Impact of letrozole co-treatment during ovarian stimulation on oocyte yield, embryo development, and live birth rate in women with normal ovarian reserve: secondary outcomes from the RIOT trial.

STUDY QUESTION: Does letrozole (LZ) co-treatment during ovarian stimulation with gonadotropins for in IVF impact follicle recruitment, oocyte number and quality, embryo quality, or live birth rate (LBR)? SUMMARY ANSWER: No impact of LZ was found in follicle recruitment, number of oocytes, quality of embryos, or LBR. WHAT IS KNOWN ALREADY: Multi-follicle stimulation for IVF produces supra-physiological oestradiol levels. LZ is an aromatase inhibitor that lowers serum oestradiol thus reducing negative feedback and increasing the endogenous gonadotropins in both the follicular and the luteal phases, effectively normalizing the endocrine milieu during IVF treatment. STUDY DESIGN, SIZE, DURATION: Secondary outcomes from a randomized, double-blind placebo-controlled trial (RCT) investigating once-daily 5 mg LZ or placebo during stimulation for IVF with FSH. The RCT was conducted at four fertility clinics at University Hospitals in Denmark from August 2016 to November 2018 and pregnancy outcomes of frozen-thawed embryo transfers (FET) registered until May 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS: One hundred fifty-nine women with expected normal ovarian reserve (anti-Müllerian hormone 8-32 nmol/l) were randomized to either co-treatment with LZ (n = 80) or placebo (n = 79). In total 1268 oocytes were aspirated developing into 386 embryos, and morphology and morphokinetics were assessed. One hundred twenty-nine embryos were transferred in the fresh cycle and 158 embryos in a subsequent FET cycle. The effect of LZ on cumulative clinical pregnancy rate (CPR), LBR, endometrial thickness in the fresh cycle, and total FSH consumption was reported. MAIN RESULTS AND THE ROLE OF CHANCE: The proportion of usable embryos of retrieved oocytes was similar in the LZ group and the placebo group with 0.31 vs 0.36 (mean difference (MD) -0.05, 95% CI (-0.12; 0.03), P = 0.65). The size and number of aspirated follicles at oocyte retrieval were similar with 11.8 vs 10.3 follicles per patient (MD 1.5, 95% CI (-0.5; 3.1), P = 0.50), as well as the number of retrieved oocytes with 8.0 vs 7.9 oocytes (MD 0.1, 95% CI (-1.4; 1.6), P = 0.39) in the LZ and placebo groups, respectively. The chance of retrieving an oocyte from the 13 to 16 mm follicles at trigger day was 66% higher (95% CI (24%; 108%), P = 0.002) in the placebo group than in the LZ group, whilst the chance of retrieving an oocyte from the ≥17 mm follicles at trigger day was 50% higher (95% CI (2%; 98%), P = 0.04) in the LZ group than in the placebo group. The proportion of fertilized oocytes with two-pronuclei per retrieved oocytes or per metaphase II oocytes (MII) (the 2PN rates) were similar regardless of fertilization with IVF or ICSI with 0.48 vs 0.57 (MD -0.09, 95% CI (-0.24; 0.04), P = 0.51), and 0.62 vs 0.64 (MD -0.02, 95% CI (-0.13; 0.07), P = 0.78) in the LZ and placebo groups, respectively. However, the MII rate in the ICSI group was significantly lower with 0.75 vs 0.88 in the LZ vs the placebo group (MD -0.14, 95% CI (-0.22; -0.06), P = 0.03). Blastocysts on Day 5 per patient were similar with 1.5 vs 2.0, P = 0.52, as well as vitrified blastocysts per patient Day 5 with 0.8 vs 1.2 in (MD -0.4, 95% CI (-1.0; 0.2), P = 0.52) and vitrified blastocysts per patient Day 6 with 0.6 vs 0.6 (MD 0, 95% CI (-0.3; 0.3), P = 1.00) in the LZ vs placebo group, respectively. Morphologic evaluation of all usable embryos showed a similar distribution in 'Good', 'Fair', and 'Poor', in the LZ vs placebo group, with an odds ratio (OR) of 0.8 95% CI (0.5; 1.3), P = 0.68 of developing a better class embryo. Two hundred and ninety-five of the 386 embryos were cultured in an embryoscope. Morphokinetic annotations showed that the odds of having a high KIDscore™ D3 Day 3 were 1.2 times higher (CI (0.8; 1.9), P = 0.68) in the LZ group vs the placebo group. The CPR per transfer was comparable with 31% vs 39% (risk-difference of 8%, 95% CI (-25%; 11%), P = 0.65) in the LZ and placebo group, respectively, as well as CPR per transfer adjusted for day of transfer, oestradiol and progesterone levels at trigger, progesterone levels mid-luteal, and number of oocytes retrieved (adjusted OR) of 0.8 (95% CI (0.4; 1.6), P = 0.72). Comparable LBR were found per transfer 28% vs 37% (MD -9%, 95% CI (-26%; 9%), P = 0.60) and per randomized women 24% vs 30% (MD of -6%, CI (-22%; 8%), P = 0.60) in the LZ group and placebo group, respectively. Furthermore, 4.8 years since the last oocyte aspiration, a total of 287 of 386 embryos have been transferred in the fresh or a subsequently FET cycle, disclosing the cumulative CPR, which is similar with 38% vs 34% (MD 95% CI (8%; 16%), P = 0.70) in the LZ vs placebo group. LIMITATIONS, REASONS FOR CAUTION: Both cleavage stage and blastocyst transfer and vitrification were permitted in the protocol, making it necessary to categorize their quality and pool the results. The study was powered to detect hormonal variation but not embryo or pregnancy outcomes. WIDER IMPLICATIONS OF THE FINDINGS: The similar utilization rate and quality of the embryos support the use of LZ co-treatment for IVF with specific indication as fertility preservation, patients with previous cancer, or poor responders. The effect of LZ on mature oocytes from different follicle sizes and LBRs should be evaluated in a meta-analysis or a larger RCT. STUDY FUNDING/COMPETING INTEREST(S): Funding was received from EU Interreg for ReproUnion, Sjaelland University Hospital, Denmark, Ferring Pharmaceuticals, and Gedeon Ricther. Roche Diagnostics contributed with assays. A.P. has received grants from Ferring, Merck Serono, and Gedeon Richter, consulting fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, & Merck A/S, speakers fees from Gedeon Richter, Ferring, Merck A/S, Theramex, & Organon, and travel support from Gedeon Richter. The remaining authors declare that they have no competing interests in the research or publication. TRIAL REGISTRATION NUMBERS: NCT02939898 and NCT02946684.

