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Introduction: Globally, COVID-19 pandemic has a significant impact on mental health. In Nepal, COVID-19 positive cases have to self-isolate at home in multi-generational and multi-family households. This could be strongly associated with depression, anxiety, and stress-related health outcomes. Additionally, COVID-19 related stigma and fear of transmission may intensify depression, anxiety, and stress symptoms. This study determined the prevalence of depression, anxiety, and stress symptoms and their association with presence of COVID-19 symptoms and comorbid conditions among home isolated COVID-19 positives in the Karnali province, Nepal., Methods: We conducted a cross-sectional study to assess depression, anxiety, and stress symptoms among 402 home isolated COVID-19 patients of Karnali province from January to May 2021 using "Depression, Anxiety and Stress Scale-21 (DASS-21)". We interviewed patients to collect socio-demographic, DASS-21, COVID-19 symptoms, comorbid conditions, and self-treatment. We conducted a telephonic interview using a standardized questionnaire using Kobotoolbox. We calculated the prevalence of depression, anxiety, and stress symptoms. We utilized univariate and multivariate logistic regression to determine their association with the presence of COVID-19 symptoms and comorbid conditions. In multivariate logistic regression, we adjusted sociodemographic factors (age, gender, ethnicity, marital status, monthly family income, education level), smoking status and history of self-treatment. We reported adjusted odds ratios (aOR) with 95% confidence intervals. All analyses were conducted in R (version: 4.0.3)., Results: The prevalence of depression, anxiety and stress symptoms among home isolated COVID-19 patients were 8.0% (95% CI: 5.5 to 11.1), 11.2% (95% CI: 8.3 to 14.7), and 4.0% (95% CI: 2.3 to 6.4) respectively. Higher odds of depression symptoms (aOR: 2.86; 95% CI: 1.10-7.44,  p  = 0.03), anxiety symptoms (aOR: 3.81; 95% CI: 1.62 to 8.93;  p  = <0.01) and stress symptoms (aOR: 7.78; 95% CI: 1.43 to 42.28;  p  = 0.02) were associated significantly with presence of COVID-19 symptoms in past week. Higher odds of anxiety symptoms were associated with the presence of comorbid conditions (aOR = 2.92; 95% CI: 1.09 to 7.80;  p  = 0.03)., Conclusion: Depression, anxiety, and stress symptoms were present in a significant proportion of home isolated COVID-19 patients in western Nepal and positively associated with the presence of COVID-19 symptoms. In this global COVID-19 pandemic, it is important to provide timely counseling to high-risk groups like those with comorbidities and COVID-19 symptoms to maintain a high level of mental health among home isolated COVID-19 patients., Competing Interests: We/ Authors declare no conflict of interests., (© 2022 The Authors.)

Competing Interests: None disclosed.

Objective: To estimate rates and identify factors associated with asymptomatic COVID-19 in the population of Olmsted County during the prevaccination era., Patients and Methods: We screened first responders (n=191) and Olmsted County employees (n=564) for antibodies to SARS-CoV-2 from November 1, 2020 to February 28, 2021 to estimate seroprevalence and asymptomatic infection. Second, we retrieved all polymerase chain reaction (PCR)-confirmed COVID-19 diagnoses in Olmsted County from March 2020 through January 2021, abstracted symptom information, estimated rates of asymptomatic infection and examined related factors., Results: Twenty (10.5%; 95% CI, 6.9%-15.6%) first responders and 38 (6.7%; 95% CI, 5.0%-9.1%) county employees had positive antibodies; an additional 5 (2.6%) and 10 (1.8%) had prior positive PCR tests per self-report or medical record, but no antibodies detected. Of persons with symptom information, 4 of 20 (20%; 95% CI, 3.0%-37.0%) first responders and 10 of 39 (26%; 95% CI, 12.6%-40.0%) county employees were asymptomatic. Of 6020 positive PCR tests in Olmsted County with symptom information between March 1, 2020, and January 31, 2021, 6% (n=385; 95% CI, 5.8%-7.1%) were asymptomatic. Factors associated with asymptomatic disease included age (0-18 years [odds ratio {OR}, 2.3; 95% CI, 1.7-3.1] and >65 years [OR, 1.40; 95% CI, 1.0-2.0] compared with ages 19-44 years), body mass index (overweight [OR, 0.58; 95% CI, 0.44-0.77] or obese [OR, 0.48; 95% CI, 0.57-0.62] compared with normal or underweight) and tests after November 20, 2020 ([OR, 1.35; 95% CI, 1.13-1.71] compared with prior dates)., Conclusion: Asymptomatic rates in Olmsted County before COVID-19 vaccine rollout ranged from 6% to 25%, and younger age, normal weight, and later tests dates were associated with asymptomatic infection., (© 2022 The Authors.)

