Intracytoplasmic sperm injection 30 years on: too much of a good thing?

Intracytoplasmic sperm injection (ICSI) was introduced for male infertility but is now used in many other techniques in assisted reproduction. Indications for ICSI use need to be re-evaluated to ensure appropriate application in infertility management.

Clinical Consumption of Compound Opioid Analgesics in China: A Retrospective Analysis of National Data 2015-2018.

Compound opioid analgesics (COA) are widely used for cancer pain relief, but few studies investigated the use of that. We aimed to report the characteristics and trend of COA consumption in different regions and health facilities in China. The procurement data of two types of COA, compound codeine phosphate (CCP) and oxycodone and acetaminophen (OAA), in all medical institutions of 20 provinces from 2015 to 2018 were used. Data were presented as defined daily dose for statistical purpose (SDDD) and expenditures per million inhabitants per day. The annual consumption of COA and ratio of two combinations were compared among regions and institutions. We found, during 2015-2018, COA consumption increased at an average rate of 7.32% in SDDD and 19.19% in expenditures, while OAA accounted for most of the consumption. Highest COA consumption appeared in Northern China, with 121.72 SDDD and 1689.87 RMB (2015), whereas the lowest COA consumption was only 11.28 SDDD appearing in Southern China. The ratio of OAA and CCP (in SDDD) was highest in Southern China (53.14 in 2018), whereas lowest in West North (0.37 in 2018). In terms of institutions, tertiary had the highest COA consumption, with 16.74 SDDD and 292.73 RMB (2018). The SDDD of OAA was 27.44 times of that of CCP in tertiary, while it was only 0.11 in primary. Overall, COA consumption is on an upward trend and different among regions and health institutions in either amount or types of COA. These findings call for establishment of COA management regulations.

ENDOCRINOLOGY IN THE TIME OF COVID-19-2021 UPDATES: The management of diabetes insipidus and hyponatraemia.

COVID-19 has changed the nature of medical consultations, emphasizing virtual patient counselling, with relevance for patients with diabetes insipidus (DI) or hyponatraemia. The main complication of desmopressin treatment in DI is dilutional hyponatraemia. Since plasma sodium monitoring is not always possible in times of COVID-19, we recommend to delay the desmopressin dose once a week until aquaresis occurs allowing excess retained water to be excreted. Patients should measure their body weight daily. Patients with DI admitted to the hospital with COVID-19 have a high risk for mortality due to volume depletion. Specialists must supervise fluid replacement and dosing of desmopressin. Patients after pituitary surgery should drink to thirst and measure their body weight daily to early recognize the development of postoperative SIAD. They should know hyponatraemia symptoms. Hyponatraemia in COVID-19 is common with a prevalence of 20-30% and is mostly due to SIAD or hypovolaemia. It mirrors disease severity and is an early predictor of mortality. Hypernatraemia may also develop in COVID-19 patients, with a prevalence of 3-5%, especially in ICU, and derives from different multifactorial reasons, for example, due to insensible water losses from pyrexia, increased respiration rate and use of diuretics. Hypernatraemic dehydration may contribute to the high risk of acute kidney injury in COVID-19. IV fluid replacement should be administered with caution in severe cases of COVID-19 because of the risk of pulmonary oedema.

Will rheumatologists ever pick up the arthroscope again?

Conditions prompting physicians and surgeons first adapting endoscopes to peer into joints were mainly the sort of synovial conditions that would concern today's rheumatologists. Rheumatologists were among the pre-World War II pioneers developing and documenting arthroscopy. The post-War father of modern arthroscopy, Watanabe, found rheumatologists among his early students, who took back the technique to their home countries, teaching orthopedists and rheumatologists alike. Rheumatologists described and analyzed the intra-articular features of their common diseases in the '60s and '70s. A groundswell of interest from academic rheumatologists in adapting arthroscopy grew considerably in the '90s with development of "needle scopes" that could be used in an office setting. Rheumatologists helped conduct the very trials the findings of which reduced demand for their arthroscopic services by questioning the efficacy of arthroscopic debridement in osteoarthritis (OA) and also developing biological compounds that greatly reduced the call for any resective intervention in inflammatory arthropathies. The arthroscope has proven an excellent tool for viewing and sampling synovium and continues to serve this purpose at several international research centers. While cartilage is now imaged mainly by magnetic resonance imaging, some OA features - such as a high prevalence of visible calcinosis - beg further arthroscopy-directed investigation. A new generation of "needle scopes" with far superior optics awaits future investigators, should they develop interest.

