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Introduction: Urine drug testing has been the standard for monitoring opioid compliance in chronic pain patients. The COVID-19 pandemic created a dilemma for opioid monitoring by severely limiting in-person testing due to safety concerns. Oral fluid toxicology emerged as a feasible, alternative test due to its ability for remote sample collection under virtual supervision while minimizing infringements on patient privacy. However, the efficacy of these two tests for reliably detecting opioids should be explored prior to transitioning to testing only with oral fluids. Method(s): In this study, we compared morphine levels in oral fluid and urine toxicology studies from 5 randomly selected patients from a Chronic Pain Center who were regularly taking high doses (>=90 mEq) of extended-release morphine. Charts from the start of the COVID-19 pandemic until July 2022 were reviewed for urine and oral fluid testing results and medication regimens. All oral fluid and urine test results and collection methods were validated by a nationally recognized toxicology lab. Prescription Monitoring Program (PMP) reports were reviewed for each patient to observe pre-testing prescription trends. Result(s): We found that the overwhelming majority of patients had at least 1 false negative oral fluid test result. The remainder of the oral fluid results were below threshold (10 ng/mL) or ranged from 11.3 to 54 ng/mL of morphine. 80% of patients (n = 5) had at least one negative or positive-but-below-threshold (10 ng/mL) result in their oral fluid sample analyses. In contrast, none of the urine studies had negative results. Urine studies for all patients were positive for morphine and well-above primary cutoff values (100 ng/mL) with levels >6000 ng/mL. PMP reports did not reveal any aberrant drug taking behavior in any of the patients. No unprescribed medications or illicit substances were detected in any of the oral or urine samples. Conclusion(s): The prevalence of false negative results for the detection of morphine metabolites in oral fluid toxicology may be higher than clinicians are currently aware of. Physicians and other providers monitoring opioid compliance in chronic pain patients should keep this possibility in mind when selecting toxicology tests and making conclusions about aberrant drug-taking behavior. Larger scale studies are needed to compare oral fluid and urine levels of morphine with extension to other commonly prescribed opioids. Disclosure: Evan Chung, MD: None, Joseph Valenza, MD: NoneCopyright © 2023
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Objectives: Many people were infected by COVID-19 and for a minority of them, symptoms persisted beyond twenty days. These symptoms are multi-systemic, fluctuating, and impact the quality of life. Long COVID was first defined by patients themselves in the spring of 2020 to describe their recovery problems. Specifically, long COVID is defined as "a constellation of physical and mental symptoms which can persist or emerge afterwards, generating a multi-systemic and disabling syndrome, which varies from patient to patient and fluctuates over time". The persistence of COVID symptoms, the decrease in the quality of life, the uncertainly about the future sometimes accompanied by a low level of social support perceived in the medical and personal entourage may have triggered the occurrence of a depressive disorder in patients with long COVID. The objective of this research was to study the effect of long COVID symptoms, of uncertainty and the impairment of quality of life on the development of depressive symptoms, while identifying the impact of moderating variables such as coping strategies and social support. Material(s) and Method(s): Two hundred and fourteen participants with long COVID (aged 18-68, M = 44, SD = 11), including 93 % females (n = 200) and 7% males (n = 14), participated in this cross-sectional quantitative study between the months of April and June 2022. They described their symptoms and responded to five scales: the Evaluation of Intolerance of Uncertainty Scale (EII), the Coping Strategies Checklist (WCC), the Medical Outcome Study Short Form 36-item health survey (MOS SF-36), the Perceived Social Support Questionnaire (QSSP), and the Hospital Anxiety and Depression Scale (HADS). Result(s): 91% of the participants reported symptoms of fatigue (n = 171), 52% a loss of concentration (n = 111), 51% pain (n = 110), 49 % trouble sleeping (n = 104), and 41% memory problems (n = 88). Compared with the general population, they presented a poorer quality of life, as well as high scores for anxiety, depression, and intolerance of uncertainty. Scores on coping strategies were also higher than the norms for the general population, and scores on satisfaction with social support were generally good. It was also found that the variables of intolerance of uncertainty, quality of life, and depression all correlated with each other. Furthermore, the regression analysis revealed predictors of depression. The areas of quality of life and emotional well-being (beta = -0.41, t(199) = -6.23, P < 0.01) and fatigue/energy (beta = -0.16, t(199) = -2.83, P < 0.01) were negative predictors of depression, as was the problem-focused coping score (beta = -0.14, t(199) = -2.84, P < 0.05). Symptoms of the disorder related to concentration difficulties (beta = 0.27, t(199) = 5.16, P < 0.01) and those impacting projects (beta = 0.18, t(199) = 3.31, P < 0.01) were positive predictors of depression. The second finding of this study is that people treated specifically for their long COVID had significantly lower scores for anxiety and intolerance of uncertainty despite lower scores for certain dimensions of quality of life. The individuals who took part in our study also developed more problem-based coping strategies and reported more availability of and satisfaction with social support. Lastly, in terms of quality of life, the treated population expressed better mental health. Conclusion(s): The study showed that, in addition to the effects of long COVID symptoms, quality of life, and coping strategies on the onset of symptoms of depression, the specific treatment of patients with long COVID seemed to constitute in itself a protective factor against depression and anxiety. It therefore would seem essential that any patient suffering from long COVID should receive multidisciplinary care specific to this pathology.Copyright © 2023 Elsevier Masson SAS