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Competing Interests: None disclosed.

Competing Interests: None disclosed.

Most women who develop cancer have not been screened regularly. One in four women in Scotland, is overdue for cervical screening. Aim was to assess the impact of offering multiple cervical screening options to women whose screening is overdue. A prospective cohort study including all women whose screening was overdue, aged 30-60 years in Dumfries and Galloway in 2012. Potentially eligible women (n = 4146) were identified split into six groups. Women aged 30-55 years were allocated to three different groups. Group 1 (letter, n = 1246), Group 2 (letter and kit, n = 221), Group 3 (letter, n = 2031). Women aged 56-60 years were allocated to: Group 4 (letter, n = 292), Group 5 (letter and kit, n = 292) and Group 6 (control, n = 64). Women who self-collected a vaginal sample were requested to complete a questionnaire. The percentages of women responding were 24 % (21-26), 32 % (25-38), 16 % (14-18), 15 % (11-20) and 12 % (9-17) in groups 1 to 5 respectively, compared with 3 % (0-11) among controls. A significantly higher number of women (n = 383, 10 % of 3815) opted for self-sampling in comparison with undergoing a cervical screening test (CST) at the GP practice (n = 197, 5 %, x 2  = 59.0, p < 0.0001). The Evalyn® Brush was well accepted (218/313 = 70 %) by those who requested self-sampling. Almost all (265/272 = 97 %) women who self-collected a vaginal sample said that if they had the option of self-sampling, they would regularly participate in future cervical screening. Offering more flexible screening options, self-sampling in particular, appears to increase cervical screening participation., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Spinal muscular atrophy (SMA) is a degenerative neuromuscular disease that causes progressive muscle weakness and atrophy due to loss of the anterior horn cells of the spinal cord. Although effective treatments, such as gene therapy, have emerged in recent years, their therapeutic efficacy depends on a restricted time window of treatment initiation. For the treatment to be effective, it must be started before symptoms of the disease emerge. For this purpose, newborn screening (NBS) for SMA is conducted in many countries worldwide. The NBS program for SMA has been initiated in Japan in several regions, including the Kumamoto Prefecture. We started the NBS program in February 2021 and detected a patient with SMA after screening 13,587 newborns in the first year. Herein, we report our experience with the NBS program for SMA and discuss an issue to be approached in the future., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Inc.)

Coronavirus disease 2019 (COVID-19), a novel etiology of end-stage lung disease, has resulted in major disruptions to the process of health care delivery worldwide. These disruptions have led to team-based innovations globally, resulting in a broad range of new processes in cardiopulmonary perioperative management. A key intersection of multidisciplinary teamwork and COVID-19 is found in lung transplantation, in which diverse teams collaborate throughout the perioperative period to achieve optimal outcomes. In this article, we describe the multidisciplinary approach taken by Mayo clinic in Florida to manage patients with COVID-19 presenting for lung transplantation., (© 2022 The Authors.)

