Changes In Guidelines Research Articles

Fasting Glucose Level on the Oral Glucose Tolerance Test Is Associated with the Need for Pharmacotherapy in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) has a rapidly increasing prevalence, which poses challenges to obstetric care and service provision, with known serious long-term impacts on the metabolic health of the mother and the affected offspring. The aim of this study was to evaluate the association between glucose levels on the 75 g oral glucose tolerance test and GDM treatment and outcomes. We performed a retrospective cohort study of women with GDM attending a tertiary Australian hospital obstetric clinic between 2013 and 2017, investigating the relationship between the 75 g oral glucose tolerance test (OGTT) glucose values, and obstetric (timing of delivery, caesarean section, preterm birth, preeclampsia), and neonatal (hypoglycaemia, jaundice, respiratory distress and NICU admission) outcomes. This time frame encompassed a change in diagnostic criteria for gestational diabetes, due to changes in international consensus guidelines. Our results showed that, based on the diagnostic 75 g OGTT, fasting hyperglycaemia, either alone or in combination with elevated 1 or 2 h glucose levels, was associated with the need for pharmacotherapy with either metformin and/or insulin (p < 0.0001; HR 4.02, 95% CI 2.88-5.61), as compared to women with isolated hyperglycaemia at the 1 or 2 h post-glucose load timepoints. Fasting hyperglycaemia on the OGTT was more likely in women with higher BMI (p < 0.0001). There was an increased risk of early term birth in women with mixed fasting and post-glucose hyperglycaemia (adjusted HR 1.72, 95% CI 1.09-2.71). There were no significant differences in rates of neonatal complications such as macrosomia or NICU admission. Fasting hyperglycaemia, either alone or in combination with post-glucose elevations on the OGTT, is a strong indicator of the need for pharmacotherapy in pregnant women with GDM, with significant ramifications for obstetric interventions and their timing.

Benefits of Acute Rehabilitation in COVID Recovered Patients and Changes in the Current Treatment Guidelines Related to COVID-19

Objective: Over the past year, clinical focus worldwide has centered on the treatment and prevention of COVID-19. The prevalence of this disease continues unabated; consequently, COVID-19 treatment modalities continue to improve. As a result, there are now more survivors of COVID-19. The expansion of this COVID-19 survivor demographic necessitates attention, specifically regarding patient rehabilitation. The benefits that rehabilitation offers to COVID-19 survivors must be examined, especially as this disease has begun to affect individuals with complex comorbidities. Design: Observational Prospective Study that followed 60 patients from admission into the Acute Medical Rehabilitation Hospital from the beginning of the pandemic up until March 2021. Data collected were analyzed to determine the benefit of acute rehabilitation in COVID-19 recovered patients in addition to the changes of the current treatment related to COVID-19. Results: Overall, acute rehabilitation significantly improved patients’ Self-Care and Mobility Section GG (GG) outcomes in their overall functional assessment. The average increase in GG overall was 29.45. Patients that only required 10 days or fewer of rehabilitation had an average GG increase of 34.1. Those that required 11-20 days of rehabilitation had an increase in GG of 26.5. Conclusions: Acute rehabilitation plays a primarily positive role in the outcome of patients with COVID-19. This increase in the GG scores can be attributed to the different therapies provided during their acute inpatient rehabilitation.

Evolving Face Mask Guidance During a Pandemic and Potential Harm to Public Perception: Infodemiology Study of Sentiment and Emotion on Twitter.

Throughout the COVID-19 pandemic, US Centers for Disease Control and Prevention policies on face mask use fluctuated. Understanding how public health communications evolve around key policy decisions may inform future decisions on preventative measures by aiding the design of communication strategies (eg, wording, timing, and channel) that ensure rapid dissemination and maximize both widespread adoption and sustained adherence. We aimed to assess how sentiment on masks evolved surrounding 2 changes to mask guidelines: (1) the recommendation for mask use on April 3, 2020, and (2) the relaxation of mask use on May 13, 2021. We applied an interrupted time series method to US Twitter data surrounding each guideline change. Outcomes were changes in the (1) proportion of positive, negative, and neutral tweets and (2) number of words within a tweet tagged with a given emotion (eg, trust). Results were compared to COVID-19 Twitter data without mask keywords for the same period. There were fewer neutral mask-related tweets in 2020 (β=-3.94 percentage points, 95% CI -4.68 to -3.21; P<.001) and 2021 (β=-8.74, 95% CI -9.31 to -8.17; P<.001). Following the April 3 recommendation (β=.51, 95% CI .43-.59; P<.001) and May 13 relaxation (β=3.43, 95% CI 1.61-5.26; P<.001), the percent of negative mask-related tweets increased. The quantity of trust-related terms decreased following the policy change on April 3 (β=-.004, 95% CI -.004 to -.003; P<.001) and May 13 (β=-.001, 95% CI -.002 to 0; P=.008). The US Twitter population responded negatively and with less trust following guideline shifts related to masking, regardless of whether the guidelines recommended or relaxed mask usage. Federal agencies should ensure that changes in public health recommendations are communicated concisely and rapidly.

