Principal component analysis (PCA) is used for dimension reduction and data summary. However, principal components (PCs) cannot be easily interpreted. To interpret PCs, this study compares two methods to approximate PCs. One uses the PCA loadings to understand how input variables are projected to PCs. The other uses forward-stepwise regression to determine the proportions of PC variances explained by input variables.

Two data sets derived from the Canadian Health Measures Survey (CHMS) were used to test the concept of PC approximation: a spirometry subset with the measures from the first trial of spirometry; and, full data set that contained representative variables. Variables were centered and scaled. PCA were conducted with 282 and twenty-three variables respectively. PCs were approximated with two methods.

The first PC (PC1) could explain 12.1 percent and 50.3 percent of total variances in respective data sets. The leading variables explained 89.6 percent and 79.0 percent of the variances of PC1 in respective data sets. It required one and two variables to explain more than 80 percent of the variances of PC1, respectively. Measures related to physical development were the leading variables to approximate PC1 and lung function variables were leading to approximate PC2 in the full data set. The leading variable to approximate PC1 of the spirometry subset were forced expiratory volume (FEV) 0.5/forced vital capacity (FVC) (percent) and FEV1/FVC (percent).

Approximating PCs with input variables were highly feasible and helpful for the interpretation of PCs, especially for the first PCs. This method is also useful to identify major or unique sources of variances in data sets. The variables related to physical development are the variables related to the most variations in the full data set. The leading variable in the spirometry subset, FEV0.5/FVC (percent), is not well studied for its application in clinical use.

Equity is the core of primary care. The issue of equity in health has become urgent and China has attached increasing attention to it. With rapid economic development and great change of the policy on medical insurance, the pattern of equity in health has changed a lot. Reform of healthcare in Zhejiang province is at the forefront of China; studies on Zhejiang are of great significance to the whole country. This paper aims to measure the equity in health from the perspectives of health needs and health seeking behavior, and provides suggestions for decision making.

A household survey was conducted in August 2016. A sample of 1000 households, 2807 individuals in Zhejiang was obtained with the multi-stage stratified cluster sampling method. Descriptive analysis and Chi-square test were adopted in the analysis. The value of concentration index was used to measure the equity.

This study finds that the poor have more urgent health needs and poorer health situation compared with the rich. The utilization of outpatient services was almost equal, whilst the utilization of hospitalization was pro-rich (the rich use more).Individuals with employer-based medical insurance use more outpatient services than those with rural and urban medical insurance. Compared to the rich, there were more people in the poorer income groups who didn't use inpatient services due to financial difficulties.

The issue of equity in health has attracted broad attention in the world, and China is no exception. We measured and analyzed the equity of health needs and absent rate of health services. We find that the poor have more urgent health needs and high absent rate of inpatient services compared with the rich. Income level and medical insurance may well explain the equity of outpatient and inequity of hospitalization. In view of the pro-rich inequity of hospitalization, more financial protection should be provided for the poor.

Stereo-electroencephalography (SEEG) has been shown to be a valuable tool for the anatomo-electroclinic definition of the epileptogenic zone (EZ) in some patients with medically refractory epilepsy considered for surgery. In Spain, many of those patients are not offered this diagnostic procedure. The objective of our health technology assessment (HTA) report was to evaluate the effectiveness, safety and cost-effectiveness of SEEG to define the EZ in patients with refractory epilepsy considered for surgery compared to no SEEG intervention (i.e. remaining with further antiepileptic drugs).

We undertook a systematic review with meta-analyses on the effectiveness and safety of SEEG. A cost-effectiveness analysis was conducted using a Markov model which simulates the costs and health outcomes of individuals for a lifetime horizon from the perspective of the Spanish National Health Service (NHS). The effectiveness measure was quality-adjusted life years (QALYs). We ran extensive sensitivity analyses, including a probabilistic sensitivity analysis.

The EZ was found in 92 percent of patients who underwent SEEG, 72 percent were eligible for epilepsy surgery and 33 percent were free of seizures after surgery (47 percent of those who received surgery). Any complications related to insertion and monitoring of SEEG and the subsequent intervention occurred in 1.3 percent of patients. In the base case analysis, SEEG led to higher QALYs and healthcare costs with an estimated incremental cost-effectiveness ratio of EUR 10,368 (USD 12,217) per QALY. The sensitivity analyses showed that the results of the study were robust.

