There are reports of a potential rise in a teaching hospital’s morbidity and mortality rates during the trainee turnover period, i.e., with the induction of new residents and house staffs, and the changeover of clinical teams. The published literature displays mixed reports on this topic with lack of reproducible observations. The current study was conducted to explore existence of any such phenomenon (January effect) in Pakistan.This retrospective cohort study was conducted at Aga Khan University Hospital, Karachi, Pakistan. Five-year (2013–2018) record of all the patients in all age groups related to these outcomes was retrieved and recorded in specifically designed questionnaire. Different outcome measures were used as indicators of patient care and change in these outcomes at the time of new induction was related to possible January effect.During the five-year study period, more than 1100 new trainees were inducted into the post graduate medical education program (average of 237 per year) with more than 22,000 inpatient admissions . Some patterns were observed in frequencies of surgical site infections, medication errors, sentinel events, patient complaints, and adverse drug reactions. However, these were not consistently reproducible and could not be directly attributed to the trainee turnover. All other indicators did not show any pattern and were considered inconclusive. No effect of overlap was observed.Inconsistency in the patient care quality indicators do not favor existence of January effect in our study. Further research is recommended to establish our results. It is commonly believed that the quality of health care declines during trainee turnover at the start of the academic year, compared to the rest of the training continuum . The risThere are mixed reports in peer-reviewed literature on this topic both in terms of whether such an effect does exist, as well as the indicators that may be studied to verify the existence of such an effect. The various indicators studied so far include, medication errors, mortality, morbidity, near misses, adverse events, and efficiency , 4. A syThe training framework in Pakistan differs from most other countries due to the presence of an extra mandatory ‘House Job’ or ‘Internship’ year, which every doctor must complete immediately after graduating from medical school. This year long training requires rotations through both medical and surgical specialties, despite the graduates’ specific clinical area of interest.Aga Khan University Hospital (AKUH) is Pakistan’s only JCIA accredited academic medical centre. AKUH has one of the country’s largest and most sought-after post-graduate training program, that includes a year-long internship, residency, and fellowship programs. In addition, AKUH also has a sought-after school of nursing and nursing education services. The academic year for internship, residency, fellowship programmes, as well as for trainee nurses begins from January. Prior to 2015, the turnover of new inductees has been like that in most programmes where the old batch leaves and the new cohort of inexperienced fresh graduates steps in. Although the existence of any January effect at AKU has never been formally studied, in 2015 an overlap of 3 days for interns was introduced, i.e., for three full days, the passing out interns and recently enrolled interns worked on the floor together. This was done because of an exercise involving focused interviews and small group discussions with graduated and chief residents who suspected increased medical errors and disruptions in service provision .This study was conducted to confirm if any such phenomenon exists at AKU, and whether the introduction of overlap made any difference. To the best of our knowledge, no such study has been conducted in this region prior to this one.This retrospective cohort study was conducted on an open cohort at Aga Khan University Hospital, Karachi, Pakistan. All records related to patients admitted in wards irrespective of age group, were retrieved from the office of the Chief Medical Officer (CMO) for five years i.e., from 2013 to 2018, and recorded using specifically designed questionnaires. Outcome measures that were used as indicators of patient care for this study included: hospital incidence of adverse drug reactions, medication errors and near miss, sentinel events, surgical site infections (SSI), hospital incidence of multiple drug resistant organisms (MDRO), quality of medical record documentation, needle stick and sharps injuries to health care staff (NSI), health care staff exposure to contaminants, wrong labeling of site/ specimen, patient satisfaction reports, and patient complaints. This data is routinely collected and compiled as per hospital’s ongoing quality improvement process as defined in Table Analysis: Descriptive analysis for each indicator including mean, standard deviation (SD), frequencies and percentages were calculated using SPSS statistical software (SPSS) version 20.0. The data was compiled for four quarters of each year.Quarter 1: January-March.Quarter 2: April-June.Quarter 3: July-September.Quarter 4: October-December.A pattern showing decline in the first quarter of the year which is also the time when new postgraduate trainees are inducted in the university, could be attributed to the turnover of trainees or the ‘January effect’.Ethical considerations: For all the data, only the total number was retrieved; individual patient records were not retrieved or reviewed to maintain the anonymity and confidentiality of any patient, health care staff or trainees. An exemption was obtained from the institutional ethics review committee (AKU-ERC) before beginning the study.During the five-year study period, an average of 237 new interns, residents and fellows were inducted into the post graduate medical education program each year with an average of 45,469 inpatient admissions per year, making this one of the largest samples to have been studied for this phenomenon. Significant results of this study included noticeable pattern changes in frequencies of surgical site infections, medication errors, sentinel events, patient complaints and adverse drug reactions. All other indicators did not show any pattern and were considered inconclusive.Apart from the year 2017, frequency of sentinel events at our hospital remained relatively higher in the first quarter of the year as compared to the previous year’s fourth quarter  the peak increase in surgical site infection rates were actually in the second quarter. Frequency of adverse drug reactions was only seen to increase in the first quarter of the years 2016 and 2018, and these years also had a peak increase in the frequency of adverse drug reactions in the second quarter. Percentage of medication errors showed an increase in the first quarter of the years 2014 and 2015. There was, however, a decreasing percentage of medication errors throughout the years 2013–2015 and an increasing percentage of medication errors seen in the years 2016–2018. The frequencies of SSI, medication error, and adverse drug reaction are shown in Table This is the first study that explored the association between trainee turn over and patient care quality outcomes or what may be called as ‘January effect’ at a University Hospital in Karachi, Pakistan. Beginning of every academic year in a teaching hospital is faced with multiple challenges, the most important being the acclimatization of the fresh medical graduates or junior trainees and residents to the newer role in providing patient care . This phOur analysis showed a marginal increase in the sentinel events and patient complaints reported in the first quarter compared to the rest of the year. The difference in actual numbers was however too small to draw meaningful conclusions. We also found an increase in the frequency of surgical site infections and adverse reactions in the first quarter of every year as compared to the previous year. This could be an indirect indicator of the possible ‘January effect’ in our set up as the fresh inductees take up responsibilities in the first quarter of every year while the experienced ones graduate in the last quarter of the previous year. This is in agreement with a large number of higher-quality studies that have consistently found greater evidence of a true “July effect” throughout training in many disciplines including surgery, orthopedics, pediatrics, neurosurgery, obstetrics and gynecology, and oral surgery for various procedures across the world , 11. In Our study showed a spike in the surgical site infections and adverse reactions in the second quarter for three years that we studied. This could be because of the lowering down of the compensatory defense mechanism of the hospital staff i.e., senior physicians and nurses who may be otherwise more vigilant in supervising the new inductees and following the protocols in the earlier months of induction. Studies have shown that more senior members of the medical team, including fellows and attending surgeons, as well as the nursing staff provide a greater level of support to the fresh trainees to ensure continuity of care and quality standards . Also neWhile most of the studies reported the existence of a July effect, there are also studies that negated the induction of new trainees as the major cause for poor patient outcomes or offered inconclusive findings . NochureLiterature suggests different measures that could minimize the July effect. One of these is developing an active orientation program, that would improve communication between caregivers, and enhance collegiality between physicians and nurses thus ultimately improving patient outcomes . LiteratThere are important limitations to our study. Aside from the inherent drawbacks like information bias in using a retrospective data set, we were unable to control for particular factors that may have influenced outcomes and compromise the reliability of the inferences drawn. Because of the way the data was available within the hospital, we were not able to analyze the outcomes for every month that may have diluted or concentrated the results. Also, it did not allow in depth statistical analyses. Finally, this was only a single center study and thus cannot be representative of all academic hospitals in the city and nationally. This calls for high quality researches, possibly prospective cohort studies, to get valid results. Furthermore, likely causes of the deteriorating indicators of patient outcomes needs to be explored further.Despite the gaps in research methodology, our findings have several implications for improving hospital systems and policies related to postgraduate medical education. This stresses the need for (1) a robust orientation for the new inductees focused on education related to hospital polices, systems and medication safety; (2) a more vigorous overlap week where the junior residents can shadow the graduating senior residents thus ensuring enhanced understanding and smooth transition of responsibilities; (3) the hospital also needs to re-evaluate the responsibilities assigned to new interns and residents and the provision of increased supervision; and (4) finally a more robust system of data management system and a system for continuous monitoring.Incorporating these changes might improve the quality standards for patient care at the hospital by reducing both fatal and non-fatal medication errors, thereby reducing the substantial associated costs as well as enhance the quality of the postgraduate training at the institute.This study contributes valuable insights into the “January effect” phenomenon and its potential impact on patient care quality outcomes. The suggested changes could potentially improve patient care quality by reducing medication errors, both fatal and non-fatal, leading to cost savings and enhanced postgraduate training quality at the institution. While certain indicators suggest a possible association, further research and the implementation of proactive measures are necessary to mitigate any adverse effects and ensure the highest standards of patient care in teaching hospitals.