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Background/Aims In April 2020 the British Society for Rheumatology (BSR) issued a risk stratification guide to identify patients at the highest risk of COVID-19 requiring shielding. This guidance was based on patients' age, comorbidities, and immunosuppressive therapies - including biologics that are not captured in primary care records. This meant rheumatologists needed to manually review outpatient letters to score patients' risk. The process required considerable clinician time, with shielding decisions not always transparently communicated. Our aim was to develop an automated shielding algorithm by text-mining outpatient letter diagnoses and medications, reducing the need for future manual review. Methods Rheumatology outpatient letters from Salford Royal Hospital, a large UK tertiary hospital, were retrieved between 2013-2020. The two most recent letters for each patient were extracted, created before 01.04.2020 when BSR guidance was published. Free-text diagnoses were processed using Intelligent Medical Objects software1 (Concept Tagger), which utilised interface terminology for each condition mapped to a SNOMED-CT code. We developed the Medication Concept Recognition tool (MedCore Named Entity Recognition) to retrieve medications type, dose, duration and status (active/past) at the time of the letter. The medication status was established based on the heading where they appeared (e.g. past medications, current medications), but incorporated additional information such as medication stop dates. The age, diagnosis and medication variables were then combined to output the BSR shielding score. The algorithm's performance was calculated using clinical review as the gold standard. Results To allow for the comparison with manual decisions, we focused on all 895 patients who were reviewed clinically. 64 patients (7.1%) had not consented for their data to be used for research as part of the national opt-out scheme. After removing duplicates, 803 patients were used to run the algorithm. 11,558 free-text diagnoses were extracted and mapped to SNOMED CT, with 15,003 free-text medications (that included past, present and any planned treatment). The automated shielding algorithm demonstrated a sensitivity of 80.3% (95% CI: 74.7, 85.2%) and specificity of 92.2% (95% CI: 89.7, 94.2%). Positive likelihood ratio was 10.3 (95% CI: 7.7, 13.7), negative likelihood ratio was 0.21 (95% CI: 0.16, 0.28), F1 score was 0.81. False positive rate was 7.9%, whilst false negative rate was 19.7%. Further evaluation of false positives/negatives revealed clinician interpretation of BSR guidance and misclassification of medications status were important contributing factors. Conclusion An automated algorithm for risk stratification has several advantages including reducing clinician time for manual review to allow more time for direct care, improving efficiency and transparently communicating decisions based on individual risk. With further development, it has the potential to be adapted for future public health initiatives that requires prompt automated review of hospital outpatient letters.
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Background/Aims Rheumatology is a complex specialty covering many conditions of varying severity, from muscle pain through inflammatory arthritis such as Rheumatoid arthritis (RA) and connective tissue diseases. Most of the conditions can be managed in an outpatient/day case setting. However, acutely ill patients require safe and prompt inpatient management including specific intravenous infusions. This need to be done urgently and cannot wait to be accommodated through the Infusion unit at our hospital. Historically Medicine Acute Admission Unit has been the route to bring in these patients. However, operational bed pressures faced challenges leading to instances of delayed treatment with complications including fatality. This led to creating a direct inpatient admission pathway to the specialist ward. Methods Ward Matron designed the following robust pathway for direct patient admission to our specialist Rheumatology ward, Jevington ward. This was implemented in February 2022 after discussion and agreement with Clinical Lead consultant, pharmacist, clinical site managers and other colleagues. Rheumatology team and nurses covered the ward during working hours and by the on-call team out of hours. The overall responsibility remained with the rheumatology team. The referrals accepted only after completing appropriate paperwork. Patients carried out Lateral Flow Test (LFT) at home prior to admission. We ensured negative results and followed the Trust COVID 19 screening protocols. Subsequent screenings were done according to the updated guidelines. The planned assessment and treatments were carried out by the ward team complying with BSR/ EULAR Guidelines, infusion protocols such as standard and continuous Iloprost Infusion Protocols of the Trust. Results We assessed the delay in patient's admission, length of stay, patient outcome and experience after implementing the pathway. The significant change has been in the time to admit;from two weeks in 2018 & 19 to two days this year. This is reflected in the patient feedback. All our acutely ill patients were assessed, treated and discharged promptly on this specialist ward. Conclusion This pathway allowed safe and prompt treatment, prognosis and excellent experience for acutely ill patients with rheumatological disorders. This additionally enabled reduced length of stay supporting financial sustainability of the Trust. (Table Presented).
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Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.
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Introduction: Nirmatrelvir/ritonavir is a new medication approved for the treatment of COVID-19 infection. It prevents viral replication by inhibiting the SARS-CoV-2 main protease. While mild adverse effects were described, including dysgeusia, diarrhea, hypertension and myalgia1, there were no reported cases of pancreatitis. Case Description/Methods: An 81-year-old female with a past medical history of hypertension and COPD presented to the hospital complaining of abdominal pain and nausea for one day. She had no history of alcohol, tobacco or marijuana use, recent travel, or trauma. Her medications included lisinopril and prednisone, and she had completed a 5-day course of nirmatrelvir/ritonavir for the treatment of COVID-19 infection 2 days prior to presentation. On abdominal exam, she had left upper and lower quadrant tenderness. Blood tests revealed an amylase of 1333 U/L, lipase of 3779 U/L, triglycerides of 297 mg/dL and calcium of 8.7 mg/dL. CT scan revealed an indurated pancreatic body and tail with peripancreatic fluid along the paracolic gutter. Ultrasound of the abdomen and MRCP did not reveal any acute findings. IgG subclasses 1-4 were normal. Discussion(s): According to the revised Atlanta criteria, the patient had clinical findings consistent with acute pancreatitis. Common causes such as gallstone, alcohol, autoimmune and hypertriglyceridemiainduced pancreatitis were ruled out. There were no masses or structural abnormalities on imaging that might have explained her diagnosis. There have been at least 2 reported cases of lisinopril and prednisone induced pancreatitis, however according to Badalov et al.2 both of these medications are class III drugs that lack any rechallenge in the literature. Moreover, the patient had been taking these medications for many years, making them an unlikely cause of the presenting diagnosis. There are no reports of nirmatrelvir/ritonavir associated pancreatitis or known pharmacologic interaction with her home medications, and a meta-analysis conducted by Babajide et al. revealed no association between acute pancreatitis and COVID-19 infection (3). Given the negative findings stated above and the recent initiation of a new medication, nirmatrelvir/ritonavir was the likely cause of acute pancreatitis.