Early colorectal cancer detection-Current and evolving challenges in evidence, guidelines, policy, and practices.

The understanding at the beginning of the last century that colorectal cancer began as a localized disease that progressed and became systemic, and that most colorectal cancer arose from adenomatous polyps gave rise to aggressive attempts at curative treatment and eventually attempts to detect advanced lesions before they progressed to invasive disease. In the last four decades, steadily greater uptake of screening has led to reductions in colorectal cancer incidence and mortality. However, the fullest potential of screening is not being met due to the lack of organized screening, where a systems approach could lead to higher rates of screening of average and high risk groups, higher quality screening, and prompt followup of adults with positive screening tests. ABSTRACT: Since the beginning of the 20th century, there has been a general understanding that colorectal cancer is a clonal disease that progresses from a localized stage with a favorable prognosis through progressively more advanced stages which have progressively worse prognosis. That understanding led first to determined efforts to detect and treat early stage symptomatic disease, and then to detect pre-symptomatic colorectal cancer and precursor lesions, where there was hope that the natural history of the disease could be arrested and the incidence and premature mortality of colorectal cancer averted. Toward the end of the last century, guidelines for colorectal cancer screening, growth in the number of technical options for screening, and a steady increase in the proportion of the adult population who attended screening contributed to the beginning of a significant decline in colorectal cancer incidence and mortality. Despite this progress, colorectal cancer remains the third leading cause of death among men and women in the United States. Screening for early detection of precursor lesions and localized cancer offers the single most productive opportunity to further reduce the burden of disease, and yet nearly four in five deaths from colorectal cancer are associated with having never been screened, not recently screened, or not followed up for an abnormal screening test. This simple observation is a call to action in all communities to apply existing knowledge to fulfill the potential to prevent avertable incidence and mortality.

Was William Harvey's commitment to experimentation reflected in his clinical practice?

The physician and physiologist Dr William Harvey is known for having discovered that the heart pumps arterial blood round the whole body and receives venous blood from the periphery, which it forwards to the lungs for reoxygenation. Harvey's discovery was based on anatomical and physiological evidence and experiments using ligatures of varying tensions. As a clinician, however, Harvey does not appear to have appreciated the value of experiments in assessing treatment effects. Although he criticised Galenic views about the clinical value of experience and authority in the absence of accompanying empirical evidence, two handwritten prescriptions that he wrote for his friend and future biographer John Aubrey provide evidence that he conformed with Galenic theory when it came to drug therapy in clinical practice. This was consistent with his senior position in the College of Physicians, whose Pharmacopoeia Londinensis was based on Galenic principles, an appreciation of which was required for entry into the College. Harvey's prescriptions reflect this and open a window onto 17th-century therapeutic practice and the personal elements on which such practice was sometimes based.

One year of the pandemic - how European endocrinologists responded to the crisis: a statement from the European Society of Endocrinology.

Changes that COVID-19 induced in endocrine daily practice as well as the role of endocrine and metabolic comorbidities in COVID-19 outcomes were among the striking features of this last year. The aim of this statement is to illustrate the major characteristics of the response of European endocrinologists to the pandemic including the disclosure of the endocrine phenotype of COVID-19 with diabetes, obesity and hypovitaminosis D playing a key role in this clinical setting with its huge implication for the prevention and management of the disease. The role of the European Society of Endocrinology (ESE) as a reference point of the endocrine community during the pandemic will also be highlighted, including the refocusing of its educational and advocacy activities.

