Search

Background: Clinical registries facilitate medical research by providing 'real data'. In the past decade, an increasing number of disease registry systems (DRS) have been initiated in Iran. Here, we assessed the quality control (QC) of the data recorded in the DRS established by Shahid Beheshti University of Medical Sciences in Tehran, the capital city of Iran, in 2021., Methods: The present study was conducted in two consecutive qualitative and quantitative phases and employed a mixed-method design. A checklist containing 23 questions was developed based on a consensus reached following several panel group discussions, whose face content and construct validities were confirmed. Cronbach's alpha was calculated to verify the tool's internal consistency. Overall, the QC of 49 DRS was assessed in six dimensions, including completeness, timeliness, accessibility, validity, comparability, and interpretability. The seventy percent of the mean score was considered a cut-point for desirable domains., Results: The total content validity index (CVI) was obtained as 0.79, which is a reasonable level. Cronbach's alpha coefficients obtained showed acceptable internal consistency for all of the six QC domains. The data recorded in the registries included different aspects of diagnosis/treatment (81.6%) and treatment quality requirements outcomes (12.2%). According to the acceptable quality cut-point, out of 49 evaluated registries, 48(98%), 46(94%), 41(84%), and 38(77.5%), fulfilled desirable quality scores in terms of interpretability, accessibility, completeness, and comparability, however, 36(73.5%) and 32(65.3%) of registries obtained the quality requirement for timeliness and validity, respectively., Conclusion: The checklist developed here, containing customized questions to assess six QC domains of DRSs, provided a valid and reliable tool that could be considered as a proof-of-concept for future investigations. The clinical data available in the studied DRSs fulfilled desirable levels in terms of interpretability, accessibility, comparability, and completeness; however, timeliness and validity of these registries needed to be improved., (© 2023. The Author(s).)

Background and Objective: Guideline development groups or other health care decision makers frequently encounter situations that require a simultaneous comparison of multiple interventions. This sometimes becomes apparent either when they identify questions of interest, before they formulate recommendations, or it may surface only when recommendations have already been formulated based on pairwise comparisons., Methods: Using examples from the World Health Organization, the European Commission, and a professional society, we developed a flexible approach to developing recommendations when a multiple-intervention comparison (MC) is needed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence to decision (EtD) frameworks. We iteratively refined this approach through user testing and then included a module in GRADE's official software GRADEpro to test the approach in two real and one theoretical guideline recommendations., Results: We found the approach feasible and that all EtD criteria should be considered in an MC approach. We judged that guideline development groups and other decision makers will benefit from the availability of a network meta-analyses (NMA) of intervention effects to support decisions; however, NMA supports only one of many criteria, that is, the balance of health benefits and harms, and is therefore helpful, but not essential to the approach we propose. When similar but not identical comparators are used to address MC, challenges may arise with intransitivity and the relative rankings of interventions., Conclusion: We successfully applied the MC approach and software module in generating recommendations across different scenarios and identified challenges. The MC approach allows guideline groups and other decision makers to transparently and critically assess multiple options for a given health question. Application of the approach by others may lead to refinement and allow for better understanding of its impact in developing recommendations and making choices., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective . In evidence synthesis, therapeutic options have to be compared despite the lack of head-to-head trials. Indirect comparisons are then widely used, although little is known about their performance in situations where cross-trial differences or effect modification are present. Methods . We contrast the matching adjusted indirect comparison (MAIC), simulated treatment comparison (STC), and the method of Bucher using a simulation study. The different methods are evaluated according to their power and type I error rate as well as with respect to the coverage, bias, and the root mean squared error (RMSE) of the effect estimate for practically relevant scenarios using binary and time-to-event endpoints. In addition, we investigate how the power planned for the head-to-head trials influences the actual power of the indirect comparison. Results . Indirect comparisons are considerably underpowered. None of the methods had substantially superior performance. In situations without cross-trial differences and effect modification, MAIC and Bucher led to similar results, while Bucher has the advantage of preserving the within-study randomization. MAIC and STC could enhance power in some scenarios but at the cost of a potential type I error inflation. Adjusting MAIC and STC for confounders that did not modify the effect led to higher bias and RMSE. Conclusion . The choice of effect modifiers in MAIC and STC influences the precision of the indirect comparison. Therefore, a careful selection of effect modifiers is warranted. In addition, missed differences between trials may lead to low power and partly high bias for all considered methods, and thus, results of indirect comparisons should be interpreted with caution.