Safety of lumbar puncture for people who are treated with ADP receptor antagonists.

Current guidelines state that clopidogrel and other adenosine-diphosphate receptor antagonists (ADPra) should be stopped for at least 7days before lumbar puncture (LP). This practice may delay the diagnosis of treatable neurological emergencies and may increase the risk of cardiovascular morbidity due to withholding antiplatelets. We aimed to summarize all cases under our care, in which LP was performed without discontinued ADPra. A retrospective case series study of all patients who underwent LP without interruption of ADPRa or with treatment interruption that was shorter than 7days. Medical records were searched for documented complications. Traumatic tap was defined as cerebrospinal fluid red cell count ≥ 1000 cell/μL. Incidence of traumatic tap among people who underwent LP under ADPRa was compared to traumatic tap incidence in two control groups: LP under aspirin and LP without any anti-platelet. 159 patients underwent LP under ADPRa [Age: 68.4 ± 12.1, Female: 63 (40%), 81 (51%) were treated with both aspirin and ADPRa]. 116 procedures were carried out without any interruption of ADPRa. In the other 43, the median delay between treatment interruption and the procedure was 2days (range: 1-6days). Incidence of traumatic tap was 8/159 (5%), 9/159 (5.7%) and 4/160 (2.5%) among those who underwent LP under ADPRa, under aspirin and without any anti-platelet, respectively. [X2(2) = 2.13, P = 0.35)]. No patient developed spinal hematoma or any neurological deficit. Lumbar puncture without discontinuation of ADP receptor antagonists seems safe. Similar case series may ultimately lead to guidelines change.

Spillover After Mammography Guideline Change: Evidence From State-Level Trends

Changes to which age groups are recommended for mammography may have affected screening rates for all women. This spillover effect has not previously been shown empirically in a national sample. Using data from the Centers for Disease Control and Prevention's Behavioral Risk Factor Surveillance System from 2002 to 2018, authors tested whether screening trends at a national level changed after the 2009 U.S. Preventive Services Task Force guideline change. The authors also tested whether state-level screening trends for women aged 40-49 years and 75+ years were associated with screening trends for women aged 50-74 years. Analyses were conducted in March-December 2022. In a model predicting state-level trends in screening for women aged 50-74 years, authors find positive, statistically significant associations with screening trends for women aged 40-49 years (p=0.033) and for women aged 75+ years (p<0.001). Deimplementation is difficult and important for controlling healthcare spending and delivering high value care. However, states most successful at reducing mammography screening rates among those aged 40-49 years and 75+ years also had greater reductions in recommended screening among women aged 50-74 years. More work is needed to understand and mitigate the unintended consequences of deimplementation.

Possibilities of using open chest cardiac massage in sudden, non-traumatic cardiac arrest.

Cardiopulmonary resuscitation is one of the most studied procedures in medicine. Over the years, despite numerous scientific studies, changes in guidelines, refining algorithms, expanding the availability of resuscitation equipment and educating the public, it has not been possible to improve the results of treatment of patients after cardiac arrest. Only 10% of them survive until hospital discharge. There is a well-tested medical procedure, wide application of which could improve results of resuscitation. This procedure is open chest cardiac massage (OCCM). OCCM is not a new technique, its use dates back to the nineteenth century, now it is reserved for patients sustaining trauma and those after surgical procedures. A number of experimental and clinical studies have proven its advantage over the currently preferred indirect massage (CCCM) also in the group of non- traumatic patients. Of course, OCCM is an invasive method with a number of possible complications accompanying surgical procedures, and its wide implementation would require a long-term training program, but it seems that it could be an impulse that would significantly improve survival in this group of patients.