Enhanced recovery after surgery (ERAS) in head and neck oncologic surgery: Impact on return to intended oncologic therapy (RIOT) and survival.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) pathways in head and neck cancer (HNC) have shown to improve perioperative outcomes and reduce complications. The longer term implications on adjuvant treatment and survival have not been studied. We hereby report the first study on the impact of an ERAS pathway on return to intended oncologic treatment (RIOT) and overall survival (OS) in HNC. METHODS: 200 patients undergoing head and neck oncologic surgery on an ERAS pathway between March 1, 2016 and March 31, 2019 were matched to controls over the same interval. Demographic, tumor and adjuvant therapy-related data were collected, including time to adjuvant therapy(TAT) and treatment package time(TPT). Risk factors for TAT > 42 days and TPT ≥ 85 days were assessed. OS was compared and risk factors for inferior OS determined. RESULTS: Baseline characteristics including co-morbidities and tumor stage were similar. Of 179 patients planned for adjuvant treatment, there was no difference in RIOT rate (89.0% vs 87.5%, p = 0.753), proportion of TAT > 42 days of surgery (55.6% vs 59.7%, p = 0.642), or TPT ≥ 85 days (48.1% vs 57.1, p = 0.258), for the ERAS and control groups, respectively. On multivariate analysis, alcohol use (OR 3.58; 95 %CI 1.11-11.52) and recurrent disease status (OR 2.88; 95 %CI 1.40-5.93) were independently associated with prolonged TAT. Three-year OS was similar between the ERAS and control groups (73% vs 76%, p = 0.521). CONCLUSION: ERAS has not shown to improve RIOT or OS in the current study. However, its benefit for perioperative outcomes is undeniable and further studies are required on longer term quality and survival outcomes.

Simultaneous determination of trace level riot control agents in environmental water by solid-phase microextraction and gas chromatography coupled with a flame ionization detector.