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Background/Aims Since the COVID-19 outbreak the rheumatology community have been concerned about the risk of SARS-CoV-2 infection in patients prescribed immunosuppressing medications. Data suggests that patients receiving Rrtuximab are at increased risk of developing severe outcomes from COVID-19 (1). In our unit all patients receiving rituximab were selected to receive a targeted vaccination and booster programme with all patients receiving at least 2 vaccinations and up to 3 booster vaccinations. We studied the efficacy of the COVID-19 vaccines in rituximab patients, by checking the the Roche Elecsys Anti-SARS-CoV-2-S (Spike) IgG/IgM total antibody levels post vaccination. Our aim was to assess the vaccination response in patients receiving rituximab and to offer advice on continued shielding or alternatively passive immunization with tixagevimab/cilgavimab in those patients who did not mount a response. Methods Taking 39 patients currently on rituximab therapy, we measured Anti- SARS-CoV-2-S (Spike) antibody levels post vaccination. We recorded whether the test was positive or negative, and the numerical result. We recorded rituximab dates of administration and dates of vaccines. We also recorded diagnosis, co-prescribed DMARDs, immunoglobulin levels, white cell and lymphocyte counts. We took record of whether or not the patient subsequently contracted COVID-19, required a hospital admission, ICU or died. Results Of our 39 patients, 21 had Anti-SARS-CoV-2-S (Spike) antibody levels checked. Of these patients, 7 (33%) had a negative spike protein result. Of the patients with a positive result, 8 (38%) had an antibody level between 0-250U/ML, and only 6 (28.6%) had a level >250U/ML (The manufacturer advises that a level above 0.8U/ML is a positive result). Of patients with a negative result, 1 patient had received 3 vaccines, 5 patients had received 4, and 1 patient had 5. All of the patients had received a vaccine >4 weeks prior to receiving the drug. Two patients were co-prescribed Belimumab, 3 were co-prescribed low-dose methotrexate and 2 were not on additional disease modifying agents. The diagnoses of these patients were, 2 patients with SLE, 4 with SPRA, and 1 MPO Vasculitis. There were no significant findings in lymphocyte count, white cell count or immunoglobulin levels. Conclusion These findings suggest that our current COVID-19 vaccination and booster programme may not provide adequate response in patients receiving rituximab therapy. Despite this being a small cohort, these results show that 33% of patients have not mounted a vaccine response and this is concerning. We suggest that vaccine response should be checked in all patients receiving rituximab therapy and those patients who do not mount a vaccine response should be offered passive immunity and advised of possible additional risks regarding COVID-19 exposure.
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Intro: The COVID-19 pandemic is caused by the SARS-CoV-2 virus, an enveloped RNA of the coronavirus family. The advancement in molecular technology and biochemistry has accelerated the development of diagnostic reagents and assays. Much attention has been focused on the S protein, but the high mutation rate in this region could lead to false negative results. Thus, a better target protein for diagnostic application is needed for accurate detection. Method(s): Nucleotide sequences encoded for membrane (M) glycoprotein gene region of SARS-CoV-2 from Malaysian isolates were extracted from GISAID, aligned, and selected accordingly. The DNA plasmid was commercially synthesized with codon optimization for Escherichia coli (E. coli), and the presence of the M gene was confirmed by PCR. The plasmid was then transformed into E. coli. Later, the expression of M glycoprotein was induced, separated on an SDS-PAGE gel, and transferred onto a nitrocellulose membrane, followed by immunostaining. Finding(s): The analysis of the M glycoprotein against the Omicron strains demonstrated that the amino acid is conserved (99.5%). The M glycoprotein was successfully expressed and detected with antibodies from SARS-CoV-2 infected patients at ~26 kDa. The protein is currently upscale for the generation of monoclonal Ab (Mab). Discussion(s): The M protein of SARS-CoV-2 is more conserved among the virus and also has been reported to confer antigenic properties. Selection of M protein perhaps a better option compared to current detection assays that use spike (S) protein, which could lead to false negative results, as this gene region particularly the ribosome-binding domain (RBD) rapidly undergoes mutations. The utilization of M protein potentially improves negative predictive value (NPV) of the diagnostic test. Conclusion(s): Further development of diagnostic reagents is needed to improve the assay's specificity. The newly developed M protein and the MAb can be used to generate a more accurate viral detection assay.Copyright © 2023
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The spread of the aggressive disease caused by the novel respiratory syndrome coronavirus-2 (SARS-CoV-2) has had an impact not only on the health and psyche of people, but also on the state of health systems in different countries, by complicating the treatment and diagnostic process. These changes have affected patients with cancers to a greater extent. The diagnosis, treatment, and follow-up of patients are of particular scientific and practical interest when working in conditions of special anti-epidemic control. Objective. To assess the possibility of reducing the frequency of hospitalization of patients with non-muscle-invasive bladder carcinoma (NMIBC) during the Covid-19 period. Subjects and methods. Sixty-four patients with urinary tract malignancy, including 19 (29.7%) patients with low-and high-risk re-current NMIBC, were followed up in two clinics (Saint Petersburg, Russia) in March to October 2020. All the patients were oper-ated on;the patients at high risk for recurrence received a cycle of adjuvant BCG therapy. Methods for cytological examination of urine sediment and the biomarkers UBC and Cyfra 21-1 were used for special laboratory diagnosis;the server stations of both clinics were applied for telehealth consultations (TCs). Results. TCs were used to reduce hospitalization rates: after TCs, all the patients reported a reduction in transport costs and recovery time after hospitalization. TCs could protect the followed-up patients against COVID-19 infection, by observing the rules of clinical examination, and achieve maximum individualization of treatment. The authors refused to perform diagnostic operations for low-risk NMIBC and to use laboratory tests using urinary biomarkers. At the place of their residence, outpatients underwent urinalysis for several indicators, transmitting the result to the clinic's servers or through a monitoring system. Inpatient treatment was used only in cases of gross hematuria or after recording abnormal laboratory test results. Control cystoscopy detected no re-current tumor. Conclusion. During the spread of COVID-19, the periods of endoscopic examinations and control diagnostic operations can be post-poned, by replacing face-to-face consultations with TC monitoring. Outpatient laboratory and radiation examinations are indicat-ed in patients with new-onset gross hematuria or after combination treatment. Repeated operations, including diagnostic ones, should be performed in the case of multiple NMIBCs or after incomplete excision of the primary tumor.Copyright © 2021.