This study aimed to conduct a measurement-based analysis of overweight and obesity prevalence among 6–9-year-old children in Montenegro.The population of this cross-sectional study included 1993 (1059 boys and 934 girls) primary-school children. The sample of anthropometric variables includes body height, body weight and body mass index, as well as nutrition status that were presented based on BMI standardized categories: underweight, normal weight, overweight, and obesity. The descriptive statistics described the means for each variable, while post hoc tests and ANOVA were applied to explore differences between the proposed means.The results indicate the overweight (including obesity) prevalence was 28% (15% of overweight and 13% of obese children), while boys have a higher overweight prevalence rate than girls. In addition, the tendency of higher prevalence rates to differ by age in both sexes is observed. This study also confirmed that overweight and obesity are affected by geographical regions but not by the level of urbanization in Montenegro.The innovation of this study is reflected in the fact that the overweight and obesity prevalence rates among 6–9-year-old children are within an acceptable range in Montenegro, since it does not deviate from the European average, but further interventions and continuous monitoring are necessary, due to the specific nature of this issue. It is widely known that overweight and obesity in children and adolescents are increasing dramatically worldwide , 2. ThisSolving overweight and obesity in children is not an easy task, especially because there are a large number of different factors that influence weight gain . Also, tWhen discussing Montenegro, practitioners and researchers from this field actively take part in the international initiatives listed in the previous paragraph and several local initiatives. The employees of the Institute of Public Health and the Faculty of Sports and Physical Education of the University of Montenegro lead in achieving these goals. However, although there have been several attempts, a national initiative and a sustainable national protocol that would continuously, year after year, monitor the entire Montenegrin population and thus create a unique database of high-quality data have not been established yet. As part of the national initiative and, with the help of a sustainable national protocol, a cross-sectional analysis would be carried out, and the trend of changes would be monitored, all to give adequate recommendations for making successful decisions in the process of mitigating the general negative trends in the prevalence of overweight and obesity in Montenegro . TherefoThis study aimed to conduct a measurement-based national analysis of overweight and obesity prevalence among 6–9-year-old children from Montenegro to confirm the rising trends in children's overweight and obesity as well as expected differences by geographical regions and level of urbanization.The population of this cross-sectional study included 1993  first- to third-grade primary-school children  who agreed to participate in the study (parents' informed consent has been obtained on a voluntary basis). The sampling process was performed in line with the COSI Protocol (2)  in line with the COSI Protocol . The sam2) . Nutriti2) . In addipost-hoc tests and ANOVA were employed to explore differences between the proposed means. The data were analyzed statistically using the Statistical Package for the Social Sciences: IBM SPSS Statistics v.20.0.1.0 . Statistical significance was set at p < 0.05.The descriptive statistics were expressed as a mean and standard deviation for each variable, as well as its range, while Analysis of study population characteristics is presented in The anthropometric characteristics of the study population are shown in p = 0.042), whereby boys were more likely to be overweight. Overweight and obesity prevalence rates are shown in Interestingly, significant differences were found in overweight prevalence between boys and girls in equivalent age groups (p = 0.01), whereby boys and girls from the northern region were more likely to be overweight (p = 0.83).This study aimed to determine the influence of geographic region and type of settlement on overweight and obesity of school children. Primarily, it was found that the geographical region significantly affects the overweight prevalence rate among 6–9-year-old children from Montenegro (erweight . In contp = 0.04), also in favor of girls. The influence of the geographic region and type of settlement on obesity is shown in p = 0.01), while the level of urbanization also did not show any influence on the obesity prevalence rates among the study population (p = 0.81).Significant differences in obesity prevalence rates were also found between boys and girls in equivalent age groups  and took into account exclusively school children aged 6–9 years.The results of this study indicate that the overall prevalence of overweight (including obesity) was 28% (15% of overweight and 13% of obese children). These results are similar to those from previous studies that included the Montenegrin population, but a noticeable increase in overall overweight, especially obesity, was observed , 23, 24.Although a slightly higher overweight prevalence rate was observed in boys compared to girls in most European countries, the situation is different in school children aged 6–9 years from Montenegro. Specifically, it has been observed that the boys have a significantly higher overweight prevalence rate. Namely, the overweight (including obesity) prevalence rate was 31% in boys (17% overweight and 14% obese school children), while in girls the rate was 25% (14% overweight and 11% obese school children). It is interesting to indicate that a lower prevalence rate in girls was observed only in France, Portugal, and Slovakia, while in most other European countries, the rate was almost uniform  prevalence rate. A tendency for higher prevalence rates in relation to the age of both sexes is observed in this study. However, the mentioned difference is much more noticeable between the school children who have just started attending school (the first grade) and the older school children who have longer school tenures (the second and third grades). The prevalence rates were significantly lower in the younger population, but drastic differences were not observed in second-grade children and onward. A similar situation was observed in all European Union member states where the data were collected for the purposes of the global report ; howeverIt was assumed that the lifestyle in Montenegro should depend significantly on the geographical region in which people live, as well as on the level of urbanization. Therefore, the hypotheses that were tested in this study were set. In support of this claim, it is important to mention that it is widely recognized that several factors influence the increase in the prevalence of overweight and obesity in childhood, such as the level of physical activity, diet, genetics, socioeconomic status and climate . MonteneIn contrast, although it was assumed that it would affect the prevalence rate, no differences were found between populations living in different types of settlements, as is the case in Serbia, where it was found that the risk of being overweight and obesity are strongly associated with a lower level of urbanization . A similIn conclusion, it should be noted that the overweight and obesity prevalence rate among 6–9-year-old children is within an acceptable range in Montenegro, since it is on the European average. However, this does not mean the situation is good enough and that solving this global problem should be neglected in the coming period. Therefore, it is necessary to undertake certain activities that should be reflected in the design of a sustainable strategy at the national level, which, with the help of decision-makers, would lead (1) to the establishment of a national protocol for the permanent monitoring and evaluation of overweight and obesity prevalence in Montenegro, (2) to apply the adequate interventions that would lead to reductions in the rates of the prevalence of overweight and obesity among Montenegrin school children and bring them as close as possible to the average prevalence rate similar to countries from Central Asia, and (3) to initiate more significant investments in scientific research in the field of health-enhancing physical activity, as decision-makers would receive updated recommendations prepared in accordance with the latest knowledge reached from contemporary scientific research.However, like any other study, this one is not without certain limitations. The limitation of this study is reflected, above all, in the fact that many cases of overweight and obesity in men and women in Europe can be attributed to inequalities in socio-economic status, whereby obesity and overweight in children are related to the socio-economic status of parents, which this study did not take into account. For this reason, it is obvious there is huge space for upcoming studies that would include the above-mentioned factors in their hypotheses, as well as many other variables related to the use of technology, and, more precisely, answer the research questions this study sets. An additional limitation is related to the fact that a significant number of studies criticized the protocol used in this study and emphasized its shortcomings, especially in the Western Balkans region, where school-age children deviate significantly from their peers from the WHO core reference sample . Therefore, the recommendation for future research is based on the fact that this protocol for assessing the rate of overweight and obesity prevalence among Western Balkan school-age children should be used with caution or some more reliable protocol might be applied such as underwater weighing, measurements with calipers, waist-to-hip ratio measurements, and dual-energy X-ray absorptiometry. Perhaps, machine learning applied to the prediction of obesity and overweight will be one of the potential solutions that might provide solutions in this area in the future.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.IV wrote the manuscript, collected the data, performed analyses, and revised the manuscript. JP wrote the manuscript, reviewed previous studies, discussed the results, and revised the manuscript. All authors contributed to the article and approved the submitted version.