Use of the prostate-specific antigen (PSA) test in the United States for men age ≥65, 1999-2015: Implications for practice interventions.

BACKGROUND: Various professional organizations have issued recommendations on use of the PSA test to screen for prostate cancer in different age groups. AIMS: Using Medicare claims databases, we aimed to determine rates of PSA testing in the context of screening recommendations during 1999-2015 for US men age ≥65, stratified by age group and census regions, after excluding claims relating to all prostate-related conditions. METHODS AND RESULTS: Medicare claims databases encompassed 9.71-11.12 million men for the years under study. PSA testing rate was the proportion of men with ≥1 test(s) per 12 months of continuous enrollment. Men diagnosed with any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 1999-2015, annual testing rate was 10.1%-23.1%, age ≥85; 16.6%-31.0%, age 80-84; 23.8%-35.8%, age 75-79; 28.3%-36.9%, age 70-74; and 26.4%-33.6%, age 65-69. From 1999 to 2015, PSA testing rate decreased 40.7%, 29.9%, 13.9%, and 2.9%, respectively, for men age ≥85, 80-84, 75-79, and 70-74. For men age 65-69, test use increased by 0.3%. Significant APC trends were: APC1999-2002  = +8.1%, P = .029 and APC2008-2015  = -9.0%, P < .001 for men age ≥85; APC2008-2015  = -7.1%, P = .001 for men age 80-84; APC2001-2015  = -2.5%, P < .001 for men age 75-79; APC2008-2015  = -3.3%, P = .007 for men age 70-74; and APC2010-2015  = -5.2%, P = .014 for men age 65-69. COCLUSION: Although decreased from 1999 to 2015, PSA testing rates remained high for men age ≥70. Further research could help understand why PSA testing continues inconsistent with recommendations.

Use of the prostate-specific antigen test in the U.S. for men age 30 to 64 in 2011 to 2017 using a large commercial claims database: Implications for practice interventions.

BACKGROUND: Given the public health relevance of PSA-based screening, various professional organizations have issued recommendations on the use of the PSA test to screen for prostate cancer in different age groups. AIM: Using a large commercial claims database, we aimed to determine the most recent rates of PSA testing for privately insured men age 30 to 64 in the context of screening recommendations. METHODS AND RESULTS: Data from employer plans were from MarketScan commercial claims database. Annual PSA testing rate was the proportion of men with ≥1 paid test(s) per 12 months of continuous enrollment. Men with diagnosis of any prostate-related condition were excluded. Annual percent change (APC) in PSA test use was estimated using joinpoint regression analysis. In 2011 to 2017, annual testing rate encompassing 5.02 to 5.53 million men was approximately 1.4%, age 30 to 34; 3.4% to 4.1%, age 35 to 39; 11% to 13%, age 40 to 44; 18% to 21%, age 45 to 49; 31% to 33%, age 50 to 54; 35% to 37%, age 55 to 59; and 38% to 41%, age 60 to 64. APC for 2011 to 2017 was -0.5% (P = .11), age 30 to 34; -3.0% (P = .001), age 35-39; -3.1% (P < .001), age 40 to 44; -2.4% (P = .001), age 45 to 49; -0.2% (P = .66), age 50 to 54; 0.0% (P = .997), age 55 to 59; and -3.3% (P = .054) from 2011 to 2013 and 1.2% (P = .045) from 2013 to 2017, age 60 to 64. PSA testing rate decreased from 2011 to 2017 for age groups between 35 and 49 by 13.4% to 16.9%. CONCLUSIONS: Based on these data, PSA testing rate has modestly decreased from 2011 to 2017. These results, however, should be considered in view of the limitation that MarketScan claims data may not be equated to actual PSA testing practices in the entire U.S. population age 30 to 64. Future research should be directed to understand why clinicians continue ordering PSA test for men younger than 50.

The Origins, Evolution, and Spread of Anesthesia Monitoring Standards: From Boston to Across the World.

