Cost-effectiveness analysis of surgical masks, N95 masks compared to wearing no mask for the prevention of COVID-19 among health care workers: Evidence from the public health care setting in India.

BACKGROUND: Nonpharmacological interventions, such as personal protective equipment for example, surgical masks and respirators, and maintenance of hand hygiene along with COVID-19 vaccines have been recommended to reduce viral transmission in the community and health care settings. There is evidence from the literature that surgical and N95 masks may reduce the initial degree of exposure to the virus. A limited research that has studied the cost-effective analysis of surgical masks and N95 masks among health care workers in the prevention of COVID-19 in India. The objective of this study was to estimate the cost-effectiveness of N95 and surgical mask compared to wearing no mask in public hospital settings for preventing COVID-19 infection among Health care workers (HCWs) from the health care provider's perspective. METHODS: A deterministic baseline model, without any mask use, based on Eikenberry et al was used to form the foundation for parameter estimation and to estimate transmission rates among HCWs. Information on mask efficacy, including the overall filtering efficiency of a mask and clinical efficiency, in terms of either inward efficiency(ei) or outward efficiency(e0), was obtained from published literature. Hospitalized HCWs were assumed to be in one of the disease states i.e., mild, moderate, severe, or critical. A total of 10,000 HCWs was considered as representative of the size of a tertiary care institution HCW population. The utility values for the mild, moderate and severe model health states were sourced from the primary data collection on quality-of-life of HCWs COVID-19 survivors. The utility scores for mild, moderate, and severe COVID-19 conditions were 0.88, 0.738 and 0.58, respectively. The cost of treatment for mild sickness (6,500 INR per day), moderate sickness (10,000 INR per day), severe (require ICU facility without ventilation, 15,000 INR per day), and critical (require ICU facility with ventilation per day, 18,000 INR) per day as per government and private COVID-19 treatment costs and capping were considered. One way sensitivity analyses were performed to identify the model inputs which had the largest impact on model results. RESULTS: The use of N95 masks compared to using no mask is cost-saving of $1,454,632 (INR 0.106 billion) per 10,000 HCWs in a year. The use of N95 masks compared to using surgical masks is cost-saving of $63,919 (INR 0.005 billion) per 10,000 HCWs in a year. the use of surgical masks compared to using no mask is cost-saving of $1,390,713 (INR 0.102 billion) per 10,000 HCWs in a year. The uncertainty analysis showed that considering fixed transmission rate (1.7), adoption of mask efficiency as 20%, 50% and 80% reduces the cumulative relative mortality to 41%, 79% and 94% respectively. On considering ei = e0 (99%) for N95 and surgical mask with ei = e0 (90%) the cumulative relative mortality was reduced by 97% and the use of N95 masks compared to using surgical masks is cost-saving of $24,361 (INR 0.002 billion) per 10,000 HCWs in a year. DISCUSSION: Both considered interventions were dominant compared to no mask based on the model estimates. N95 masks were also dominant compared to surgical masks.

Cost-effectiveness analysis of typhoid vaccination in Lao PDR.

BACKGROUND: Typhoid vaccination has been shown to be an effective intervention to prevent enteric fever and is under consideration for inclusion in the national immunization program in Lao PDR. METHODS: A cost-utility analysis was performed using an age-structured static decision tree model to estimate the costs and health outcomes of introducing TCV. Vaccination strategies combined with five delivery approaches in different age groups compared to no vaccination were considered from the societal perspective, using the Gavi price of 1.5 USD per dose. The vaccination program was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of 1 GDP per capita for Lao PDR, equivalent to USD 2,535 in 2020. RESULTS: In the model, we estimated 172.2 cases of enteric fever, with 1.3 deaths and a total treatment cost of USD 7,244, based on a birth cohort of 164,662 births without TCV vaccination that was followed over their lifetime. To implement a TCV vaccination program over the lifetime horizon, the estimated cost of the vaccine and administration costs would be between USD 470,934 and USD 919,186. Implementation of the TCV vaccination program would prevent between 14 and 106 cases and 0.1 to 0.8 deaths. None of the vaccination programs appeared to be cost-effective. CONCLUSIONS: Inclusion of TCV in the national vaccination program in Lao PDR would only be cost-effective if the true typhoid incidence is 25-times higher than our current estimate.