SEEG is a cost-effective technology in patients with refractory epilepsy considered for surgery when compared to no SEEG intervention.

The therapy using molecular-targeted (MTT) and monoclonal antibodies (MA) are examples of new therapeutic technologies in search of greater clinical effectiveness and reduction of adverse effects in the fight against frequent diseases. Generally, new technologies have a high cost impact on the health system. The objective of this study was to evaluate the financial impact generated by the use of MTT and MA therapies in the teaching Hospital de Clínicas, Porto Alegre, Brazil.

The first 60 higher monetary spending drug items of the last 12 months were analyzed. From them, drugs which fit in the categories under study, and have been regularly used, were identified. The monthly expenditures with each item were tabulated and compared with the total expenditures on drugs, in order to calculate the budgetary impact. The major groups of diseases treated with each agent were analyzed.

Two MTT agents (gefitinib and infliximab) and three MAs (rituximab, basiliximab and abciximab) were identified. The highest expenditure items, respectively, per year, were the oncological medicines rituximab (USD127,890) and gefitinib (USD96,923), followed by the immunosuppressive basiliximab (USD88,998) and the immunomodulatory infliximab (USD68,642), and the platelet aggregation inhibitor abciximab (USD47,886). These values corresponding to, respectively, 1.1 percent, 0.8 percent, 0.8 percent, 0.6 percent and 0.4 percent of total drug expenditure per year (USD11,866,124). Trastuzumab, bortezomib and imatinib were often used, but directly supplied by the public system, in a way that didn't impact the hospital budgetary management.

MTT and MA have an important impact on health budgets, and are mainly used to treat some types of cancer, cardiovascular disease and autoimmune disorders. These aspects should be considered in the management of drugs in hospitals of high complexity.

Health Technology Assessment (HTA) is important to the rational decision in healthcare systems. In Brazil, HTA is carried out by the national commission for the incorporation of technologies in the public system (Conitec), which issues reports with recommendations. This work aims to describe these recommendations and the factors influencing them.

A descriptive analysis was conducted on Conitec's reports of incorporation of medicines between 2012 and 2016. The medicines were classified according to the Anatomical Therapeutic Chemical system (ATC).

One hundred and twenty-eight reports were assessed. Most requests were issued by the pharmaceutical industry (n=72; 47 percent), followed by the Ministry of Health (n=63; 41 percent). More reports issued by the Ministry of Health had positive recommendations compared to manufacturers (n=22 vs. n=50; χ2=30.231, df=1, p<0.001). Other antivirals were the most common class with requisitions (n=16), followed by TNF-α inhibitors (n=14) and selective immunosuppressants (n=12). Other antivirals had the most positive recommendations (n=12; 75 percent), followed by TNF-α inhibitors (n=7; 50 percent) and selective immunosuppressants (n=7; 58 percent). The difference was significant (χ2=88.65, df=63, p=0.02). TNF-α inhibitors was the class with the most negative recommendations (n=7; 50 percent), followed by monoclonal antibodies (n=6; 67 percent). Sixty-two reports contained economic assessments. Fifty-four presented incremental cost-effectiveness ratio (ICER) data and 57 presented the budget impact. Twenty-three reports showed data indicating dominance of the medicine, but only five of these were recommended for incorporation. Drugs for cancer have been recommended despite high ICER values. Decision makers accepted all the recommendations issued by Conitec.

Data suggest that the economic evaluation is secondary to the decision of incorporation. The pharmaceutical industry is the largest applicant for the incorporation of medicines, but these requests are significantly less accepted than those made by the Ministry of Health. Conitec's recommendations are well-accepted by policy-makers. It was not possible to determine an implicit cost-effectiveness threshold.

Death from congenital heart disease (CHD) can be avoided, contributing to reduced infant mortality. The objective of this study was to identify the profile of patients undergoing surgical correction for CHD in three São Paulo State hospitals, and to determine factors that contribute to morbidity and mortality.

The Voluntary Pediatric Cardiovascular Surgery Multicenter Registry (ASSIST) was created in 2014 through a Research Grant Program for the Public Healthcare System (Pesquisas para o Sistema Único de Saúde, PPSUS)* project, a federal-state joint strategic public policies research grant, coordinated by the Hospital das Clínicas of Faculdade de Medicina of Universidade de São Paulo (InCor-HCFMUSP-SP) and Ribeirão Preto's Hospital das Clínicas, both linked to the São Paulo University Medical School.