Shared decision making (SDM) involves the patient and family in medical decisions regarding treatment. The purpose of this article is to utilize the 2016 National Survey of Children's Health to explore whether family engagement in SDM increases the odds of treatment for children with ADHD, and more specifically, if the presence of SDM is associated with the reduction of racial and ethnic disparities in treatment. Multivariate logistic regression was used to model the odds of treatment for each racial/ethnic group controlling for sociodemographic and health-related variables. Results indicated that White and Multiracial families engaged in SDM were twice as likely to report treatment for ADHD. Black and Latinx families, however, showed no difference in treatment for ADHD when SDM was present. Based on these findings, we conclude that SDM may be less important for Black and Latinx families when making treatment decisions for children with ADHD.

Globally, male factor infertility accounts for 20%-70% of couples struggling to conceive. Certain male pediatric developmental conditions, such as cryptorchidism, hypospadias, testicular and other childhood cancers, infections, and pediatric varicocele have been associated with future infertility. Early fertility preservation, especially in those with pending chemotherapy or genetic conditions such as Klinefelter syndrome, should be strongly considered in patients expected to experience testicular loss. Although optimal treatment timing may be unknown owing to a paucity of long-term prospective studies, early diagnosis and targeted treatment may optimize fertility potential in adulthood., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Therapeutic apheresis is a treatment option for several subspecialities. It is a relatively expensive intervention, which can only be done by dedicated centers based on specific indications. The Therapeutic Apheresis Committee and the National Health Insurance Fund of Hungary jointly control the number of interventions to be made, the introduction of new diagnoses and the application of new apheresis procedures in Hungary. In this work, we review the therapeutic practice of the period between 2013 and 2017 in Hungary, describing also the new modalities under implementation. Orv Hetil. 2019; 160(19): 727-738.

In this paper, I will explore the concept that healing activities shape the objects of therapy and seek to construct those objects through therapeutic activities. Objects of therapy are the persons, patients, human bodies, diseases, physiological processes and personal suffering-that which clinical medicine constructs through its distinctive formative processes, practices and knowledge. The rationale for choice of philosophical sources namely, Cassirer, Foucault, the anthropological perspective of Good and the sociological account of Frank will be discussed. The claim articulated by Good will be examined and its relationship to culture, illness, medical knowledge, practice, truth, and science. I then focus on Frank's concepts of the patient and the body and how medical knowledge and practices affects it. The concept that the medicalization of the illness narrative silences the patient's voice requiring an ethic of listening will be emphasized, described and further supported by Charon's (2006, Narrative medicine: Honoring the stories of illness. New York, NY: Oxford University Press) and Cassell's (2015, The nature of suffering and the goals of medicine. New York, NY: Oxford University Press) thoughts on narrative of illness in clinical medicine. My position concludes that healing activities construct the objects of therapy: as the medical culture's way of seeking truth; as medicine's way of mediating and organizing forms of reality through culture and symbolic forms; and, as medicine's way of entering the body and constructing the disease. Lastly, I suggest that in spite of the remarkable progress in the control of disease, the failure to address the interpretation of illness meanings is a fundamental flaw in the work of "doctoring." The experience and meanings of illness are at the centre of clinical practice and is a moral, political, ethical and professional obligation. The person is a cultural construct, a complex and culturally shaped way of experiencing self and other, and cultural "work" is required to constitute the person who is the object of medical attention and it also necessitates the ethic of listening., (© 2019 John Wiley & Sons Ltd.)