How to model the impact of vaccines for policymaking when the characteristics are uncertain: A case study in Thailand prior to the vaccine rollout during the COVID-19 pandemic.

Thailand faced a dilemma of which groups to prioritise with a limited first tranche of COVID-19 vaccinations in early 2021, at a time when there was low incidence and low mortality in the country. A mathematical modelling analysis was performed to compare the potential short-term impact of allocating the available doses to either the high severity group (over 65-year-olds) or the high transmission group (aged 20-39). At the time of the analysis, there was uncertainty about the precise characteristics of the vaccines available, in terms of their potential impact on transmission and reductions to the severity of infection. As such, a range of vaccine characteristic scenarios, with differing levels of severity and transmission reductions were explored. Using the evidence available at the time regarding severity reduction of infection due to the vaccines, the model suggested that vaccinating high severity group should be the priority if reductions in deaths is the priority. Vaccinating this group was found to have a direct impact on reducing the number of deaths, while the incidence and hospitalisations remained unchanged. However, the model found that vaccinating the high transmission group with a vaccine with sufficiently high protection against infection (more than 70%) could provide enough herd effects to delay the expected epidemic peak, resulting in both case and death reductions in both target groups. The model explored a 12-month time horizon. These analyses helped to inform the vaccination strategy in Thailand throughout 2021 and can inform future modelling studies for policymaking when the characteristics of vaccines are uncertain.

Assessing the cost-effectiveness of COVID-19 vaccines in a low incidence and low mortality setting: the case of Thailand at start of the pandemic.

OBJECTIVE: This study aimed to assess the cost-effectiveness of COVID-19 vaccines, preferred COVID-19 vaccine profiles, and the preferred vaccination strategies in Thailand. METHODS: An age-structured transmission dynamic model was developed based on key local data to evaluate economic consequences, including cost and health outcome in terms of life-years (LYs) saved. We considered COVID-19 vaccines with different profiles and different vaccination strategies such as vaccinating elderly age groups (over 65s) or high-incidence groups, i.e. adults between 20 and 39 years old who have contributed to more than 60% of total COVID-19 cases in the country thus far. Analyses employed a societal perspective in a 1-year time horizon using a cost-effectiveness threshold of 160,000 THB per LY saved. Deterministic and probabilistic sensitivity analyses were performed to identify and characterize uncertainty in the model. RESULTS: COVID-19 vaccines that block infection combined with social distancing were cost-saving regardless of the target population compared to social distancing alone (with no vaccination). For vaccines that block infection, the preferred (cost-effective) strategy was to vaccinate the high incidence group. Meanwhile, COVID-19 vaccines that reduces severity (including hospitalization and mortality) were cost-effective when the elderly were vaccinated, while vaccinating the high-incidence group was not cost-effective with this vaccine type. Regardless of vaccine type, higher vaccination coverage, higher efficacy, and longer protection duration were always preferred. More so, vaccination with social distancing measures was always preferred to strategies without social distancing. Quarantine-related costs were a major cost component affecting the cost-effectiveness of COVID-19 vaccines. CONCLUSION: COVID-19 vaccines are good value for money even in a relatively low-incidence and low-mortality setting such as Thailand, if the appropriate groups are vaccinated. The preferred vaccination strategies depend on the type of vaccine efficacy. Social distancing measures should accompany a vaccination strategy.