Cancer is a significant threat to public health and a leading cause of morbidity across the globe. Of all cancers, brain cancer can be particularly catastrophic as treatment often fails to achieve the desired degree of effectiveness and diagnosis remains associated with a high mortality rate. Africa, as a continent with resource‐limited countries, needs to allocate the necessary proper healthcare infrastructure to significantly reduce cancer rates and improve patient survival. In addition, the relative paucity of data within this field in Africa makes effective management a challenge.This review is aimed at elucidating the currently available evidence base with regard to the epidemiology and etiology of brain cancer within resource‐limited African countries. This review hopes to bring to the attention of the wider clinical community the growing burden of brain cancer within Africa and to encourage future research into this field of research.The available literature for this Systematic Review was searched on two bibliographic databases, PubMed and Scopus, using an individually verified, prespecified approach. In addition, the Global Cancer Observatory and Global Burden of Disease databases were also utilized. Studies reporting on the epidemiology, etiology, and impact of brain cancer in Africa were suitable for inclusion. The level of evidence of the included studies was considered as per the Centre for Evidence‐Based Medicine recommendations.Out of the four databases searched, 3848 articles were initially screened rigorously, filtered into 54 articles, and finally assessed qualitatively and quantitatively. We have demonstrated a poor survival rate and lack of proper funds/resources necessary to report, identify, and treat cases, as well as the dearth of comprehensive research on the subject of brain cancer that has become a challenging healthcare concern in many African developing nations. Also, because of the gradual improvement in healthcare facilities and the increasing population within many countries in Africa, the number of patients with central nervous system and intracranial tumors is rising specifically in the elder population. In addition, the population in West Africa is at a higher risk of HIV‐related malignancies due to the high prevalence of HIV in West Africa. The burden of brain cancer in Africa is increasing in comparison with the developed parts of the world in which it is decreasing. Moreover, the mismanagement of cancers in Africa leads to higher morbidity and mortality and decreased quality of life.This study addresses the burden of brain cancer as a major public health crisis in Africa. Improved treatment modalities and access to screening are required to better address the burden of this disease. Therefore, there is a clear need for more substantial and comprehensive research on etiology, epidemiology, and treatment of brain cancer within Africa to understand its epidemiological distribution and provide a means for managing and reducing the associated morbidity and mortality. However, more than 90% occur in the brain  has increased by 45% since 2000, resulting in more than 500,000 deaths each year Bollyky, . In contThe histologic profile and method of treatment are two important prognostic factors  and Global Burden of Disease (GBD) were the databases screened for literature using an independently approved, predetermined search strategy . The following criteria were specified as inclusion criteria: (i) publications discussing epidemiology; (ii) articles discussing etiology; (iii) the effect of brain cancer in Africa; (iv) studies published after 2005; and (v) articles published in English. Commentaries, editorials, and nonclinical investigations were excluded.2.3All African continent populations were included in the study; however, there were no data on the North African population.2.4The Centre for Evidence‐Based Medicine criteria  in blind duplicate. Additionally, the risk of bias was independently inspected and rated at the study and outcome levers in accordance with the Cochrane Handbook for Evaluating Study Quality .3n = 1060), while another one was excluded because of lack of retrieval. Only 130 articles were included after the full‐text screening and further 77 articles were removed from the final cluster of articles. The reasons for exclusion ranged from irrelevant subjects to not focusing on brain tumor/neoplasms and statistical data pertaining to countries not from Africa or artificial intelligence predictive models. Fifty‐three studies were finally included for quantitative and qualitative analysis . The database search returned 3848 articles. After deduplication and title and abstract screening, 1191 articles (30.95 %) remained. Most articles were excluded because they aggregated cancer of all organs without distinctions  inclusion criteria cover just 1% of the covered population  of these cases were present in children  is positive (22.5%) in the low‐sociodemographic index (SDI) and negative (−13.4%) in medium‐SDI countries ., 2008. Yet, after accounting for the increase in CNS malignancies between 1990 and 2016, as well as its role in causing significant morbidity and mortality worldwide, the burden of CNS cancer in Africa is underreported. Variability in diagnostic and reporting techniques, as well as unidentified environmental and genetic risk factors, is likely to contribute to a considerable geographical and regional disparity in the incidence of CNS malignancies.Consequently, there is a mismanagement of cancers in Africa, leading to higher morbidity and mortality and a worse quality of life. Despite its limited resources and diagnostic abilities, Africa has a huge battle to fight the dual burden of the rising communicable diseases and the ever‐present noncommunicable diseases.This review reveals the scarcity of proper reporting on the disease and suggests that the real burden of brain cancer, already positive, is yet to be appropriately reported in Africa.The table below Table  summariz4In conclusion, this study addresses the major public health crisis caused by brain cancer in the African continent, which has been overshadowed by the historic focus on communicable infectious diseases. First, the study revealed unreliable and discrepant data; thus, it would be inaccurate to report that the incidence increase is true across all African countries. However, this review recognizes several contributing factors to the increasing prevalence of brain tumors within Africa and identifies these factors as individual opportunities for strategies to address the growing burden of this disease. If brain tumors are to be effectively managed and controlled within Africa, then these factors must be addressed in a multimodal and multidisciplinary manner.Consequently, the lack of a proper and well‐structured healthcare system in the African continent has led to an incomplete understanding of brain cancer's actual impacts: diagnosis, symptoms, risk factors, screening, and treatment of brain cancer are incompletely studied. However, knowledge and awareness about these deficiencies are crucial in providing appropriate medical services and establishing a trustworthy database of brain cancer statistics in Africa. This should be a priority, as the incidence of brain cancer is increasing due to demographic changes and other modifiable factors such as radiation, HIV, and nutrition.Secondary prevention of brain cancer and the establishment of effective strategies are needed to overcome the population's lack of awareness of this rising threat. Further efforts should focus on fighting the increasing incidence, morbidity, and mortality of these cancers as well as their impacts on the community. This requires a strong healthcare system that consists of well‐structured healthcare facilities and the incorporation of public health agencies and brain cancer societies. It will also need international organizations to collaborate and fund research regarding epidemiology, etiology, and treatment of brain cancer in Africa, as well as to share their experience.This review recommends that evidence‐based brain cancer treatment and prevention should be implemented in Africa, and a greater degree of related research should be done locally to bridge the existing knowledge gap. These requirements, which are currently considered obstacles toward controlling brain cancer in Africa, can be overcome by ensuring adequate human resources and adequate budgetary allocation to the health sector and brain cancer research within Africa.Olivier Uwishema conceptualized the idea of the study, administered the project, and reviewed and designed the manuscript. Kristian Steen Frederiksen performed supervision, reviewed the final draft, edited the first and second drafts, and made critical comments. Olivier Uwishema reviewed and edited the first draft. Burhan Dost and Ignatius Esene reviewed and edited the third draft. Gail Rosseau reviewed and edited the fourth draft. Rawa Badri reviewed and edited the final draft and performed data analysis and interpretation. All authors collected and assembled the data, wrote the manuscript, and given final approval to the manuscript.This study has not received any financial support.The authors declare no conflicts of interest.https://publons.com/publon/10.1002/brb3.3112.The peer review history for this article is available at


