Neoadjuvant talazoparib in patients with germline BRCA1/2 mutation-positive, early-stage triple-negative breast cancer: exploration of tumor BRCA mutational status.

BACKGROUND: Talazoparib monotherapy in patients with germline BRCA-mutated, early-stage triple-negative breast cancer (TNBC) showed activity in the neoadjuvant setting in the phase II NEOTALA study (NCT03499353). These biomarker analyses further assessed the mutational landscape of the patients enrolled in the NEOTALA study. METHODS: Baseline tumor tissue from the NEOTALA study was tested retrospectively using FoundationOne®CDx. To further hypothesis-driven correlative analyses, agnostic heat-map visualizations of the FoundationOne®CDx tumor dataset were used to assess overall mutational landscape and identify additional candidate predictive biomarkers of response. RESULTS: All patients enrolled (N = 61) had TNBC. In the biomarker analysis population, 75.0% (39/52) and 25.0% (13/52) of patients exhibited BRCA1 and BRCA2 mutations, respectively. Strong concordance (97.8%) was observed between tumor BRCA and germline BRCA mutations, and 90.5% (38/42) of patients with tumor BRCA mutations evaluable for somatic-germline-zygosity were predicted to exhibit BRCA loss of heterozygosity (LOH). No patients had non-BRCA germline DNA damage response (DDR) gene variants with known/likely pathogenicity, based on a panel of 14 non-BRCA DDR genes. Ninety-eight percent of patients had TP53 mutations. Genomic LOH, assessed continuously or categorically, was not associated with response. CONCLUSION: The results from this exploratory biomarker analysis support the central role of BRCA and TP53 mutations in tumor pathobiology. Furthermore, these data support assessing germline BRCA mutational status for molecular eligibility for talazoparib in patients with TNBC.

Emerging Risk of Adolescent Depression and Suicide Detected Through Pediatric Primary Care Screening.

OBJECTIVE: The goal of the current study was to document patterns of stability and change in adolescent depression and suicide risk detected via universal depression screening in pediatric primary care and to determine who may go on to experience emerging risk. METHODS: Retrospective electronic health record information (sociodemographic data and depression screening results for 2 timepoints) was extracted for adolescents aged 12-17 who attended well-visits between November 15, 2017, and February 1, 2020, in a large pediatric primary care network. A total of 27,335 adolescents with 2 completed depression screeners were included in the current study. RESULTS: While most adolescents remained at low risk for depression and suicide across the 2 timepoints, others experienced emerging risk (i.e., low risk at time 1 but elevated risk at time 2), decreasing risk (i.e., high risk at time 1 but low risk at time 2) or stable high risk for depression or suicide. Odds of experiencing emerging depression and suicide risk were higher among adolescents who were female (compared to males), Black (compared to White), and had Medicaid insurance (compared to private insurance). Odds of experiencing emerging depression risk were also higher among older adolescents (compared to younger adolescents) as well as adolescents who identified as Hispanic/Latino (compared to non-Hispanic/Latino). CONCLUSIONS: Findings can inform symptom monitoring and opportunities for prevention in primary care.

Adolescent Depression Symptom Trajectories Detected Via Universal Screening in Pediatric Primary Care.

Unique trajectories of adolescent depression symptoms have been identified, yet less is known about whether such patterns translate to real-world clinical settings. Because annual adolescent depression screening is becoming more prevalent in primary care, we examined whether longitudinal patterns of depression symptoms documented in the developmental psychopathology literature can also be detected via routine screening in primary care and explored how membership in the identified trajectories varied based on concurrent suicide risk and sociodemographic factors. A total of 1,359 adolescents aged 12-16 years old at the first timepoint were included in the current analyses. These adolescents completed three depression screeners during their well-visits in a large pediatric primary care network between November 15, 2017 and February 1, 2020. Retrospective electronic health record data were extracted, including sociodemographic variables and depression screening results. Dynamic functional time series clustering results indicated the optimal number of clusters was five. The five depression symptom trajectories were: (1) A-Shaped (i.e., relatively low depression symptoms at Time 1, a substantial increase in symptoms at Time 2, and a return to low symptoms at Time 3), (2) Increasing, (3) Low-Stable, (4) High-Decreasing, and (5) Low-Decreasing. Cluster differences in suicide risk largely mapped onto depression symptom levels at each assessment. We found cluster differences based on practice location, insurance type, and adolescent race. The symptom trajectories observed in this study resemble those found in the developmental psychopathology literature, though some key differences were noted. Findings can inform future research and symptom monitoring in primary care.