Background: To investigate boosting effects on treatment stabilization in the mandatory treatment modality for patients of amphetamine-type stimulant use disorder., Methods: This is a retrospective follow-up study over a period from January 2013 to December 2018. We analyzed 425 patients of amphetamine-type stimulant use disorder under mandating treatments. Treatment stabilization for a given patient was defined once 4 negative urinalysis had been observed. We developed a dynamic monitoring model of boosting effects informed by the available data, specifically the number of negative urine samples required to reach stabilization, the sum of urinalyses done at the time when the given number of negative urine samples had been observed and who the patient was. To represent the simulated population, a Monte Carlo method was used to generate p-values from 1000 experiments conducted on a computer., Results: In the observed samples, the probability of 4 negative results in urinalysis from 4 outpatient visits was 75.5%. In comparison, the probability for achieving 4th negative results in urinalysis over 4 visits from negative binominal distribution was 57.3%, and from the computer simulation, 49.8%. The observed samples had significantly higher probability of achieving 4 negative results in urinalysis over 4 outpatient visits (p < 0.001)., Conclusions: The mandatory treatment modality boosted treatment stabilization for patients of amphetamine-type stimulant use disorder. The major benefit of using the monitoring model is the ability to monitor boosting effects of stabilization. Results supported the effectiveness of this mandatory treatment modality and can be implemented in deferred-prosecution based treatment modality., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Effective behavioral and pharmacological treatments are available and recommended for patients with alcohol use disorders (AUD) but rarely received. Barriers to receipt and provision of evidence-based AUD treatments delivered by specialists may be greatest in rural areas., Methods: A targeted subanalysis of qualitative interview data collected from primary care providers at 5 Veterans Affairs clinics was conducted to identify differences in provider perceptions and practices regarding AUD treatment across urban and rural clinics. Key contacts were used to recruit 24 providers from 3 "urban" clinics at medical centers and 2 "rural" community-based outpatient clinics. Providers completed 30-minute semistructured interviews, which were recorded, transcribed, and analyzed using inductive content analysis., Results: Thirteen urban and 11 rural providers participated. Urban and rural providers differed regarding referral practices and in perceptions of availability and utility of specialty addictions treatment. Urban providers described referral to specialty treatment as standard practice, while rural providers reported substantial barriers to specialty care access and infrequent specialty care referral. Urban providers viewed specialty addictions treatment as accessible and comprehensive, and perceived addictions providers as "experts" and collaborators, whereas rural providers perceived inadequate support from the health care system for AUD treatment. Urban providers desired greater integration with specialty addictions care while rural providers wanted access to local addictions treatment resources., Conclusions: Providers in rural settings view referral to specialty addictions treatment as impractical and resources inadequate to treat AUD. Additional work is needed to understand the unique needs of rural clinics and decrease barriers to AUD treatment., (© 2018 National Rural Health Association.)

Objectives: To understand the nonlinear relationship between out-of-pocket (OOP) payments and disease-modifying treatment (DMT) use and adherence, primarily to pinpoint the threshold at which the use of DMTs becomes price sensitive., Methods: Individuals with more than two multiple sclerosis (MS) diagnoses (International Classification of Diseases, Ninth Revision code 340) were identified from the MarketScan database (2006-2009). Heterogeneity in treatment was normalized by calculating an annual OOP payment as the average OOP payment for purchasing a fixed basket of DMTs at the insurance plan level. A local linear regression with a model-based recursive partitioning algorithm was applied to explore the relationship between OOP and consequently lower DMT use and adherence as measured by days covered by DMT., Results: We identified the inflection points in annual OOP payments as $442 for DMT use and $890 for DMT adherence. For patients with annual OOP payments of more than $442, a $100-increase in OOP payment was associated with a decline of 0.6% in DMT use; for annual OOP payments of more than $890, a $100-increase in OOP payment was associated with two fewer days of DMT treatments., Conclusions: Although the use of DMTs and DMT adherence appeared unassociated with OOP payment below $442 and $890, respectively, an excessive OOP payment was a barrier to DMT access. This information can inform maximum monthly and yearly payment caps when designing valued-based insurance plans., (Copyright © 2018 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

When baseline risk of an outcome varies within a population, the effect of a treatment on that outcome will vary on at least one scale (e.g., additive, multiplicative). This treatment effect heterogeneity is of interest in patient-centered outcomes research. Based on a literature review and solicited expert opinion, we assert the following: (1) Treatment effect heterogeneity on the additive scale is most interpretable to health-care providers and patients using effect estimates to guide treatment decision-making; heterogeneity reported on the multiplicative scale may be misleading as to the magnitude or direction of a substantively important interaction. (2) The additive scale may give clues about sufficient-cause interaction, although such interaction is typically not relevant to patients' treatment choices. (3) Statistical modeling need not be conducted on the same scale as results are communicated. (4) Statistical testing is one tool for investigations, provided important subgroups are identified a priori, but test results should be interpreted cautiously given nonequivalence of statistical and clinical significance. (5) Qualitative interactions should be evaluated in a prespecified manner for important subgroups. Principled analytic plans that take into account the purpose of investigation of treatment effect heterogeneity are likely to yield more useful results for guiding treatment decisions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