Menkes disease (MD) is an X-linked recessive disorder caused by mutations in ATP7A . Patients with MD exhibit severe neurological and connective tissue disorders due to copper deficiency and typically die before 3 years of age. Early treatment with copper injections during the neonatal period, before the occurrence of neurological symptoms, can alleviate neurological disturbances to some degree. We investigated whether early symptoms can help in the early diagnosis of MD. Abnormal hair growth, prolonged jaundice, and feeding difficulties were observed during the neonatal period in 20 of 69, 16 of 67, and 3 of 18 patients, respectively. Only three patients visited a physician during the neonatal period; MD diagnosis was not made at that point. The mean age at diagnosis was 8.7 months. Seven patients, who were diagnosed in the prenatal stage or soon after birth, as they had a family history of MD, received early treatment. No diagnosis was made based on early symptoms, highlighting the difficulty in diagnosing MD based on symptoms observed during the neonatal period. Patients who received early treatment lived longer than their elderly relatives with MD. Three patients could walk and did not have seizures. Therefore, effective newborn screening for MD should be prioritized., Competing Interests: The study protocol was approved by the Institutional Review Board of Teikyo University School of Medicine (TEIRIN No. 12-014, No. 08-114, No. 10-053).The authors declare no conflict of interest. The funding body had no role in the study design; in the collection, analysis, and interpretation of the data; in the writing of the report; or in the decision to submit the paper for publication., (© 2022 The Authors.)

Competing Interests: None disclosed.

Regulation of 5-aminolevulinate synthase 1 (ALAS1) for nonerythroid heme is critical for respiration, cell signaling mechanisms and steroid/drug metabolism. ALAS1 is induced in some genetic disorders but unlike other genes in the heme pathway, a gene variant of ALAS1 associated with inherited disease has not been reported. BALB/c mice carrying a null ALAS1 allele caused by a βGEO insert were developed and used to determine the consequences of heme demand of a semi gene copy number. Homozygous disruption of ALAS1 (-/-) was lethal for embryo development post day 6.5 but expression in heterozygotes (+/-) was sufficient for the number of offspring and survival. In both wild type (WT +/+) and +/- mice expression of ALAS1 RNA was greatest in liver and harderian gland and much lower in kidney, lung, heart, brain and spleen. The effects of one WT ALAS1 allele in +/- mice on mRNA levels in liver and harderian gland were less marked compared to brain and other organs that were examined. Many other genes were up-regulated by heterozygosity in liver and brain but to a minimal extent. Hepatic heme oxygenase 1 (HMOX1) mRNA expression was significantly lower in +/- mice but not in brain. No elevated translation of WT allele ALAS1 mRNA was detected in +/- liver as a compensatory mechanism for the disabled allele. Fasting induced ALAS1 mRNA in both WT and +/- mice but only in +/- was this manifest as increased ALAS1 protein. The hepatic protoporphyria-inducing drug 4-ethyl-DDC caused induction of hepatic ALAS1 mRNA and protein levels in both WT and +/- mice but markedly less in the mice with only one intact allele. The findings illustrate the complex response of ALAS1 expression for heme demand but limited evidence that upregulation of a wild type allele can compensate for a null allele., (© 2021 The Authors.)

Objective: To reduce health care facility-onset (HCFO) Clostridioides difficile infection (CDI) incidence by improving diagnostic stewardship and reducing the inappropriate testing of C difficile assays., Patients and Methods: A multidisciplinary team conducted a quality improvement initiative from January 1, 2020, through March 31, 2021. Clostridioides difficile infection and inappropriate testing were identified via electronic health records using predefined criteria related to stool quantity/caliber, confounding medications, and laboratory data. An intervention bundle was designed including (1) provider education, (2) implementation of an appropriate testing algorithm, (3) expert review of C difficile orders, and (4) batch testing of assays to facilitate review and cancellation if inappropriate., Results: Compared with a baseline period from January to September 2020, implementation of our intervention bundle from December 2020 to March 2021 resulted in an 83.6% reduction in inappropriate orders tested and a 41.7% reduction in HCFO CDI incidence., Conclusion: A novel prevention bundle improved C difficile diagnostic stewardship and HCFO CDI incidence by reducing testing of inappropriate orders. Such initiatives targeting HCFO CDI may positively affect patient safety and hospital reimbursement., (© 2021 The Authors.)