We analyzed 1,842 patients, with an average age of 1.2 (range 0.4–8.6) years, 50.9 percent were male. Procedural complexity was classified as “Risk Adjustment in Congenital Heart Surgery” version 1 score, RACHS-1: 18.2 percent RACHS1, 25.5 percent RACHS2, 41.2 percent RACHS3, 9.6 percent RACHS4 and 5.4 percent RACHS5–6. Overall hospital mortality was 12.2 percent, and preoperative risk factors included: age <30 days (Odds Ratio, OR = 1.7 p = 0.012), prolonged ICU admission (OR = 3.3 p = 0.001). Other significant factors were RACHS score >4 (OR = 5.3 p < 0.001), heart dysfunction (OR = 3.4 p = 0.001), sepsis (OR = 3 p = 0.001), hemodynamic or surgical re-intervention required (OR = 6.2 p < 0.001), cardiorespiratory arrest (CPR, OR = 24.9 p < 0.001) and renal failure (OR = 5.4 p<0.001). The frequency of related morbidity was 16.2 heart failure, 7.1 percent arrythmia, 5.9 percent pneumonia, 5.9 percent pneumotórax, 4.2 percent pleural and pericardial effusion, 10 percent mechanical ventiation > 7 days, 13.2 percent late sternal closure, 2.8 percent had wound infection, 3.7 percent neurological alterations, 2.3 percent diaphragmatic dysfunction, 11.5 percent CPR, 3.2 percent renal failure, 4.5 percent sepsis, 55.1 percent length of hospital stay longer than 5 days with 45.8 percent postoperative hospital admission longer than 15 days and 6.1 percent needed surgical or hemodynamic re-intervention.

The information collected in the ASSIST registry was of great importance in the São Paulo State CHD surgical practice evaluation. Morbi-mortality related factors elicited critical points and allowed improvement actions. Excluding age and intrinsic procedure complexity, identified outcome modifier factors can be manageable, aiming to increase patient safety and program resolubility or performance.

In 2016, Global Burden of Disease (GBD) data was used to identify the top twenty percent of disease causes in the Philippines, which happened to account for eighty percent of the burden, following the Pareto principle. This study follows from that initial work, aimed at creating a list of cost-effective interventions recommended for priority-setting to achieve universal health coverage (UHC).

A comprehensive literature review search was done, from global sources such as the Disease Control Priorities (DCP) for Developing Countries Project and World Health Organization's (WHO) Choosing Interventions that are Cost-Effective (CHOICE), and local sources such as clinical practice guidelines (CPGs). Forty-seven local experts from thirty-eight medical societies were also consulted on the applicability, appropriateness, adaptability, feasibility of implementation, ability to maintain fidelity, ease of dissemination, and sustainability of selected interventions in the Philippine setting. Resource requirements were then derived using the WHO OneHealth Tool, CPGs, and key informant interviews.

A list of 745 interventions categorized by life stages and by level of intervention with estimates of cost-effectiveness was produced. From these, fifty seven percent had cost-effectiveness studies. Primary interventions were found to be the least costly for the pregnant women, newborn, infant, adolescents, adults, and elderly life stages, while tertiary interventions were found to be the least costly for children.

The interventions are potential targets for inclusion by policymakers. Additional factors to consider include the appropriateness of the context in which the cost-effectiveness study was conducted, the feasibility of conducting primary HTA locally, the local costs of the intervention, and the need to act quickly before the policy window closes.

Acute myocardial infarction (AMI) is one of the leading causes of death and disability worldwide. The European Society of Cardiology Guidelines have established a new definition of myocardial infarction and have strengthened the central role of cardiac troponins in cardiology diagnostics for rule-in and rule-out of non ST-elevation myocardial infarction (NSTEMI). High-sensitivity cardiac troponin I assays (hsTnI) should increase diagnostic sensitivity, and a shorter interval for ruling-in and ruling-out AMI. This analysis aims to provide an overview of the clinical, economic, organizational and ethical impact of the use of hsTnI in clinical practice of Emergency Departments (ED) in Italy.