When there is substantial heterogeneity of treatment effectiveness, it is crucial to identify individualized treatment assignment rules for comparative treatment selection. Traditional approaches directly model clinical outcome and define optimal treatment rule according to the interactions between treatment and covariates. This approach relies on the success of separating the main effects from the covariate-treatment interaction effects, which may not be easy. To overcome this shortcoming, a recent approach, called outcome weighted learning, focuses on building an optimal treatment rule by maximizing the expected clinical outcome related with differential treatments. However, there seems to be a lack of approaches to explicitly deal with three or more treatments. In this article, we propose an outcome weighted learning method that extends estimating individualized treatment rules to multi-treatment case by using a vector hinge loss as a target function. Consistency of the resulting estimator is shown in the article. We demonstrate the performance of our approach in simulation studies and in a real data analysis., (© 2017, The International Biometric Society.)

In patients with immune thrombocytopenia who do not adequately respond to first-line therapy, there is no clear consensus on which second-line therapy to initiate and when. This situation leads to suboptimal approaches, including prolonged exposure to treatments that are not intended for long-term use (eg, corticosteroids) and overuse of off-label therapies (eg, rituximab) while approved, more efficacious options exist. These approaches may not only fail to address symptoms and burden of disease, but may also worsen health-related quality of life. A better understanding of available second-line treatments may ensure best use of therapeutic options and thereby optimize patient outcomes., (© 2018 The Authors American Journal of Hematology Published by Wiley Periodicals, Inc.)

Choosing Wisely encourages dialogue about reducing unnecessary procedures, tests, or treatments in healthcare. The American Society for Blood and Marrow Transplantation (ASBMT) and Canadian Blood and Marrow Transplant Group (CBMTG) established a Choosing Wisely BMT Task Force whose objective was to create a list of top 5 practices in blood and marrow transplantation to be questioned. The Task Force consisted of representatives from ASBMT's Quality Outcomes, Education, and Practice Guidelines committees; ASBMT's Pharmacy Special Interest Group; CBMTG Program Directors; and Center for International Blood and Marrow Transplant Research (CIBMTR). Suggestions for current transplantation practices to question were elicited from the CBMTG Program Directors; members of ASBMT's Quality Outcomes, Practice Guidelines, and Education committees; and chairs of the CIBMTR scientific working committees. We received 119 unique suggestions that were ranked based on their potential impact on harm reduction, cost reduction, necessity of the test or practice, and the strength of available evidence. Through a modified Delphi process, suggestions were narrowed down to 6, which were then subjected to systematic reviews. The final 5 recommendations focus on graft source for patients with aplastic anemia, corticosteroid dose for initial treatment of graft-versus-host-disease, optimal number of umbilical cord blood units for transplantation, graft source in matched unrelated donor transplantation, and use of prophylactic intravenous immunoglobulin in transplant recipients. These Choosing Wisely BMT recommendations are relevant to the current clinical practice of blood and marrow transplantation and focus on tests, treatments, or procedures that may be harmful, wasteful, or for which there is no apparent clinical benefit., (Copyright © 2018 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: To prepare the Simplified Therapeutic Intervention Scoring System (TISS-28) to measure nursing workload in Intensive Care Units in Guangdong Province of China., Methods: A non-experimental descriptive study was conducted in the intensive care units in the Province. TISS-28, TISS-76, Acute Physiology and Chronic Health Evaluation (APACHE II) were all measured., Results: There were significant positive correlations between TISS-28 and APACHE II (n=91, r=0.432, p<0.001), TISS-76 scores (n=83, r=0.764, p<0.001). A significant difference was found between the mean TISS-28 score in the first day of the intensive care stay and the last day (30.76±6.86 vs 24.67±5.48, p<0.001). A significant intra-class correlation was found between TISS-28 scores collected by the researcher and research associates (ICC=0.959, p<0.001)., Conclusion: The reliability and validity of TISS-28 were shown in Chinese intensive care units. It is a practical tool for estimating the nursing workload and providing opportunities to compare the data between intensive care units in different facilities. The TISS-28 Chinese version is recommended to guide the allocation of nursing manpower in Chinese intensive care units., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The 7 th edition of the American Society for Apheresis (ASFA) guidelines was composed by an international physicians committee, and includes 14 new diseases, and 2 new indications for diseases described in the former guidelines. Several indications have either changed names or were excluded from this edition. The guidelines are developed after taking into account documented evidence, either supporting or negating use of apheresis technology in the treatment of diseases. Based on this evidence, the committee revises, updates and includes or excludes disease entities/indications in the guidelines. This article describes the revisions to the 7 th edition of the ASFA guidelines, in a comprehensive manner., (© 2017 Wiley Periodicals, Inc.)

Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research. The CONSORT (Consolidated Standards of Reporting Trials) Statement is an evidence-based reporting guideline that aims to improve research transparency and reduce waste. In 2008, the CONSORT Group developed an extension to the original statement that addressed methodological issues specific to trials of nonpharmacologic treatments (NPTs), such as surgery, rehabilitation, or psychotherapy. This article describes an update of that extension and presents an extension for reporting abstracts of NPT trials. To develop these materials, the authors reviewed pertinent literature published up to July 2016; surveyed authors of NPT trials; and conducted a consensus meeting with editors, trialists, and methodologists. Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers' understanding and the addition of 3 new items. These items address whether and how adherence of participants to interventions is assessed or enhanced, description of attempts to limit bias if blinding is not possible, and specification of the delay between randomization and initiation of the intervention. The CONSORT extension for abstracts of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstracts. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers. The second addresses reporting of important changes to the intervention versus what was planned. Both the updated CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstracts should help authors, editors, and peer reviewers improve the transparency of NPT trial reports.

Natural product drugs, or botanical drugs, are drugs composed of natural substances which have constituents with healthenhancing or medicinal activities. In Korea, government-led projects brought attention to botanical drugs invigorating domestic botanical drug industry. Foreign markets, as well, are growing bigger as the significance of botanical drugs stood out. To follow along with the tendency, Korea puts a lot of effort on developing botanical drugs suitable for global market. However, standards for approving drug sales vary by countries. And also, thorough standardization, certification, clinical studies and data of these will be required as well as data confirming safety and effectiveness. Meanwhile, as an international exchange in botanical drug market continues, the importance of plant resources was emphasized. Thus countries' ownership of domestic natural resources became vital. Not only establishing a systematic method to secure domestic plant resources, but also cooperation with other countries on sharing natural resources is essential to procure natural resources effectively. Korea started to show visible results with botanical drugs, and asthma/COPD treatment made out of speedwell is one example. Sufficient investment and government's active support for basic infrastructure for global botanical drugs will bring Korea to much higher level of botanical drug development. [BMB Reports 2017; 50(3): 111-116].

Objectives: People often hold unduly positive expectations about the outcomes of medicines and other healthcare products. Here the following explanation is tested: people who have a positive outcome tend to tell more people about their disease/treatment than people with poor or average outcomes. Akin to the file drawer problem in science, this systematically and positively distorts the information available to others., Method: If people with good treatment outcomes are more inclined to tell others, then they should also be more inclined to write online medical product reviews. Therefore, average treatment outcomes in these reviews should be more positive than those found in randomised controlled trials (RCTs). Data on duration of treatment and outcome (i.e., weight/cholesterol change) were extracted from user-generated health product reviews on Amazon.com and compared to RCT data for the same treatments using ANOVA. The sample included 1675 reviews of cholesterol reduction (Benecol, CholestOff) and weight loss (Orlistat) treatments and the primary outcome was cholesterol change (Bencol and CholestOff) or weight change (Orlistat)., Results: In three independent tests, average outcomes reported in the reviews were substantially more positive than the outcomes reported in the medical literature (η 2  = 0.01 to 0.06; p = 0.04 to 0.001). For example, average cholesterol change following use of Benecol is -14 mg/dl in RCTs and -45 mg/dl in online reviews., Conclusions: People with good treatment outcomes are more inclined to share information about their treatment, which distorts the information available to others. People who rely on word of mouth reputation, electronic or real life, are likely to develop unduly positive expectations., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