Objective: To investigate the association of voice analysis with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection., Patients and Methods: A vocal biomarker, a unitless scalar with a value between 0 and 1, was developed based on 434 voice samples. The biomarker training was followed by a prospective, multicenter, observational study. All subjects were tested for SARS-CoV-2, had their voice recorded to a smartphone application, and gave their informed consent to participate in the study. The association of SARS-CoV-2 infection with the vocal biomarker was evaluated., Results: The final study population included 80 subjects with a median age of 29 [range, 23 to 36] years, of whom 68% were men. Forty patients were positive for SARS-CoV-2. Infected patients were 12 times more likely to report at least one symptom (odds ratio, 11.8; P <.001). The vocal biomarker was significantly higher among infected patients (OR, 0.11; 95% CI, 0.06 to 0.17 vs OR, 0.19; 95% CI, 0.12 to 0.3; P =.001). The area under the receiver operating characteristic curve evaluating the association of the vocal biomarker with SARS-CoV-2 status was 72%. With a biomarker threshold of 0.115, the results translated to a sensitivity and specificity of 85% (95% CI, 70% to 94%) and 53% (95% CI, 36% to 69%), respectively. When added to a self-reported symptom classifier, the area under the curve significantly improved from 0.775 to 0.85., Conclusion: Voice analysis is associated with SARS-CoV-2 status and holds the potential to improve the accuracy of self-reported symptom-based screening tools. This pilot study suggests a possible role for vocal biomarkers in screening for SARS-CoV-2-infected subjects., (© 2021 The Authors.)

Background: As the daily number of coronavirus infection disease 19 (COVID19) patients increases, the necessity of early diagnosis becomes more obvious. In this respect, we aimed to develop a serological test for specifically detecting anti-SARS-CoV2 antibodies., Methods: We collected serum and saliva samples from 609 individuals who work at TBZMED affiliated hospitals in Tabriz, Iran, from April to June of 2020. Real-time PCR technique was used to detect SARS-CoV-2 genome using specific primers. An enzyme linked immunosorbent assay (ELISA) test was designed based on virus nucleocapsid (N), spike (S) and its receptor binding domain (RBD) protein, and the collected sera were subjected to IgM and/or IgG analysis., Result: Real-time PCR results showed that 66 people were infected with the SARS-CoV-2. Our designed ELISA kit showed 93.75% and 98% of sensitivity and specificity, respectively. In this study, 5.74% of participants had specific IgG against RBD, whereas the percentage for IgM positive individuals was 5.58%. Approximately the same results were observed for S protein. The number of positive participants for NP increased further, and the results of this antigen showed 7.38% for IgG and 7.06% for IgM., Conclusion: The ELISA test beside real-time PCR could provide a reliable serologic profile for the status of the disease progress and early detection of individuals. More importantly, it possesses the potential to identify the best candidates for plasma donation according to the antibody titers., Competing Interests: The authors declare no conflict of interests., (© 2021 Elsevier Inc. All rights reserved.)

Objective: To explore the survival benefit of tofacitinib in addition to dexamethasone in hospitalized patients treated for coronavirus disease 2019 (COVID-19)-related pneumonia., Patients and Methods: This is a single-center retrospective observational study. All patients who were hospitalized at Delta Regional Medical Center (a regional hospital in the Mississippi Delta) with a COVID-19 diagnosis and discharged between March 1 and September 30, 2020, are included. The primary outcome was in-hospital mortality in relation to receipt of tofacitinib alone or in addition to dexamethasone (designated as the tofacitinib group), versus dexamethasone alone (designated as the dexamethasone group)., Results: Of 269 eligible patients, 138 (51.3%) received tofacitinib uniformly and 131 (48.7%) patients received dexamethasone without tofacitinib. A total of 44 patients expired: 14 (31.8%) in the tofacitinib group and 30 (68.2%) in the dexamethasone group. The proportions of death among the tofacitinib and dexamethasone groups were, respectively, 10.1% and 22.9%. This represents a 70% reduction in odds of dying among the tofacitinib group compared to the dexamethasone group after adjusting for age and clinical parameters captured at hospitalization (adjusted odds ratio: 0.30; 95% CI: 0.12 to 0.76; P =.01)., Conclusion: The in-patient treatment of COVID-19 pneumonia has rapidly evolved. The addition of dexamethasone has made a relevant improvement on survival. Other immunomodulators have yet to show an impact. Here we present the potential survival benefit of the Janus kinase-signal transducer and activator of transcription inhibitor tofacitinib on COVID-19 pneumonia. We found that adding tofacitinib-based anti-inflammatory therapy to a treatment regimen including dexamethasone in COVID-19 pneumonia seems to have potential benefit of improving survival when compared to dexamethasone alone., (© 2021 The Authors.)