Impact of changes in clinical practice guidelines for intra-articular injection treatments for knee osteoarthritis on public interest and social media

To summarize changes in recommendations for injection treatments for knee osteoarthritis (OA) in current clinical practice guidelines (CPGs) and to assess whether these changes have affected public interest according to Google data and content in YouTube videos. A literature search to identify CPGs revised since 2019 that provide recommendations regarding the five intra-articular injection treatments for knee OA (corticosteroid [CS], hyaluronic acid [HA], stem cell [SC], platelet-rich plasma [PRP], and botulinum toxin [BT]) was conducted to assess perspective changes for each treatment. Data from Google Trends were examined to identify changes in search volume from 2004 to 2021 using a join-point regression model. Relevant YouTube videos were divided into those uploaded before and after changes in CPGs and compared according to degrees of recommendation for each treatment to identify the effect of changes in CPGs on video production. All eight identified CPGs released after 2019 recommended HA and CS use. Most CPGs were the first to state a neutral or opposing stance concerning the use of SC, PRP, or BT. Interestingly, relative searches on Google for SC, PRP, and BT has increased greater than those for CS and HA. YouTube videos produced after CPGs changed continue to recommend SC, PRP, and BT as much as those produced before CPGs were revised. Although knee OA CPGs have changed, public interest and healthcare information providers on YouTube have not reacted to this shift. Improved methods to propagate updates to CPGs warrant consideration.

Temporal changes of patient characteristics over 12 years in a single-center transcatheter aortic valve implantation cohort

BackgroundBeneficial results of transcatheter aortic valve implantation (TAVI) compared to surgical aortic valve replacement (SAVR) in patients at all risk strata have led to substantial changes in guideline recommendations for valvular heart disease.AimTo examine influence of these guideline changes on a real-world TAVI cohort, we evaluated how risk profiles and outcomes of TAVI patients developed in our single-center patient cohort over a period of 12 years.MethodsBaseline, procedural and 30-day outcome parameters of TAVI patients were retrospectively compared between three time periods (period 1: 2008–2012, period 2: 2013–2017, period 3: 2018–2020).ResultsBetween 03/2008 and 12/2020, a total of 3678 patients underwent TAVI at our center. The median age was 81.1 years (25th, 75th percentile: 76.7, 84.9) with no significant change over time. The EuroSCORE II showed a continuous and significant decline from 5.3% (3.3, 8.6) in period 1 to 2.8% (1.7, 5.0) in period 3 (p < 0.001). Furthermore, rates of permanent pacemaker implantation, acute kidney injury, and paravalvular leakage ≥ moderate continuously declined over time. Accordingly, the 30-day mortality fell from 9.3% in period 1 to 4.3% in period 3 (p < 0.001).ConclusionDespite substantial guideline alterations, median patient age remained largely unchanged in our TAVI cohort over the past 12 years. Therefore, increased age still appears to be the main reason to choose TAVI over SAVR. However, risk profiles declined substantially. Significant improvements in early outcomes suggest favorable influence of less invasive access routes, improved device platforms and growing user experience.Graphical abstract

Impact of changes in diabetes screening guidelines on testing eligibility and potential yield among adults without diagnosed diabetes in the United States

AimsRecent USPSTF and ADA guidelines expanded criteria of whom to test to identify prediabetes and diabetes. We described which Americans are eligible and report receiving glucose testing by USPSTF 2015 and 2021 as well as ADA 2003 and 2022 recommendations, and performance of each guideline. MethodsWe analyzed cross-sectional data from 6,007 non-pregnant U.S. adults without diagnosed diabetes in the 2013–2018 National Health and Nutrition Examination Surveys. We reported proportions of adults who met each guideline’s criteria for glucose testing and reported receiving glucose testing in the past three years, overall and by key population subgroups,. Defining prediabetes (FPG 100–125 mg/dL and/or HbA1c 5.7–6.4 %) or previously undiagnosed diabetes (FPG ≥ 126 mg/dL and/or HbA1c ≥ 6.5 %), we assessed sensitivity and specificity. ResultsDuring 2013–2018, 76.7 million, 90.4 million, 157.7 million, and 169.5 million US adults met eligibility for glucose testing by USPSTF 2015, 2021, and ADA 2003 and 2022 guidelines, respectively. On average, 52 % of adults reported receiving glucose testing within the past 3 years. Likelihood of receiving glucose testing was lower among younger adults, men, Hispanic adults, those with less than high school completion, those living in poverty, and those without health insurance or a usual place of care than their respective counterparts. ADA recommendations were most sensitive (range: 91.0 % to 100.0 %) and least specific (range: 18.3 % to 35.3 %); USPSTF recommendations exhibited lower sensitivity (51.9 % to 66.6 %), but higher specificity (56.6 % to 74.5 %). ConclusionsAn additional 12–14 million US adults are eligible for diabetes screening. USPSTF 2021 criteria provide balanced sensitivity and specificity while ADA 2022 criteria maximize sensitivity. Glucose testing does not align with guidelines and disparities remain.