Spindle Cell-Predominant Trichodiscoma With Palisading Arrangement: A Rare Variant.

ABSTRACT: Spindle cell-predominant trichodiscoma (SCPT) is a benign adnexal neoplasm, best categorized within the trichodiscoma-fibrofolliculoma continuum. SCPTs clinically present as dome-shaped papules usually on the face, particularly on the nose or the nasolabial fold. The SCPT variant has been described as a particularly cellular trichodiscoma composed of small interweaving fascicles and sheets of spindle cells. Identical lesions were previously referred to as neurofollicular hamartomas because of their predominantly fascicular stromal cellularity and focal S100 positivity. In this article, we report a rare variant of SCPT with a palisaded arrangement. The patient is a middle-aged man with no significant dermatologic history who presented with a skin-colored papule on the left nasal ala. It had been present for approximately 10 years with only minimal growth over that time. A biopsy was obtained. Histopathological analysis revealed a dermal papule composed of bland spindle cells arranged in a striking palisading pattern within a fibromyxoid stroma with associated peripheral hyperplasia of sebaceous glands. The palisaded pattern shared features reminiscent of Verocay bodies of a schwannoma. Immunohistochemical studies revealed stromal spindled cells with a strong and diffuse pattern of CD34 expression and absent S100 and SOX10 expressions. To our knowledge, only 2 cases of SCPT with a palisaded pattern have been presented. SCPT with a palisaded pattern is a rare histopathologic variant that may resemble a schwannoma but can be recognized by its strong epithelial components and immunohistochemical staining pattern.

Neoadjuvant Talazoparib in Patients With Germline BRCA1/2 Mutation-Positive, Early-Stage Triple-Negative Breast Cancer: Results of a Phase II Study.

BACKGROUND: The undetermined efficacy of the current standard-of-care neoadjuvant treatment, anthracycline/platinum-based chemotherapy, in patients with early-stage triple-negative breast cancer (TNBC) and germline BRCA mutations emphasizes the need for biomarker-targeted treatment, such as poly(ADP-ribose) polymerase inhibitors, in this setting. This phase II, single-arm, open-label study evaluated the efficacy and safety of neoadjuvant talazoparib in patients with germline BRCA1/2-mutated early-stage TNBC. PATIENTS AND METHODS: Patients with germline BRCA1/2-mutated early-stage TNBC received talazoparib 1 mg once daily for 24 weeks (0.75 mg for moderate renal impairment) followed by surgery. The primary endpoint was pathologic complete response (pCR) by independent central review (ICR). Secondary endpoints included residual cancer burden (RCB) by ICR. Safety and tolerability of talazoparib and patient-reported outcomes were assessed. RESULTS: Of 61 patients, 48 received ≥80% talazoparib doses, underwent surgery, and were assessed for pCR or progressed before pCR assessment and considered nonresponders. pCR rate was 45.8% (95% confidence interval [CI], 32.0%-60.6%) and 49.2% (95% CI, 36.7%-61.6%) in the evaluable and intent-to-treat (ITT) population, respectively. RCB 0/I rate was 45.8% (95% CI, 29.4%-63.2%) and 50.8% (95% CI, 35.5%-66.0%) in the evaluable and ITT population, respectively. Treatment-related adverse events (TRAE) were reported in 58 (95.1%) patients. Most common grade 3 and 4 TRAEs were anemia (39.3%) and neutropenia (9.8%). There was no clinically meaningful detriment in quality of life. No deaths occurred during the reporting period; 2 deaths due to progressive disease occurred during long-term follow-up (>400 days after first dose). CONCLUSIONS: Neoadjuvant talazoparib monotherapy was active despite pCR rates not meeting the prespecified threshold; these rates were comparable to those observed with combination anthracycline- and taxane-based chemotherapy regimens. Talazoparib was generally well tolerated. CLINICALTRIALS.GOV IDENTIFIER: NCT03499353.