Efficacy and Safety of Immunomodulators in Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Many immunomodulators have been studied in clinical trials for the treatment of coronavirus disease 2019 (COVID-19). However, data identifying the most effective and safest treatment are lacking. We conducted a systematic review and network meta-analysis to rank immunomodulators in the treatment of COVID-19 according to their efficacy and safety. METHODS: Published and peer-reviewed randomized controlled trials assessing the efficacy of immunomodulators in hospitalized patients with COVID-19 were searched up to June 30, 2021. Direct and network meta-analyses were applied to assess the outcomes. The probability of efficacy and safety was estimated, and the drugs were awarded a numerical ranking. RESULTS: Twenty-six studies were eligible. Compared with standard of care, dexamethasone and tocilizumab had significantly lower mortality rates with pooled risk ratios (RRs) of 0.91 (95% confidence interval [CI] 0.84-0.99) and 0.88 (95% CI 0.82-0.96), respectively. Meanwhile, the most effective corticosteroid, interleukin-6 antagonist, and Janus kinase (JAK) inhibitor were hydrocortisone, sarilumab, and ruxolitinib, respectively. However, when superimposed infection was considered, ruxolitinib was the best treatment followed by baricitinib. Moreover, methylprednisolone had the worst combined efficacy and safety among the examined treatments. CONCLUSIONS: Overall, immunomodulators were more effective than standard of care. Important differences exist among immunomodulators regarding both efficacy and safety in favor of ruxolitinib and baricitinib. Further well-conducted randomized controlled trials should focus on JAK inhibitors. Methylprednisolone use should be discouraged because of its poor efficacy and high risk of superimposed infection. TRIAL REGISTRATION: PROSPERO registration identifier CRD 42021257421.

Antimicrobial resistance detection in Southeast Asian hospitals is critically important from both patient and societal perspectives, but what is its cost?

Antimicrobial resistance (AMR) is a major threat to global health. Improving laboratory capacity for AMR detection is critically important for patient health outcomes and population level surveillance. We aimed to estimate the financial cost of setting up and running a microbiology laboratory for organism identification and antimicrobial susceptibility testing as part of an AMR surveillance programme. Financial costs for setting up and running a microbiology laboratory were estimated using a top-down approach based on resource and cost data obtained from three clinical laboratories in the Mahidol Oxford Tropical Medicine Research Unit network. Costs were calculated for twelve scenarios, considering three levels of automation, with equipment sourced from either of the two leading manufacturers, and at low and high specimen throughput. To inform the costs of detection of AMR in existing labs, the unit cost per specimen and per isolate were also calculated using a micro-costing approach. Establishing a laboratory with the capacity to process 10,000 specimens per year ranged from $254,000 to $660,000 while the cost for a laboratory processing 100,000 specimens ranged from $394,000 to $887,000. Excluding capital costs to set up the laboratory, the cost per specimen ranged from $22-31 (10,000 specimens) and $11-12 (100,000 specimens). The cost per isolate ranged from $215-304 (10,000 specimens) and $105-122 (100,000 specimens). This study provides a conservative estimate of the costs for setting up and running a microbiology laboratory for AMR surveillance from a healthcare provider perspective. In the absence of donor support, these costs may be prohibitive in many low- and middle- income country (LMIC) settings. With the increased focus on AMR detection and surveillance, the high laboratory costs highlight the need for more focus on developing cheaper and cost-effective equipment and reagents so that laboratories in LMICs have the potential to improve laboratory capacity and participate in AMR surveillance.

Implementation of field detection devices for antimalarial quality screening in Lao PDR-A cost-effectiveness analysis.

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducing such devices in post-market surveillance in pharmacies in Laos, conservatively focusing on their outcome in detecting SF artemisinin-based combination therapies (ACTs). We simulated the deployment of six portable screening devices: two handheld near-infrared [MicroPHAZIR RX, NIR-S-G1], two handheld Raman [Progeny, TruScan RM]; one portable mid-infrared [4500a FTIR] spectrometers, and single-use disposable paper analytical devices [PADs]. We considered two scenarios with high and low levels of SF ACTs. Different sampling strategies in which medicine inspectors would test 1, 2, or 3 sample(s) of each brand of ACT were evaluated. Costs of inspection including device procurement, inspector time, reagents, reference testing, and replacement with genuine ACTs were estimated. Outcomes were measured as disability adjusted life years (DALYs) and incremental cost-effectiveness ratios were estimated for each device compared with a baseline of visual inspections alone. In the scenario with high levels of SF ACTs, all devices were cost-effective with a 1-sample strategy. In the scenario of low levels of SF ACTs, only four devices (MicroPHAZIR RX, 4500a FTIR, NIR-S-G1, and PADs) were cost-effective with a 1-sample strategy. In the multi-way comparative analysis, in both scenarios the NIR-S-G1 testing 2 samples was the most cost-effective option. Routine inspection of ACT quality using portable screening devices is likely to be cost-effective in the Laos context. This work should encourage policy-makers or regulators to further investigate investment in portable screening devices to detect SF medicines and reduce their associated undesired health and economic burdens.

