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BackgroundABBV-599 is a novel combination of elsubrutinib (ELS;a selective BTK inhibitor) and upadacitinib (UPA;a JAK inhibitor) that targets non-overlapping signaling pathways associated with systemic lupus erythematosus (SLE).ObjectivesTo report results from SLEek, a phase 2, randomized, placebo (PBO)-controlled, parallel-group, multicenter study evaluating efficacy and safety of ABBV-599 and UPA monotherapy in adults with moderately to severely active SLE (NCT03978520).MethodsPatients (pts) were randomized 1:1:1:1:1 to once daily (QD) ABBV-599 high dose (HD;ELS 60 mg + UPA 30 mg), ABBV-599 low dose (LD;ELS 60 mg + UPA 15 mg), ELS 60 mg, UPA 30 mg, or PBO. The primary endpoint was the proportion of patients at W24 achieving SLE Responder Index-4 (SRI-4) and steroid dose ≤ 10 mg QD;additional efficacy and safety endpoints through W48 are also reported. The pre-specified 2-sided alpha level was 0.1.Results341 patients were enrolled. After a planned interim analysis when 50% of pts reached W24, the ABBV-599LD and ELS 60 mg arms were discontinued for lack of efficacy (no safety concerns). Of 205 continuing pts (ABBV-599HD n = 68, UPA 30 mg n = 62, PBO n = 75), baseline characteristics were well balanced. The primary endpoint (proportion achieving SRI-4 and steroid dose ≤ 10 mg QD at W24 vs PBO) was met by ABBV-599HD and UPA 30 mg. Key secondary endpoints were also achieved at W48 in both groups (Table 1). Overall flares and time to first flare were substantially reduced in the ABBV-599HD and UPA 30 mg groups through W48 (Figure 1). Anti-double stranded DNA antibodies were significantly decreased with both treatments. TEAEs considered related to study drug were 42.6% ABBV-599HD, 32.3% UPA 30 mg, and 33.3% PBO. There were no malignancies or VTE. There were 3 non-fatal CV events (1 MI on PBO and 2 ruptured cerebral aneurysms [1 each on ABBV-599HD and UPA 30 mg]);all were assessed as unrelated to study drug by investigators. No new safety signals were observed beyond previously known data for UPA or ELS.ConclusionABBV-599HD (ELS 60 mg + UPA 30 mg) and UPA 30 mg demonstrated significant improvements in SLE disease activity and flares with acceptable safety through 48 weeks.Table 1.Key Endpoints at Week 48PBO (n = 75)ABBV-599HD (n = 68)UPA 30 mg (n = 62)SRI-4 and steroid dose ≤ 10 mg QD, n (%) [95% CI]a24 (32.0) [21.4, 42.6]33 (48.5) [36.7, 60.4]*27 (43.5) [31.2, 55.9]SRI-4, n (%) [95% CI]a24 (32.0) [21.4, 42.6]35 (51.5) [39.6, 63.3]*28 (45.2) [32.8, 57.5]+BICLA, n (%) [95% CI]a19 (25.3) [15.5, 35.2]33 (48.5) [36.7, 60.4]***33 (53.2) [40.8, 65.6]***LLDAS, n (%) [95% CI]a18 (24.0) [14.3, 33.7]27 (39.7) [28.1, 51.3]*31 (50.0) [37.6, 62.4]***Joint-Count 50 in patients with ≥ 6 affected joints at baseline, n/n (%) [95% CI]a26/59 (44.1) [31.4, 56.7]37/58 (63.8) [51.4, 76.2]*34/59 (57.6) [45.0, 70.2] +CLASI-50 in patients with baseline CLASI ≥ 10, n/n (%) [95% CI]a5/14 (35.7) [10.6, 60.8]6/12 (50.0) [21.7, 78.3]5/8 (62.5) [29.0, 96.0]*Change from baseline in steroid dose, mg, LS mean (SE)b−1.5 (0.5)−1.5 (0.5)−1.2 (0.5)SFI, events/patient-years (95% CI)c Overall flares2.8 (2.4, 3.3)1.5 (1.2, 1.9)***2.0 (1.6, 2.4)** Mild/moderate flares2.5 (2.1, 2.9)1.3 (1.0, 1.6)***1.9 (1.5, 2.3)* Severe flares0.3 (0.2, 0.5)0.2 (0.1, 0.3)0.2 (0.1, 0.3) +Time to first flare by SFI, days, median (Q1, Q3)c141 (57, NE)312 (114, NE)*311 (99, NE)**BILAG-based flare rate, estimated incidence ratec0.570.19*0.26Data are presented for the full analysis set.aMissing data imputed using NRI incorporating multiple imputation to handle missing data due to COVID 19.bMissing data imputed using MMRM.cObserved data w/o imputation.