Reproducibility of the Magnitude of Lens Rotation Following Implantation of a Toric Intraocular Lens with Modified Haptics.

Purpose: To evaluate the reproducibility of magnitude of postoperative IOL rotation following implantation of a toric intraocular lens (IOL) with modified haptics, in comparison with a Proof-of-Concept (POC) study of prototype IOLs featuring the same haptic design. Patients and Methods: A post-market, prospective, multicenter, single-arm, open-label clinical study was conducted. TECNIS Toric II IOL (Johnson & Johnson Vision, Irvine, CA, USA, Models ZCU150 to 600) were implanted in 125 subjects and evaluated at 1-day and 1-week postoperatively. An objective photographic method was used to determine postoperative IOL rotation. Uncorrected distance visual acuity (UCDVA), postoperative astigmatism, and surgeon satisfaction were also assessed. Rotation data were compared to the POC study in which two prototype non-toric monofocal IOLs, one with the same haptic design as Model ZCU, were studied. Results: Mean absolute rotation was 0.82° ± 1.0° and 0.84° ± 0.92°at 1-day and 1-week visits, respectively. The percentage of eyes with ≤5° of absolute rotation was 98.9% and 99.5% at the 1-day and 1-week visits, respectively. The magnitude of rotation was similar to the POC study prototype IOLs. At 1-week, mean monocular UCDVA was 0.026 ± 0.135 (~20/21) logMAR and mean residual manifest refractive cylinder was 0.30 D ± 0.35 D. The mean signed axis difference (postoperative minus operative) of the TECNIS Toric II IOL was 0.23° ± 1.27° at 1-day and -0.07° ± 1.25° at 1-week, indicating a clockwise drift. At 1-week, surgeons were very satisfied or satisfied with overall clinical outcomes and rotational stability in 98% of implanted eyes. Conclusion: The TECNIS Toric II IOL, with frosted, squared haptics, demonstrated low magnitude of postoperative IOL rotation, excellent uncorrected distance vision, and minimal residual astigmatism. The POC study design was supported, demonstrating that prototype non-toric monofocal IOLs can predict clinical performance of toric IOLs with the same haptic design.

Most Facial Fractures Do Not Require Surgical Intervention.

PURPOSE: Literature describing the number of patients that had a facial fracture that required surgical intervention in the United States is very limited. The purpose of this study was to evaluate the percentage of patients who required surgical intervention after presenting to a Level 1 Trauma Center with 1 or more facial fractures. MATERIALS AND METHODS: This was a retrospective cross-sectional study of all patients who presented with facial fracture(s) to University Hospital, a Level 1 Trauma Center (San Antonio, Texas), over a 5-year period from July 2015 to July 2020. Patients' charts that had 1 or more International Classification of Diseases 10 codes pertaining to facial fractures were collected. Cases were subdivided by fracture location: mandible, midface, upper face, or a combination of any of the aforementioned locations (predictor variables). After subdividing based on location, each chart was then reviewed and separated based on whether or not surgical intervention was provided (primary outcome variable). Data were tabulated and analyzed with descriptive and inferential statistics. RESULTS: Over the 5-year period, 3,416 patients presented with facial fractures. Of the 3,126 patients who survived their injuries and were not lost to follow-up, the vast majority (80.9%) did not require surgical intervention for their facial fractures. Mandible fractures required surgical intervention, whether isolated or in combination, much more frequently than in patients who did not have any type of mandible fracture (RR 8.01, 95% CI 6.92-9.27, P < .05 and RR 4.60, 95% CI 3.42-6.18, P < .05, respectively). Patients aged 50 years or less were also more likely to receive surgical intervention than those aged 51 years and more (RR 1.98 95% CI 1.63-2.41, P < .05). CONCLUSIONS: The vast majority of facial fractures that present to a Level 1 Trauma Center do not require surgical intervention. Patients who present with any type of mandible fracture and are aged 50 years or less are more likely to need surgical intervention.

Outcomes of total joint alloplastic reconstruction in TMJ ankylosis.