In this paper, a direct immersion solid-phase microextraction procedure for the simultaneous analyses of four primary riot control agents: 2-chloroacetophenone, o-chlorobenzylidene malonitrile, dibenz(b,f)-1,4-oxazepine, and oleoresin capsicum at µg/L concentration from environmental water was developed. Several parameters that influence the extraction effectiveness were investigated, including fiber type, extraction temperature, extraction time, starring rate, and salinity. Under the recommended conditions, the optimized method had reasonable linearity and accuracy. The average recovery of this method ranged from 84 to 108.1%. The limit of detection for all the analytes ranged from 0.2 to 3 µg/L and the limit of quantification ranged from 1 to 10 µg/L, respectively. A relative standard deviation from 3.0 to 4.3% can be achieved depending on the compounds. The procedure was applied to analyze all the four riot control agents simultaneously in several environmental samples.

Tonsil Riots and Vaccine Hesitancy: A 100-Year Legacy of Medical Mistrust.

The "tonsil riots" of 1906 were panics that developed at several public schools in historically immigrant-dominated neighborhoods of New York City (NYC). Per archived newspaper articles, several NYC public schools asked for parental consent to have Board of Health physicians come and perform tonsillectomy and adenoidectomy on their students. When children subsequently returned home from school "drooling mouthfuls of blood and barely able to speak," mothers reacted with panic and flocked to the schools demanding the safe return of their children. Police, ultimately, had to be called in to manage the crowds, and the events of 1906 largely faded from the public eye. However, these events can offer important lessons in communication and cultural humility as the United States continues its mass vaccination against coronavirus disease 2019.

Riot-related injuries managed at a hospital in Beirut, Lebanon.

BACKGROUND: Between October 2019 and February 2020, massive crowds protested in Lebanon against economic collapse. Various less than lethal weapons including riot control agents and rubber bullets were used by law enforcement, which led to several traumatic and chemical injuries among victims. This study describes the clinical presentation, management, outcome, and healthcare costs of injuries. METHODS: A retrospective review of the hospital records of all the casualties presenting to the Emergency Department of the American University of Beirut Medical Center between October 17th, 2019, and February 29th, 2020, was conducted. RESULTS: A total of 313 casualties were evaluated in the ED, with a mean age of 30.2 +/- 9.6 years and a predominance of males (91.1%). Most were protestors (71.9%) and arrived through EMS (43.5%) at an influx rate of one patient presenting every 2.7-8 min. Most patients (91.1%) presented with an Emergency Severity Index of 3. Most patients (77.6%) required imaging with 10% having major findings including fractures and hemorrhages. Stones, rocks, and tear gas canisters (30.7%) were the most common mechanism of injury. Musculoskeletal injuries were most common (62.6%), followed by lacerations (44.7%). The majority (93.3%) were treated and discharged home and 3.2% required hospital admission, with 2.6% requiring surgery. CONCLUSION: Less-than-lethal weapons can cause severe injuries and permanent morbidity. The use of riot control agents needs to be better controlled, and users need to be well trained in order to avoid misuse and to lessen the morbidity, mortality, and financial burden.

Pellet gunfire injuries among agitated mobs in Kashmir.

BACKGROUND: Pellet gunfire injuries inflicted while controlling agitated mobs has been studied. METHODS: A total of 198 patients admitted to the Accident and Emergency Department with pellet gun injuries were studied in terms of anatomic site, severity and type of injury, treatment, and outcomes. RESULTS: 72.7% of patients were aged 16-25 years. The most common sites of injury were the extremities (47.9%), abdomen (36.3%) and chest (31.3%). 59.5% of patients were found to have minor injuries. Of the 80 patients admitted to the hospital for their injuries, 43 (53.7%) required an operative procedure. Six deaths (3.03%) were observed. CONCLUSION: While the pellet wound itself may seem trivial, if not appreciated for the potential for tissue disruption and injuries to the head, chest, and abdomen, there can be catastrophic results. Patients should be evaluated and managed in the same way as those sustaining bullet injuries.:

A revolta da vacina / The rebellion of the vaccine

Explora, de forma mais sistematica, as fontes primarias relacionadas a rebeliao que durante uma semana abalou a cidade do Rio de Janeiro e ameacou a estabilidade do governo de Rodrigues Alves - a chamada Revolta da Vacina. Busca na comparacao, tanto ao nivel da propria cidade do Rio de Janeiro como no de outras cidades, um elemento capaz de colocar em perspectiva os acontecimentos e integra-los em tipo mais abrangente de manifestacoes populares violentas, conhecido na literatura como historia da multidao.

Injuries caused by rubber bullets: a report on 90 patients.

The injuries in 90 patients caused by rubber bullets are described. There was 1 death and 17 people in the series had permanent disabilities or deformities. In 41 patients the injuries necessitated admission to hospital. One fatality outside this series is known. Injuries to the head and neck were frequent and severe.