+P <.1;*P <.05;**P <.01, ***P <.001 vs PBO.ABBV-599HD, elsubrutinib 60 mg QD and UPA 30 mg QD;CLASI-50, ≥ 50% reduction in CLASI activity score;Joint-Count 50, ≥ 50% improvement in tender or swollen lupus joints;LLDAS, Lupus Low Disease Activity State;NE, not estimated;PBO, placebo;SFI, SELENA SLEDAI Flare Index;UPA, upadacitinib.AcknowledgementsAbbVie and the authors thank the patients who particip ted in the study and all study investigators for their contributions. Medical writing assistance, funded by AbbVie, was provided by Callie A S Corsa, PhD, of JB Ashtin.Disclosure of InterestsJoan T Merrill Consultant of: AbbVie, Alexion, Alumis, Amgen, Astra Zeneca, Aurinia, Bristol Myers Squibb, EMD Serono, Genentech, Gilead, GlaxoSmithKline, Lilly, Merck, Pfizer, Provention, Remegen, Sanofi, UCB, and Zenas, Grant/research support from: Astra Zeneca, Bristol Myers Squibb, and GlaxoSmithKline, Yoshiya Tanaka Speakers bureau: AbbVie, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Gilead, Lilly, Mitsubishi-Tanabe, and Pfizer, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eisai, and Takeda., David d'cruz Consultant of: GlaxoSmithKline, Lilly, and UCB., Karina Vila Consultant of: AbbVie, Daniel Siri Grant/research support from: AbbVie, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, Gilead, Hoffman Laroche, Jansen, Lilly, and Sanofi, Xiaofeng Zeng: None declared, Kristin D'Silva Shareholder of: AbbVie, Employee of: AbbVie, Ling Cheng Shareholder of: AbbVie, Employee of: AbbVie, Thierry Sornasse Shareholder of: AbbVie, Employee of: AbbVie, Thao Doan Shareholder of: AbbVie, Employee of: AbbVie, Denise Kruzikas Shareholder of: AbbVie, Employee of: AbbVie, Alan Friedman Shareholder of: AbbVie, Employee of: AbbVie.
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PURPOSE: To investigate the impact of the COVID-19 pandemic on the clinical impact of the clinical outcomes of robotic inguinal hernia repair. METHODS: Patients who underwent RIHR 2 years before and after March 10, 2020, were included in this retrospective study and assigned accordingly to the pre- or post-COVID group. Pre-, intra-, and postoperative variables including patients' demographics, hernia characteristics, complications, and hernia recurrence rates were compared between groups. RESULTS: 183 (94.5% male) and 141 (96.4% male) patients were assigned to the pre- and post-COVID groups, respectively. Patient demographics and medical comorbidities did not differ between groups. Operative time was approximately 40 min longer in the post-COVID group (p < 0.001) with higher rates of bilateral IHR (pre-COVID: 30.1% vs. post-COVID: 46.4%, p = 0.003). Mesh material differed between groups with predominance of polyester mesh in the pre-COVID group vs. polypropylene in the post-COVID one. Median hospital length of stay (LOS) was 0 days in both groups, and same-day discharge rates were 93.4% pre-pandemic and 92.8% post-pandemic (p = 0.09). There were no pulmonary complications recorded in either group or no cases of COVID-19 detected within two weeks postoperatively in the post-COVID group. Seromas were more frequent in the post-COVID group (pre-COVID: 2 vs. post-COVID: 8, p = 0.018) and no hernia recurrences were recorded. CONCLUSION: This is the first study to describe the impact of COVID-19 on RIHR. Clinical outcomes and hernia-specific complications were not impacted by the COVID-19 pandemic.