In the mid-1980s, the anesthesia departments at hospitals affiliated with Harvard Medical School were faced with a challenge: mounting medical malpractice costs. Malpractice insurance was provided by the Controlled Risk Insurance Company (CRICO), a patient safety and medical malpractice insurance company owned by and providing service to the Harvard medical community. CRICO spearheaded an effort to reduce these costs and ultimately found a way to decrease the risks associated with anesthesia. Here, we chronicle events that led to the dramatic changes in medical practice that resulted from the activities of a small group of concerned anesthesiologists at Harvard-affiliated hospitals. We place these events in a historical perspective and explore how other specialties followed this example, and end with current strategies that minimize the risk associated with anesthesia. We conducted interviews with principals who formulated original standards of patient monitoring. In addition, we consulted documents in the public domain and primary source material. Efforts of these pioneers resulted in the establishment of the seminal Harvard-based anesthesia monitoring standards for minimal monitoring. What followed was an unprecedented transformation of the entire field. After the implementation of these standards at Harvard-affiliated hospitals, the American Society of Anesthesiologists (ASA) adopted "Standards for Basic Anesthetic Monitoring" for use during the administration of all anesthetics in the United States. Other nations have since adopted similar guidelines and these practices have resulted in significant improvements in patient safety. Currently, we estimate mortality due to anesthesia in healthy patients to be 1:400,000-perhaps as much as 10 times lower since the early 1980s. What began as an attempt to lower medical malpractice costs in a group of university hospitals became a worldwide effort that resulted in improvements in patient safety. Other specialties have adopted similar measures. Currently, an attitude and appreciation of safety are exemplified by several practices that include among others-the adherence to these patient safety guidelines, simulator training, the promulgation of standards and guidelines by ASA, and the use of a safety checklist before induction of anesthesia.

Role of phototherapy in the era of biologics.

Phototherapy is a safe and effective treatment for many dermatologic conditions. With the advent of novel biologics and small molecule inhibitors, it is important to critically evaluate the role of phototherapy in dermatology. Surveys have shown that many dermatology residency programs do not dedicate time to teaching residents how to prescribe or administer phototherapy. Limitations of phototherapy include access to a center, time required for treatments, and insurance approval. Home phototherapy, a viable option, is also underused. However, it should be emphasized that modern phototherapy has been in use for over 40 years, has an excellent safety profile, and does not require laboratory monitoring. It can be safely combined with many other treatment modalities, including biologics and small molecule inhibitors. In addition, phototherapy costs significantly less than these novel agents. Dermatologists are the only group of physicians who have the expertise and proper training to deliver this treatment modality to our patients. Therefore, to continue to deliver high-quality, cost-effective care, it is imperative that phototherapy be maintained as an integral part of the dermatology treatment armamentarium.

Confidence vanished or impaired until distrust in the doctor-patient relationship because of COVID-19: Confidence vanished or impaired until distrust: "COVID" in relationship.

Since Hippocrates, the cornerstone of medical practice has been the doctor-patient relationship. The question here is whether these basic principles are still compatible with this unusual COVID-period. This pandemic represents a serious threat to human health, leading to profound changes in behavior in daily life but also in health care. Because of limited resources, health-managers must choose well-balanced solutions able to protect patients and citizens on the one hand and to provide maximal benefit for the society on the other hand. We are going through a moment of rupture that we must acknowledge. Here, we discussed how the doctor-patient relationship could be compromised. Doctors are focused on cares whereas patients are focused on scare. Profound changes occur presently, from the way we present ourselves to each other (including the masks), the poor conditions for physical examination, the mental suffering of both patient and caregiver until sometimes terrible end-of-life conditions. The historical point-of-view helps us to keep in mind previous experiences, and the philosophical perspective helps to contextualize this unedited situation. We should stop briefly our daily rush to put these considerations into perspective to overcome these challenges. Nothing is as effective as trust: let's rebuild it.

Is ovarian cancer surgery stuck in the dark ages?: a commentary piece reviewing surgical technologies.

Ovarian cancer surgery endeavours to remove all visible tumour deposits, and surgical technologies could potentially facilitate this aim. However, there appear to be barriers around the adoption of new technologies, and we hope this article provokes discussion within the specialty to encourage a forward-thinking approach to new-age surgical gynaecological oncology.