HsTnl for rule-in and rule-out of AMI in the ED is being evaluated using the EUnetHTA Core Model® framework for health technology assessment. The hsTnI HTA assessment will be completed with real-world evidence derived from a multicenter observational study which has been designed to be conducted in 12 Italian EDs, enrolling 6000 patients with chest pain of suspected cardiac origin, aiming to provide data from the Italian context on clinical, organizational and economic aspects of the use of the test in the ED. Endpoints of the study include: time lapses related to diagnosis, admission, treatment and discharge of patients; number of tests performed; and number of patients diagnosed with AMI.

Initial results from a literature review confirm the usefulness of the hsTnI assay in diagnosing AMI. Generated real-world data will be collected, analyzed and integrated to existing evidence to assess the utility of the test in real contexts, providing details relevant for organizational aspects of the use of the test in the ED.

The use of hsTnl could improve diagnosis of AMI by allowing a faster ruling-in or ruling-out, and reducing inappropriate hospitalizations. Furthermore, this technology could represent an opportunity to reduce overall costs for the healthcare system.

New therapeutic strategies have been established in chronic wound healing procedures, such as the use of platelet-rich plasma (PRP). There is currently still uncertainty about the effectiveness, cost-effectiveness and real safety of PRP in promoting chronic wound healing and what specific types of chronic wounds can benefit most from its use.

We conducted a systematic review of available scientific literature on the effectiveness, safety and cost-effectiveness of PRP compared to placebo, standard care or alternative topical therapies for the treatment of chronic wounds in adults. Overall effect size was estimated through a meta-analysis. A cost-effectiveness analysis was conducted using a Markov model which simulates the costs and health outcomes of individuals for a 5-year horizon, from the perspective of the Spanish National Health Service (NHS) for the PRP versus standard treatment in patients with diabetic foot ulcers. The effectiveness measure was quality-adjusted life years (QALYs). We ran extensive sensitivity analyses, including a probabilistic sensitivity analysis.

Sixteen RCTs and four observational studies were included for the effectiveness and safety meta-analysis. The primary outcome was the proportion of chronic wounds completely healed: 143 patients out of 334 (42.8 percent) were cured in the standard treatment arm and 251 patients out of 375 (66.9 percent) in the PRP arm, relative risk (RR) 1.68 (95% CI: 1.22–2.31). It was unclear whether there was a difference in the risk of infection (RR 0.53, 95% CI: 0.10–2.71) or adverse events (RR 1.05, 95% CI: 0.29–3.88) between PRP and standard care. Three studies were considered for the cost-effectiveness analysis. In the base case analysis, PRP led to higher QALYs and healthcare costs with an estimated incremental cost-effectiveness ratio (ICER) of EUR 41,767 (USD 48,323)/QALY.

PRP treatment is more expensive and more effective than standard treatment. The estimated ICER is above the acceptability threshold in Spain.

In Italy, the central government sets the health benefit package (denominated “Livelli Essenziali di Assistenza” - LEAs) of the National Health System (NHS), which must be provided to all residents. In 2004, the Italian Ministry of Health established a new technical body, the National LEA Commission, responsible for updating LEAs.

Recently, the Ministry has commissioned to the National Institute of Health (NIH) the development of a new value-based procedure for updating the health benefit package for the Italian NHS, supporting the National LEA Commission. A review and comparison of value frameworks and decisional models was performed in order to select a framework and a model that can be applied to the Italian context, design an administrative process for the update procedure, and propose approaches for: (i) the assessment of services currently included in the health benefit basket and of those planned to be incorporated, (ii) the process of appraisal and decision-making to be adopted by the Commission.

The NIH outlined an evidence and value-based three-step (i.e. priority setting, assessment and appraisal) administrative process that integrates roles and responsibilities of the different Italian healthcare institutions involved in LEA updating and HTA.

The NIH is proposing to the Ministry of Health and to the National LEA Commission a new evidence and value-based procedure for updating the health benefit package for the Italian NHS. This procedure is entering a pilot phase in which potential gaps can be identified and minimized for its subsequent implementation.

Current practice in cost-effectiveness analysis (CEA) involves the estimation of the incremental cost-effectiveness ratio (ICER) between a new intervention and one alternative comparator reflecting the standard of care. As this focuses on pairwise comparisons, rather than considering the whole range of available alternatives at any given time, this method fails to capture the full impact of bringing the new intervention to market.

A multi-comparator ICER (MC-ICER) evaluating the impact of the new technology on patients treated with all comparators used in clinical practice, rather than a theoretical ‘second-best’ alternative only, was estimated. This can be achieved by weighting the incremental costs and benefits for each comparator by its change in market share to generate an MC-ICER. This is shown using a stylized example with three comparators.