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Background: Evolution evidence of Coronavirus disease 2019 (COVID-19) and viral clearance time remains limited in tropical settings. Understanding this is crucial for public health control measures at community-level. We evaluated the viral dynamics of SARS-CoV-2 infection and factors associated with positivity duration in COVID-19 cases in Cameroon. Method(s): We conducted a prospective cohort-study of SARS-CoV-2 positive cases from the first to third wave (March 2020-October 2021) in Yaounde- Cameroon. RT-PCR was performed on nasopharyngeal swabs. SARS-CoV-2 positivity duration was evaluated from the first to last positive test before a negative result. Epi-info V.7.0 was used for data analyses with p< 0.05 considered statistically significant Results: A total of 282 participants were enrolled. The mean age was 41+/-14 years, with male predominant (62.1%). We had 15.6% symptomatic cases and cough most common (59.09%). The overall median positivity duration was 15[IQR: 9-23] days with 15[ IQR: 13-16] in the first, 17[ IQR: 11-26] in the second and 8[ IQR: 4-12] in the third wave (p= 0.007). Positivity duration was significantly higher in males (16 versus 14 days, p=0.03) and people aged >40 years (15 versus 14 days, p=0.02). Positivity duration was not affected by presence or absence of symptoms (p=0.80). No significant correlation was found with viral load (r=0.03;p=0.61). Considering baseline (24.7+/-7.2Ct) and last viral load (29.3+/-5.9 Ct), the DELTACt (4.6+/-1.3) and positivity duration (15 days) revealed a kinetic in viral decay of 0.3+/-0.087 Ct/day. Conclusion(s): A median positivity duration of 15 days is in accordance with viral clearance around 2 weeks for optimal confinement at community-level. Men and/or the elderly stand at higher risk of prolonged infection. Given the viral decay (0.3 Ct daily), we suggest personalized confinement periods. The variability of positivity duration according to phases could be function of strains which could be a factor of positivity duration.
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Résumé Objectifs De nombreuses personnes ont été infectées par le COVID-19 et pour une minorité d'entre elles, des symptômes multi-systémiques, fluctuants et impactant la qualité de vie, ont persisté au-delà de 20jours. Le COVID long a été d'abord défini par les patients eux-mêmes au printemps 2020 pour décrire leurs parcours de non-récupération. Plus précisément, le COVID long est défini comme « une constellation de symptômes physiques et mentaux qui peut persister ou émerger par la suite, façonnant un syndrome multi-systémique et invalidant, qui varie d'un patient à l'autre et qui fluctue dans le temps ». La persistance des symptômes du COVID, la diminution de la qualité de vie, l'incertitude quant à l'avenir, assorties parfois d'un faible soutien social perçu dans l'entourage médical et personnel, ont pu favoriser la survenue d'un trouble dépressif chez les patients atteints de COVID-long. L'objectif de cette recherche a été d'étudier l'effet des symptômes du COVID-long, des incertitudes et de l'altération de la qualité de vie sur les symptômes anxiodépressifs, tout en identifiant l'impact de variables modératrices comme les stratégies de coping et le soutien social. Matériel et méthode Deux cent quatorze participants atteints de COVID long (âgés de 18 à 68 ans, M=44ans, ET=11), dont 93 % de femmes (n=200) et 7 % d'hommes (n=14), ont participé à cette étude quantitative transversale entre les mois d'avril et de juin 2022. Ils ont décrit leurs symptômes et répondu à cinq échelles : l'échelle d'intolérance à l'incertitude (EII), l'échelle des stratégies de coping (WCC), l'échelle de mesure de la qualité de vie (MOS SF-36), l'échelle de soutien social perçu (QSSP), et l'échelle de mesure d'anxiété et de dépression (HADS). Résultats Les participants ont déclaré des symptômes de fatigue 91 % (n=171), de perte de concentration 52 % (n=111), de douleurs 51 % (n=110), de troubles du sommeil 49 % (n=104) et des difficultés de mémorisation 41 % (n=88). En comparaison avec la population générale, ils présentaient une qualité de vie dégradée, ainsi que des scores d'anxiété, de dépression et d'intolérance à l'incertitude élevés. Les scores aux stratégies de coping étaient également supérieurs aux normes relatives à la population générale, et ceux de la satisfaction du soutien social étaient généralement bons. Il est également apparu que les variables de l'intolérance à l'incertitude, de la qualité de vie et de la dépression étaient toutes corrélées entre elles. Par ailleurs, l'analyse de régression a permis de mettre en évidence les prédicteurs de la dépression. Ainsi les domaines de la qualité de vie Bien être émotionnel (β=–0,41, t (199)=–6,23, p<0,01) et Fatigue/énergie (β=–0,16, t (199)=–2,83, p<0,01) étaient des prédicteurs négatifs de la dépression, tout comme le score de coping centré sur le problème (β=–0,14, t (199)=–2,84, p<0,05). Les symptômes de la maladie en lien avec les difficultés de concentration (β=0,27, t (199)=5,16, p<0,01) et ceux impactant les projets (β=0,18, t (199)=3,31, p<0,01) étaient quant à eux des prédicteurs positifs de la dépression. Le deuxième constat de cette étude est que les personnes prises en charge spécifiquement pour leur COVID long présentaient des scores significativement moins élevés d'anxiété et d'intolérance à l'incertitude malgré des scores à certaines dimensions de la qualité de vie plus faibles. Également, les personnes prises en charge dans notre étude développaient davantage de stratégies de coping basées sur le problème et déclaraient davantage de disponibilité et de satisfaction liées au soutien social. Enfin, sur le plan de la qualité de vie, la population prise en charge a exprimé une meilleure santé psychique. Conclusions L'étude a montré, outre l'influence des symptômes du COVID long, de la qualité de vie, et des stratégies de coping sur les symptômes dépressifs, que la prise en charge spécifique des patients atteints de COVID long semble constituer en elle-même un