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Purpose: Rapid evolution of the SARS-CoV-2 pandemic over the past 24 months has demanded agility in managing selection criteria for deceased organ donors, with the goal of saving every possible life while avoiding disease transmission to recipients. At 1 large organ procurement organization (OPO), the detection of any SARS-CoV-2 in a naso-pharyngeal (NP) specimen by polymerase chain reaction (PCR) was initially an absolute contraindication to organ donation. That approach gradually became more refined utilizing clinical evidence along with detection of low levels of viremia. Method(s): A retrospective analysis of all patients with authorization for organ donation after brain death or circulatory death from 3/16/2020 - 11/9/2021 was undertaken. Patients with any positive result for a COVID-19 test were identified. Donors with any positive result of an NP +/- broncho-alveolar fluid (BAL) PCR were selected for this analysis. Organ allocation was accompanied by the expectation of written confirmation that the recipient had provided informed consent for use of an organ from a SARS-CoV-2 donor. Result(s): A total of 18 deceased donors from whom 49 organs were transplanted, were identified. Multiple test results were often available for a single patient. Results were mixed in all 18 donors. At least one of the positive NP PCR test results included a cycle threshold in 16/18 patients and ranged from 31.4 to 42.5. In 2 donors a BAL PCR was also positive;1 heart was donated from one of these donors. With a follow-up of > 53 days for all transplants, no known transmission of SARS-CoV-2 to recipients or transplant teams has been reported. Conclusion(s): Available laboratory testing for SARS-CoV-2 and deepening understanding of COVID-19, increasing treatment options, and evolution of infection prevention practices have facilitated a growing confidence in safely transplanting non-lung organs from donors with a positive SARS-CoV-2 test. (Figure Presented).
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Previous literature has identified important principles of geriatrics to consider in older adult dermatology patients, including cognition, polypharmacy, mobility, and social support. We aimed to assess provider perceptions and attitudes about the unique needs of older adult patients in dermatology. 169 health care practitioners completed the survey. 92.9% of the survey respondents were dermatologists, and 6.5% were dermatology advanced practice providers. The following barriers to care in older adult patients were identified by dermatology providers (%): hearing problems (82.9%), lack of a social support system (82.8%), immobility (74.4%), ability of the patient to communicate clearly (69.5%), transportation (77.5%), financial limitations (72.2%), Medicare limitations (66.9%), poor psychosocial functioning (77.5%), and telehealth due to the COVID-19 pandemic (71.2%). In addition, providers identified the following barriers to treatment in the older adult population: poor psychosocial functioning (89.9%), polypharmacy (87.8%), lack of social support system (88.5%) poor adherence to medications (81.1%), and lack of a primary care physician (72.3%). Overall, practitioners selected lack of social support system, difficulty in comprehending treatment plans and limited financial means as the 3 most pressing issues affecting the care of older adult patients. Additional research is warranted to develop interventions to reduce barriers to care and treatment for older adult patients in dermatology clinics.