Evaluation of portable devices for medicine quality screening: Lessons learnt, recommendations for implementation, and future priorities.

Céline Caillet and co-authors discuss a Collection on use of portable devices for the evaluation of medicine quality and legitimacy.

Avoiding Trouble Ahead: Lessons Learned and Suggestions for Economic Evaluations of COVID-19 Vaccines.

With vaccines for coronavirus disease 2019 (COVID-19) being introduced in countries across the world, policy makers are facing many practical considerations about how best to implement a vaccination programme. The supply of vaccines is insufficient for the global population, so decisions must be made as to which groups are prioritised for any vaccination and when. Furthermore, the aims of vaccination programmes will differ between countries, with some prioritising economic benefits that could stem from the relaxation of non-pharmaceutical interventions and others seeking simply to reduce the number of COVID-19 cases or deaths. This paper aims to share the experiences and lessons learned from conducting economic evaluations in Singapore and Thailand on hypothetical COVID-19 vaccines to provide a basis for other countries to develop their own contextualised economic evaluations, with particular focus on the key uncertainties, technical challenges, and characteristics that modellers should consider in partnership with key stakeholders. Which vaccines, vaccination strategies, and policy responses are most economically beneficial remains uncertain. It is therefore important for all governments to conduct their own analyses to inform local policy responses to COVID-19, including the implementation of COVID-19 vaccines in both the short and the long run. It is essential that such studies are designed, and ideally conducted, before vaccines are introduced so that policy decisions and implementation procedures are not delayed.

Cost-effectiveness and budget impact analyses for the prioritisation of the four available rotavirus vaccines in the national immunisation programme in Thailand.

BACKGROUND: Rotavirus is a major cause of diarrhoea in children less than five years old in Thailand. Vaccination has been shown to be an effective intervention to prevent rotavirus infections but has yet to be enlisted in the national immunisation programme. This study aimed to assess the cost-utility of introducing rotavirus vaccines, taking all WHO-prequalified vaccines into consideration. METHODS: A cost-utility analysis was performed using a transmission dynamic model to estimate, from a societal perspective, the costs and outcomes of four WHO-prequalified rotavirus vaccines: Rotarix®, RotaTeq®, ROTAVAC® and ROTASIIL®. The model was used to simulate the impact of introducing the vaccines among children aged < 1 year and compare this with no rotavirus vaccination. The vaccination programme was considered to be cost-effective if the incremental cost-effectiveness ratio was less than a threshold of USD 5,110 per QALY gained. RESULTS: Overall, without the vaccine, the model predicted the average annual incidence of rotavirus to be 312,118 cases. With rotavirus vaccination at a coverage of more than 95%, the average number of rotavirus cases averted was estimated to be 144,299 per year. All rotavirus vaccines were cost-saving. ROTASIIL® was the most cost-saving option, followed by ROTAVAC®, Rotarix® and RotaTeq®, providing average cost-savings of USD 32, 31, 23 and 22 million per year, respectively, with 999 QALYs gained. All vaccines remained cost-saving with lower QALYs gained, even when ignoring indirect beneficial effects. The net saving to the healthcare system when implementing any one of these vaccines would be between USD 13 and 33 million per year. CONCLUSION: Rotavirus vaccines should be included in the national vaccination programme in Thailand. Implementing any one of these four WHO-prequalified vaccines would reduce government healthcare spending while yielding health benefits to the population.

Azithromycin and cefixime combination versus azithromycin alone for the out-patient treatment of clinically suspected or confirmed uncomplicated typhoid fever in South Asia: a randomised controlled trial protocol.