When I started my career in managed care in 1980, the pharmacy benefit was an add-on to the standard medical coverage and not viewed as a particularly valuable benefit by employer groups. A separate rider was offered to employers to add this coverage, and many balked at the additional modest cost to expand their benefits to include drugs. One third of the membership had this benefit in those early years, with a 2-tier generic-brand design and copays of $1 and $3 for up to a 30-day supply. Some plans even offered up to a 6-month supply at a single dispensing and chose to market the pharmacy benefit as a point of differentiation from competitors. The uptake of this benefit option was significant over the next 10 years because patients wanted insurance coverage for medications and predictable out-of-pocket costs. By the end of the decade, nearly 100% of members had a drug benefit, and employers required this as part of the standard benefit package for their employees.JMCP article “Effects of a 3-Tier Pharmacy Benefit Design on the Prescription Purchasing Behavior of Individuals with Chronic Disease” examines the shift from 2-tier to 3-tier designs 10 years later, with a focus on achieving 2 primary objectives: (1) to promote an increase in the use of lower-cost generic products and (2) to increase the use of formulary agents while reducing the use of nonformulary products. The results of the analysis supported these objectives and also raised concerns regarding the need for patients with chronic diseases to have access to appropriate medications at reasonable out-of-pocket costs.Published in 2003, the accompanying The pharmacy benefit has come a long way since these early versions when drug costs were very low, many diseases could be treated with branded and generic drugs from different therapeutic classes, and the categories of orphan disease treatments or specialty drugs were essentially nonexistent. These early pioneers of pharmacy benefit management shared the same clinical, professional, financial, and patient-focused concerns of pharmacy managers in the health care market today.Rebates were not mentioned in the 2003 article as a key driver for the formulary tiering, although they were used in the market at that time. The total volume and dollar values of the rebate programs were not significant enough to aggressively drive formulary decisions. This has certainly changed in the market today, with rebates playing a significant role in the drug review and coverage process. In many cases, rebates may be a principle driver for formulary positioning in competitive therapeutic classes. Formulary managers must balance the clinical, qualitative, and financial components of each medication to achieve an optimal benefit design that meets the needs of patients, providers, and payers.JMCP article, the challenges of addressing double-digit cost increases while maintaining choice for providers and patients is practiced today, as well. While adherence was identified as a concern, the article focused more on the potential for reduced adherence due to increased patient cost or restrictions due to the nonformulary positioning of products. Today, we continue to be concerned about adherence; however, additional factors are considered because of the scientific complexity and toxicities of many agents in the market today. The nonadherence issue continues to plague our system, with rates hovering around 50% for many chronic diseases.As referenced in the We are all well aware of the typical benefit designs employed today in the market, with 4-tier and 5-tier closed formulary designs as the most prevalent. Patients are often required to pay full price for nonformulary or noncovered products. The significant number of approvals by the U.S. Food and Drug Administration in recent years, including many orphan drugs and other high-cost specialty drugs, has led to an explosion of unique tier designs and structures to blunt the cost of these agents. Copays are being replaced by coinsurance, and many patients must satisfy deductibles for pharmacy and medical expenses before more broad coverage and reduced out-of-pocket benefits are available.In the market today, we continue to see significant use of generic drugs at rates of 85%-90% of total prescription volume across all patient groups, including commercial, Medicare, Medicaid, and the health exchanges. The bigger challenge that health plans face today is the management of high-cost specialty medications, and traditional formulary tier designs that do not provide the adequate methodology to control the cost of these agents. Coinsurance is used for most of these agents, although, there is usually a cap on the total out-of-pocket cost per prescription to help the patients afford these medications.Employers continue to pressure health plans to lower their monthly premiums for the fully insured business or the administrative fees for the self-insured business. These demands have led to an increase in the use of deductibles for pharmacy and medical benefits. These deductibles can be $2,000-$5,000 per year for an individual or family plan, with most patients experiencing these costs for medication use. Virtually all specialty medications would require the patients to spend $2,000-$5,000 for the first prescription of the benefit year before traditional benefits would apply. Plans continue to struggle with balancing the need to lower costs and allow reasonable access to products for patients with chronic or rare diseases.A majority of manufacturers now offer copay assistance programs for select medications, and patients can access these to offset the cost of the medications at the pharmacy. In many cases, this assistance can apply to the deductibles and help the patients satisfy this requirement and gain access to more standard copay or coinsurance coverage for their medications. Recently, a number of plans have begun to employ copay-accumulator programs that do not allow manufacturer assistance to satisfy deductible requirements for the pharmacy benefit. This would be an interesting area of future study to examine the effect of these programs on patient compliance and persistence with drug therapy or the potential use of the emergency room as a lower cost option due to standard copays that may be lower than the patient’s pharmacy deductible limits.Another significant market change has been a focus on shifting from volume to value in how we manage benefits and medications. Many plans have now turned their attention to value-based insurance designs and outcomes-based pharmaceutical contracting. For many years, the health plan formulary committees would evaluate new drugs and make coverage decisions based on the pivotal clinical trial data and rarely track or monitor actual outcomes going forward. Today, we see many plans requiring manufacturers to go at risk for the cost of medications when expected clinical outcomes are not achieved. This is a particular need as we see an expansion of multimillion-dollar cell and gene therapies that may provide long-term benefit provided that patients respond to treatment.We now face unprecedented changes in our health care system with the explosion of new treatments and technologies. New pioneers are needed to develop innovative and comprehensive strategies to meet this demand. AMCP continues to provide the tools, resources, and forum to help drive this process as we face a future with endless possibilities to discover and unlock the keys to successful management and treatment of chronic and rare diseases in our patient populations.


The Directive 2010/63/EU has been in force for more than a decade and has brought about significant improvements and novel requirements for the welfare of animals used for scientific purposes, while safeguarding research integrity. The Directive sets clear provisions for its scope, the authorization procedures, animal welfare bodies, national committees, cost/benefit analysis, severity classification, retrospective assessment, and statistical reporting, among many others. From this perspective, indicative areas in the existing legislative texts and guidance documents, which may influence animal welfare and scientific integrity, have been identified by the authors. Suggested solutions to address these areas by potential future revisions in the legislation are discussed, with the aim to clarify and simplify them for all actors involved.The Directive 2010/63/EU of the European Parliament and of the Council has been in force for more than a decade and has brought about significant improvements and novel requirements for the welfare of animals used for scientific purposes, while safeguarding research integrity. The Directive sets clear provisions for its scope, the authorization procedures, animal welfare bodies, national committees, cost/benefit analysis, severity classification, retrospective assessment, and statistical reporting, among many others. From this perspective, indicative areas in the existing legislative texts and guidance documents, which may influence animal welfare and scientific integrity, have been identified by the authors after years of working in this field. Suggested solutions to address these areas by potential future revisions in the legislation or other actions to benefit animal welfare are discussed, with the aim to clarify and simplify them for all stakeholders involved. The Directive 2010/63/EU is the outcome of a decade of consultation among stakeholders in order to uphold animal welfare, while concomitantly enabling scientists to conduct research under specific regulations [The revision, which led to the Directive 2010/63/EU, was based on four main sectors, including scope, authorization procedures, ethical review process, and cost/benefit analysis. Furthermore, significant issues such as education and training of staff, national committees for the protection of animals used for scientific purposes, alternative approaches, new requirements for social housing, and provision of enrichment to animal enclosures were included. Regulated procedures were defined as those that are at least equivalent to the insertion of a needle in accordance with good veterinary practice.The Directive 2010/63/EU currently provides a high welfare standard for animals used for scientific purposes. Furthermore, the amendment of the Directive with Regulation 2019/1010/EU contributed significantly to the increase in the transparency of information for the public, since the latter imposes horizontal provisions on the alignment of reporting obligations in the field of environmental legislation “and increasing transparency for the benefit of the public, for instance with the use of harmonized templates for the publication on non-technical summaries, related retrospective assessments as well as implementation and statistics” , as wellThe aim of the present perspective is to highlight areas that can be seen as grey zones that may affect animal welfare and scientific integrity in the existing legislative framework and guidance documents, as well as to indicate some gaps and issues identified in practice during recent years in Greece that could be addressed by potential revisions. This perspective is not intended to come across as overly critical, but aims very much at trying to be beneficial and to have a positive impact on the application of the Directive and animal welfare.In the following sections, indicative areas in the legislative or guidance documents, identified as having a potential effect on animal welfare with possibilities for improvement, have been selected based on our experience with the issues that have arisen during the implementation of Directive 2010/63/EU in Greece, without this selection being exhaustive. While we acknowledge that our experience with the Directive derives from working in one Member State, several of these issues may also potentially be