OBJECTIVE: The purpose of this study was to evaluate subjective and objective outcomes in patients with temporomandibular joint (TMJ) ankylosis treated with TMJ alloplastic reconstruction (TMJR). STUDY DESIGN: All patients diagnosed with TMJ ankylosis that underwent TMJR at our institution between 2010 and 2019 were retrospectively reviewed. Patients were divided into 2 cohorts: bony and fibrous ankylosis. Subjective variables assessed were facial pain and headaches, TMJ pain, jaw function, diet, and disability. Objective variables assessed were maximum interincisal opening and lateral excursions. The Mann-Whitney test was employed to analyze subjective variables and an unpaired t-test was used to analyze the objective variables. P < .05 was considered statistically significant. RESULTS: Twenty-eight patients met the inclusion criteria (21 female, 7 male). The mean age at the time of surgery was 42 years, and the mean number of prior TMJ surgeries was 3. A total of 52 TMJRs were performed in the 28 patients, and the mean follow-up time was 46 months. All subjective variables were significantly improved, and the mean maximum interincisal opening increased from 16.9 mm to 37.25 mm. CONCLUSIONS: The results of the study demonstrate that TMJR is an effective and reliable method for the management of both fibrous and bony TMJ ankylosis.

Comparison of the Accuracy of Maxillary Positioning With Interim Splints Versus Patient-Specific Guides and Plates in Executing a Virtual Bimaxillary Surgical Plan.

PURPOSE: An extension of digital technology is to provide patient-specific hardware to reposition the first jaw in a bimaxillary case without the use of an intermediate splint. The purpose of our study was to determine if there were significant differences in maxillary repositioning using interim splints versus patient-specific guides and implants (PSIs) in executing a bimaxillary virtual surgical plan (VSP). MATERIALS AND METHODS: This is a retrospective cohort study of patients who underwent bimaxillary orthognathic surgery with interim splints or PSIs planned with VSP at our institution. The difference in maxillary positions from the VSP to the postoperative cone-beam computed tomography (CBCT) was evaluated in both groups. The primary predictor variable was the method by which the maxilla was repositioned (interim splint vs PSI). The primary outcome variable was the postoperative 3D position of the maxillary incisors and right and left first molars in the anteroposterior, transverse, and vertical dimensions. Differences in the planned and postoperative positions of the above landmarks in all three planes of space between the two groups were statistically analyzed. RESULTS: A total of 82 patients were included. 13 patients had their maxillae repositioned with an interim splint between the unoperated mandible and the mobile maxilla, and 69 patients had their maxilla repositioned using custom drill/cutting guides and a PSI. The mean difference between the planned and actual position of the maxilla in the PSI group was smaller than in the splint group. In the PSI group alone, vertical changes were accurate whether the maxilla was being superiorly or inferiorly repositioned. CONCLUSION: The use of a PSI provides more accurate maxillary repositioning during bimaxillary surgery than the use of an interim splint.

The Phase II MutHER Study of Neratinib Alone and in Combination with Fulvestrant in HER2-Mutated, Non-amplified Metastatic Breast Cancer.

PURPOSE: HER2 mutations (HER2mut) induce endocrine resistance in estrogen receptor-positive (ER+) breast cancer. PATIENTS AND METHODS: In this single-arm multi-cohort phase II trial, we evaluated the efficacy of neratinib plus fulvestrant in patients with ER+/HER2mut, HER2 non-amplified metastatic breast cancer (MBC) in the fulvestrant-treated (n = 24) or fulvestrant-naïve cohort (n = 11). Patients with ER-negative (ER-)/HER2mut MBC received neratinib monotherapy in an exploratory ER- cohort (n = 5). RESULTS: The clinical benefit rate [CBR (95% confidence interval)] was 38% (18%-62%), 30% (7%-65%), and 25% (1%-81%) in the fulvestrant-treated, fulvestrant-naïve, and ER- cohorts, respectively. Adding trastuzumab at progression in 5 patients resulted in three partial responses and one stable disease ≥24 weeks. CBR appeared positively associated with lobular histology and negatively associated with HER2 L755 alterations. Acquired HER2mut were detected in 5 of 23 patients at progression. CONCLUSIONS: Neratinib and fulvestrant are active for ER+/HER2mut MBC. Our data support further evaluation of dual HER2 blockade for the treatment of HER2mut MBC.