Background: Typhoid and paratyphoid fever (enteric fever) is a common cause of non-specific febrile infection in adults and children presenting to health care facilities in low resource settings such as the South Asia.  A 7-day course of a single oral antimicrobial such as ciprofloxacin, cefixime or azithromycin is commonly used for its treatment. Increasing antimicrobial resistance threatens the effectiveness of these treatment choices. We hypothesize that combined treatment with azithromycin (active mainly intracellularly) and cefixime (active mainly extracellularly) will be a better option for the treatment of typhoid fever in South Asia. Methods: This is a phase IV, international multi-centre, multi-country, comparative participant-and observer-blind, 1:1 randomised clinical trial. Patients with suspected uncomplicated typhoid fever will be randomised to one of the two interventions: Arm A: azithromycin 20mg/kg/day oral dose once daily (maximum 1gm/day) and cefixime 20mg/kg/day oral dose in two divided doses (maximum 400mg bd) for 7 days, Arm B: azithromycin 20mg/kg/day oral dose once daily (max 1gm/day) for 7 days AND cefixime-matched placebo for 7 days. We will recruit 1500 patients across sites in Bangladesh, India, Nepal and Pakistan. We will assess whether treatment outcomes are better with the combination after one week of treatment and at one- and three-months follow-up. Discussion: Combined treatment may limit the emergence of resistance if one of the components is active against resistant sub-populations not covered by the other antimicrobial's activity. If the combined treatment is better than the single antimicrobial treatment, this will be an important result for patients across South Asia and other typhoid endemic areas. Clinicaltrials.gov registration: NCT04349826 (16/04/2020).

Economic evaluation of rotavirus vaccination in children of Bhutan.

BACKGROUND: Diarrhoea remains one of the top ten causes of under-five child morbidity in Bhutan, and rotavirus is a significant cause of child diarrhoeal hospitalisations. This study sought to determine the health outcomes, cost-effectiveness, and budget and human resource implications of introducing rotavirus vaccines in the routine immunisation program to inform Bhutan's decision-making process. METHODS: We used UNIVAC model (version 1.3.41) to evaluate the cost-effectiveness of a rotavirus vaccination programme compared with no vaccination from a government perspective. We also projected the impact of rotavirus vaccination on human resources and budget. Acost-effectiveness threshold was determined to be 0.5 times the gross domestic product (GDP) per capita (equivalent to the United States dollar ($) 1,537) per Disability-Adjusted Life-Year (DALY) averted.One-way deterministic and probabilistic sensitivity analyses, and threshold analyses were performed to capture parameter uncertainties. RESULTS: In Bhutan, a rotavirus vaccination programme over 10 years (2020 to 2029) can avert between 104 and 115 DALYs, at an incremental cost ranging from $322,000 to $1,332,000. The incremental cost-effectiveness ratio (ICER) across four vaccination programmes compared to no vaccination scenario were $9,267, $11,606, $3,201, and $2,803 per DALY averted for ROTARIX, RotaTeq, ROTAVAC, and ROTASIIL, respectively. The net five-year budget impact of introducing a rotavirus vaccination programme ranged from $0.20 to $0.81 million. The rotavirus vaccination programme has a potential to reduce the workload of health care workers such as paediatricians, nurses, dieticians, and pharmacists; however, the programme would require an additional 1.93-2.88 full-time equivalent of health assistants. CONCLUSION: At the current cost-effectiveness threshold, routine rotavirus vaccination in Bhutan is unlikely to be cost-effective with any of the currently available vaccines. However, routine vaccination with ROTASIIL was under the cost-effectiveness threshold of one times the GDP per capita ($3,074). ROTASIIL and ROTAVAC would provide the best value for money in Bhutan.

Quantifying the economic cost of antibiotic resistance and the impact of related interventions: rapid methodological review, conceptual framework and recommendations for future studies.