Objective: To assess the safety and efficacy of convalescent plasma (CP) transfusion in elderly people with moderate to severe coronavirus disease 2019 (COVID-19) living in a long-term care facility (LTCF)., Patients and Methods: Twenty-two consecutive elderly patients with COVID-19 infection living in an LTCF in Lombardy, Italy, who were given CP during May 15 to July 31, 2020, were enrolled in a prospective cohort study. Their clinical, instrumental, and laboratory parameters were assessed following the CP treatment. The overall mortality rate in this group was compared with that recorded in other LTCFs in Lombardy during the 3-month period from March to May 2020., Results: Of the 22 patients enrolled, 68.2% (n=15) received 1 CP unit, 27.3% (n=6) received 2 units, and 4.5% (n=1) received 3 units. Of the CP units transfused, 76.7% (23/30) had a neutralizing antibody titer of 1:160 or greater. No adverse reactions were recorded during or after CP administration. Improvements in clinical, functional, radiologic, and laboratory parameters during the 14 days after CP transfusion were observed in all 19 patients who survived. Viral clearance was achieved in all patients by the end of follow-up (median, 66 days; interquartile range, 48-80 days). The overall mortality rate was 13.6% (3/22), which compared favorably with that in the control group (38.3% [281/733]; P =.02) and corresponded to a 65% reduction in mortality risk., Conclusion: Early administration of CP with an adequate anti-severe acute respiratory syndrome coronavirus 2 antibody titer to elderly symptomatic patients with COVID-19 infection in an LTCF was safe and effective in eliminating the virus, restoring patients' immunity, and blocking the progression of COVID-19 infection, thereby improving patients' survival., Trial Registration: ClinicalTrials.gov: NCT04569188., (© 2021 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Competing Interests: None disclosed.

Objective: To describe the design, implementation, and utilization of electronic health record (EHR)-based digital health surveillance strategies used to manage the coronavirus disease 2019 (COVID-19) pandemic and to ensure delivery of high-quality clinical care, such as case identification, remote monitoring, telemedicine services, and recruitment to clinical trials at Mayo Clinic., Methods: The design and implementation work described in this report was performed at Mayo Clinic, a large multistate integrated health care system with more than 1.5 million annual patient visits that uses the Epic EHR system. Rule-based live registries were designed in the EHR system to classify patients who currently test positive for COVID-19, patients who test positive but have recovered from COVID-19, patients who are thought to have COVID-19 but do not yet meet clinical diagnostic criteria, patients who test negative for COVID-19, and patients who exceed a risk score for serious complications from COVID-19., Results: By use of registries, custom dashboards and operational reports were developed to provide a daily high-level summary for clinical practice use and up-to-date information to manage individual patients affected by COVID-19, including support of case identification, contact isolation, and other care management tasks., Conclusion: We developed and implemented a systematic approach to the use of EHR patient registries to manage the COVID-19 pandemic that proved feasible and useful in a large multistate group clinical practice. The key to harnessing the potential of digital surveillance tools to promote patient-centered care during the COVID-19 pandemic was to use the registry data, reports, and dashboards as informatics tools to inform decision-making ., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Objective: To study the impact of a 60-day pilot of an innovative virtual-care model using general internal medicine physicians and nurses to respond rapidly to more than 1200 coronavirus disease-2019 (COVID-19)-positive nasopharyngeal polymerase chain reaction tests., Patients and Methods: The current study was approved by the Mayo Clinic COVID-19 Research Committee and the Mayo Clinic Institutional Review Board. The data for all SARS-CoV-2-positive patients treated by our team were entered into a prospectively maintained internal research electronic data capture database. We searched this database retrospectively for the first 60 days of our program (March 23, 2020 to May 22, 2020). The data included basic deidentified demographics; symptoms at intake into the program; date of symptom onset; risk factors; location; and outcomes including hospitalization, admission to intensive care unit, and death., Results: Patients were contacted, on average, 6.3 hours after their results became available. There was a total of 138 ED visits. Of these, 40% were admitted to the hospital, with 36% of those admitted requiring intensive care unit level of care. Of the 849 patients in this sample, there were only 2 deaths (0.23%) at 60 days., Conclusion: Our innovative multidisciplinary COVID team provided excellent clinical care for patients with COVID, with a very low mortality rate compared with the national average. Although data are not available on a national scale for time to contact patient, our team was able to contact patients within the established recommendation for contact within 48 hours of testing, which is optimal., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

