulting interpretation and an existing cross section demonstrates that AEM can be an effective method for mapping the large-scale hydrostratigraphy of aquifer systems in the Central Valley. The methods employed and developed in this study have widespread application in the use of the AEM method for groundwater management in similar geologic settings.

Graduate capabilities for health service managers: reconfiguring health management education @UNSW.

The Master of Health Administration program at UNSW was extensively revised in 2006 to ensure that it effectively meets the challenging and dynamic environment of health service managers in local and global health contexts. This paper describes the innovative approach to the redesign of the health management program within the Faculty of Medicine. It outlines the method and considerations undertaken, particularly in identifying and embedding new graduate capabilities within the program. The paper concludes that using an outcomes-based approach and engaging with key stakeholders provides opportunity to identify and promote critical capabilities needed by managers to support the challenges confronting health services, including workforce flexibility. Further research is required on how such curriculum initiatives might impact on the performance of health service managers, but initial indications are that the health industry recognises the need and value of this approach.

Inflated medicine prices in Vietnam: a qualitative study.

One third of the world's population lacks regular access to essential medicines partly because of the high cost of medicines. In Vietnam, the cost to patients of medicines was 47 times the international reference price for originator brands and 11 times the price for generic equivalents in the public sector. In this article, we report the results of a qualitative study conducted to identify the principal reasons for inflated medicine prices in Vietnam.Between April 2008 and December 2009, 29 semi-structured interviews were conducted with staff from pharmaceutical companies, private pharmacies, the Ministry of Health, and the Ministry of Finance of Vietnam. Study participants were recruited using a combination of purposive and snowball sampling techniques. Interviews were recorded, transcribed and coded using NVivo8® software and analyzed using a framework of structure-conduct-performance (SCP).Participants attributed high prices of originator medicines to a monopoly of supply. The prices of generic medicines were also considered to be excessive, reportedly due to the need to recoup the cost of financial inducements paid to prescribers and procurement officers. These inducements constituted a dominant cost component of the end price of generic medicines. Poor market intelligence about current world prices, as well as failure to achieve economies of scale because of unwarranted duplication in pharmaceutical production and distribution system were also factors contributing to high prices. This was reported to be further compounded by multiple layers in the supply chain and unregulated retail mark-ups.To address these problems a multifaceted approach is needed encompassing policy and legislative responses. Policy options include establishing effective monitoring of medicine quality assurance, procurement, distribution and use. Rationalization of the domestic pharmaceutical production and distribution system to achieve economies of scale is also required. Appropriate legal responses include collaborations with the justice and law enforcement sectors to enforce existing laws.

A randomised controlled trial investigating the effect of n-3 long-chain polyunsaturated fatty acid supplementation on cognitive and retinal function in cognitively healthy older people: the Older People And n-3 Long-chain polyunsaturated fatty acids (OPAL) study protocol [ISRCTN72331636].

The number of individuals with age-related cognitive impairment is rising dramatically in the UK and globally. There is considerable interest in the general hypothesis that improving the diet of older people may slow the progression of cognitive decline. To date, there has been little attention given to the possible protective role of n-3 long-chain polyunsaturated fatty acids (n-3 LCPs) most commonly found in oily fish, in age-related loss of cognitive function. The main research hypothesis of this study is that an increased dietary intake of n-3 LCPs will have a positive effect on cognitive performance in older people in the UK. To test this hypothesis, a double-blind randomised placebo-controlled trial will be carried out among adults aged 70-79 years in which the intervention arm will receive daily capsules containing n-3 LCP (0.5 g/day docosahexaenoic acid and 0.2 g/day eicosapentaenoic acid) while the placebo arm will receive daily capsules containing olive oil. The main outcome variable assessed at 24 months will be cognitive performance and a second major outcome variable will be retinal function. Retinal function tests are included as the retina is a specifically differentiated neural tissue and therefore represents an accessible window into the functioning of the brain. The overall purpose of this public-health research is to help define a simple and effective dietary intervention aimed at maintaining cognitive and retinal function in later life. This will be the first trial of its kind aiming to slow the decline of cognitive and retinal function in older people by increasing daily dietary intake of n-3 LCPs. The link between cognitive ability, visual function and quality of life among older people suggests that this novel line of research may have considerable public health importance.

Characterizing Heterogeneity in Infiltration Rates During Managed Aquifer Recharge.

Infiltration rate is the key parameter that describes how water moves from the surface into a groundwater aquifer during managed aquifer recharge (MAR). Characterization of infiltration rate heterogeneity in space and time is valuable information for MAR system operation. In this study, we utilized fiber optic distributed temperature sensing (FO-DTS) observations and the phase shift of the diurnal temperature signal between two vertically co-located fiber optic cables to characterize infiltration rate spatially and temporally in a MAR basin. The FO-DTS measurements revealed spatial heterogeneity of infiltration rate: approximately 78% of the recharge water infiltrated through 50% of the pond bottom on average. We also introduced a metric for quantifying how the infiltration rate in a recharge pond changes over time, which enables FO-DTS to be used as a method for monitoring MAR and informing maintenance decisions. By monitoring this metric, we found high-spatial variability in how rapidly infiltration rate changed during the test period. We attributed this variability to biological pore clogging and found a relationship between high initial infiltration rate and the most rapid pore clogging. We found a strong relationship (R2 = 0.8) between observed maximum infiltration rates and electrical resistivity measurements from electrical resistivity tomography data taken in the same basin when dry. This result shows that the combined acquisition of DTS and ERT data can improve the design and operation of a MAR pond significantly by providing the critical information needed about spatial variability in parameters controlling infiltration rates.