applicable to other Member States to a certain degree. The areas of concern are briefly described and discussed, in the sequence that they are presented in the Directive, and future solutions or actions to be taken are suggested.The Education and Training (E&T) Framework document developed by the European Commission, as guidance to assist the Member States on how the requirements of the Directive may be met, and to facilitate its implementation, sets out the knowledge and skills required to ensure competence and facilitate free movement of personnel . It is rMember States may of course set strict educational requirements in their transposition of the Directive to safeguard animal welfare.Additionally, it may be beneficial to animal welfare if there were many available courses to train official inspectors in their duties, who work for the Competent Authorities and conduct audits of establishments, i.e., official controls for the implementation of the Directive 2010/63/EU in breeder, supplier and user establishments. A possible solution could be for the European Commission to organize training courses similar to those of DG SANTE “Better Training for Safer Food” (BTSF), which is a training initiative for Competent Authorities and stakeholders in Member States and non-EU countries, for various topics including animal welfare official controls [This is an important topic regarding the purposes for which procedures on live animals may be carried out, as mentioned in element (f) of Article 5 of the Directive 2010/63/EU  manages In addition to veterinary students, scientists using animals for scientific purposes also need to be trained using healthy live animals for some procedures in order to acquire the necessary skills and become competent in the conduct of these procedures. As a general conclusion, education and training needs, particularly of some scientific professions whose hands-on learning components on live animals are basic for the acquisition of competence and expertise, should be better defined, indicating, where appropriate, a tier-level approach, e.g., from dummy alternatives to dead animals to anesthetized animals to awake animals ,9. Addithttps://courses.etplas.eu/en, accessed on 30 June 2023) [https://felasa.eu/education-training/course-listings, accessed on 30 June 2023) [The process of project evaluation as described in article 38 of the Directive 2010/63/EU requests the participation of experts in the required fields, but also in the process itself, e.g., the evaluation of application forms according to legal provisions, the application of an ethical evaluation, and a harm/benefit analysis of the use of animals for the approval of a project. In most Member States, there are courses that are developed for Functions A, B, C, and D, designed according to their description in article 23 of Directive 2010/63/EU and in the E&T Framework document . The E&Tne 2023) . The proThe composition of the Animal Welfare Bodies (AWBs) in most Member States is defined by the Directive and its transposition to national legislation. In practice, the diversity of AWB’s membership depends on the availability of specialties within each establishment. The input of the designated Veterinarian is required by the Directive, without defining a mandatory participation amongst the AWB’s members. Many Member States have incorporated this designated Veterinarian membership requirement into their national legislation , which wNon-technical summaries of projects with severe procedures, the use of non-human primates, or for other reasons justified by the evaluating Competent Authority  need to be updated by the latter with the results of a retrospective assessment report according to article 43 (2) of the Directive 2010/63/EU as amended by Regulation 2019/1010/EU . To dateNTSs that are produced in EU Member States have been published in the NTS European Commission open webpage  since 1/National Reference Laboratories (NRLs) for the development and validation of alternative methods as suggested in Article 47 (2) of the Directive 2010/63/EU [There is guidance developed by the European Commission for all those involved in the oversight of and in the care and use of animals used in scientific procedures, to meet the requirements of the Directive with regard to the composition and duties of establishment Animal Welfare Bodies and the National Committee, which leave flexibility to the Member States . HoweverThe European Commission has been publishing statistical reports regarding the use of animals for scientific purposes in Member States since 1991. The reports were published every five years and then every three years from Member States . These rNarratives are drafted by the Member States’ Central Competent Authorities and are sent annually to the European Commission, which has published them separately for each Member State since 2018, in Part C of the Commission Staff Working Documents on Summary Report on the statistics on the use of animals for scientific purposes . The narFor instance, in many cases, significant increases or decreases in the use of animals are not sufficiently justified as remarkable trends by the Central Competent Authorities of Member States. Exact numbers of the species used, the re-use of some animals, and the use of Genetically Altered (GA) animals are presented repetitively by most Member States, although these are already presented in EU statistical reports on the use of animals for scientific purposes . The treAnother reason for an increase in project authorizations and, relatively, the use of animals, could be large-scale scientific project funding, such as that of Horizon 2020. In certain occasions, this is not often explained by the Competent Authorities of Member States with low numbers of animals used, despite the fact that this declaration is not required by legislation. We suggest that these Competent Authorities could try to offer a general overview of this fact, always taking into account EU data protection and national legislation, plus sensitive data on individual funding of scientists. The aim of this observation is to try to show trends in general funding that significantly increases the number of animals used during some particular years, and not presentation of specific examples that would add unnecessary administrative burden.Annex III  amendments of the Directive 2010/63/EU [The severity classification of procedures is very well described in the Directive (Annex VIII)  and inclThere was no clear provision in the Directive 2010/63/EU for GA animals. The European Commission has tried to address the above issue, plus other important issues regarding GA animals, with updated detailed guidelines, which have indeed proven to be very helpful to users and Competent Authorities . ReportiDuring these years of the implementation of Directive 2010/63/EU, Central Competent Authorities of Member States have addressed questions originating from tentative project leaders or user establishments’ supervisors about scientific ideas that need to be defined in terms of whether they fall into the scope of the Directive. Some specific examples to illustrate these issues are presented below.Projects using farmed fish , both in user establishments and commercial fish farms that have been authorized as such, have a nutritional aim and might not always be considered as projects under the scope of the Directive. It remains unclear if, for instance, changing the diet of fish is considered a procedure under the scope of the Directive 2010/63/EU, and thus needs to undergo a project evaluation and authorization. Several of these nutritional studies may be considered to belong to a grey zone regarding their licensing and reporting. These cases need to be clarified in a potential Revision of the Directive. It is noteworthy that some peer-reviewed journals require a project authorization license to have been issued for these studies, in order to be considered for publication, whereas this requirement is not clear in the Directive, despite the fact that these cases could be considered as procedures according to article 5.b.(ii) [Central Competent Authorities of Member States often receive queries about whether a research idea is considered a clinical trial or a basic research project under the scope of Directive 2010/63/EU. Clinical trials do not fall under the scope of this Directive. It often remains unclear which studies should be considered as projects and therefore need an authorization, and which do not. For example, there is a dilemma if the application of an authorized medicine  to farm animals is considered a procedure under the Directive or a veterinary clinical trial. The latter usually requires authorization by the respective national medicines’ agencies of Member States. However, no relevant clear rules are presented in the current text of the Directive 2010/63/EU [The European legislative bodies and the scientific community, as years pass, have acknowledged the need for additional guidance to be issued on topics that are not clearly addressed in the available legislative text. The aforementioned issues are only examples that have been identified by the authors that present a need of specific legislative guidance and clarifications, at least in some Member States, in order to maintain animal welfare to the highest standards and provide valuable advice to the user community for the conduct of their duties. One of these is the reporting of non-Technical Project Summaries and their related retrospective assessments, which needs to be conducted in a uniform manner throughout the Member States, including substantial information about the overall animal experience within each project.Another issue noted is the reporting of surplus animals that are euthanized without having undergone a procedure according to the Directive, which is an important matter regarding the Reduction principle applied by the management of breeder and user establishments. The experience of Central Competent Authorities of the Member States of the need for project authorizations of various scientific ideas that might not necessarily fall within the scope of the Directive 2010/63/EU but remain vague in the current text, should be effectively used by European legislative bodies, in order to further contribute to the justified use of animals for scientific purposes in the EU.It is to be hoped that all actors involved in the protection of animals used for scientific purposes will contribute with their expertise to promote new legislative and guidance documents that will address these and other issues, which will enhance animal welfare.