Projecting the Impact of Socioeconomic and Policy Factors on Greenhouse Gas Emissions and Carbon Sequestration in U.S. Forestry and Agriculture.

Understanding greenhouse gas mitigation potential of the U.S. agriculture and forest sectors is critical for evaluating potential pathways to limit global average temperatures from rising more than 2° C. Using the FASOMGHG model, parameterized to reflect varying conditions across shared socioeconomic pathways, we project the greenhouse gas mitigation potential from U.S. agriculture and forestry across a range of carbon price scenarios. Under a moderate price scenario ($20 per ton CO2 with a 3% annual growth rate), cumulative mitigation potential over 2015-2055 varies substantially across SSPs, from 8.3 to 17.7 GtCO2e. Carbon sequestration in forests contributes the majority, 64-71%, of total mitigation across both sectors. We show that under a high income and population growth scenario over 60% of the total projected increase in forest carbon is driven by growth in demand for forest products, while mitigation incentives result in the remainder. This research sheds light on the interactions between alternative socioeconomic narratives and mitigation policy incentives which can help prioritize outreach, investment, and targeted policies for reducing emissions from and storing more carbon in these land use systems.

Adolescent depression screening in primary care: Who is screened and who is at risk?

BACKGROUND: Limited research has simultaneously focused on sociodemographic differences in who receives recommended adolescent depression screening in primary care and who endorses elevated depression and suicide risk on these screeners. We describe screening and risk rates in a large pediatric primary care network in the United States after the network expanded its universal depression screening guideline to cover all well-visits (i.e., annual medical checkups) for adolescents ages 12 and older. METHODS: Between November 15, 2017 and February 1, 2020, there were 122,682 well-visits for adolescents ages 12-17 (82,531 unique patients). The Patient Health Questionnaire - Modified for Teens (PHQ-9-M) was administered to screen for depression. RESULTS: A total of 99,961 PHQ-9-Ms were administered (screening rate=81.48%). The likelihood of screening was higher among adolescents who were female, 12-14 years of age at their first well-visit during the study, White, Hispanic/Latino, or publicly-insured (i.e., Medicaid-insured). Additionally, 5.92% of adolescents scored in the threshold range for depression symptoms and 7.19% endorsed suicidality. Heightened depression and suicide risk were observed among adolescents who were female, 15-17 years of age at their first well-visit during the study, Black, Hispanic/Latino, attending urban primary care practices, or Medicaid-insured. Odds of endorsing suicidality were also higher among teens who identified as other races. LIMITATIONS: Limitations related to data available in the electronic health record and reliance on data from a single hospital system are noted. CONCLUSIONS: Findings highlight misalignments in screening and risk status that are important to address to ensure more equitable screening implementation and health outcomes.

A Minimally Invasive Approach for Temporomandibular Joint Replacement: A Pilot Study.

Temporomandibular joint replacement (TJR) with an alloplastic (metal/ultra-high-molecular-weight polyethylene) device has proven to be a successful and predictable procedure. This paper describes a novel technique for performing TJR with an endaural incision alone. The technique we are describing uses only an endaural incision with supplemental trocar incision(s), to perform a TJR. There were 4 patients for a total of 8 temporomandibular joints that were selected. All 4 patients were assessed immediately following surgery, on postoperative days 1 and 7 and at 6 months following surgery. Maximal interincisal opening and subjective variables were assessed at each of the time points. Additionally, the total operative time was measured and compared to a previous age and diagnosis matched control group using the traditional 2 incisions TJR.There were 3 females and 1 male (ages 19-67) who underwent TJR with an endaural incision alone. There were 4 females (ages 19-68) who underwent traditional TJR surgery. None of the patients in either group had major complications and all patients were discharged on postoperative day 1. All patients in the endaural incision alone group had increased maximal interincisal opening and reported a quicker subjective decrease in pain and disability following surgery with less average time in the operating room. However, all patients in the endaural incision alone group had CN VII weakness that lasted longer than those in the traditional TJR group.The minimally invasive approach for TJR was successful in the present pilot study and could be used in specific situations to decrease the morbidity associated with additional incisions for this procedure. Ultimately, the endaural only incision approach offers promising outcomes for future patients undergoing temporomandibular joints TJR in the right patient population.