facteur de protection de la dépression et de l'anxiété. Il apparaît donc essentiel que tout patient présentant un COVID long puisse bénéficier d'une prise en charge pluridisciplinaire spécifique à cette pathologie. Objectives Many people were infected by COVID-19 and for a minority of them, symptoms persisted beyond twenty days. These symptoms are multi-systemic, fluctuating, and impact the quality of life. Long COVID was first defined by patients themselves in the spring of 2020 to describe their recovery problems. Specifically, long COVID is defined as "a constellation of physical and mental symptoms which can persist or emerge afterwards, generating a multi-systemic and disabling syndrome, which varies from patient to patient and fluctuates over time”. The persistence of COVID symptoms, the decrease in the quality of life, the uncertainly about the future sometimes accompanied by a low level of social support perceived in the medical and personal entourage may have triggered the occurrence of a depressive disorder in patients with long COVID. The objective of this research was to study the effect of long COVID symptoms, of uncertainty and the impairment of quality of life on the development of depressive symptoms, while identifying the impact of moderating variables such as coping strategies and social support. Materials and methods Two hundred and fourteen participants with long COVID (aged 18–68, M=44, SD=11), including 93 % females (n=200) and 7% males (n=14), participated in this cross-sectional quantitative study between the months of April and June 2022. They described their symptoms and responded to five scales: the Evaluation of Intolerance of Uncertainty Scale (EII), the Coping Strategies Checklist (WCC), the Medical Outcome Study Short Form 36-item health survey (MOS SF-36), the Perceived Social Support Questionnaire (QSSP), and the Hospital Anxiety and Depression Scale (HADS). Results 91% of the participants reported symptoms of fatigue (n=171), 52% a loss of concentration (n=111), 51% pain (n=110), 49 % trouble sleeping (n=104), and 41% memory problems (n=88). Compared with the general population, they presented a poorer quality of life, as well as high scores for anxiety, depression, and intolerance of uncertainty. Scores on coping strategies were also higher than the norms for the general population, and scores on satisfaction with social support were generally good. It was also found that the variables of intolerance of uncertainty, quality of life, and depression all correlated with each other. Furthermore, the regression analysis revealed predictors of depression. The areas of quality of life and emotional well-being (β=–0.41, t(199)=–6.23, P<0.01) and fatigue/energy (β=–0.16, t(199)=–2.83, P<0.01) were negative predictors of depression, as was the problem-focused coping score (β=–0.14, t(199)=–2.84, P<0.05). Symptoms of the disorder related to concentration difficulties (β=0.27, t(199)=5.16, P<0.01) and those impacting projects (β=0.18, t(199)=3.31, P<0.01) were positive predictors of depression. The second finding of this study is that people treated specifically for their long COVID had significantly lower scores for anxiety and intolerance of uncertainty despite lower scores for certain dimensions of quality of life. The individuals who took part in our study also developed more problem-based coping strategies and reported more availability of and satisfaction with social support. Lastly, in terms of quality of life, the treated population expressed better mental health. Conclusions The study showed that, in addition to the effects of long COVID symptoms, quality of life, and coping strategies on the onset of symptoms of depression, the specific treatment of patients with long COVID seemed to constitute in itself a protective factor against depression and anxiety. It therefore would seem essential that any patient suffering from long COVID should receive multidisciplinary care specific to this pathology.
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Introduction/Aim: The interferon gamma release assay (IGRA), used in diagnosing latent tuberculosis infections (LTBI), relies on the release of interferon gamma from T-cells exposed to M. tuberculosis specific peptides. An 'indeterminate' IGRA result is most commonly due an inadequate control (or 'mitogen') response, which may reflect underlying T-cell dysfunction, that is potentially associated with markers of severity in patients with COVID-19. The aim of this study was to determine associations and predictors of an indeterminate IGRA in hospitalised patients with COVID-19. Method(s): We performed a single centre, retrospective study on COVID-19 patients admitted to a tertiary referral hospital who had IGRA testing performed over a 5 months period. Demographics, markers of COVID-19 severity and other parameters were recorded, along with outcomes of COVID-19 infection. The primary outcomes included predictors of indeterminate IGRA results and associations with COVID-19 outcomes (severity, length of stay and mortality). Result(s): A total of 181 patients were included for analysis. Outcomes of IGRA testing included negative (n = 117) and indeterminate (n = 60) results. Patients with a positive IGRA (n = 4) were excluded from analysis. The odds of an indeterminate IGRA were increased with a higher severity grade of COVID-19 (OR 2.5;95% CI 1.3-4.9), immunosuppression at baseline (OR 2.3;95% CI 1.1-4.7) and when IGRA testing was done after immunosuppression for COVID-19 was commenced (OR 1.4;95% CI 1.1-1.8). A longer length of stay was more likely with an indeterminate IGRA compared to a negative result (OR 1.08;95% CI 1.03-1.14), No difference in mortality between the two IGRA subgroups was found. Conclusion(s): Our study demonstrates an indeterminate IGRA was associated with markers of disease severity and immunosuppression. In this cohort an indeterminate result was also associated with worse COVID-19 outcomes in hospitalised patients. This result could potentially be used as a prognostic marker for patients admitted with COVID-19.