To evaluate a new therapy versus a control via a randomized, comparative clinical study or a series of trials, due to heterogeneity of the study patient population, a pre-specified, predictive enrichment procedure may be implemented to identify an "enrichable" subpopulation. For patients in this subpopulation, the therapy is expected to have a desirable overall risk-benefit profile. To develop and validate such a "therapy-diagnostic co-development" strategy, a three-step procedure may be conducted with three independent data sets from a series of similar studies or a single trial. At the first stage, we create various candidate scoring systems based on the baseline information of the patients via, for example, parametric models using the first data set. Each individual score reflects an anticipated average treatment difference for future patients who share similar baseline profiles. A large score indicates that these patients tend to benefit from the new therapy. At the second step, a potentially promising, enrichable subgroup is identified using the totality of evidence from these scoring systems. At the final stage, we validate such a selection via two-sample inference procedures for assessing the treatment effectiveness statistically and clinically with the third data set, the so-called holdout sample. When the study size is not large, one may combine the first two steps using a "cross-training-evaluation" process. Comprehensive numerical studies are conducted to investigate the operational characteristics of the proposed method. The entire enrichment procedure is illustrated with the data from a cardiovascular trial to evaluate a beta-blocker versus a placebo for treating chronic heart failure patients., (© 2015, The International Biometric Society.)

One of the characteristics of HBV transmission is the age structure of the host population and the vertical transmission of the disease. That is the infection is transmitted directly from infected mother to an embryo, fetus, or baby during pregnancy or childbirth (the perinatal infection). We formulated an age-structured model for the transmission dynamics of HBV with differential infectivity: symptomatic and asymptomatic infections. The model without intervention strategies is completely analyzed. We compute the basic reproduction number which determines the outcome of the disease. We also compute equilibria and study their stability. The sensitivity analysis of the initial model parameters is performed (to determine the impact of control-related parameters on outbreak severity). Using optimal control theory, we determine the cost-effective balance of three interventions methods which minimizes HBV-related deaths as well as the costs associated with intervention.

Ineffective treatments continue to be given to nursing home residents with dementia, and many more treatments are started than stopped. The Track and Trigger Treatment (T(3)) Protocol assists nurses to track responses to new treatments and get ineffective treatments stopped or altered. This preliminary study determined feasibility for end users and examined differences between two randomized groups in assessments, treatment changes, nurse time, and drug costs over 8 weeks. Controlling for number of medical diagnoses, 41 residents in the T(3) group had significantly more treatments stopped than 37 residents in the usual care group. Treatments were most commonly stopped because of ineffectiveness (33%), followed by the problem being resolved (29%), side effects (18%), and a change in goals of care (20%). Assessment quality was a statistically significant mediator, and drug costs were significantly less for the T(3) group. The T(3) processes were rated as useful and easy, with one caveat., (© The Author(s) 2015.)

Purpose: The purpose of this study was to examine changes over time in the pooled effect size of randomized, double-blinded, placebo-controlled trials (RCTs) published on the protective effects of antioxidants and low dose aspirin against preeclampsia, and to identify determinants that may affect such changes., Methods: Two recently published meta-analyses of RCTs examining the effects of antioxidant treatment or low dose aspirin on the rates of preeclampsia and its adverse effects were used. Chronological, cumulative meta-analyses were conducted to investigate the possibility of a time-dependent effect. The journal's impact factor, citation numbers of each paper, and their sample size, were correlated with the risk ratio (RR) of the study., Results: The median sample size of positive antioxidant trials (i.e., showing protective effect) was tenfold smaller (median 267) than that of the negative trials (median 2120) (P = 0.017). A similar trend was seen for low dose aspirin studies. There was a significant correlation between study size and RR for the effects of antioxidants and low dose aspirin on intrauterine growth restriction (IUGR). There was no correlation between RR and citation number, or between RR and the journal's impact factor for the two therapeutic modalities. For both modalities, the journal's impact factor correlated significantly with the number of citations per year. Cumulative meta-analyses revealed that during the first few years and studies, there was a seeming significant protective effect of antioxidant or aspirin against preeclampsia. For both treatment, the initial protective effects gradually disappeared and nullified by larger, later studies., Conclusions: Initial studies, often published in high impact factor journals, are cited significantly more times but do not exhibit a higher likelihood of predicting a correct long term answer. Studies with smaller sample sizes are more likely to be biased against the null hypothesis. As such, cumulative meta-analysis is an effective tool in predicting potential bias against the null hypothesis and the need for additional studies.