Clinical and histopathological findings in the dead bag syndrome.

PURPOSE: To describe the findings of a recently described syndrome, the dead bag syndrome, in which the capsular bag appears to be clear many years postoperatively, becoming diaphanous and floppy and unable to support the intraocular lens (IOL) within it. SETTING: John A. Moran Eye Center, University of Utah, Salt Lake City, Utah. DESIGN: Case series with clinicopathological correlation. METHODS: Of 10 cases suspected to represent a dead bag syndrome, 8 IOLs and 7 capsular bags were removed because of subluxation or dislocation. The 7 capsular bags available for analysis were fixed in formalin and submitted to histopathological examination (hematoxylin-eosin and Masson trichrome stains). The associated explanted IOLs in 5 cases were also examined microscopically. RESULTS: Histopathologic examination of the 7 capsular bags showed capsular thinning and/or splitting. Lens epithelial cells (LECs) were completely absent on 2 specimens, whereas the other 5 specimens had rare LECs on the inner surface of the capsule. Explanted IOLs were 3-piece silicone IOLs or single-piece hydrophobic acrylic IOLs. 1 IOL optic showed a small amount of granular pigment deposition, but the optics of the other 4 IOLs were unremarkable. CONCLUSIONS: In this syndrome, there seems to be an absence of secondary proliferation of LECs and fibrotic changes. The capsule shows some signs of degradation, such as thinning and/or splitting. Weakness of zonular attachments seems to be an associated finding, with subsequent in-the-bag IOL dislocation. Further studies are necessary to ascertain the etiology of this condition.

Visual outcomes and safety of an extended depth-of-focus intraocular lens: results of a pivotal clinical trial.

PURPOSE: To compare the effectiveness and safety of the TECNIS Symfony intraocular lens (IOL; ZXR00) with the TECNIS 1-piece monofocal IOL (ZCB00). SETTING: 15 sites in the United States. DESIGN: Prospective, randomized, patient-masked/evaluator-masked clinical trial. METHODS: Randomized participants received either the ZXR00 or ZCB00 IOL bilaterally. The 6-month postoperative outcomes included monocular and binocular distance, intermediate, and near visual acuity (VA), spherical equivalent refraction and refractive cylinder, spectacle wear, and visual symptoms. RESULTS: Overall, 299 patients were implanted with a study IOL (ZXR00 IOL, n = 148; ZCB00 IOL control, n = 151). At the 6-month follow-up, mean binocular uncorrected distance VA was comparable between ZXR00 and ZCB00 IOL recipients (P = .1011). The ZXR00 IOL group had significantly better mean binocular uncorrected intermediate VA and uncorrected near VA (both P < .0001) than the ZCB00 IOL group. The mean binocular distance-corrected intermediate VA and distance-corrected near VA were also better in the ZXR00 IOL group (both P < .0001). More ZXR00 IOL recipients reported wearing spectacles none of the time or a little of the time for overall vision at 6 months compared with the ZCB00 IOL group (85.0% vs 59.9%, P < .0001). In the ZXR00 IOL-implanted patients, low incidence rates of night glare (mild to moderate, 2.7%), halo (mild to moderate, 13.6%; severe, 2.7%), and starbursts (mild to moderate, 7.5%; severe, 1.4%) were reported. CONCLUSIONS: The TECNIS Symfony IOL provided comparable distance vision and improved uncorrected and distance-corrected intermediate and near vision, along with decreased spectacle wear and low incidence rates of dysphotopsia, compared with the TECNIS 1-piece monofocal IOL.

Autotransplantation of a mature mandibular third molar as alternative to dental implant placement: Case report.

Dental autotransplantation is defined as the movement of one tooth from one position to another, within the same patient. Autotransplantation has predictable results; in fact, many studies describe a success rate of over 90%. This article describes a case report concerning the surgical management of this surgical technique. An 18-year-old patient comes for the treatment of her left first mandibular molar (3.6) involved in decay process. An accurate radiological analysis (periapical X-ray and orthopantomographic evaluation) showed an immature left mandibular third molar (3.8), suitable as donor tooth. The mandibular first molar was extracted in an atraumatic way. The intra-alveolar septum was modified with a piezoelectric device. The tooth was slightly depressed in the socket and remained in infra-occlusion. It was stabilized by sutures and a metallic splint. Then, the autotransplanted molar was fixed with a double splinting for 4 weeks. In conclusion, the autotransplantation was followed by endodontic treatment. After 36 months of follow-up, wisdom tooth showed an improvement in clinical features in agreement with radiological examination. The success of this case can be attributed to the atraumatic surgical technique and the immature stage of the transplanted element.

COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients.

BACKGROUND: The COVID-19 pandemic remains a significant global threat. However, despite urgent need, there remains uncertainty surrounding best practices for pharmaceutical interventions to treat COVID-19. In particular, conflicting evidence has emerged surrounding the use of hydroxychloroquine and azithromycin, alone or in combination, for COVID-19. The COVID-19 Evidence Accelerator convened by the Reagan-Udall Foundation for the FDA, in collaboration with Friends of Cancer Research, assembled experts from the health systems research, regulatory science, data science, and epidemiology to participate in a large parallel analysis of different data sets to further explore the effectiveness of these treatments. METHODS: Electronic health record (EHR) and claims data were extracted from seven separate databases. Parallel analyses were undertaken on data extracted from each source. Each analysis examined time to mortality in hospitalized patients treated with hydroxychloroquine, azithromycin, and the two in combination as compared to patients not treated with either drug. Cox proportional hazards models were used, and propensity score methods were undertaken to adjust for confounding. Frequencies of adverse events in each treatment group were also examined. RESULTS: Neither hydroxychloroquine nor azithromycin, alone or in combination, were significantly associated with time to mortality among hospitalized COVID-19 patients. No treatment groups appeared to have an elevated risk of adverse events. CONCLUSION: Administration of hydroxychloroquine, azithromycin, and their combination appeared to have no effect on time to mortality in hospitalized COVID-19 patients. Continued research is needed to clarify best practices surrounding treatment of COVID-19.

Three-Year Findings of the HORIZON Trial: A Schlemm Canal Microstent for Pressure Reduction in Primary Open-Angle Glaucoma and Cataract.

PURPOSE: To report 3-year outcomes of the HORIZON study comparing cataract surgery (CS) with Hydrus Microstent (Ivantis, Inc) implantation versus CS alone. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: Five hundred fifty-six eyes from 556 patients with cataract and primary open-angle glaucoma (POAG) treated with 1 or more glaucoma medication, washed out diurnal intraocular pressure (IOP) of 22 to 34 mmHg, and no prior incisional glaucoma surgery. METHODS: After phacoemulsification, eyes were randomized 2:1 to receive a Hydrus Microstent or no stent. Follow-up included comprehensive eye examinations through 3 years. MAIN OUTCOME MEASURES: Outcome measures included IOP, medical therapy, reoperation rates, visual acuity, adverse events, and changes in corneal endothelial cell counts. RESULTS: Three hundred sixty-nine eyes were randomized to microstent treatment and 187 to CS only. Preoperative IOP, medication use, washed-out diurnal IOP, and glaucoma severity did not differ between the two treatment groups. At 3 years, IOP was 16.7 ± 3.1 mmHg in the microstent group and 17.0 ± 3.4 mmHg in the CS group (P = 0.85). The number of glaucoma medications was 0.4 ± 0.8 in the microstent group and 0.8 ± 1.0 in the CS group (P < 0.001), and 73% of microstent group eyes were medication free compared with 48% in the CS group (P < 0.001). The microstent group included a higher proportion of eyes with IOP of 18 mmHg or less without medications compared with the CS group (56.2% vs. 34.6%; P < 0.001), as well as IOP reduction of at least 20%, 30%, or 40% compared with CS alone. The cumulative probability of incisional glaucoma surgery was lower in the microstent group (0.6% vs. 3.9%; hazard ratio, 0.156; 95% confidence interval, 0.031-0.773; P = 0.020). No difference was found in postoperative corneal endothelial cell loss between groups. No procedure- or device-related serious adverse events resulting in vision loss occurred in either group. CONCLUSIONS: Combined CS and microstent placement for mild to moderate POAG is safe, more effective in lowering IOP with fewer medications, and less likely to result in further incisional glaucoma filtration surgery than CS alone at 3 years.