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Federated learning is the process of developing machine learning models over datasets distributed across data centers such as hospitals, clinical research labs, and mobile devices while preventing data leakage. This survey examines previous research and studies on federated learning in the healthcare sector across a range of use cases and applications. Our survey shows what challenges, methods, and applications a practitioner should be aware of in the topic of federated learning. This paper aims to lay out existing research and list the possibilities of federated learning for healthcare industries.© 2022 Copyright held by the owner/author(s).
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Background: Respiratory cultures are an important part of clinical care for people with cystic fibrosis (CF). Telemedicine visits during the COVID-19 pandemic have not allowed for routine collection. To address this, the University of Michigan Adult Cystic Fibrosis Program mailed home culture kits to patients. We hypothesized that results from home sputum samples would be consistent with prior cultures obtained in sputum collected in clinic but that self-collected throat swabs would provide false-negative results. We also sought to determine percentage return rate. Method(s): Adults with CF were sent culture kits containing a specimen cup and a throat swab. Patients had the choice to submit either sample for processing. Medical personnel provided written instructions with the culture kits and, on occasion, instructed patients on proper collection techniques via phone. Samples were then refrigerated for up to 24 hours before a delivery service returned the specimen to a University of Michigan laboratory for analysis. Data collected from December 2020 to December 2021 (N = 77) included percentage return rate, result, source, and presence of microorganisms. Pairwise culture data of samples collected in clinic versus home-collected samples within 1 yearwere included in the analysis. Descriptive statistics and Cohen kappa correlation coefficients were computed for all culture data and subgroups (Table 1A-E). Result(s): Of 77 culture kits returned, 46 had corresponding clinic samples collected using the same method, and the remaining 21 were collected using different methods (throat swab vs sputum sample). Overall, approximately 200 kits were mailed to patients, with a return rate of 38.5%. A similar percentage of positive culture results was obtained with same method of collection: sputum and throat samples (Table 1C, D, E), although the discordance rate between cultures collected in clinic and at home ranged from approximately 10% to 30%. Correlation between clinic and home culture data was generally good throughout, except for clinic Table 1 ( 115): Analysis of respiratory culture results for (A) all cultures, (B) different collection, and (C, D, E) same collection method. *p < 0.05. Cohen kappa correlation coefficient between groups: poor agreement <0.20;fair agreement = 0.21-0.40;moderate agreement = 0.41-0.60;good agreement = 0.61-0.80;very good agreement = 0.81-1.00. PsA = Pseudomonas aeruginosa;Staph = Staphylococcus aureus.(Table Presented)versus home throat swabs, probably because of a lowevent rate in the small sample size. Conclusion(s): The data suggest that, overall, clinic and home culture kits provide similar positive results, although discordance in specific culture results was common. This may be due to natural fluctuations from culture to culture in people with CF. A limitation of this study is that the cultures being compared in our study were not completed on the same day. Nevertheless, our data also indicate that collection technique may influence results for certain microorganisms. How these differences might influence antibiotic selection and treatment outcomes in the era of telemedicine requires more investigation. The return rate was found to be relatively low, demonstrating the need for interventions to improve patient outreach and compliance.Copyright © 2022, European Cystic Fibrosis Society. All rights reserved
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Introduction. Primary mediastinal lymphoma (PML) is an aggressive lymphoid tumor treatment success of which is determined by induction therapy. To date, none of the standard chemotherapy regimens (CT) have demonstrated an advantage in efficacy. Intensive therapy programs are associated with high toxicity. Aim - to evaluate the efficacy and toxicity of two pilot prospective treatment protocols PML-16 and PML-19 as well as the possibility of using the analysis of freely circulating tumor DNA (ctDNA) to assess MRD in patients with PML. Materials and methods. From January 2016 to January 2022, 34 previously untreated PML patients were included in the study;average age - 32;stage > I - in 60 %;extramediastinal lesions - in 14.7 %;bulky disease - in 73.5 % of patients. Positron emission tomography combined with computed tomography (PET-CT) was performed;ctDNA was determined to assess the completeness of remission. Results. Eighteen patients received treatment according to the PML-16 protocol (6 courses of chemotherapy;2 blocks of RmNHL-BFM-90 + 4 courses of R-EPOCH). After the end of therapy, all 18 patients achieved PET-negative remission. The next 16 patients received treatment according to the PML-19 protocol (4 courses of chemotherapy;2 blocks of R-mNHL-BFM-90 + 2 courses of R-EPOCH) in combination with lenalidomide. After the end of therapy, 9 (56 %) patients achieved PET-negative remission;7 (44 %) retained pathological activity (D4-5 points). After 3 and 6 months 15 (94 %) patients achieved normalization of metabolic activity. Considering the high frequency of false-positive results in patients with PML, a ctDNA study was performed to determine the depth of remission in 15 patients. After the end of therapy, all 15 patients had complete elimination of ctDNA. Of these, 5 (33 %) remained PET-positive at the end of treatment. During further observation, after 3-6 months, in 4 patients the level of metabolic activity decreased to physiological without the use of consolidating therapy. After the end of therapy, one patient suffered the new coronavirus infection, COVID-19. A month later, residual formation of SUVmax 14.2 remained in the mediastinum. The patient is currently under observation. With a median follow-up of 36 months (9 to 76 months) all 34 patients are in remission. Conclusion. The effectiveness of PML-16 made it possible to abandon the consolidation therapy and refuted the idea of the need for 6 courses of CT. The combination of programs based on the application of the principle of high-dose short-pulse induction of remission (R-mNHL-BFM-90) in combination with the prolonged administration of medium doses (R-EPOCH) was crucial in achieving a successful result. The inclusion of lenalidomide in the "PML-19" program made it possible to achieve complete remission in 100 % of cases after 4 courses. The possibility of using DNA analysis to assess MRD in patients with PML was shown.Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.