Background: To curb rising healthcare expenditures in the U.S.A., the factors underlying this growth must be well understood., Objective: We aim to explore how chronic disease prevalence, obesity, and improved disease detection and treatment rates contributed to the growth in health spending in the U.S.A. between 1987 and 2011., Methods: We use spending decomposition equations to estimate the portion of spending growth attributable to prevalence increases, rising treatment costs, and population growth, respectively. We use two-part models to estimate the portion of prevalence-related spending that is potentially due to obesity. We examine changing diagnosis and treatment rates to assess how much of the growth in spending might be desirable., Results: We find that the share of total healthcare spending associated with the treatment of chronic disease has risen dramatically from 1987-2011. In particular, we estimate that 77.6% of healthcare spending growth is attributable to patients with four or more chronic conditions. We find that rising obesity levels may explain between 11.4 and 23.5% of the increase in healthcare expenditure for several specific chronic conditions. Diagnosis and treatment rates for chronic disease are improving., Conclusions: Individuals with multiple chronic conditions are disproportionately responsible for rising healthcare expenditure. Much of spending growth associated with rising rates of chronic disease can be linked to rising obesity rates. Though much of the growth in spending is generally considered undesirable, disease detection and treatment rates are also rising, suggesting that at least some of the recent growth in healthcare expenditure may be beneficial.

Standard skin care procedures for percutaneous endoscopic gastrostomy (PEG) tubes and peristomal skin care for colostomy and ileostomy patients are not always sufficient to prevent peristomal skin problems. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to compare the effectiveness of standard peristomal skin care to adjunctive techniques or barriers (including glycogel dressings, gelatin- and pectin-based skin barriers, glycerin hydrogel wound dressing, Acacia senegal fiber pockets, hydrocolloid powder crusting, and German chamomile) to manage or treat patients with a stoma. Using systematic literature search techniques, all healthcare databases were searched up through September 2014. No language restrictions were applied. Studies were included if they met criteria for published RCTs or quasi-RCTs that evaluated the outcome of standardized peristomal skin care and other adjunctive techniques or barriers used among patients with a stoma or PEG tube. A meta-analysis was performed to calculate a pooled effect size by using random-effect models for the primary (skin irritation/reaction) and secondary (length of pouch wear time) outcomes. Six RCTs comprising 418 total patients were identified. Four evaluated the outcome of colostomy or ileostomy peristomal skin care, and no significant differences were detected in the incidence of skin problems (RR 0.67; 95% CI: 0.31-1.41). In the two studies that included length of pouch wear time, no significant differences were observed (RR 0.48; 95% CI: 0.03-7.97). No significant differences were seen in the rate of skin irritations of gastrostomy patients (RR 0.56; 95% CI: 0.20-1.59), but the difference in treatment outcomes of peristomal damage in patients with a colostomy was significant (P = 0.01). The limited number of studies, study quality, heterogeneity of variability in peristomal care strategies and techniques, clinical factors, and nonuniform reporting of clinical parameters contributed to the heterogeneity among the trials. Well-designed RCTs are needed to investigate the efficacy of various barriers and techniques for peristomal skin care and to help develop evidence-based standards of caring for the skin of patients with a colostomy, ileostomy, or gastrostomy.

Achieving the best possible outcomes requires the reliable implementation of best practices for every patient. Specifically, optimizing outcomes requires a spectrum of research spanning basic science, drug development, clinical efficacy and effectiveness, health services, quality improvement, and implementation research. However, our rapid increase in understanding the mechanisms of health and disease and their treatment has far outpaced our ability to reliably provide that care, resulting in poor reliability and enormous variation in care. T3 translational research studies attempt to answer questions surrounding reliable implementation of interventions, decreasing variations in care, and spreading effective therapies. To answer these questions, T3 research may use traditional research methodology such as randomized controlled trials (RCTs); however, various other approaches such as quasiexperimental designs (eg, time-series analysis) are often used. Although uncommon, T3 research has shown promise in not only improving process measures such as correct dosing of medications, but also outcome measures such as improved remission rates in patients with IBD. A more complete integration of T3 translational research into the more traditional research continuum is necessary if we are to achieve the best possible outcomes for our patients., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In July 2012, Congress passed the Food and Drug Administration Safety and Innovation Act (FDASIA). The Advancing Breakthrough Therapies for Patients Act was incorporated into a Title of FDASIA to expedite clinical development of new, potential "breakthrough" drugs or treatments that show dramatic responses in early-phase studies. Using this regulatory pathway, once a promising new drug candidate is designated as a "Breakthrough Therapy", the U.S. Food and Drug Administration (FDA) and sponsor would collaborate to determine the best path forward to abbreviate the traditional three-phase approach to drug development. The breakthrough legislation requires that an FDA guidance be drafted that details specific requirements of the bill to aid FDA in implementing requirements of the Act. In this article, we have proposed criteria to define a product as a Breakthrough Therapy, and discussed critical components of the development process that would require flexibility in order to enable expedited development of a Breakthrough Therapy., (©2013 AACR.)