The traditional ICER against the second-best alternative was USD 200,000 per QALY, while the estimated multi-comparator ICER is USD 133,548 per QALY, corresponding to a 33 percent decrease. This reflects the fact that patients who switch to the new intervention are not only those who had been previously treated with one particular comparator, as is assumed in a traditional CEA. The difference between the traditional ICER and the MC-ICER depends on how the new intervention impacts on the uptake of each comparator.

Results show that, when comparator selection was made excluding dominated and extendedly-dominated alternatives, the MC-ICER, produced using the method described above, is lower than the traditional ICER comparing the new intervention to the second-best comparator. This captures the fact that patients may switch to the new intervention not only from the second-best comparator, but from the whole range of alternative treatments. Such patient movements determine the real impact, or opportunity cost, of the new intervention on the healthcare system and, therefore, should be captured in CEA alongside traditional one-way ICERs.

The hypoglossal nerve stimulation (HNS) produces a tongue protrusion for the treatment of mod-severe obstructive sleep apnea (OSA). It is one of the emerging health technologies prioritized to assess its possible inclusion on the Spanish National Health System. The objective of this study is to evaluate the efficacy and safety of this system in the treatment of OSA.

An early assessment (horizon scanning) was performed. The searched databases were: PubMed, WOS, Tripdatabase, Dynamed, Cochrane Library and ICTRP. Clinical studies of OSA patients treated with HNS published until 01 March 2017 were reviewed. Outcomes considered were: AHI (Apnea Hypopnea Index) ODI (Oxygen Desaturation Index) ESS (Epworth sleepiness scale) and AE (adverse events).

Four devices of HNS were founded: Inspire™, HGNS®, Aura6000™, and Nixoah™. We found two randomized controlled trials (RCT). The Inspire™ RCT showed significant results on mean differences on AHI (−16.9, 95% CI −24.7 to −9.0); ODI (−15.1, 95% CI −22.7 to −7.5) and ESS (−4.5, 95% CI −7.5 to −1.4) in 46 patients, after one week of follow-up. The HGNS® RCT showed non-significant differences on AHI (device active 22.1 ± 5.2 vs control 29.7 ± 6.2), ODI (11.4 ± 4.1 vs 19.5 ± 5.2) and ESS (9.8 ± 1.0 vs 14.1 ± 2.5) in 21 patients at 6 months. A systematic review that included 6 cases series (3 with HGNS®, 2 with Inspire™ and 1 with Aura6000™) without device subgroup analysis and 7 cohorts studies (6 with Inspire™ and one with Aura6000™) showed significant differences comparing AHI, ODI and ESS results to before treatment values. Major AE reported from the studies varied from 4 to 4.5%. No study with Nixoah™ was found.

Inspire™ seems to be an effective option for OSA patients although the evidence is scarce and of low quality for all HNS devices. It would be necessary further well-designed studies.

Ovarian cancer (OC) has the highest mortality rate of all gynecologic malignancies. Completeness of cytoreductive surgery is a key prognostic factor for survival. To differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is difficult and can lead to incomplete tumour removal. OTL38 is a folate analogue conjugated to a near-infrared fluorescent dye which has high specificity and affinity for folate receptor alpha (FRα) expressed in OC. OTL38 together with a specific imaging system can help the surgeon to visualize diseased tissue. The objective of this work is to know the effectiveness and safety of OTL38 in of OC surgery.

Early assessment of OTL38 identified through the early-awareness and alert-system, “SINTESIS-new technologies”, of AETS-ISCIII. The searched databases were: PubMed, WOS, Tripdatabase, Dynamed, Cochrane Library and ICTRP. Clinical studies using the OTL38 in cytoreductive surgery in OC published until September 2017 were reviewed.

Only one publication, supported by industry, was retrieved. The study assesses the pharmacokinetics and tolerability of OLT38 in 30 healthy people randomized into 4 groups with different doses and a control group. The study also analyses the percentage of cytoreduction in 12 OC patients. Infusion of 0.025, 0.05, and 0.1 mg/kg OTL38 doses was associated with mild adverse events which did not require intervention. The 0.2 mg/kg dose was associated to adverse events of moderate severity. In OC patients, 0.0125 mg/kg dose was considered the optimal dose with mild adverse events. OTL38 accumulated in FRα-positive tumours and metastases allowed the surgeon to resect an additional 29 percent of malignant lesions which were not detected using standard inspection and palpation methods.