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BACKGROUND: Reports of silent hypoxia in patients with Covid-19 have raised concerns that patients monitored at home should receive pulse oximeters to objectively measure oxygen saturation rather than relying on subjective dyspnea as an indicator of clinical deterioration. METHODS: In this pragmatic randomized control trial, patients with suspected or confirmed Covid-19 were randomly assigned (1:1) to receive a text message based remote monitoring program (“Covid Watch”) or the program supplemented with SpO2 monitoring using a home pulse oximeter (“COVID Watch + Pulse Oximetry”). Covid Watch is a an automated 14-day text program that enquires about patients' symptoms of dyspnea. The primary outcome was days alive and out of hospital (DAOH) at 30 days. RESULTS: A total of 1056 patients (611 Covid-19 positive) were assigned to receive automated remote monitoring of both peripheral oxygen saturation (SpO2) levels and self-reported symptoms of dyspnea and 1041 (606 Covid-19 positive) to receive symptom monitoring alone. Among Covid-19 patients, the addition of SpO2 monitoring provided no significant difference in mean DAOH at 30 days (29.38 vs 29.46;difference -0.08;95% CI, -0.37 to 0.21). Patients in the intervention arm were more likely to use more clinical resources such as telephone calls and telemedicine visits. These finding were consistent across subgroups defined by race, age, and clinical status. CONCLUSIONS: SpO2 monitoring added no clinical value to subjective assessments of dyspnea in an automated text-message remote monitoring program of Covid-19 patients, while simultaneously increasing utilization of clinical resources. These findings reveal that home pulse oximetry may be ineffective and inefficient in supporting the management of Covid-19 patients in outpatient settings relative to remotely monitoring symptoms of dyspnea alone.
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STATEMENT OF PROBLEM/QUESTION: The Covid-19 pandemic disproportionally affected low-income and Black and Latinx New Yorkers, led to disengagement from primary care, increased social needs, and worsened chronic diseases. DESCRIPTION OF PROGRAM/INTERVENTION: Community Health Workers (CHWs) are front line public health workers who are trusted members of and/or have a close understanding of the community served. Integrating CHWs into clinical teams can help to bridge gaps between the healthcare system and a patient's community. In 2021, NYC Health + Hospitals (NYC H+H) established a branch of the NYC Public Health Corps, comprised of over 200 CHWs and program staff in multiple care settings to address the health inequities exacerbated by the pandemic. CHWs are embedded in and hired by clinics while a centralized team coordinates training, program models, data/documentation tools and coaching by a team of CHW coaches. CHWs in adult primary care implement a model informed by the UPenn IMPaCT program in which CHWs provide tailored social support, advocacy and navigation to help patients achieve health goals. (Kangovi et al 2014, 2017, 2018). CHWs work intensively with patients who have 2+ chronic conditions over 3 months on a set of patient-driven goals. Goals fall into four categories: social needs, medical system navigation, medication management, and chronic disease risk factors. CHWs are provided guides and training on how to address specific patient goals. MEASURES OF SUCCESS: Initial measures include: 1. Launch success (# CHWs hired, development of documentation workflows). 2. Implementation of program model (# patients enrolled, goals identified). Long-term measures of success will include a cost effectiveness analysis. FINDINGS TO DATE: Between August and December 2021, approximately 200 CHWs were hired to staff 17 different clinical sites. 147 CHWs were hired for adult primary care and 58 have begun working with patients. All CHWs have completed IMPaCT and supplemental training. All CHWs document in the EMR using a specific build. 924 patients have been outreached, 365 enrolled, and 54 completed the program to-date. CHW median caseload is 7 with a goal to ramp up to 20. CHWs address an average of 5 goals per patient. The most common goals are primary care engagement, medication management, health insurance gaps/medical bills, and food insecurity. 60% of patients identified at least one social need to work on with the CHWs. KEY LESSONS FOR DISSEMINATION: 1. H+H was able to quickly build one of the largest CHW workforces in the country in response to patient needs elevated by the pandemic and availability of public funding by embedding CHW teams in clinics with central program support, increasing the likelihood of sustainability over time. 2. The development of a structured CHW program supported by training, coaching and documentation tools to address the most common issues affecting patient ability to manage health and wellbeing including social needs was critical in supporting this new workforce while allowing for flexibility to meet individual patient needs.