BACKGROUND: Antibiotic resistance (ABR) poses a major threat to health and economic wellbeing worldwide. Reducing ABR will require government interventions to incentivise antibiotic development, prudent antibiotic use, infection control and deployment of partial substitutes such as rapid diagnostics and vaccines. The scale of such interventions needs to be calibrated to accurate and comprehensive estimates of the economic cost of ABR. METHODS: A conceptual framework for estimating costs attributable to ABR was developed based on previous literature highlighting methodological shortcomings in the field and additional deductive epidemiological and economic reasoning. The framework was supplemented by a rapid methodological review. RESULTS: The review identified 110 articles quantifying ABR costs. Most were based in high-income countries only (91/110), set in hospitals (95/110), used a healthcare provider or payer perspective (97/110), and used matched cohort approaches to compare costs of patients with antibiotic-resistant infections and antibiotic-susceptible infections (or no infection) (87/110). Better use of methods to correct biases and confounding when making this comparison is needed. Findings also need to be extended beyond their limitations in (1) time (projecting present costs into the future), (2) perspective (from the healthcare sector to entire societies and economies), (3) scope (from individuals to communities and ecosystems), and (4) space (from single sites to countries and the world). Analyses of the impact of interventions need to be extended to examine the impact of the intervention on ABR, rather than considering ABR as an exogeneous factor. CONCLUSIONS: Quantifying the economic cost of resistance will require greater rigour and innovation in the use of existing methods to design studies that accurately collect relevant outcomes and further research into new techniques for capturing broader economic outcomes.

The global impact and cost-effectiveness of a melioidosis vaccine.

BACKGROUND: Every year, 90,000 people may die from melioidosis. Vaccine candidates have not proceeded past animal studies, partly due to uncertainty around the potential market size. This study aims to estimate the potential impact, cost-effectiveness and market size for melioidosis vaccines. METHODS: Age-structured decision tree models with country-specific inputs were used to estimate net costs and health benefits of vaccination, with health measured in quality-adjusted life years (QALYs). Four target groups of people living in endemic regions were considered: (i) people aged over 45 years with chronic renal disease, (ii) people aged over 45 years with diabetes, (iii) people aged over 45 years with diabetes and/or chronic renal disease, (iv) everyone aged over 45 years. Melioidosis risk was estimated using Bayesian evidence synthesis of 12 observational studies. In the base case, vaccines were assumed to have 80% efficacy, to have 5-year mean protective duration and to cost USD10.20-338.20 per vaccine. RESULTS: Vaccination could be cost-effective (with incremental cost-effectiveness ratio below GDP per capita) in 61/83 countries/territories with local melioidosis transmission. In these 61 countries/territories, vaccination could avert 68,000 lost QALYs, 8300 cases and 4400 deaths per vaccinated age cohort, at an incremental cost of USD59.6 million. Strategy (ii) was optimal in most regions. The vaccine market may be worth USD268 million per year at its threshold cost-effective price in each country/territory. CONCLUSIONS: There is a viable melioidosis vaccine market, with cost-effective vaccine strategies in most countries/territories with local transmission.

Using machine learning to guide targeted and locally-tailored empiric antibiotic prescribing in a children's hospital in Cambodia.

Background: Early and appropriate empiric antibiotic treatment of patients suspected of having sepsis is associated with reduced mortality. The increasing prevalence of antimicrobial resistance reduces the efficacy of empiric therapy guidelines derived from population data. This problem is particularly severe for children in developing country settings. We hypothesized that by applying machine learning approaches to readily collect patient data, it would be possible to obtain individualized predictions for targeted empiric antibiotic choices. Methods and Findings: We analysed blood culture data collected from a 100-bed children's hospital in North-West Cambodia between February 2013 and January 2016. Clinical, demographic and living condition information was captured with 35 independent variables. Using these variables, we used a suite of machine learning algorithms to predict Gram stains and whether bacterial pathogens could be treated with common empiric antibiotic regimens: i) ampicillin and gentamicin; ii) ceftriaxone; iii) none of the above. 243 patients with bloodstream infections were available for analysis. We found that the random forest method had the best predictive performance overall as assessed by the area under the receiver operating characteristic curve (AUC). The random forest method gave an AUC of 0.80 (95%CI 0.66-0.94) for predicting susceptibility to ceftriaxone, 0.74 (0.59-0.89) for susceptibility to ampicillin and gentamicin, 0.85 (0.70-1.00) for susceptibility to neither, and 0.71 (0.57-0.86) for Gram stain result. Most important variables for predicting susceptibility were time from admission to blood culture, patient age, hospital versus community-acquired infection, and age-adjusted weight score. Conclusions: Applying machine learning algorithms to patient data that are readily available even in resource-limited hospital settings can provide highly informative predictions on antibiotic susceptibilities to guide appropriate empiric antibiotic therapy. When used as a decision support tool, such approaches have the potential to improve targeting of empiric therapy, patient outcomes and reduce the burden of antimicrobial resistance.

