The pediatric patient and future fertility: optimizing long-term male reproductive health outcomes.

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.

[National survey of the therapeutic apheresis in Hungary, 2013-2017]. / A terápiás apheresisek számának és indikációjának változása, valamint új eljárások megjelenése Magyarországon 2013 és 2017 között.

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.

Choosing Wisely BMT: American Society for Blood and Marrow Transplantation and Canadian Blood and Marrow Transplant Group's List of 5 Tests and Treatments to Question in Blood and Marrow Transplantation.

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.

CONSORT Statement for Randomized Trials of Nonpharmacologic Treatments: A 2017 Update and a CONSORT Extension for Nonpharmacologic Trial Abstracts.

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.

T3 translational science in gastroenterology: getting to best outcomes.

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.

Developing standards for breakthrough therapy designation in oncology.

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.

Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration.

Adequate reporting of randomized, controlled trials (RCTs) is necessary to allow accurate critical appraisal of the validity and applicability of the results. The CONSORT (Consolidated Standards of Reporting Trials) Statement, a 22-item checklist and flow diagram, is intended to address this problem by improving the reporting of RCTs. However, some specific issues that apply to trials of nonpharmacologic treatments (for example, surgery, technical interventions, devices, rehabilitation, psychotherapy, and behavioral intervention) are not specifically addressed in the CONSORT Statement. Furthermore, considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement. Therefore, the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments. A consensus meeting of 33 experts was organized in Paris, France, in February 2006, to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments. The participants extended 11 items from the CONSORT Statement, added 1 item, and developed a modified flow diagram. To allow adequate understanding and implementation of the CONSORT extension, the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting. This extension, in conjunction with the main CONSORT Statement and other CONSORT extensions, should help to improve the reporting of RCTs performed in this field.

[Is prevention better than healing?]. / Ist Vorbeugen besser als Heilen?

Preventive and screening interventions have been met with great enthusiasm. This is due to a widespread misunderstanding of what prevention can do and what it cannot do. Initiatives for prevention or early diagnosis of disease are almost always considered beneficial. Meanwhile, however, there are many impressive examples of detrimental failures of such initiatives documented by large high-quality randomised controlled trials (RCTs). These include treatment with vitamin pills to prevent cancer or cardiovascular disease or treatment of healthy women with sexual hormones which has finally turned out to be one of the biggest scandals in medicine. Systematic self-examination of the breast to detect breast cancer early does more harm than good. Most dogmas of the modern so-called healthy diet are not supported by several recently published high-quality RCTs. On the other hand, many of the promoted prevention initiatives lack evidence from high-quality RCTs such as health checks, rectal examination, screening for renal disease or diabetes, screening for colorectal cancer by coloscopy, for prostate cancer or skin cancer. Even if effective, most screening programmes will benefit only a few but harm many more, though. Harm is due to overdiagnosis and overtreatment as well as to side effects related to the investigation itself. This includes psychological and other distress related to work-up of false test results. All prevention programmes have to undergo sound scientific evaluation before they can be recommended or implemented. Ethical guidelines ask for complete, objective, unbiased, evidence-based and understandable information for potential participants of prevention programmes. Rarely is such information provided or even available. Non-participation is an explicit option for most preventive programmes and must not be penalised.