The OTL38 is an emergent health technology, which could help in cytoreductive surgery for ovarian cancer. However, the evidence is scarce and it would be necessary to continue further studies.

It is established that the current cost effectiveness health technology assessment (HTA) paradigm does not appropriately value rare disease technologies. Social willingness-to-pay (SWTP) has been suggested to be higher for rare disease technologies, it's inclusion into existing HTA framework could better reflect social preferences (SP) and enable a more equitable evaluation of rare disease technologies. Our study aims to estimate SP and SWTP for a rare disorder, CLN2 disease.

Relevant attributes for CLN2 disease were developed and validated by literature review and focus groups with patient's primary caregivers. An elicitation survey (discrete choice experiment (DCE) WTP and relative social willingness to pay (RS-WTP)) was developed using the selected attributes and levels of each attribute. The survey instruments and attributes/levels were tested and validated in a pre-pilot survey (n = 103) and a subsequent pilot survey (n = 286) of the United Kingdom (UK) general population. Information about CLN2 disease was provided to respondents and their understanding of the disease was tested including assessment of framing effects. The main survey with the general UK population (n = 4,009) is now complete.

Eight hundred and twenty-six people were contacted, of which 286 completed the DCE, 113 abandoned the survey before the DCE and 92 abandoned after the DCE. There were no significant differences in characteristics of respondents completing the DCE and those starting but not completing the DCE. Median survey completion time was 20 minutes with 90 percent of participants completing in a single sitting. Median score for the understanding test was 3 (Min = 0 and Max = 4). Incoherencies in WTP estimates were analyzed enabling us introduce relevant modifications and select the most appropriate attribute levels.

DCE and RS-WTP potentially are appropriate methods for assessment of social preferences. The selected attributes/levels for the experiment in CLN2 disease have been validated in this pilot.

As part of a national aging and technology network, AGE-WELL, one work group aims to promote the understanding of potential policy and regulatory hurdles among innovators and decision-makers. This study describes the development of resources to help innovators to navigate policy and regulatory systems to have their technologies adopted.

A policy primer was created that highlights considerations for innovators during the innovation process (from development to implementation). The content of the policy primer was developed by identifying resources through the Canadian Agency for Drugs and Technology in Health Grey Matters search tool, and in consultation with legal and regulatory consultants. By surveying AGE-WELL technology-developing projects (n=15) we characterized the technologies being developed within the network. Survey questions included: intended end-user/purchaser of the technology and past/anticipated facilitators/barriers in their innovation process. The policy primer and survey data were combined to create tailored innovation maps with considerations for each technology being developed within the network. These materials were used to develop a beta website where users can receive information relevant to various innovation stages, as it pertains to their technology. We gained feedback about our materials via surveys and interviews with AGE-WELL technology developers.

The tailored innovation maps and website were seen as helpful resources for understanding policy and regulatory processes required for technology adoption. Technology developers expressed interest in gaining further access to these resources. Innovators desired additional resources about demonstrating value and measuring technology effectiveness.

Resources were developed to help guide technology innovators through policy and regulatory processes; preliminary feedback suggests these were valued by innovators. Next steps include refining the website and releasing these resources to innovators beyond the AGE-WELL Network.

Hyperphosphatemia is a most common problem in dialysis patients. Phosphorus imbalance in dialysis patients increases the risk of developing the bone mineral disorder and cardiovascular mortality. Randomized controlled trials (RCTs) presented variable findings concerning the reduction of phosphorous level in nicotinamide user. So, this systematic review is aimed to explore the efficacy and safety of nicotinamide in hemodialysis patients.

This systematic review was conducted by adhering to the PRISMA guidelines. Study for inclusion was identified by running the suitable keywords in databases including PubMed, Embase, and Cochrane central from inception to 31 October 2017. Cochrane risk of bias tool was used to judge the quality of included RCTs. The change in serum phosphorus level was the primary outcome, while the change in other biochemical parameters including serum calcium, calcium-phosphorus product level, iPTH, platelets, lipid profile parameters, and the safety profile was considered under secondary outcomes. Review Manager (RevMan v5.3) was used for statistical analysis.