Why sensitive bacteria are resistant to hospital infection control.

Background: Large reductions in the incidence of antibiotic-resistant strains of Staphylococcus aureus and Clostridium difficile have been observed in response to multifaceted hospital-based interventions. Reductions in antibiotic-sensitive strains have been smaller or non-existent. It has been argued that since infection control measures, such as hand hygiene, should affect resistant and sensitive strains equally, observed changes must have largely resulted from other factors, including changes in antibiotic use. We used a mathematical model to test the validity of this reasoning. Methods: We developed a mechanistic model of resistant and sensitive strains in a hospital and its catchment area. We assumed the resistant strain had a competitive advantage in the hospital and the sensitive strain an advantage in the community. We simulated a hospital hand hygiene intervention that directly affected resistant and sensitive strains equally. The annual incidence rate ratio ( IRR) associated with the intervention was calculated for hospital- and community-acquired infections of both strains. Results: For the resistant strain, there were large reductions in hospital-acquired infections (0.1 ≤ IRR ≤ 0.6) and smaller reductions in community-acquired infections (0.2 ≤ IRR ≤  0.9). These reductions increased in line with increasing importance of nosocomial transmission of the strain. For the sensitive strain, reductions in hospital acquisitions were much smaller (0.6 ≤ IRR ≤ 0.9), while communityacquisitions could increase or decrease (0.9 ≤ IRR ≤ 1.2). The greater the importance of the community environment for the transmission of the sensitive strain, the smaller the reductions. Conclusions: Counter-intuitively, infection control interventions, including hand hygiene, can have strikingly discordant effects on resistant and sensitive strains even though they target them equally, following differences in their adaptation to hospital and community-based transmission. Observed lack of effectiveness of control measures for sensitive strains does not provide evidence that infection control interventions have been ineffective in reducing resistant strains.

Comparative efficacy of interventions to promote hand hygiene in hospital: systematic review and network meta-analysis.

OBJECTIVE: To evaluate the relative efficacy of the World Health Organization 2005 campaign (WHO-5) and other interventions to promote hand hygiene among healthcare workers in hospital settings and to summarize associated information on use of resources. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Medline, Embase, CINAHL, NHS Economic Evaluation Database, NHS Centre for Reviews and Dissemination, Cochrane Library, and the EPOC register (December 2009 to February 2014); studies selected by the same search terms in previous systematic reviews (1980-2009). REVIEW METHODS: Included studies were randomised controlled trials, non-randomised trials, controlled before-after trials, and interrupted time series studies implementing an intervention to improve compliance with hand hygiene among healthcare workers in hospital settings and measuring compliance or appropriate proxies that met predefined quality inclusion criteria. When studies had not used appropriate analytical methods, primary data were re-analysed. Random effects and network meta-analyses were performed on studies reporting directly observed compliance with hand hygiene when they were considered sufficiently homogeneous with regard to interventions and participants. Information on resources required for interventions was extracted and graded into three levels. RESULTS: Of 3639 studies retrieved, 41 met the inclusion criteria (six randomised controlled trials, 32 interrupted time series, one non-randomised trial, and two controlled before-after studies). Meta-analysis of two randomised controlled trials showed the addition of goal setting to WHO-5 was associated with improved compliance (pooled odds ratio 1.35, 95% confidence interval 1.04 to 1.76; I(2)=81%). Of 22 pairwise comparisons from interrupted time series, 18 showed stepwise increases in compliance with hand hygiene, and all but four showed a trend for increasing compliance after the intervention. Network meta-analysis indicated considerable uncertainty in the relative effectiveness of interventions, but nonetheless provided evidence that WHO-5 is effective and that compliance can be further improved by adding interventions including goal setting, reward incentives, and accountability. Nineteen studies reported clinical outcomes; data from these were consistent with clinically important reductions in rates of infection resulting from improved hand hygiene for some but not all important hospital pathogens. Reported costs of interventions ranged from $225 to $4669 (£146-£3035; €204-€4229) per 1000 bed days. CONCLUSION: Promotion of hand hygiene with WHO-5 is effective at increasing compliance in healthcare workers. Addition of goal setting, reward incentives, and accountability strategies can lead to further improvements. Reporting of resources required for such interventions remains inadequate.