The optimal management of hand fractures requires a multidisciplinary approach. Initial assessment should include a thorough medical history and clinical examination, followed by appropriate radiological imaging. These are crucial in determining the appropriate management. Following joint stabilisation to allow fractures to unite, early mobilisation is needed to maximise the functional restoration of the hand. In this review, the principles of operative and non-operative management of these injuries are discussed. Hand fractures are breaks in any of the five metacarpals and the associated phalanges of the hand . This tyThe multidisciplinary team consists of the preoperative team, the intraoperative team and the postoperative team. The preoperative team, which consists of the nurse practitioner and the A&E physician and surgeon or surgeons (orthopaedic and/or plastic surgeon), are responsible for first assessing the patient in the Accident & Emergency department. The intraoperative team consists of the surgeon, the anaesthetist and theatre practitioners. Finally, the postoperative team, consisting of the ward staff and hand therapist, is in charge of the patient’s rehabilitation. The coordinated input from the aforementioned individuals is essential for the optimal restoration of hand function.This narrative review outlines the principles of management of adult hand fractures based on the latest guidelines by the National Institute for Health and Care Excellence (NICE) and the British Society for Surgery of the Hand (BSSH). This review considers the perioperative management principles that help restore optimal hand function for a patient with a hand fracture.This article will focus on the management of both closed and open fractures. Patients with hand fractures usually present to the A&E department following a fall, a sporting incident or a crush injury to the hand . On presHand examination is facilitated by comparing the injured hand to the uninjured hand, based on Apley’s principles of ‘look, feel, move’ . Any skiNeurovascular assessment must be performed. Extremities should be warm and well perfused, with a normal capillary refill time of two or less seconds, and skin temperature compared with the unaffected side . The intPain assessment should be carried out at the first presentation. This can be carried out in several ways, ranging from published tools like the visual analogue scale (VAS) which may be more useful in children, or by simply asking the patient to rate their pain on a scale of 0 to 10, with 0 being no pain, and 10 the worst possible pain . Frequeno–30o of supination for the index metacarpal, and approximately 30o of pronation for the ring and small fingers  prophylaxis . VTE is Hand dominance is an indication of how debilitating the injury will be, but other factors including the nature of the injury, occupation and medical comorbidities are all taken into account, to decide the optimal treatment plan for each patient.o–90o of flexion  see , screws Internal fixation with screws and plates stabilises the fracture site and allows for early mobilisation due to enhanced stability . In a syExternal fixators are preferred for small fracture fragments that cannot be fixed well with the aforementioned methods . ExternaA management plan is compiled by the clinical team, which includes the recovery practitioner, an anaesthetist and a surgeon .Following the patient’s surgery, a series of postoperative assessments need to take place in the post-anaesthetic care unit (PACU) and repeated on the surgical ward. First, an ABCDE assessment is carried out in PACU. After initial assessment of airway and breathing, a neurovascular assessment is carried out where possible, within the circulatory assessment. This involves assessing the capillary refill time (which should be ⩽two seconds) on the digit of the operated hand, and the integrity of the peripheral nerves  through If the patient has undergone local anaesthesia (LA), then the sensory assessment should take place after the LA has worn off. At this point, the patient is moved to the surgical ward where the patient’s pain levels should be evaluated, with analgesia prescribed in accordance with local protocols. Oral analgesia is the mainstay of pain control once the patient leaves the hospital. Analgesia prescribed should allow the patient to perform normal activities of daily living, produce minimal side effects and be easy to manage by the patient. An analgesia regime typically involves a combination of oral medications including paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs) and/or opioid-containing oral analgesics, but this is dependent on both the procedure performed and the patient’s medical history. Regardless of the choice of analgesia, the patient is counselled on what to expect, how to manage and how to use the medications prescribed.Moreover, an assessment of the patient’s wound is essential to make sure that it remains clean and intact . When chFollowing the operation, the surgeon refers the patient to the hand therapist, who manages the postoperative needs, concerns and expectations of the patient for their recovery. This can be either a physiotherapist or an occupational therapist. Their aim is to direct rehabilitation in a way that best serves the individual patient to meet their expectations and restore optimum hand function . The hanPostoperative management of hand fractures aims to balance two contradicting objectives: maintaining stability to allow for fracture healing and encouraging movement so as to permit restoration of function. Immobilisation of the joints around the operated bone will aid healing and reduce the chance of malunion while also providing greater pain relief (Stewart 2019). However, early mobilisation, through physical therapy, reduces the risk of postoperative joint stiffness while increasing the likelihood of better functional outcomes (Luschki 2016).Hand therapy is a crucial element of postoperative rehabilitation. It is a specialised process that can be performed by either a physiotherapist or an occupational therapist, and aims to optimise the patient’s hand function . Hand thIn the first few weeks, the patient is offered a range of exercises, starting from mostly passive, then active-assisted and finally active movements . As the oC during the protective phase of rehabilitation can increase the blood flow to the affected area, reduce swelling and minimise the concentration of pain mediators (There are several interventions that a hand therapist can use to adjust the physiological processes of inflammation and healing, so as to control pain management and accelerate recovery. The application of heat or thermotherapy has been documented as a supportive intervention. Superficial thermotherapy of 41–45ediators . In addiediators . Furtherediators , as wellediators . FinallyAppropriate management of hand fractures involves the provision of coordinated care across the preoperative, intraoperative and postoperative settings. Preoperative management relies on an accurate evaluation of the injury. Closed fractures can often be treated with closed reduction followed by splinting and early protected mobilisation. When surgery is indicated, internal fixation using K-wires, screws or plates is generally performed. Postoperative care should involve the input of a specialist hand therapist to maximise the restoration of function.


The minimum data set (MDS) is a collection of data elements to be grouped using a standard approach to allow the use of data for clinical and research purposes. Health data are typically voluminous, complex, and sometimes too ambiguous to generate indicators that can provide knowledge and information on health. This complexity extends further to the rare disease (RD) domain. MDSs are essential for health surveillance as they help provide services and generate recommended population indicators. There is a bottleneck in international literature that reveals a global problem with data collection, recording, and structuring in RD.This study aimed to identify and analyze the MDSs used for RD in health care networks worldwide and compare them with World Health Organization (WHO) guidelines.The population, concept, and context methodology proposed by the Joanna Briggs Institute was used to define the research question of this systematic review. A total of 4 databases were reviewed, and all the processes were reported using the PRISMA  methodology. The data elements were analyzed, extracted, and organized into 10 categories according to WHO digital health guidelines. The quality assessment used the STROBE  checklist.We included 20 studies in our review, 70% (n=14) of which focused on a specific health domain and 30% (n=6) of which referred to RD in general. WHO recommends that health systems and networks use standard terminology to exchange data, information, knowledge, and intelligence in health. However, there was a lack of terminological standardization of the concepts in MDSs. Moreover, the selected studies did not follow the same standard structure for classifying the data from their MDSs. All studies presented MDSs with limitations or restrictions because they covered only a specific RD, or their scope of application was restricted to a specific context or geographic region. Data science methods and clinical experience were used to design, structure, and recommend a fundamental global MDS for RD patient records in health care networks.Our study highlights the difficulties in standardizing and categorizing findings from MDSs for RD because of the varying structures used in different studies. The fundamental RD MDS designed in this study comprehensively covers the data needs in the clinical and management sectors. These results can help public policy makers support other aspects of their policies. We highlight the potential of our results to help strategic decisions related to RD.PROSPERO CRD42021221593; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=221593RR2-10.1016/j.procs.2021.12.034 The minimum data set (MDS) is a collection of data elements to be grouped in a standard approach to allow the use of data for clinical and research purposes. An MDS is designed to capture essential data elements, which can be aggregated, at an individual level, or a combination of both, depending on the specific requirements of the registry and research objectives.Data standardization allows for the accurate comparability of collected data and, consequently, improved generalization of findings . Many coWith the high volume of fragmented data in different health services, a validated, stable, and safe MDS is essential to support the use of clinical-administrative elements and information to generate national health statistics. As noted by the World Health Organization (WHO), it can help elaborate models of service performance and patient satisfaction to meet the growing health demands of HISs worldwide. Therefore, the development of HISs relevant to public health should be able not only to generate data but also understand and manage the produced information. They should also provide indicators to represent the true health context of a given population and provide subsidies to monitor the quality of treatments offered by health services .However, health data are typically voluminous, complex, and sometimes ambiguous to generate indicators that can provide knowledge and information on health. Thus, raw data must be ordered, interpreted, and transformed into information  that musThis complexity extends further to the rare disease (RD) domain. RDs are pathologies with a low prevalence in the general population, with <50 cases per 100,000 individuals . AlthougMany countries have initiated national plans to promote care, research, and technology in RD. These plans focus on enabling health managers to improve the services provided in