Universal antiretroviral therapy for HIV‐infected children: a review of the benefits and risks to consider during implementation

Background : The 2016 World Health Organization (WHO) consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection, recommended to start all HIV‐infected children on antiretroviral therapy (ART). Here, we explore the possible benefits and risks of implementing universal ART for all HIV‐infected children and adolescents and outline some of the key considerations that led to the 2016 revision of WHO guidelines. Methods : We conducted a review of the published data from 2000 to 2016, to ascertain the clinical and programmatic benefits, as well as the risks of implementing universal ART for all children. Results and discussion : Universal ART for all children has the potential to increase treatment coverage, which in 2015 was only 51% globally, as well as providing several biological benefits, by preventing: premature death/loss to follow‐up, progressive destruction of the immune system, poor growth and pubertal delay, poor neuro‐cognitive outcomes and future burden to the health care system with complications of untreated HIV‐infection. However, the strategy could be associated with risks, notably development of HIV drug resistance, antiretroviral drug toxicities and increased costs to an already stretched health system. Conclusion : Overall, our findings suggest that the benefits could outweigh the risks and support universal ART for all HIV‐infected children, but recognize that national programmes will need to put measures in place to minimize the risks if they choose to implement the strategy.     

《2020年世界卫生组织运动和久坐行为指南》解读

世界卫生组织(World Health Organization,WHO)于2020年11月发布了《2020年WHO运动和久坐行为指南》.此次指南相较于2010年WHO运动指南纳入了更广泛的医学证据,并对特殊人群进行了针对性的推荐.其主要内容包括对儿童及青少年、成年人、老年人、孕产妇、慢性病群体及残障群体的运动和久坐建...     

Updates of pancreatic neuroendocrine neoplasm in the 2017 World Health Organization classification

The new 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNEN) modifies the previous 2010 version with new grading and staging systems to provide a better prognostic stratification and therapeutic guidance. The discovery of heterogeneity in WHO 2010 G3 category leads to the introduction of the new ‘well‐differentiated neuroendocrine tumor G3’ entity, which is distinct from the poorly‐differentiated pancreatic neuroendocrine carcinoma (PanNEC). The latest findings from molecular studies of PanNEN allow us to have a better understanding of respective biology of PanNET and PanNEC. This review aims at highlighting refinements in the 2017 classification and discusses some of the molecular updates in PanNEN.     

Latest Novelties on the World Health Organization Morphological Classifications of Genitourinary Cancers

The World Health Organization (WHO) releases a periodic press classification describing updates of standard worldwide nomenclature of tumors in different organs and a brief synopsis on their primarily pathological diagnostic criteria and clinical significance. The prior edition of the WHO book on the classification of Tumors of the Urinary System and Male Genital Organs was published in 2004. In the current review, we provide the updates that were included in the 2016 edition of the WHO Classification of Tumors of the Urinary System and Male Genital Organs and are most pertinent to clinical practice. Due to a large time gap between the 2004 and 2016 editions, there are many changes that are substantially influential for both clinical and pathological practices of urological oncology. This review covers the updates in the urothelial tract, kidney, testicular, and prostate tumors as well as authors’ practices in the areas that remained unresolved.     

Determination of age-specific bone mineral density and comparison of diagnosis and prevalence of primary osteoporosis in Chinese women based on both Chinese and World Health Organization criteria

The aim of this study was to determine age-specific bone mineral density (BMD) at various skeletal regions in a native Chinese reference population, and to explore the differences in the diagnosis of primary osteoporosis and estimated prevalence of osteoporosis based on both Chinese criteria (BMD of subjects, 25% lower than the peak BMD) and WHO criteria (BMD of subjects, 2.5 SD [T-score –2.5] lower than the young adult mean [YAM]). There were 3406 subjects in our female reference population, ranging in age from 10 to 90 years. A dual-energy X-ray absorptiometry (DXA) fan-beam bone densitometer (Hologic QDR 4500A) was used to measure the BMD in subjects at the posteroanterior (PA) spine (L1–L4), supine lateral spine (L2–L4 including areal BMD [aBMD] and volumetric BMD [vBMD]), hip (including femoral neck and total hip), and radius + ulna ultradistal (R + UUD) of the forearm. Cross-sectional data analysis in stratified 5-year age intervals revealed that the peak BMD (PBMD) at various skeletal regions occurred within the age range of 30–44 years, with PBMD at the lateral spine and femoral neck occurring at 30–34 years, posteroanterior spine and total hip at 35–39 years, and ultradistal forearm at 35–44 years. The reference values of BMD (PBMD) calculated using Chinese criteria for the diagnosis of primary osteoporosis were significantly higher than the young adult mean (YAM) using WHO criteria for all skeletal regions except for the total hip, at a range of 0.9%–3.8% higher. The BMD cutoff values using Chinese criteria for the diagnosis of osteoporosis were 3.7%–10.9% higher than those using WHO criteria for various skeletal regions. The prevalence rate of primary osteoporosis according to Chinese criteria in subjects ranging from 50 to 90 years was 41.5% at the PA spine, 53.9% at the lateral spine, 34.2% at the femoral neck, 30.7% for total hip, and 51.4% at R + UUD; while according to WHO criteria, this rate was 32.1% at the PA spine, 34.9% at the lateral spine, 16.3% at the femoral neck, 18.9% for total hip, and 45.2% at R + UUD. The prevalence of primary osteoporosis according to both criteria varied with the age and skeletal region of the subjects. The prevalence of primary osteoporosis using Chinese criteria, compared with WHO criteria was 31% higher at the lumbar spine, 109% higher at the femoral neck, and 14% higher at the ultradistal forearm. In conclusion, PBMD occurs in the age range of 30–44 years in native Chinese females. The BMD reference values, BMD cutoff values, and prevalence of primary osteoporosis determined by Chinese criteria are all higher than those determined by the WHO criteria; thus, the application of Chinese criteria may overestimate the number of patients with primary osteoporosis.     