The coronavirus disease 2019 (COVID-19) pandemic created an extremely disruptive challenge for health care leaders that required a rapid, dynamic, and innovative response. The purpose of this manuscript is to share the leadership actions and decisions at Mayo Clinic in Florida during the first 6 months of the pandemic (February to July 2020). We note 4 strategies that contributed to an effective response: (1) leverage experience with disaster preparedness and mobilize regional and national networks; (2) use surge models to anticipate and to address supply chain issues as well as practical and financial effects of the pandemic; (3) adapt creatively to establish new safety and procedural protocols in various areas for various populations; and (4) communicate timely information effectively and be the common source of truth. Mayo Clinic in Florida was able to address the surges of patients with COVID-19, to provide ongoing tertiary care, and to restore function within the first 6 months with new, strengthened practices and protocols., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

The biotinidase (BTD) enzyme is essential for recycling biotin, a water-soluble B-complex vitamin that is the coenzyme of four carboxylases involved in fatty acid synthesis, amino acid catabolism and gluconeogenesis. If untreated, total or partial BTD deficiencies lead to an autosomal recessive inherited organic aciduria whose clinical features, mainly presenting in the first years of life, include, seizures, skin rash, and alopecia. Based on residual BTD enzyme activity it is possible to identify partial or total biotinidase deficiency. The incidence of profound and partial biotinidase deficiency worldwide is estimated to be about 1 in 60.000. We report twelve years of experience in the newborn screening of biotinidase deficiency on 466.182 neonates. When a positive screening result occurred, a clinical evaluation was made of the patient and genetic counselling was offered to the family. Molecular analysis the BTD gene was carried out in all recalled neonates. Newborn screening lead to the identification of 75 BTD deficiencies with an incidence of about 1:6.300 births, ten times higher than the reported worldwide incidence. BTD deficiency was confirmed at a genomic level in all patients, demonstrating a high frequency of the p.(Asp444His) amino acid substitution and the complex allele p.(Ala171Thr)/p.(Asp444His) in the analyzed Italian newborns. Four new mutations (two small deletions, one stop mutation and one missense mutation) and a new combined allelic alteration were identified. Our data suggests that there is a high incidence of the biotinidase defect in the Italian population, most likely due to the high frequency of certain mutations., Competing Interests: None of the authors has a financial or not-financial interests that could influence this paper., (© 2020 The Authors.)

Objective: To assess the effect of a pharmacist-driven, polymerase chain reaction (PCR)-based nasal screening protocol for methicillin-resistant Staphylococcus aureus (MRSA) on vancomycin therapy duration and on rates of adverse drug events and 30-day hospital readmission., Patients and Methods: From July 8, 2017, through January 31, 2019, we performed a retrospective, multicenter, preimplementation-postimplementation study. Patients with a vancomycin order to treat lower respiratory tract infection (LRTI) underwent MRSA PCR screening; tests were ordered by health care providers, including physicians, physician assistants, and advanced practice registered nurses. During the preimplementation period (July 8, 2017, through September 30, 2018), pharmacists could order MRSA PCR screening only after receiving a verbal order from a health care provider. During the postimplementation period (October 1, 2018, through January 31, 2019), a collaborative practice agreement allowed pharmacists to order MRSA PCR screening tests., Results: The preimplementation group included 241 patients, and the postimplementation group included 74 patients. Of these patients, 124 in the preimplementation group and 62 in the postimplementation group received MRSA PCR screening. Twenty patients (16.1%) in the preimplementation group and 9 (14.5%) in the postimplementation group had a positive MRSA PCR screening test result (between-group difference, 1.6%; P =.80). Duration of therapy was significantly shorter in the postimplementation group (median [interquartile range], 14.3 [5.0-28.6] hours vs 24.0 [12.4-47.0] hours; P <.001)., Conclusion: Vancomycin therapy carries a risk of adverse events and may increase health care costs. A pharmacist-driven protocol for MRSA nasal swab PCR screening effectively reduces the duration of vancomycin therapy for patients with lower respiratory tract infection., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)