a contextualized way . In addiOwing to the complexity of the areas of knowledge related to RD, initiatives have been developed to provide informational support to health networks that provide services, care, and research in RD . The besIn Brazil, the Brazilian Policy for Comprehensive Care for People with Rare Diseases of the Ministry of Health of Brazil established reference services in RD that offer preventive, diagnostic, and therapeutic actions for people with rare conditions . There iRede Nacional de Doenças Raras [RARAS]) was designed to create an epidemiological surveillance structure. This network encompasses all reference services for RDs enabled in Brazil and brings together university hospitals and reference services for neonatal screening from all regions of the country [MDS is essential for health surveillance, providing services, and generating recommended population indicators. However, the national policy in Brazil does not support the structured use of validated MDS in health services . To addr country .The RARAS project is conducting the first nationally representative survey in Brazil on the epidemiology, clinical scenarios, diagnostic and therapeutic resources, and costs related to individuals with RD of genetic and nongenetic origin. Project managers developed their own data collection protocol in the absence of a standardized global MDS reference. Although we identified this information bottleneck in Brazil, the international literature describes a global problem with data collection, recording, and structuring in RD .This study aimed to identify and analyze the MDSs used for RD in health care networks worldwide and compare them against WHO guidelines. The secondary objectives were to verify MDS implementation and study quality, map the collection of data elements, suggest a global fundamental MDS for RD, improve diagnostic and care processes, and optimize public planning and decision-making.The population, concept, and context (PCC) methodology proposed by the Joanna Briggs Institute was used to define the research question of this systematic review. The PCC strategy is recommended as an alternative to the population, intervention, comparison, and outcome model for investigations without well-defined clinical intervention . A totalThese questions were formulated to help answer the following central question: “What is the minimum data set used in registries for RDs in health networks?”To improve the transparency and reproducibility of the review, we registered it in the Prospective Register of Systematic Reviews international database under the identifier CRD42021221593 .The inclusion criteria were research papers , national plans, policies, industry reports, position papers, and program reports. Studies published in Portuguese, English, and Spanish were included. Owing to the specificity and novelty of the proposal, we included publications from any time. Only studies that fully described MDS for RD and its practical implementation as a health strategy were included. Furthermore, only studies that answered our research question and provided clear evidence on the subject were included.Publications without the scientific rigor to answer our research question using clear and objective evidence were excluded from this systematic review. We excluded personal editorials, studies using only theoretical approaches without practical implementation , and social media publications. Studies published in languages other than those listed in the inclusion criteria were also excluded. In addition, studies that used an MDS for RD but did not describe all the data elements that comprised the MDS were excluded.The concepts used to create the search strategy came from PCC methodology and were adapted using Medical Subject Headings, the vocabulary thesaurus of the National Library of Medicine used for indexing articles, and metadata for health sciences .Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS). We also searched for documents from the WHO and government websites for additional studies. These databases were chosen because of their robustness and relevance in the clinical and health arenas. A total of 4 databases were reviewed: PubMed, Scopus, Web of Science, and The Google Scholar database was also used for manual searches and searching for references to theses and dissertations. These documents are part of the gray literature because they are not published in commercial media. Searching through such sources can reduce publication bias, increase the comprehensiveness and timeliness of reviews, and provide a balanced picture of available information . RD clinAfter conducting searches using the terms specified for the mentioned databases, the review authors independently screened the titles and abstracts of each retrieved article for eligibility for synthesis according to the inclusion and exclusion criteria. Next, the full texts were retrieved, and the investigators independently performed another round of reviews to determine whether these full texts met the eligibility criteria. The reviewers were not blinded to the journal titles, study authors, or associated institutions.The points of divergence between the 2 reviewers were identified, and a third independent evaluator resolved the disparities. Search results and the process used to screen for eligibility in this phase were reported using the PRISMA   methodolWe initially conducted a pilot test to extract data from the selected articles. Subsequently, we aligned our data extraction method with the PRISMA checklist . A serieThe general characteristics and context of the selected studies were extracted and organized into tables: authors, publication year, title, study design, territorial dimension, national context, study objective or objectives, sample size, data analysis method, study population, guidelines followed, the health domain in which the MDS was deployed, and the main findings of the selected studies.After defining the articles included and extracting their general characteristics, we analyzed these documents to identify the MDSs used in health networks. We extracted all data elements that formed each of the implemented MDSs. To do this in an organized manner, we classified the informational elements into 10 categories: eligibility, identification, diagnosis, treatment, medical consultation, comorbidity, hospitalization, examination, outcome, and others. These categories were determined according to WHO digital health guidelines  and pracWe organized all identified MDS data elements from each included study into one of these categories. We observed that many articles described MDS data elements with different names corresponding to the same information . For example, the data element that represents the information about the age at which the first symptoms of the disease were identified in diagnosed patients were described in different forms in different papers, such as “Age at onset,” “Age at first symptoms in clinically diagnosed patients,” or “Age at initial symptoms.” Clinical experts in RD identified these ambiguities, and different terms with the same meaning were aggregated as unique terms (the most commonly used), synonyms were recorded, and analyses of the terms’ frequencies were adjusted.We initially compiled and categorized all the findings from the primary studies included in the systematic review to develop the base structure for fundamental MDS. This preliminary categorization followed WHO guidelines and recommendations for health indicators ,23. SubsSeveral guidelines for reporting clinical research results are available on the Equator Network website . None ofThe last STROBE recommendation includes 2 topics directly relevant to data quality reporting. The first refers to the importance of measuring each data element of interest and providing data sources and details of the assessment methods, describing the comparability of the assessment methods when applicable. The second section explains how to address and treat the missing data. In addition, qualitative evaluations of the evidence were independently performed by 2 researchers. If disagreements occurred, the issue was referred to a third researcher for a decision .We adopted the STROBE recommendations to specifically cover the normalization of the importance of each data set found in the reported articles and their evaluation methods regardless of study design. After normalization into data set categories and study designs, we also qualitatively compared descriptions of their features and how to overcome and map the gaps reported in these findings.In addition, we have used the PRISMA methodology to organize and formally present the overall results obtained by comparing individual reports and to provide a transparent evaluation according to the topics described by the PRISMA checklist. These checklist items are essential for the transparent reporting of a systematic review. We addressed most of these items, except topics related to meta-analysis, which did not apply to this review .We aimed to combine the findings of similar studies into subcategories using a consensus among specialists. We did not exclude studies with inadequate quality from the data synthesis. Descriptive statistics were used to report the frequency and proportion of the outcome measures.The subgroup analysis method was used to describe the possible reasons for the heterogeneity of the data extracted from the selected studies and to facilitate the synthesis of information via tabulation and visual arrangement so that we could later carry out the necessary analyses.When considering the reporting method of a single instrument, proportions indicating the percentage of studies using that instrument were calculated. Next, the selected resources were analyzed and interpreted. The main contents related to the research objective were classified as RD minimum data elements. The sections were then classified into 2 general categories, management data and clinical data, which is an efficient method for categorizing health data .We identified 407 studies in the initial database search phase. After removing duplicates, 337 articles remained for the title and abstract screening stage, 290 of which were excluded because they were irrelevant to this review. We evaluated 47 full-text articles based on the inclusion criteria. Of these, 19 articles were excluded because they did not answer the stipulated research question, and 8 articles were excluded because they only mentioned an MDS strategy for RD and did not describe the data elements or provide information about implementation in practice. The detailed process is shown in A total of 20 unique studies were included in this systematic review. The general characteristics of these studies are described in Of the 20 selected studies, 70% (n=14) referred to a specific health domain and the remaining 30% (n=6) referred to RD in general. Of the studies that referred to a specific domain, 2 studies were dedicated to the composition of MDS for juvenile dermatomyositis ,41, 2 toThe remaining 6 studies that presented MDSs focused on the domain of RD in general ,37,43,44All the data collected and compiled, as well as their occurrences in the MDSs of the studies included in this systematic review, have been described in In the eligibility category, the term “patient consent” appeared the most; of the 17 terms in this category, 13 were unique. In the identification category, “patient’s name” was the most common term, and 5 unique terms were observed among the 25 included in this group. Of the 148 terms in the diagnostic category, “diagnosis” was the most frequent (appearing 11 times), and 32 were unique. In the treatment category, “date treatment started” was the most common term, appearing 6 times; of the 72 terms in this category, 29 were unique. In the medical consultation category, “anthropometric