Finally four articles were qualified for inclusion in this study with a total of 274 participants of which 136 were in the treatment (nicotinamide) group. All the included studies showed statistically significant reduction in mean serum phosphorous, calcium-phosphorus product level in the treatment arm at the end point of the study, while the reduction in the placebo group was not statistically significant in all the studies. Among other biochemical parameters analyzed, only high-density lipoprotein (HDL) was found to be significantly increased from baseline to the endpoint of the study in the nicotinamide group, while the placebo group showed no significant change in all the included studies except the study by Shahbazian et al. Thrombocytopenia was the most commonly reported adverse event in the treatment group followed by diarrhea.

Nicotinamide was found to be effective in the management of hyperphosphatemia in hemodialysis patients. The safety profile was found to be satisfactory.

Renal transplantation is considered a cost-effective treatment compared to dialysis and represents a significant percentage of public health resources. Post-transplant treatment requires the use of three immunosuppressive drugs. The immunosuppressive regimens consists of a corticosteroid, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antiproliferative agent (azathioprine or mycophenolate) and also by sirolimus or everolimus. In Brazil, the Unified Health System (as known as Sistema Único de Saúde - SUS) is responsible for 95 percent of all kidney transplants performed, as well as ensuring access to immunosuppressive drugs. Therefore, there is a huge and growing economic impact caused by the distribution of these drugs in SUS. We evaluated the factors associated with kidney graft loss in patients who received deceased donor organ and used maintenance immunosuppressive regimens in SUS, in fifteen years.

We analyzed a nationwide cohort of kidney transplant recipients from January 2000 to December 2015 developed through deterministic-probabilistic linkage of SUS administrative databases: Hospital Information System (SIH/SUS); Subsystem for High Complexity Procedures (SIA/SUS) and the Mortality Information System (SIM). Graft loss was defined as death or dialysis for more than three months. All regimens included corticosteroid. We used Cox proportional hazards model to evaluate the factors associated with progression to graft loss.

In total, 18,333 patients were included; 58.5 percent used tracolimus+mycophenolate, 11.7 percent cyclosporine+mycophenolate, 8.9 percent tacrolimus+azathyoprine, 5.5 percent cyclosporine+azathyoprine and 15.4 percent received other immunosuppressive regimens (sirolimus+mycophenolate, everolimus+mycophenolate, tacrolimus, mycophenolate, cyclosporine, azathyoprine) . Most patients were male with a median age of 46 years. A higher risk of graft loss was associated with the use of tracolimus+mycophenolate (HR = 1.069; 95% CI, 0.999–1.146), sirolimus+mycophenolate (HR1.395;95% CI, 1 .150–1.692), tracolimus (monotherapy) (1.468;1.239–1.739); mycophenolate (monotherapy) (1.297;1.126–1.493), male gender (1.144; 1.072–1.221), an additional year of age (1.010; 1.007–1.013), a median dialysis period greater than 38 months (1.266; 1.182–1.356), a diagnosis of diabetes (1.211; 1.071–1.367) and a diagnosis of arterial hypertension (1.209; 1.134–1.288) (HR=1.468;95% CI,1.239 −1.739); mycophenolate (monotherapy) (HR = 1.297; 95% CI, 1.126–1.493), male gender (HR = 1.144; 95% CI 1.072–1.221), an additional year of age (HR = 1.010; 95% CI, 1.007–1.013), a median dialysis period greater than 38 months (HR = 1.266; 95% CI, 1.182–1.356), a diagnosis of diabetes (HR = 1.211; 95% CI, 1.071–1.367) and a diagnosis of arterial hypertension (HR = 1.209; 95% CI, 1.134–1.288)as the primary cause of chronic kidney disease.

In Brazil, the use of regimens mycophenolate, tacrolimus, tacrolimus+mycophenolate was associated a higher risk of graft loss, among other factors. The choice of drug therapy is one of the few factors that influence survival amenable to direct action by health professionals. Therefore, the results of this study are important and should be disseminated aiming to better outcomes for kidney transplant patients.

Antimicrobial resistance is a serious public health problem at the global level. The sensitivity test in liquid and solid media-based techniques is traditionally used in Brazil for the diagnosis of resistant tuberculosis (TB). However, the time required for the diagnosis of this test is, on average, 60 (sixty) days, a period considered to be very high, especially considering certain vulnerable populations (street dwellers), since the long time to the result of the test makes it difficult to establish a second contact between the health institution and the individual, resulting in people without access to diagnosis and appropriate treatment. The line probe assay (LPA) technique often replaces the use of the sensitivity test in many countries, being considered of low time for the diagnosis, ranging from 24 to 48 hours.