Implementation of the World Health Organization checklist and debriefing improves accuracy of surgical wound class documentation

Background

Surgical wound classification (SWC) is a component of surgical site infection risk stratification. Studies have demonstrated that SWC is often incorrectly documented. This study examines the accuracy of SWC after implementation of a multifaceted plan targeted at accurate documentation.

Methods

A reviewer examined operative notes of 8 pediatric operations and determined SWC for each case. This SWC was compared with nurse-documented SWC. Percent agreement pre- and postintervention was compared. Analysis was performed using chi-square and a P value less than .05 was significant.

Results

Preintervention concordance was 58% (112/191) and postintervention was 83% (163/199, P = .001). Appendectomy accuracy was 28% and increased to 80% (P = .0005). Fundoplication accuracy increased from 44% to 84% (P = .016) and gastrostomy tube from 56% to 100% (P = .0002). The most accurate operation preintervention was pyloromyotomy and postintervention was gastrostomy tube and inguinal hernia. The least accurate pre- and postintervention was cholecystectomy.

Conclusion

Implementation of a multifaceted approach improved accuracy of documented SWC.     

Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumors: Hypopharynx,Larynx, Trachea and Parapharyngeal Space

In this article, we review the chapter on tumors of the larynx, hypopharynx, trachea and parapharyngeal space in the new edition of the WHO book, focusing on the new developments in comparison to the previous edition. Squamous cell carcinoma (SCC) and its variants are by far the most common malignancies at these locations, with very limited new insights. The most important is the introduction of new targeted treatment—checkpoint inhibitors, with a new task for pathologists, who may help to predict the response to treatment by analyzing the expression of targeted proteins in biopsy samples. Precancerous lesions remain a controversial topic and, similarly to other organs, it is acceptable to use the terms “dysplasia” or “squamous intraepithelial lesion” (SIL), but there is a slight difference between low-grade dysplasia and low-grade SIL: in the former, mild atypia must be present, while the latter also includes hyperplastic epithelium without atypia. Two approaches have been proposed: a two-tiered system with low- and high-grade dysplasia/SIL and a three-tiered system with an additional category, carcinoma in situ. We are still searching for reliable diagnostic markers to surpass the subjectivity in biopsy diagnosis, with a few potential candidate markers on the horizon, e.g., stem cell markers. Other tumors are rare at these locations, e.g., hematolymphoid, neuroendocrine and salivary gland neoplasms, and are no longer included in Chapter 3. They must be diagnosed according to criteria described in specific chapters. The same holds true for soft tissue tumors, with the exception of cartilaginous neoplasms, which are still included in Chapter 3.     

A Clinical Tool to Measure the Components of Health-Care Transition from Pediatric Care to Adult Care: The UNC TRxANSITION Scale

Objective: To describe the development of the University of North Carolina (UNC) TR_xANSITION Scale that measures the health-care transition and self-management skills by youth with chronic health conditions. Methods: Item and scale development of the UNC TR_xANSITION Scale was informed by two theoretical models, available literature, and expert opinion interviews and feedback from youth with chronic conditions, their parents, and interdisciplinary collaboration. Through an iterative process, three versions of the scale were piloted on a total of 185 adolescents and emerging adults with different chronic illnesses. This clinically administered scale relies on a semi-structured interview format of the patient and does not rely solely on patient report, but is verified with information from the medical record to validate responses. Results: Following the item development and the three iterations of the scale, version 3 was examined in a more intensive fashion. The current version of the UNC TR_xANSITION Scale comprises 33 items scattered across the following 10 domains: Type of illness, Rx=medications, Adherence, Nutrition, Self-management, Informed-reproduction, Trade/school, Insurance, Ongoing support, and New health providers. It requires approximately 7–8 min to administer. With a sample of 128 adolescents and young adults, ranging in age from 12 to 20, inter-rater reliability was strong (r = 0.71) and item-total correlation scores were moderate to high. Content and construct validity were satisfactory, and the overall score was sensitive to advancing age. The univariate linear regression yielded a beta coefficient of 1.08 (p < 0.0001), indicating that the total score increased with advancing age. Specifically, there was about a one point increase in the total score for each year of age. Conclusion: The UNC TR_xANSITION Scale is a disease-neutral tool that can be used in the clinical setting. Initial findings suggest that it is a reliable and valid tool that has the potential to measure health-care transition skill mastery and knowledge in a multidimensional fashion.     