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Case report Trometamol (tromethamine, tris(hydroxymethyl)aminomethane (TRIS)) is an excipient frequently used as buffer in fluids and semisolid agents, including many drugs such as antibiotics, iodinated contrast agents and the COVID-19 vaccine mRNA-1273. Here, we report the first case of a delayed-type hypersensitivity after oral intake of trometamol. A 64-year- old female patient presented to our emergency department with generalized erythematous rash, pruritus and swelling of the face five hours after the intake of one tablet of fosfomycin trometamol for a urinary tract infection. Further medical history revealed a previous erythematous rash five to six hours after administration of the iodinated contrast agent iopromide. We performed skin prick and intradermal tests with trometamol, fosfomycin trometamol and various iodinated contrast agents, including iopromide, iomeprol, iobitridol, iopamidol and iodixanol. These tests showed no reactions initially. However, 48 hours after intradermal testing, macular erythematous lesions developed at the sites tested with trometamol 0.1%, trometamol 0.01% and all sites tested with iodinated contrast agents. Furthermore, when we performed a lymphocyte transformation test with trometamol, fosfomycin trometamol and iopromide, we recorded a positive reaction with cytokine release after stimulating T cells with trometamol and iopromide. In contrast, basophil activation testing showed a negative result for these agents. Based on these results and our patient's history, we diagnosed a clinically relevant type IV sensitization to trometamol. There are only a few case reports about immediate-type allergic reactions to gadolinium contrast agents caused by the excipient trometamol. There are some published cases which report contact dermatitis after topical administration of trometamol-containing agents. To our knowledge, ours is the first case to report a delayed hypersensitivity reaction to oral administration of trometamol. Excipients are indispensable for drugs, vaccines and other products since they stabilize and preserve the active agents. Nevertheless, excipients should always be considered during an allergy workup, especially if the patient reports prior drug reactions that cannot be explained by a chemical cross-reaction. In our case, we diagnosed delayed-type hypersensitivity to the excipient trometamol. This is a consequential diagnosis for the patient, because trometamol is contained in many drugs and in the COVID-19 vaccine mRNA-1273.
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Background: Remote rhythm monitoring with wearable devices is increasingly used especially for early detection of atrial fibrillation/flutter (AF/Afl), being the access to hospital discouraged, especially for frail elderly patients, due to the burden and risk of COVID-19 pandemic. Whereas devices using photo plethysmography (PPG) may misinterpret as AF pulse irregularities due to extrasystoles, patient-directed recording of a single (usually wrist-to-wrist) lead ECG (LEAD I) with hand-held devices or smartwatches have been developed to increase accuracy in AF detection. However, although recent studies validating such devices single-lead ECG recording have shown high sensitivity and specificity, false negative findings such as those reported here are still possible and must be prevented [1]. Purpose(s): Given previous experience of diagnostic uncertainty or failure of the smartwatch ECG (SW-ECG) LEAD I to detect AF/Afl, we have tested if false negative diagnosis could be avoided by recording in addition at least one right precordial (pseudo-V1) lead analyzed by a trained healthcare professional. Method(s): Over one calendar year observation, five patients with previous history of ablated supraventricular arrhythmias suffering sudden palpitations suspected of paroxysmal AF/Afl were instructed to record with their smartwatch at least one precordial lead in addition to LEAD I, to monitor ECG until the termination of symptoms. The SW-ECG strips were sent by telephone for professional interpretation. Diagnostic accuracy based on LEAD I and pseudo-V1 were independently validated by two cardiologists (diagnostic goldstandard - DGS). Result(s): 22 AF/Afl events occurred. Pharmacological cardioversion to sinus rhythm (SR) was obtained in 64%. 192 ECG strips were transmitted. 43,7% of the strips were automatically classified as not significant (or not valid ). Compared to DGS, out of 108 valid strips, correct automatic identification of AF/Afl was obtained in 36,4% with LEAD I, in 33,3% with pseudo V1 and in 54,5% with combined leads, respectively. Interestingly, the SW algorithm has wrongly diagnosed as SR, not only LEAD I, but also 39,4% of pseudo-V1 strips, despite clear-cut evidence of typical flutter waves (Figure 1), when RR intervals were regular due to high degree (e.g., 4:1) A-V block. Conclusion(s): With simple instructions, patients (or their relatives) can easily record an additional precordial (pseudo-V1) SW-ECG lead, that may enhance sensitivity and specificity for remote detection of AF/Afl. However, at present, visual interpretation of SW-ECG by a trained healthcare professional is still needed to guarantee 100% correct diagnosis of AF/Afl, crucial to reduce thromboembolic risk and timely initiate the appropriate treatments. The automatic interpretation of SW's ECG could be improved by appropriate training of a machine learning approach to detect and analyze the atrial waveform provided by an additional pseudo-V1 lead.