Calling multinational enterprises to account: CSOs, supranational institutions and business practices in the global south

AbstractHow do civil society organizations (CSOs) use state‐backed supranational institutions to call multinational enterprises (MNEs) to account? There are few studies of precisely how CSOs—union and other—use institutional power in global value chain (GVC) governance or the impact of institutional change on actor behaviour. To address this gap, we assess the impact of changes in the OECD Guidelines for Multinational Enterprises on CSO engagement with MNEs, comparing complaints lodged by CSOs before and after the Guidelines were revised in June 2011 to accommodate the rise in global prominence of the human rights and business frame. In our analysis, we focus on how constitutive and institutional power plays out in GVC governance, with special attention to the impact of institutional change on actor behaviour. Our analysis reveals that this state‐backed mechanism provides CSOs with a structure through which to address human rights violations in some MNEs’ supply chains but also that, despite its high degree of reflexivity, ongoing design flaws limit its capacity to address the uneven distribution of power not only between CSOs and MNEs, but among CSOs themselves. In doing so, we draw attention to the need for further research on the dynamic multilevel interactions between the configuration and adjustment of supranational institutions and how these mediate CSO and MNE interactions.

Current patterns of care in low-risk thyroid cancer-A national cross-sectional survey of Australian thyroid clinicians.

De-escalated treatment of hemithyroidectomy without radioactive iodine (RAI) is now accepted for patients with low-risk, well-differentiated thyroid cancer (WDTC). The benefit of long-term follow-up care remains controversial. This study aims to describe parameters associated with less than total thyroidectomy, and discharge from specialist follow-up in patients with low-risk WDTC in Australia. An online survey was distributed to Australian members of Endocrine Society of Australia, Australian and New Zealand Endocrine Surgeons, and Australian Society of Otolaryngology, Head and Neck Surgery. Clinicians completed a survey of management and follow-up care preferences for four clinical vignettes (all low-risk WDTC). 119 clinicians (48% endocrinologists, 55% male) answered at least one question. The majority (59%) of respondents recommended less than total thyroidectomy and omission of RAI in patients with WDTC <2 cm. Most (62%) would discharge a patient with micropapillary thyroid cancer within 1 year following total thyroidectomy. In contrast, for WDTC 1-4 cm, >90% of clinicians would continue specialist follow-up for at least 5 years. The majority of clinicians felt that patients experienced disproportionate fear of recurrence and were reassured by follow-up. After multivariable analysis, clinicians who participated in multidisciplinary teams (MDTs) were more likely to choose de-escalated care for both initial treatment (p = .005) and follow-up care (>5 years, p = .05). Clinician attitudes captured by this survey reflect recent changes in guidelines towards hemithyroidectomy for low-risk WDTC, particularly amongst MDT attendees. There is a need to further examine the impact of de-escalated care on fear of recurrence and quality of life in thyroid cancer survivors.

Is There a Need to Undertake Conventional Gastroscopy and Biopsy When Making the Diagnosis of Coeliac Disease in Adults?

Celiac disease is a common autoimmune condition characterized by small intestinal inflammation and mucosal damage triggered by an inappropriate immune response to ingested gluten. Gastroscopy and duodenal biopsy are currently the gold standard approach to diagnosing celiac disease in adults. However, the emergence of highly accurate serological tests for celiac disease in the last 2 decades led to a change in the pediatric guidelines to diagnose celiac disease without biopsy in selected patients. Adopting this no-biopsy approach to diagnose celiac disease in adults remains controversial, but the evidence supporting it is growing.