Increasing incidence of hospital-acquired and healthcare-associated bacteremia in northeast Thailand: a multicenter surveillance study.

BACKGROUND: Little is known about the epidemiology of nosocomial bloodstream infections in public hospitals in developing countries. We evaluated trends in incidence of hospital-acquired bacteremia (HAB) and healthcare-associated bacteremia (HCAB) and associated mortality in a developing country using routinely available databases. METHODS: Information from the microbiology and hospital databases of 10 provincial hospitals in northeast Thailand was linked with the national death registry for 2004-2010. Bacteremia was considered hospital-acquired if detected after the first two days of hospital admission, and healthcare-associated if detected within two days of hospital admission with a prior inpatient episode in the preceding 30 days. RESULTS: A total of 3,424 patients out of 1,069,443 at risk developed HAB and 2,184 out of 119,286 at risk had HCAB. Of these 1,559 (45.5%) and 913 (41.8%) died within 30 days, respectively. Between 2004 and 2010, the incidence rate of HAB increased from 0.6 to 0.8 per 1,000 patient-days at risk (p<0.001), and the cumulative incidence of HCAB increased from 1.2 to 2.0 per 100 readmissions (p<0.001). The most common causes of HAB were Acinetobacter spp. (16.2%), Klebsiella pneumoniae (13.9%), and Staphylococcus aureus (13.9%), while those of HCAB were Escherichia coli (26.3%), S. aureus (14.0%), and K. pneumoniae (9.7%). There was an overall increase over time in the proportions of ESBL-producing E. coli causing HAB and HCAB. CONCLUSIONS: This study demonstrates a high and increasing incidence of HAB and HCAB in provincial hospitals in northeast Thailand, increasing proportions of ESBL-producing isolates, and very high associated mortality.

Long-term survival after intensive care unit discharge in Thailand: a retrospective study.

INTRODUCTION: Economic evaluations of interventions in the hospital setting often rely on the estimated long-term impact on patient survival. Estimates of mortality rates and long-term outcomes among patients discharged alive from the intensive care unit (ICU) are lacking from lower- and middle-income countries. This study aimed to assess the long-term survival and life expectancy (LE) amongst post-ICU patients in Thailand, a middle-income country. METHODS: In this retrospective cohort study, data from a regional tertiary hospital in northeast Thailand and the regional death registry were linked and used to assess patient survival time after ICU discharge. Adult ICU patients aged at least 15 years who had been discharged alive from an ICU between 1 January 2004 and 31 December 2005 were included in the study, and the death registry was used to determine deaths occurring in this cohort up to 31st December 2010. These data were used in conjunction with standard mortality life tables to estimate annual mortality and life expectancy. RESULTS: This analysis included 10,321 ICU patients. During ICU admission, 3,251 patients (31.5%) died. Of 7,070 patients discharged alive, 2,527 (35.7%) were known to have died within the five-year follow-up period, a mortality rate 2.5 times higher than that in the Thai general population (age and sex matched). The mean LE was estimated as 18.3 years compared with 25.2 years in the general population. CONCLUSIONS: Post-ICU patients experienced much higher rates of mortality than members of the general population over the five-year follow-up period, particularly in the first year after discharge. Further work assessing Health Related Quality of Life (HRQOL) in both post-ICU patients and in the general population in developing countries is needed.