data” was the term that appeared the most; of the 180 terms, 78 were unique.Of the 17 terms, “disease malignancy” was the most common in the comorbidity category, with 8 unique terms. In hospitalization, of the 5 terms, “history of hospitalization” appeared most frequently (3 times). In the examination category, “general and specialized laboratory tests” were the most common among the 42 terms, of which 29 were unique. In the outcome category, “date of death” was the term that appeared the most, comprising 11 of the 57 terms, and in the others category, “the patient having previously provided a biological sample for research” was the most frequent term, comprising 2 of the 26 terms used in this category.By combining these findings with the extraction, categorization, and synthesis techniques mentioned earlier, we used data science methods and clinical experience to design, structure, and recommend a fundamental global MDS for RD patient records in health care networks. It aims to comprehensively cover the data needed in clinical and management contexts. These summarized results can be found in The results of the risk of bias evaluations for the 20 included studies are presented in Using a matrix of 440 cells generated by crossing the 22 STROBE recommendations with the 20 selected studies, we found that 48.4% (213/440) of the items evaluated in all studies showed a low risk of bias and 39.1% (172/440) of these items had an unclear risk of bias. The remaining 12.5% (55/440) of the items assessed across all the studies had a high risk of bias.In addition, the STROBE recommendations with the highest number of low risk of bias assessments for this set of studies were item 5, “Setting,” and item 14, “Descriptive data,” with 17 occurrences. The recommendation with the highest number of unclear risk of bias assessments was item 12, “Statistical methods,” with 14 occurrences. The STROBE recommendation that received the highest number of high-risk bias assessments was item 3, “Objectives,” with 12 occurrences.We carried out this systematic review to elucidate the MDSs used for RD in health care network records in health care systems worldwide. The results showed a lack of terminological standardization of the concepts used in these MDSs. Different health systems may use different terms for the same concepts, hindering the interoperability, integration, and sharing of highly relevant information and knowledge to describe phenomena and generate health indicators.The WHO recommends that health systems and networks use standardized terminology to exchange data, information, knowledge, and intelligence in health. Thus, health observatories that integrate population and epidemiological data require standard semantics to collect and organize this information to enable the generation of indicators capable of positively influencing public health policies . OrphaneWe encountered difficulties in the standardization and classification of the MDSs findings. Notably, the selected studies did not follow the same standard structure for classifying the data from their MDSs. Thus, we classified all data into 10 categories.This process allowed us to summarize the information, verify its frequencies, perform statistical analysis, and analyze and identify synonyms . Clinical experts in RD and information and data scientists met in groups to verify and analyze these synonyms.Other studies have proposed MDSs for specific groups of RDs -42,45,46Europe also has some examples of registries developed nationally and applied to an international consortium, such as the Fabry Disease Registry  and REGIThe Italian National Rare Diseases Registry  and ItalA Spanish study addressed the importance of linking data to strengthen national RD registries . HoweverOther studies have developed MDSs for RD designed for international applications; however, the MDSs were determined by a national committee. This is the case for the National Institutes of Health, National Center for Advancing Translational Sciences, and Global Rare Diseases Patient Registry Data common data elements . All theTherefore, the most innovative aspect of this study is the compilation of all the data used in MDSs for RD published worldwide. The fundamental MDS developed based on the analysis of this compilation by clinical and health data specialists can benefit services, assistance, research, and management in RD. Most national health systems and RD policies can also contribute to developing methods and processes and producing information. Thus, defining an MDS may improve data reliability to align strategies to enhance and manage health planning . AlthougThus, the literature indicates the need to identify and implement common data elements  to improMDS is usually developed by reviewing the scientific literature, consulting with experts, and considering existing guidelines and recommendations. Although some of our findings report that they followed these processes in a combined or individual way, all were performed considering only a specific geographic context or addressed aspects related to a condition or subgroup of RD. Although a systematic review is an approach to synthesizing comprehensive scientific evidence, developing MDS involves reviewing the scientific literature, consulting with experts, and considering existing guidelines to identify essential data for RDs. Our systematic review approach provided a rigorous and transparent methodology to ensure the reliability and validity of the information collected and synthesized.Identifying common trends and patterns can further simplify and streamline the information-gathering process, avoiding the need to develop and implement different data sets for each RD. This mapping saves time and resources, allowing for more efficient data collection. Sharing resources and knowledge plays a key role in supporting the research and development of therapies for rare conditions.Variations in documentation practices in health systems can also lead to inconsistencies in data collection and standardization related to RD. These variations may include differences in the terminology used, coding systems, and data recording policies. Gaps in capturing these essential data elements can arise because of a lack of consensus on the most relevant information for understanding and studying RD. Existing data sets do not encompass all the aspects necessary for a comprehensive investigation, leading to the need for an MDS that identifies and incorporates essential data elements for scientific research in this field. This will allow for better comparison between different studies and registries.Our study has some potential limitations. Among these, we highlight the methodological aspects of choosing the quality assessment method, publications, and generalization bias. In addition, we emphasize the potential for further investigations and possible outcome variations in different populations, contexts, and types of RD.Owing to the originality and nature of the proposal, we did not define restrictions regarding the study design in our inclusion and exclusion criteria. Thus, all study designs were considered for inclusion in this systematic review. Therefore, selecting a method for assessing the quality of these studies is a nontrivial task, as such methods are usually designed to assess specific types of study designs. To mitigate this limitation, it was necessary to adopt the STROBE method in our proposal so that we could assess the quality of each of the selected studies using a standard tool. In addition, in the sequence, we cite possible biases and describe how to mitigate them.This review may be affected by publication bias, as studies with positive results are more likely to be published than those with negative or inconclusive results. This can lead to a distorted view of the existing MDSs for RD. Therefore, we took several steps to reduce the risk of publication bias affecting our results, such as searching for multiple sources, recording the review, and contacting specialists. Recording the review process increases transparency, reduces the risk of publication bias, and promotes a more rigorous and impartial evaluation of available evidence. This helps avoid omitting relevant studies or data that may not align with the desired results. By keeping a comprehensive record, reviewers and readers can assess the potential impact of any publication bias and ensure that the review is conducted objectively and impartially .Measures adopted to minimize the risk of excluding studies that were not published in scientific journals included the use of gray literature databases, prepublication repositories, clinical trial records, and scientific conferences. Finally, we contacted experts in the field to identify unpublished or ongoing studies that were not found in the systematic search.Possible biases that may affect the generalizability and comparability of the findings must also be mentioned. Although there was no specific tool to mitigate the issue of generalization bias, it is worth highlighting that the studies included in this analysis were selected based on clear and well-defined criteria. During the data analysis process, we considered the differences between studies, such as population characteristics, study design, and data quality. Ultimately, our goal was to present the findings of our work clearly and transparently using valid instruments from the literature . We alsoOur work discusses the difficulties in standardizing and classifying findings from MDSs for RD because of differences between studies. Clinical experts and data scientists have defined categories based on WHO guidelines to address this issue. This study aimed to compile MDS data from around the world and suggest a fundamental MDS for use in RD services, assistance, research, and management. The fundamental RD MDS designed in this study comprehensively covers the data needs in the clinical and management sectors.The results can also help public policy makers achieve other aspects of their policies. For example, analyzing the state data produced by HISs is essential for qualifying and quantifying the care provided to people with RDs. It can also allow comparisons with local data regarding preventive actions provided to a community. This can improve decision-making at the managerial and local levels and contribute data that can inform strategic decisions at the national level .In conclusion, the solid base of information compiled regarding MDSs for RD is a technical and social contribution to improving the health network’s ability to map its demands and better understand the public health scenario regarding rare conditions. Although the proposal of a fundamental MDS for RDs is highly relevant and, to our knowledge, unprecedented in the literature, we also suggest collecting data elements to be used in addition to this fundamental MDS, if necessary, for each group or type of RD, to increase the completeness and specificity of the data structure.Owing to the high complexity of care processes involving RDs, structured information can significantly impact the quality of services offered to the population. A curated description of the methodology for developing an MDS for RD in low- and middle-income countries has not yet been published. We encourage further research in this context.National data gathering for RD based on standard data sets to encourage interoperability by disseminating agreed-upon data-sharing guidelines can facilitate semantic data standardization. On an organizational level, it can assist institutions in establishing a registry, sharing deidentified data with research networks, and building specific and rich databases. On the basis of these results and the proposal of a fundamental MDS, we aimed to provide evidence-based subsidies to assist managerial and clinical RD processes in health systems.