Trends in Gestational Diabetes Screening Practices in British Columbia from 2005–2019

ObjectivesTo examine trends in the frequency and method (one-step vs. two-step) of gestational diabetes mellitus (GDM) screening in British Columbia (BC), Canada, across subgroups of pregnant individuals in the context of changing local and national clinical practice guidelines. MethodsWe conducted a retrospective cohort study using de-identified, linked perinatal and laboratory billing data. We included all pregnancies delivered in BC after 28 weeks gestation, with screening dates between June 2004 and May 2019. We calculated the prevalence of each screening method with 95% CI overall and over time, and we examined screening practices in subgroups and different geographic regions. In October 2010, BC began recommending a one-step method; therefore, we examined time periods relative to this and other Canadian guideline changes. ResultsScreening completion increased over the study period, from 88% in 2004 to 96% in 2019. After a guideline change in 2010, use of one-step screening increased sharply from 2.0% (95% CI 1.9–2.0) to 45.2% (95% CI 44.9–45.6). Following the 2013 Diabetes Canada guideline change, one-step screening decreased to 42.8% (95% CI 42.5–43.1). Of those receiving one-step screening, 18% were diagnosed with GDM compared to 9% with two-step screening. Use of one-step screening was higher in pregnant people with risk factors and in larger urban centres. ConclusionGDM screening in BC demonstrated higher use of one-step screening among people with risk factors; however, there were strong regional disparities and considerable variation in screening practices over time and across subgroups.

Decreasing incidence of knee arthroscopy in Sweden between 2002 and 2016: a nationwide register-based study.

Several randomized trials have demonstrated the lack of effect of arthroscopic lavage as treatment for knee osteoarthritis (OA). These results have in turn resulted in a change in Swedish guidelines and reimbursement. We aimed to investigate the use of knee arthroscopies in Sweden between 2002 and 2016. Patient demographics, regional differences, and the magnitude of patients with knee OA undergoing knee arthroscopy were also analyzed. Trends in knee arthroscopy were investigated using the Swedish Hospital Discharge Register (SHDR) to conduct a nationwide register-based study including all adults (>18 years of age) undergoing any knee arthroscopy between 2002 and 2016. The total number of knee arthroscopies performed during the studied period was 241,055. The annual surgery rate declined in all age groups, for males and females as well as patients with knee OA. The incidence dropped from 247 to 155 per 105inhabitants. Over 50% of arthroscopies were performed in metropolitan regions. We showed a dramatic decline in knee arthroscopy. There is variability in the surgery rate between males and females and among the regions of Sweden.

Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

Pediatric Dysphagia: A Look Into the Training Received During Graduate Speech-Language Pathology Programs to Support This Population.

The purpose of this study was to examine academic preparation in pediatric swallowing and feeding, specifically, how speech-language pathology graduate programs were addressing pediatric swallowing and feeding, both academically and clinically, prior to guideline changes and modifications in 2020 due to updates and the global health pandemic. To gain a rounded image of speech-language pathology academic programs, two different methodological approaches were utilized. First, courses from 272 accredited programs were analyzed. Second, survey results from 100 participants were analyzed to investigate clinical clock hours and experiences received during participation in a graduate speech-language pathology academic program. Less than 1% (0.4%) of academic courses analyzed were categorized as pediatric swallowing and feeding. Greater than 90% of participants reported receiving 20 hr or less in pediatric dysphagia, assessment, or treatment. Sixty percent of participants reported not feeling well prepared at all to provide pediatric swallowing and feeding services. There are a growing number of children requiring swallowing and feeding services, a trend that looks to continue its rise. Pediatric dysphagia is a complex area requiring unique knowledge and skills. Academic programs have a responsibility to their students, and the individuals requiring speech-language pathology services, to provide experiences that allow for knowledge and skill development across the entire scope of practice and life span.

O01 Auditing the duration of antibiotic therapy for children treated as inpatients for community acquired pneumonia