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Background and aims: COVID-19 infections are reported in numerous case-reports as a trigger for development of Parkinson's disease (PD). We report 4 patients with symptoms of PD developed or exagerated after SARSCoV2 infection. Methods: Patients were retrospectively recruited in an outpatient clinic of Department of Neurology, Faculty of Health Science, Medical University of Warsaw. Patients were independently assessed by 2 neurologists experienced in movement disorders. Results: We identified 4 patients with rapid onset of PD symptoms following COVID-19. All patients were female. Symptoms of COVID-19 included headache in 4/4 cases and anosmia in 3/4 cases. PCR test confirmed SARS-CoV2 infection in all cases. The age of onset was between 28 and 62 years old. The rest tremor was present in all patients, ridgidity in 3/4 patients. Non-motor symptoms included RBD in 2/4 patients. Two patients were treated with levodopa with good response. MRI findings were nonsignificant. The SPECT-DatScan was performed in one patient and was typical for parkinsonian disorders. The positive family history was present in two patients. Conclusion: We conclude that COVID-19 may trigger development of parkinsonian motor symptoms or exaggerate the slight disease progression. The cause is unknown. Involvement of olfactory bulb could trigger neuroinflammation in line with Braak's hypothesis. COVID-19 may also induce parkinsonism in patients with genetic predisposition.
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Objective: During the COVID-19 pandemic, many hospitals provided expedited postpartum discharge (EPD) for patients wishing to leave the hospital soon after birth. This study was performed to assess whether acute postpartum care utilization increased after EPD during COVID-19. Study Design: Birth hospitalization data from a single teaching hospital from two 6-week periods (3/22-4/30/19 and 3/22-4/30/20) were used for this retrospective cohort study. EPD, defined as discharge on postpartum day 1 or 2 following vaginal or cesarean birth, respectively, was the primary exposure. The primary outcome was acute postpartum care utilization defined as emergency or obstetrical triage unit visits within 6 weeks of delivery. Secondary outcomes included 6-week postpartum readmission. We fit logistic regression models to assess the risk for the primary and secondary outcomes. Categorical comparisons were made with the chi square test. Results: Of 1,358 deliveries in the study, 5.0% of deliveries in 2019 (n=36) compared to 60.3% of deliveries in 2020 (n=388) underwent EPD (p< 0.01). Rates of acute postpartum care utilization were 8.8% and 5.6% for 2019 and 2020, respectively (Figure 1). In 2020, patients with hypertensive disorders of pregnancy (HDP), chorioamnionitis/endometritis, or a positive COVID test were less likely to be discharged early (Table 1). There were no significant differences in rates of acute postpartum care utilization (OR 0.9, 95% CI 0.5, 1.8) or readmissions (OR 1.3, 95% CI 0.5, 3.6) between patients with EPD as compared to routine discharge. Among patients with HDP, readmission risk was significantly higher among those who had early discharge as compared to routine discharge (OR 6.1, 95% CI 2.1, 17.3). Conclusion: Rates of EPD were significantly higher in 2020 compared to 2019 with no impact on acute postpartum care utilization or readmission rates. Among patients with hypertensive disorders of pregnancy, expedited discharge was associated with higher risk of readmission. EPD discharge does not appear to be associated with increased acute postpartum care utilization among low-risk patients. [Formula presented] [Formula presented]
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Purpose: To prevent transmission of SARS CoV 2 via solid organ donation from deceased donors. Methods: Comprehensive medical and psychosocial evaluation of potential deceased organ donors included a risk assessment for active infection w2ith SARS CoV 2 which was considered an absolute contraindication. Patients lacking active infection for whom authorization for donation was present, underwent testing for detectable SARS CoV 2 in specimens from the nasopharynx (PCR), bronchoalveolar lavage (PCR) and blood (antibody). Results: From 3/16/2020-12/2/2020 a total of 828 specimens were collected from 208 patients. Nearly all samples were negative for SARS CoV 2. 7 patients were confirmed to have antibody to SARS CoV 2;6 became donors and 1 was ruled out. Nasopharyngeal specimens were PCR positive in 7 patients, 6 pf them were ruled out. The 7th patient was remotely infected and also was antibody positive;this patient did become a donor.No reports of donor transmission of SARS CoV 2 have been mreport3ed to us. Conclusions: Active evolution of the evaluation of SARS CoV 2 in deceased organ donor candidates has taken place during the initial phase of the pandemic. Systematic testing of nasopharyngeal, bronchoalveolar lavage and antibody status whenever feasible, facilitated donation by most authorized donors. This strategy has resulted in multiple organ transplants without evidence of SARS CoV-2 transmission.