We searched the Medline databases (via Pubmed), Embase, and The Cochrane Library, with the aim of finding systematic reviews with meta-analyses. The articles were screened by titles and abstracts and later the full text reading was carried out, according to the inclusion criteria.

Three systematic reviews with meta-analysis were selected. The interventions evaluated the LPA technique compared to the conventional drug sensitivity test. The evaluated tests showed good performance as rapid screening tests for resistance to rifampicin in high prevalence sites. However, although the test results for resistance to isoniazid showed good specificity, there was a high variability in sensitivity estimates.

This study reinforces the idea that the LPA technique may contribute to the previous diagnosis, and this is a probable strategy to control the disease, especially in vulnerable populations that are more likely to be affected by tuberculosis. For a broader analysis of the benefit of the technique, further studies are suggested.

Dalbavancin is a new innovative long-acting antimicrobial treatment that allows clinicians to endorse an early discharge program for patients suffering from acute bacterial skin and skin structure Infections (ABSSSI). The aim of this study was to develop a spending predictor model for evaluating the direct costs associated with the management of ABSSSI from the National Health Service (NHS) perspective of Italy, Spain, and Romania. The main purpose is to compare the hospitalization and drug costs due to the treatment of ABSSSI patients treated with standard antibiotics therapy or innovative long-acting treatment dalbavancin.

A decision-analytic model was performed to evaluate the diagnostic and clinical pathways of ABSSSI patients in the hospital, based on clinicians’ expert opinion. The standard of care scenario was compared with the dalbavancin scenario. The epidemiological and cost parameters were extrapolated from national administrative databases (hospital information system) and from a systematic literature review for each country. Only direct costs in the national payer's perspective were considered. Probabilistic sensitivity analysis (PSA) and one-way sensitivity analysis (OSA) were performed to check the robustness of the model assumptions.

Overall, the model estimated an average annual number of patients with ABSSSI equal to around 50,000 in Italy, Spain, and Romania. The introduction of dalbavancin reduced the length of stay of, on average, 3.3 days per ABSSSI patient. From the economic point of view, dalbavancin did not incur any additional cost from the NHS perspective with homogenous results between countries. The PSA and OSA demonstrated the robustness of the results.

The preliminary results highlight that the introduction of dalbavancin could generate a significant reduction in term of length of stay with no incremental cost from the NHS perspective. This model could represent a good tool for policymakers to provide information on the early discharge approach in the ABSSSI management.

In Brazil, the medicines marketed for acute external otitis are ciprofloxacin and the combination polymyxin B, neomycin, and fluocinolone. The aim of this study was to evaluate the proportion of cure and cost-effectiveness of quinolone versus polymyxin B, neomycin, and steroid combined (PNS) for acute external otitis from the perspective of the Brazilian Public health system.

A systematic review was conducted using Medline, Cochrane Library, CRD and Lilacs databases. Studies evaluating quinolones versus PNS in the treatment of acute external otitis were included. A cost-effectiveness model was made using a decision tree, considering the direct cost of treatment. Univariate sensitivity analysis was conducted, considering the confidence interval of clinical outcomes and a 15 percent variation in cost.

The proportion of cure in up to 10 days was 70.1 percent with quinolone and 60.4 percent with PNS (p = 0.004). The treatment costs were BRL 16.22 (USD 5.02) with quinolone and BRL 3.04 (USD 0.94) with PNS. The incremental cost-effectiveness ratio was BRL 136.25 (USD 42.15) per cure in up to 10 days for quinolone in relation to PNS. This value was more sensitive to clinical outcomes, ranging from BRL 95.48 (USD 29.54) to BRL 254.25 (USD 78.65) for cure with quinolone and from BRL 90.77 (USD 28.08) to BRL 262.57 (USD 81.23) for cure with PNS. These values should be considered with caution because acute external otitis is resolved within a few days and treatment effectiveness is not measured by life years.

There are few studies on therapeutic alternatives available in Brazil. Through the available evidence, there is a lack of results on the effects attributed to each drug. Considering the higher effectiveness, low cost and rational use of antibiotics, quinolone is considered a cost-effective alternative for acute external otitis in Brazil.