Introduction: Mitochondrial fatty acid oxidation disorders (FAODs) are a heterogeneous group of hereditary autosomal recessive diseases included in newborn screening (NBS) program in Italy. The aim of this study was to analyse FAODs cases, identified either clinically or by NBS,for clinical and genetic characterization and to evaluate a five years' experience of NBS, in the attempt to figure out the complexity of genotype-phenotype correlation and to confirm the clinical impact of NBS in our centre experience., Materials and Methods: We analysed FAODs patients diagnosed either by NBS or clinically, followed since February 2014 to April 2019 at the Regional Screening Centre and Inherited Metabolic Diseases Unit of Verona. Diagnosis was confirmed by plasma acylcarnitines, urinary organic acids, enzymatic and genetic testing. For not clear genotypes due to the presence of variants of uncertain significance, in silico predictive tools have been used as well as enzymatic activity assays. Patients underwent clinical, nutritional and biochemical follow up., Results: We diagnosed 30 patients with FAODs. 20 by NBS: 3 CUD, 6 SCADD, 5 MCADD, 4 VLCADD, 2 MADD. Overall incidence of FAODs diagnosed by NBS was 1:4316 newborns. No one reported complications during the follow up period. 10 patients were diagnosed clinically: 2 CUD, 2 CPT2D, 1 VLCADD, 5 MADD. Mean age at diagnosis was 29.3 years. Within this group, complications or symptoms were reported at diagnosis, but not during follow-up. 12 mutations not previously reported in literature were found, all predicted as pathogenic or likely pathogenic., Discussion and Conclusions: Our study highlighted the great phenotypic variability and molecular heterogeneity of FAODs and confirmed the importance of a tailored follow up and treatment. Despite the short duration of follow up, early identification by NBS prevented diseases related complications and resulted in normal growth and psycho-motor development as well., Competing Interests: The authors declare that they have no conflict of interest., (© 2020 The Author(s).)

An understanding of the molecular basis of liver regeneration will open new horizons for the development of novel therapies for chronic liver failure. Such therapies would solve the drawbacks associated with liver transplant, including the shortage of donor organs, long waitlist time, high medical costs, and lifelong use of immunosuppressive agents. Regeneration after partial hepatectomy has been studied in animal models, particularly fumarylacetoacetate hydrolase-deficient ( FAH -/- ) mice and pigs. The process of regeneration is distinctive, complex, and well coordinated, and it depends on the interplay among several signaling pathways (eg, nuclear factor κβ, Notch, Hippo), cytokines (eg, tumor necrosis factor α, interleukin 6), and growth factors (eg, hepatocyte growth factor, epidermal growth factor, vascular endothelial growth factor), and other components. Furthermore, endocrinal hormones (eg, norepinephrine, growth hormone, insulin, thyroid hormones) also can influence the aforementioned pathways and factors. We believe that these endocrinal hormones are important hepatic mitogens that strongly induce and accelerate hepatocyte proliferation (regeneration) by directly and indirectly triggering the activity of the involved signaling pathways, cytokines, growth factors, and transcription factors. The subsequent induction of cyclins and associated cyclin-dependent kinase complexes allow hepatocytes to enter the cell cycle. In this review article, we comprehensively summarize the current knowledge regarding the roles and mechanisms of these hormones in liver regeneration. Articles used for this review were identified by searching MEDLINE and EMBASE databases from inception through June 1, 2019., (© 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc.)