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Rationale: Covid-19 infection is most commonly associated with respiratory symptoms, the most serious being acute hypoxic respiratory failure, often requiring intubation and mechanical ventilation with an elevation in inflammatory markers often seen. Of note are also the observed elevations in D-dimer which correlated with disease severity and mortality. It has also has been theorized that microthrombi may play a role in the dysfunction of the respiratory system which may correspond with the elevation of D-dimer. We decided to observe the relationship between D-dimer on presentation and changes in right heart function and hemodynamics as measured by right ventricular systolic pressure (RVSP). Methods: This was a retrospective analysis of 21 patients who had D-dimer measured on arrival to the hospital and also had transthoracic echocardiography (TTE) done during the course of their hospital stay. RVSP was calculated on each of the 21 patients. Results: In our sample of 21 patients, there was a statistically significant association between D-dimer levels and RVSP. Conclusions: Based on our results, there is evidence that elevated D-dimer levels in patients infected with Covid-19 are associated with elevated RVSP. This raises the question as to whether or not there would be benefit in treatment (i.e. therapeutic anticoagulation) to try and prevent right ventricular dysfunction in patients with Covid-19;this question would require further research to fully answer.
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BACKGROUND: The COVID-19 pandemic has drastically changed the practice of dermatology as social distancing guidelines have led to a shift from in-office care to virtual telehealth (teledermatology). We aimed to determine patient satisfaction, perceived barriers, as well as indications for teledermatology appointments during the COVID-19 pandemic. METHODS: A survey was sent out via SurveyMonkey's online platform to patients of the George Washington Medical Faculty Associates' Dermatology department who attended telehealth appointments during the COVID-19 pandemic. RESULTS: Out of 894 invitations sent, 168 patients completed our survey.The most common reasons for making a telehealth appointment were for a new rash (11.6%), eczema (9.8%), and psoriasis (9.1%). The most common reasons respondents liked telehealth were because of time efficiency (81.1%), not requiring transportation (74.2%), and maintaining social distancing (73.6%). The most common reasons respondents did not like telehealth were due to lack of physical touch (26.8%) and feeling they received an inadequate assessment (15.7%). Very few patients reported that they were unlikely to undertake another telehealth visit (9.94%) or recommend a telehealth visit to others (6.92%). CONCLUSION: Dermatology patients likely perceive telehealth visits as a convenient and safe method for quality care during the COVID-19 pandemic. The lack of physical touch, inability to provide close inspection and/or procedural intervention can be frustrating for patients and therefore meaningful selection of appropriate cases for telehealth visits can optimize the patient experience. Overall, telemedicine represents an effective and safe vehicle for delivering care especially during a global pandemic. J Drugs Dermatol. 2021;20(2):178-183. doi:10.36849/JDD.2021.5714.
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The coronavirus disease 2019 pandemic has quickly and abruptly altered workflow and education across medical specialties. As the health crisis persists in the United States, change will be the norm for the foreseeable future. Dermatology residents report high levels of anxiety, with concerns ranging from redeployment to career prospects.1.
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Human coronaviruses are highly pathogenic viruses that pose a serious threat to human health. Examples include the severe acute respiratory syndrome outbreak of 2003 (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) outbreak of 2012, and the current SARS-CoV-2 (COVID-19) pandemic. Herein, we review the neurological manifestations of coronaviruses and discuss the potential pathogenic role of blood-brain barrier dysfunction. We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood of neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood-brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavirus neuropathology, and to test the diagnostic potential of minimally-invasive screening tools (e.g. serum biomarkers, fluorescein retinal angiography and dynamic-contrast MRI).