Prognostic Accuracy of Individual Uropathologists in Noninvasive Urinary Bladder Carcinoma: A Multicentre Study Comparing the 1973 and 2004 World Health Organisation Classifications

Background

Grading of noninvasive papillary urinary bladder carcinoma (PUC) is routinely performed in clinical oncologic practice; however, reports regarding diagnostic and prognostic accuracy are contradictory.

Objective

To compare the 1973 and 2004 World Health Organisation (WHO) classifications in terms of interobserver variability and prognostic implications.

Design, setting, and participants

Two hundred PUC were retrospectively reviewed by four independent expert genitourinary pathologists blinded with respect to patient identity and clinical outcome. Tumour grading was assigned according to the 1973 and 2004 WHO classifications. Surveying a mean postsurgical follow-up of 71.8 mo (range: 18–163 mo), clinical outcome in terms of recurrence-free and progression-free survival was recorded for all patients.

Intervention

All of the patients underwent transurethral resection of the bladder.

Measurements

The generalised κ (kappa statistic) for interobserver variability was calculated, and Kaplan-Meier analysis as well as univariate regression analysis were performed to evaluate prognostic implications in terms of recurrence and progression rates.

Results and limitations

During the follow-up, a total of 84 (42%) patients experienced recurrence, whereas another 18 (9%) patients featured disease progression. Owing to the rare presence of papillary urothelial neoplasms of low malignant potential (PUNLMP) in our cohort (0–3.5%), the 2004 WHO classification approached a two-tier system (low and high grade), which showed less interobserver variability than the 1973 classification (κ: 0.30–0.52 vs 0–0.37, respectively). In comparing the power of both classifications to separate indolent from aggressive PUC, striking pathologist-dependent differences became apparent.

Conclusions

Both WHO classifications for grading of PUC suffer from substantial interobserver variability, with the 2004 WHO classification showing less interobserver variability. Stark differences in the prognostic power of the individual grading approaches were also found. These significant differences in the individual interpretation of the WHO grading schemes for noninvasive PUC highlight the necessity of better-defined criteria for conventional tumour grading; otherwise, the subdivision into prognostically different groups by conventional histomorphology might remain of limited value.     

General application of the National Institute for Health and Clinical Excellence (NICE) guidance for active surveillance for men with prostate cancer is not appropriate in unscreened populations

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Active surveillance (AS) is a well‐recognised management strategy to minimise the morbidity associated with radical treatment of prostate cancer. The National Institute for Health and Clinical Excellence guidelines initially suggested that all men with low‐risk prostate cancer should first be offered AS. The cohort of men with upstaging and upgrading of prostate cancer from diagnosis to final pathology has been described in North American and European populations. As the rate of PSA testing in Britain is lower than North America and parts of Europe, the risk of more advanced disease at diagnosis of prostate cancer is higher. The present study is one of the first to examine this cohort in a British population and found the rate of features of advanced disease (extracapsular extension, seminal vesicle involvement and Gleason 4 + 3, or 8–10) to be 37.2%.

OBJECTIVE

• ? To determine if the National Institute for Health and Clinical Excellence (NICE) guidelines for men with low‐risk prostate cancer were generally applicable in unscreened populations.

PATIENTS AND METHODS

• ? Retrospective analysis of prospectively collected case series from a single tertiary care centre in England.
• ? In all, 700 consecutive men treated for prostate cancer from 2005 by robot‐assisted laparoscopic prostatectomy (RALP) were included.
• ? Patients satisfying NICE criteria for low‐risk disease (PSA level < 10 ng/mL and Gleason score ≤ 6 and cT1–2a) had their pathological samples analysed for advanced disease, defined as extracapsular extension (ECE: pT3), seminal vesicle involvement (SVI), Gleason sum 7, or 8–10 or node‐positive disease.

RESULTS

• ? In all, 275 patients (39.2%) met the NICE low‐risk criteria, but pathologically advanced disease was found in 37.2% of this group.
• ? There was ECE in 71 patients (25.8%), 10 had SVI (3.6%), nine (3.3%) had Gleason score 7 (4 + 3), and 12 had Gleason sum 8–10 (4.4%).

CONCLUSIONS

• ? The NICE guidance was developed largely on data from North America where populations are highly screened using PSA testing. In the UK, many men with low‐risk disease features have high‐risk disease and the general applicability of the NICE guidance is questionable in unscreened populations.
• ? We recommend that radical therapy is discussed as an alternative option to active surveillance.