Prescribing Paradigm Shift? Applying the 2019 European Society of Cardiology-Led Guidelines on Diabetes, Prediabetes, and Cardiovascular Disease to Assess Eligibility for Sodium-Glucose Cotransporter 2 Inhibitors or Glucagon-Like Peptide 1 Receptor Agonists as First-Line Monotherapy (or Add-on to Metformin Monotherapy) in Type 2 Diabetes in Scotland.

OBJECTIVE: In 2019, the European Society of Cardiology led and released new guidelines for diabetes cardiovascular risk management, reflecting recent evidence of cardiovascular disease (CVD) reduction with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) and some glucagon-like peptide 1 receptor agonists (GLP-1RAs) in type 2 diabetes (T2D). A key recommendation is that all those with T2D who are (antihyperglycemic) drug naïve or on metformin monotherapy should be CVD risk stratified and an SGLT-2i or a GLP-1RA initiated in all those at high or very high risk, irrespective of glycated hemoglobin. We assessed the impact of these guidelines in Scotland were they introduced as is. RESEARCH DESIGN AND METHODS: Using a nationwide diabetes register in Scotland, we did a cross-sectional analysis, using variables in our register for risk stratification at 1 January 2019. We were conservative in our definitions, assuming the absence of a risk factor where data were not available. The risk classifications were applied to people who were drug naïve or on metformin monotherapy and the anticipated prescribing change calculated. RESULTS: Of the 265,774 people with T2D in Scotland, 53,194 (20.0% of those with T2D) were drug naïve, and 56,906 (21.4%) were on metformin monotherapy. Of these, 74.5% and 72.4%, respectively, were estimated as at least high risk given the guideline risk definitions. CONCLUSIONS: Thus, 80,830 (30.4%) of all those with T2D (n = 265,774) would start one of these drug classes according to table 7 and figure 3 of the guideline. The sizeable impact on drug budgets, enhanced clinical monitoring, and the trade-off with reduced CVD-related health care costs will need careful consideration.

Trends in antidiabetic drug utilization and expenditure in Denmark: A 22-year nationwide study.

AIMS: To examine the nationwide trends in antidiabetic drug utilization and expenditure in Denmark over the past 22 years. METHODS: Data on antidiabetic use and expenditure from 1996 to 2017 were retrieved from the Register of Medicinal Product Statistics. Antidiabetic drug use is reported as defined daily dose (DDD) in total counts and per 1000 inhabitants/d. Expenditure is reported as volume sold in total counts per 1000 inhabitants and as annual mean expenditure. RESULTS: Throughout the study period, the total use of antidiabetic drugs increased from 16.4 to 55.8 DDDs per 1000 inhabitants/d, while total expenditure increased from €59 to €286 m. The introduction of glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors has, since 2005, led to considerable variation in the proportional use of the different drug classes. Use of insulin and insulin analogues accounted for the majority of the cost of antidiabetic drugs, peaking at 75% in 2008; however, its proportional impact on overall antidiabetic drug expenditure decreased to ~44% in 2017. In contrast, a steep increase in GLP-1RA expenditure was observed from 2010 to 2017, reaching an annual cost of €85 m (~29% of all antidiabetic expenditure). CONCLUSION: Antidiabetic drug utilization and cost in Denmark has increased considerably over the last 22 years, in accordance with the increased incidence of type 2 diabetes and changes in treatment guidelines. The release of several novel antidiabetic drugs seems to be responsible for the increase in antidiabetic drug expenditure.

Cost-effectiveness of Interventions to Manage Diabetes: Has the Evidence Changed Since 2008?