Abstract Background Antibiotics are commonly prescribed for children with respiratory symptoms when a bacterial infection is suspected, or the patient is felt to be at higher risk of complications. However, in the context of the significant threat posed by antimicrobial resistance, it is vital for clinicians to avoid over-prescription. In November 2021, the CAP-IT randomized clinical trial reported that lower-dose and shorter duration prescriptions (3 days) of amoxicillin for community acquired pneumonia (CAP) was noninferior to higher-dose and longer-duration (7 days), with regards to the primary outcome of later need for antibiotic re-treatment. Consequently, we wanted to audit the prescribing habits for inpatient children at our hospital in relation to our trust guidelines, which at the time recommended 5–7 days of amoxicillin in simple cases of CAP. Methods We conducted a retrospective audit of children treated with antibiotics for a community acquired pneumonia on the inpatient ward of our district general hospital, between 1 November and 15 December 2021. Audit registration number was 3204–3892. We collected information on antibiotics prescribed, route of administration, allergies, duration of antibiotics, infection markers, febrile episodes, oxygen requirement, past medical history and details of X-ray performed. Results We identified a total of 30 children within the time period fulfilling inclusion criteria with a median age of 2 years (range 2 months–12 years). 12 (40%) of these children received at least one dose of IV or IM antibiotics, 18 (60%) received oral antibiotics only. 12 (40%) received amoxicillin only, 8 (26.7%) received co-amoxiclav only, and the remainder (33.3%) received a combination of antibiotics. No child had any allergy to antibiotics. The median duration of the course of antibiotics (including any prescribed as a TTA) was 7 days (range 1–9), and seven children (23.3%) received greater than 7 days of antibiotics. The median length of stay in hospital was 2 days (range 1–8 days). The median peak white cell count was 12.05, median CRP was 44. Overall 20 children (66%) required oxygen, and 6 children (20%) required high-flow oxygen. Eleven (36.7%) children were never febrile during their admission and only 3 (10%) of children had a severe underlying chronic disease. 28 (93.3%) of children had a chest X-ray performed, of which nine (32.1%) had no focal changes on the formal X-ray report, despite all receiving antibiotics. Conclusions From this audit, we identified that many children are receiving prolonged courses of antibiotics for community acquired pneumonia (7 days or more) and many are receiving antibiotics despite no focal changes identified on chest X-ray. Prescribing decisions are complex and relate to many factors including the degree of clinical concern. However, we believe this audit identified a degree of over-prescribing, particularly in the context of the results of the CAP-IT trial. Following this audit we implemented a change in trust guidelines via Paediatric Microguide, allowing prescription of a 3 day course of amoxicillin for appropriate cases of CAP. It is our aim that this will reduce over-prescribing and hence improve antimicrobial stewardship in future, with a re-audit planned for Winter 2022–23.

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non–muscle-invasive Spectrum

BackgroundTa grade 3 (G3) non–muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. ObjectiveTo evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. Design, setting, and participantsIndividual patient data for 5170 primary Ta–T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. Outcome measurements and statistical analysisTime to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. Results and limitationsTa G3 represented 7.5% (387/5170) of Ta–T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7–4.8%) of Ta G2, 13% (95% CI 9.3–17%) of Ta G3, and 20% (95% CI 17–23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. ConclusionsThe prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. Patient summaryWe used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non–muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.

Allergy: Mechanistic insights into new methods of prevention and therapy.

In the past few decades, the prevalence of allergic diseases has increased worldwide. Here, we review the etiology and pathophysiology of allergic diseases, including the role of the epithelial barrier, the immune system, climate change, and pollutants. Our current understanding of the roles of early life and infancy; diverse diet; skin, respiratory, and gut barriers; and microbiome in building immune tolerance to common environmental allergens has led to changes in prevention guidelines. Recent developments on the mechanisms involved in allergic diseases have been translated to effective treatments, particularly in the past 5 years, with additional treatments now in advanced clinical trials.

Late-onset efavirenz toxicity: A descriptive study from Pretoria, South Africa.

The neuropsychiatric side effects of efavirenz occur mainly early during treatment and are usually mild. A lesser-known and serious complication is late-onset efavirenz toxicity causing ataxia and encephalopathy. Data regarding this condition are limited. We describe the clinical picture of late-onset efavirenz toxicity, investigate co-morbidities and report outcomes. This descriptive study of all patients with late-onset efavirenz toxicity was conducted over three years at Kalafong Provincial Tertiary Hospital, Pretoria, South Africa. Forty consecutive patients were identified. Mean age was 42.1 years, three patients (7.5%) were male and the mean efavirenz level was 49.0 μg/mL (standard deviation [s.d.]: 24.8). Cerebellar ataxia (82.5%) and encephalopathy (47.5%) were the most common presenting features (40.0% had both); four patients presented with psychosis. Presence of encephalopathy and/or cerebellar ataxia was associated with higher efavirenz levels compared with psychosis (52.1 μg/mL, s.d.: 24.1 vs 25.0 μg/mL, s.d.: 17.1). In most patients, symptoms resolved, but four patients (10.0%) died, and one patient remained ataxic. Late-onset efavirenz toxicity typically presented with ataxia and encephalopathy, but psychosis can be the presenting feature. The outcome after withdrawal was good, but the mortality of 10.0% is concerning. Recent changes in guidelines favour dolutegravir, but many patients remain on efavirenz, and awareness of the condition is vital. This large, single-centre study contributes to the limited data of HIV-positive patients with late-onset efavirenz toxicity and emphasises its ongoing relevance in clinical practice.