The paper discusses approaches to improving educational technologies in therapeutic disciplines taught at higher medical education institutes according to the basic curricula in Therapeutics (060101).

In a survey conducted in 2010/2011 data from the 28 EU member states, four EU candidate states (Croatia, FYROM, Iceland, Turkey), three potential EU candidate states (Bosnia Herzegovina, Montenegro, Serbia), and two EFTA states (Norway and Switzerland) were collected. The status and function of newborn screening (NBS) programmes were investigated from the information to prospective parents and the public via confirmation of a positive screening result up to decisions on treatment. This article summarises the results from screening laboratory findings to start of treatment. In addition we asked about the existence of feedback loops reporting the conclusions of confirmation of screening results to the screening laboratory and communication of long-term outcome to diagnostic units and possibly existing central registries. Parallel to the description of actual practices of where, how and by whom the different steps of the programmes are executed, we also asked for the existence of guidelines or directives regulating the screening programmes, material to support information of parents about diagnoses and treatment and training facilities for professionals involved in the programmes. This survey gives a first comprehensive overview of the steps following a positive screening result in European NBS programmes. The 37 data sets reveal substantial variation of national screening panels, but also a lot of similarities. Analysis across all countries revealed that actual practice is often organised but not regulated by guidelines. Material to inform patients is available more often for explaining treatment (69 %) than explaining the necessity of confirmatory diagnostics (41 %). Training of professionals is rarely regulated by a guideline (2 %), but is offered for paediatricians (40 %) and dieticians (29 %) and only rarely for other professions (e.g. geneticists, clinical nurse specialists, psychologists). Registry-based evaluation of long-term outcome is as yet almost nonexistent (3 %).

Background: Recent consensus guidelines have recommended uniformity in procedural training in family medicine residency programs. The consensus documentation suggestions are based on expectations of procedural training prior to residency. Few studies have evaluated the perceived baseline level of procedural competency prior to residency training., Methods: Twenty incoming PGY-1 residents completed a "procedural experience survey," asking respondents to identify their prior experience and current comfort levels with 19 "basic" procedures., Results: For seven procedures, no prior experience was the most common response. For 15 of the 19 procedures, at least one respondent reported no prior experience. The residents' self-reported comfort levels varied widely for each procedure., Conclusions: The survey results showed that experience and comfort with procedures often performed in family medicine varies widely among incoming residents. This raises the question of whether documentation of resident competence in these procedures should be recommended as a baseline and monitored throughout residency training.

Trials assessing the effects of therapies on symptoms, functional capacity, health-related quality of life and other aspects of health status are becoming more common in an era of chronic disease management. Such trials involve instruments for measuring health status whose reliability, validity and responsiveness need to be understood by clinicians and policy-makers in interpreting trial results. Deciding whether a treatment is clinically efficacious requires prior determination, based on empirical evidence, of what constitutes a minimal important difference (MID) between active treatment and control groups in the change in health status between study start and end. This MID should be used to calculate the sample size that will confer adequate power to detect a treatment effect if it truly exists. Many trials assessing health status have major methodological flaws: use of inappropriate or psychometrically unsound measurement instruments, lack of specification of MID, assumption that statistically significant results represent clinically significant treatment effects, and statement of conclusions inconsistent with observed results. This article provides guidance to clinicians in interpreting results of such trials in regard to clinical decision-making., (© 2011 Blackwell Publishing Ltd.)

The quality of evidence supporting the use of apheresis in the treatment of individual diseases and disorders is often limited. For most diseases and disorders, randomized controlled trials of the use of apheresis have not been performed and for many, due to rarity of the condition, it is unlikely that they will ever be performed. In keeping with its vision, the American Society for Apheresis (ASFA) has created and regularly updated guidelines on the use of apheresis in the treatment of disease. These guidelines seek to summarize the literature on the use of apheresis in treating diseases, provide a critical review of this literature, and give practical guidance to apheresis practitioners. The most recent ASFA guidelines were published in 2010. This article reviews the history of the ASFA guidelines, the changes that were made in the 2010 guidelines, and future directions and plans for these guidelines. The 2010 ASFA guidelines on the use of therapeutic apheresis in clinical practice represent the state of the art in apheresis medicine in 2010., (Copyright © 2011 Wiley-Liss, Inc.)