OBJECTIVE: To synthesize updated evidence on the cost-effectiveness (CE) of interventions to manage diabetes, its complications, and comorbidities. RESEARCH DESIGN AND METHODS: We conducted a systematic literature review of studies from high-income countries evaluating the CE of diabetes management interventions recommended by the American Diabetes Association (ADA) and published in English between June 2008 and July 2017. We also incorporated studies from a previous CE review from the period 1985-2008. We classified the interventions based on their strength of evidence (strong, supportive, or uncertain) and levels of CE: cost-saving (more health benefit at a lower cost), very cost-effective (≤$25,000 per life year gained [LYG] or quality-adjusted life year [QALY]), cost-effective ($25,001-$50,000 per LYG or QALY), marginally cost-effective ($50,001-$100,000 per LYG or QALY), or not cost-effective (>$100,000 per LYG or QALY). Costs were measured in 2017 U.S. dollars. RESULTS: Seventy-three new studies met our inclusion criteria. These were combined with 49 studies from the previous review to yield 122 studies over the period 1985-2017. A large majority of the ADA-recommended interventions remain cost-effective. Specifically, we found strong evidence that the following ADA-recommended interventions are cost-saving or very cost-effective: In the cost-saving category are 1) ACE inhibitor (ACEI)/angiotensin receptor blocker (ARB) therapy for intensive hypertension management compared with standard hypertension management, 2) ACEI/ARB therapy to prevent chronic kidney disease and/or end-stage renal disease in people with albuminuria compared with no ACEI/ARB therapy, 3) comprehensive foot care and patient education to prevent and treat foot ulcers among those at moderate/high risk of developing foot ulcers, 4) telemedicine for diabetic retinopathy screening compared with office screening, and 5) bariatric surgery compared with no surgery for individuals with type 2 diabetes (T2D) and obesity (BMI ≥30 kg/m2). In the very cost-effective category are 1) intensive glycemic management (targeting A1C <7%) compared with conventional glycemic management (targeting an A1C level of 8-10%) for individuals with newly diagnosed T2D, 2) multicomponent interventions (involving behavior change/education and pharmacological therapy targeting hyperglycemia, hypertension, dyslipidemia, microalbuminuria, nephropathy/retinopathy, secondary prevention of cardiovascular disease with aspirin) compared with usual care, 3) statin therapy compared with no statin therapy for individuals with T2D and history of cardiovascular disease, 4) diabetes self-management education and support compared with usual care, 5) T2D screening every 3 years starting at age 45 years compared with no screening, 6) integrated, patient-centered care compared with usual care, 7) smoking cessation compared with no smoking cessation, 8) daily aspirin use as primary prevention for cardiovascular complications compared with usual care, 9) self-monitoring of blood glucose three times per day compared with once per day among those using insulin, 10) intensive glycemic management compared with conventional insulin therapy for T2D among adults aged ≥50 years, and 11) collaborative care for depression compared with usual care. CONCLUSIONS: Complementing professional treatment recommendations, our systematic review provides an updated understanding of the potential value of interventions to manage diabetes and its complications and can assist clinicians and payers in prioritizing interventions and health care resources.

Twenty-five years of change in the management of the axilla in breast cancer.

Sentinel lymph node (SLN) biopsy is now used worldwide. It has led to many changes in how we manage the axilla in patients with breast cancer. This review covers four areas of management of the axilla in breast cancer: assessing the clinically node-negative axilla, managing the clinically negative axilla found to be involved at SLN biopsy, management of the clinically positive axilla in the context of neo-adjuvant chemotherapy, and treatment of the diseased axilla when radical therapy is required. We suggest that the evidence supports an optimum number of 3 nodes to be removed for accurate SLN biopsy. Breast cancer departments that have not adopted Z0011 patient management cannot continue to avoid change. The evidence is clear: Not all patients with limited axillary nodal disease on sentinel node biopsy need axillary lymph node dissection. For patients who do need axillary treatment, axillary radiotherapy continues to be under-used. Patients undergoing neo-adjuvant chemotherapy can be safely assessed by post-therapy SLN biopsy, with retrieval of any previously biopsied involved nodes by targeted axillary dissection. There is much to support the trend to doing less in the axilla. We are obliged to act based on the available robust clinical trial data in a way that limits morbidity while at the same time does not increase the risk of disease recurrence.