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Introduction: COVID-19 pandemic has resulted in more than 6.1 million deaths and more than 480 million infections worldwide (1). Left ventricular assist device patients (LVAD) with their multiple co-morbidities are at high risk for morbidity and mortality from the COVID-19 infection. Few studies and case reports demonstrating the outcomes of COVID-19 infection in LVAD patients have been published, with the most recent study in 2021 (2-4). However, none of these studies spanned the entire stretch of the pandemic. Hypothesis: : COVID-19 infection would result in significant mortality and multi-system complications among patients with an LVAD. Method(s): IRB approval was obtained for our retrospective cohort study. 225 LVAD patients across two large centers in Texas, USA were screened for COVID-19 infection from December 1, 2019 to February 28, 2022. 68 events of COVID-19 infection were identified among 64 patients. One patient was excluded due to false positive test and 3 patients were infected twice and counted as separate events. Outcomes including mortality, respiratory failure, bleeding, and thromboembolic complications were assessed. Result(s): Baseline characteristics and results are summarized in Table 1. 51% of the patients needed hospitalization or emergency department visit for COVID infection. Five patients were intubated (7.4%). 6 patients developed chronic hypoxic respiratory failure requiring outpatient supplemental oxygen. 4 patients suffered from ventricular tachycardias while three other patients had Implantable cardioverter Defibrillator (ICD) shocks during COVID infection. 9 patients had epistaxis or gastrointestinal bleeding within 1 month of testing COVID positive. One HM2 patient had confirmed LVAD outflow cannula thrombus on CT heart and another patient with HeartWare had confirmed inflow cannula thrombus requiring emergent exchange to HM3 due to pump stoppage. Three patients suffered a stroke (5%). No events of pulmonary emboli or DVTs were noted. The mortality rate among this cohort was 14% (9 out of 64 patients). Four patients died during the same hospitalization. 33% had HM2 and 67% had HM3 LVADs, making a mortality rate of 37% (3 out of 8) for HM2 patients and 9% for HM3 (6 out of 55). 88% were males, 56% were African Americans, 67% had NICM, and 78% had at least moderate RV dysfunction at baseline. Conclusion(s): COVID-19 infection resulted in significant mortality and complications including stroke, pump thrombus, arrhythmias, respiratory failure, and bleeding events among LVAD patients.Copyright © 2022
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Background: A variety of skin conditions are reported in association with COVID-19. Among these clinical patterns, urticarial lesions are described. We present a case of new-onset urticaria in an adult patient with mild COVID-19. In addition, we performed a comprehensive structured literature search to evaluate the temporal relationship between COVID-19 and urticarial manifestations and their duration. Method(s): This case report presents an adult patient with new-onset urticaria and confirmed diagnosis of COVID-19, assessed according to international guidelines. A systematic review was conducted for relevant studies published in Pubmed/Medline database, between January 2020 and January 2022, using specific keywords for clinical and temporal features of skin lesions. Result(s): A 28-year- old male with a 24-hour history of fever and headache presented new-onset urticarial lesions. In the context of COVID-19 pandemic, infection with SARS-CoV- 2 was suspected, and a PCR test detected viral RNA in a nasopharynx sample confirming the diagnosis in this patient. Other clinical manifestations and abnormal laboratory findings were not detected. A diagnosis of SARS-CoV- 2 infection-associated urticaria was established. The urticarial rash improved with oral new-generation H1 antihistamines and was remitted in 5 days. The outpatient treatment did not include systemic corticosteroid and antiviral therapy. Out of 3542 articles published in PubMed on cutaneous manifestations linked to COVID-19/ SARS-CoV- 2 infection, 53 met the criteria of assessing urticaria in these conditions. From these, 30 were case reports, 13 were case series and 10 were cohort studies. From 273 patients reported with urticaria, only 53 had a clear mention of a positive antigen or nucleic acid amplification viral test. Urticaria preceded the onset of respiratory/systemic COVID-19 symptoms in 12 patients, appeared at the same time in 81 patients, and as a late manifestation in 45 patients. For 135 patients, the timing was not specified. Urticarial lesions were remitted between several hours to 12 weeks, either spontaneously or with symptomatic treatment. Conclusion(s): Based on reported cases, urticaria may be associated with COVID-19. There is a need for more relevant studies regarding urticaria in these infectious conditions, with detailed data on clinical pattern, time of onset, duration, severity, need for specific treatment and prognosis.
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Objective. To evaluate the efficacy of therapy for acute respiratory viral infections (ARVIs) in children with antiviral medications: inosine pranobex (Groprinosin, Gedeon Richter) and Kagocel (Kagocel, Niarmedic Pharma LLC) in comparison with symptomatic treatment without etiotropic agents based on clinical and laboratory parameters. Patients and methods. The clinical and laboratory observation was conducted in an outpatient setting in the pre-COVID-19 period between 2018 and 2020. Acute respiratory infections were diagnosed using licensed testing systems by multiplex polymerase chain reaction (PCR) with detection of nucleic acid viral genomes: influenza, rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza, seasonal coronaviruses, adenoviruses, and bocavirus). A total of 151 children aged 3 to 15 years were examined and monitored in dynamics, with 78.7% of positive and 21.3% of negative results detected by PCR in the nasopharyngeal and oropharyngeal swabs. The patients were randomized into three groups depending on the antiviral medication prescribed: group 1 (53 children) received Groprinosin;group 2 (52 children) received Kagocel;group 3 (control, 46 children) received only symptomatic therapy without antiviral agents. Results. The study demonstrated a significant positive effect in patients in group 1 treated with Groprinosin (n = 53). At the end of therapy for both mono- and mixed infections, there were 95.8% of negative results (according to PCR diagnosis, that is, the absence of viral genome). In children in group 2 (n = 52) treated with Kagocel, the absence of viral nucleic acids (NAs) was observed less frequently (in 77.3% of cases). In children in group 3 (n = 46) who did not receive etiotropic antiviral therapy, there were only 40.3% of negative results after the end of treatment, and viral NAs were detected in 59.7% of patients. In this case, a 5-day course of Groprinosin was prescribed, after which the PCR results became negative in all patients. Therefore, children with recurrent respiratory infections, mixed infections, and herpesvirus infections require longer therapy. Additionally, a high frequency of ARVI complications was noted in group 3 (5 (10.9%) patients, where otitis was observed in 1 case, sinusitis - in 2 cases, bronchitis - in 2 cases), whereas 1 (1.8%) patient taking Groprinosin had otitis, and 1 (1.9%) patient taking Kagocel had pneumonia. Conclusion. This study was the first to investigate antibody titers to respiratory viruses in dynamics at 3, 6 and 12 months after the onset of ARVI. It showed that the development of antibodies to respiratory viruses is very unstable and does not occur in all patients. Antibodies almost disappeared by the third month after ARVI and were no longer detectable by the sixth month. After 12 months, patients suffered a new ARVI and developed the corresponding antibodies. This information will be especially relevant in conditions of the rise in the incidence of ARVIs, as well as the COVID-19 pandemic observed in recent years.Copyright © 2022, Voprosy Prakticheskoi Pediatrii. All rights reserved.