Baricitinib: A drug originally marketed to treat rheumatoid arthritis, in November, the FDA issued an emergency use authorization for baricitinib as a treatment for COVID-19. GuttmanYassky E, Silverberg JI, Nemoto O, etal. 12, Body clearance of baricitinib is 8.9 L/h, with a halflife of nearly 12 hours. 10 Satarker S, Tom A, Shaji R, Alosious A, Luvis M, Nampoothiri M. JAK-STAT Pathway Inhibition and their Implications in COVID-19 Therapy. Tehran Given the trend in preventing supplemental oxygen need in ACCT-2 among inpatients, I would be curious if JAKIs are being considered/studied as a potential outpatient intervention to prevent hospitalization in those at risk/ with worsening course prior to requiring admission (as opposed to corticosteroids, which showed a trend towards harm in RECOVERY). [Accessed September 11, 2021]. In vitro studies also demonstrated the efficacy of baricitinib in reducing the viral reservoir in macrophages. (Olumiant) to treat COVID-19 in some cases. Baricitinib has anti-inflammatory properties and it is hoped that it could help against the inflammatory cytokine storm seen in severe cases of COVID-19. The efficacy of combination treatment was highest in patients with a baseline ordinal score of 6 (receiving high-flow oxygen or noninvasive ventilation). 5 The ACTT-2 trial demonstrated that baricitinib hastened recovery and reduced the need for intubation. 2021 Jan 5;60(1):399-407. doi: 10.1093/rheumatology/keaa587. 37 Moreover, the total Dermatologic Life Quality Index improved in both baricitinib groups compared with placebo. Baricitinib is a reversible Janusassociated kinase (JAK)inhibitor that interrupts the signaling of multiple cytokines implicated in COVID19 immunopathology. Khaledi M, Sameni F, Yahyazade S, Radandish M, Owlia P, Bagheri N, Afkhami H, Mahjoor M, Esmaelpour Z, Kohansal M, Aghaei F. Front Med (Lausanne). This combination therapy resulted in the overall recovery of 12 of 15 patients, but 3 patients died. In addition, the rate of progressive radiographic joint damage assessed by modified Total Sharp Score (mTSS) and HAQDI was better in week 24. shortness of breath, tiredness, or pale skin. 28 This would be expected to reduce immobility and thereby, Patients with COVID-19 experience a prothrombotic state due to increased systemic inflammation. Favalli E, Biggioggero M, Maioli G, Caporali R. Baricitinib for COVID-19: a suitable treatment? Fridman JS, Scherle PA, Collins R, etal. 54, During the recent year, there were several clinical trials evaluating the efficacy of baricitinib in managing COVID19 patients. Wang J, Wang Y, Wu L, et al. 2022 Oct 14;13:1004308. doi: 10.3389/fphar.2022.1004308. Two group of patients received lopinavir/ritonavir/hydroxychloroquine plus either highdose corticosteroids or corticosteroids/baricitinib. This could potentially reduce viral replication. Baricitinib may cause an increase in your blood cholesterol levels. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00331-3/fulltext, https://www.drugs.com/clinical_trials/baricitinib-remdesivir-combination-receives-emergency-authorization-fda-hospitalized-patients-covid-19037.html, https://www.drugs.com/clinical_trials/fda-broadens-existing-emergency-lilly-incyte-s-baricitinib-patients-hospitalized-covid-19-requiring-19513.html, https://clinicaltrials.gov/ct2/show/NCT04340232?term=baricitinib&draw=2&rank=2, https://investor.lilly.com/news-releases/news-release-details/lilly-begins-clinical-testing-therapies-covid-19, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=866e9f35-9035-4581-a4b1-75a621ab55cf, https://doi.org/10.1016/S1473-3099(20)30132-8, https://techcrunch.com/2020/04/14/potential-new-treatment-for-covid-19-uncovered-by-benevolentai-enters-trials/. These patients may also be more vulnerable to the metabolic dysregulation compared with healthy individuals. Likewise, the RABEACON study recruiting 527 patients with adequate response to biologics (more than 1 TNF inhibitor for more than 3 months) compared the efficacy of baricitinib 2 or 4 mg with placebo. Concise summaries and expert physician commentary that busy clinicians need to enhance patient care. There were neither thromboembolic events nor considerable hematological changes in baricitinib groups. Without baricitinib therapy, levels of C-reactive protein and IL-6 didnt decrease over the first week of illness whereas these levels dropped rapidly in the baricitinib group. Nonetheless, this supports the utility of baricitinib. 27 The primary concern involving the combination of dexamethasone and baricitinib is that excessive immunosuppression could increase the risk of opportunistic infections. Learn more about what to do if you are sick. However, despite overall encouraging results, many adverse effects have been observed in baricitinibtreated patients, ranging from simple infections to increased risk of malignancies, particularly in longterm use. According to these findings, a doubleblind doseranging study investigated the potential of baricitinib to prevent diabetic kidney disease (DKD). Most people with COVID-19 have mild illness and can recover at home. Considerably, the SARS virus might cause CPK rise, which is usually associated with poor prognosis and later rhabdomyolysis; the aggravating effect of baricitinib in this process should also be taken into account. An international team of scientists has found that the arthritis drug baricitinib shows promise for increasing the survival of older adults with COVID-19. When eliminated, 69% of the drug is excreted unchanged in urine and 15% via feces. Long-term use of the drug is known to be associated with an increased risk of serious infection, lymphoma and other cancers, as well as blood clots. Baricitinib is an anti-inflammatory treatment normally used to treat rheumatoid arthritis. In week 16, the EASI 50 of patients treated with baricitinib 4 mg was significantly better than other patients, whereas their Scoring Atopic Dermatitis scores decreased. 55 For instance, BREEZEAD1 and BREEZEAD2 recruited more than 1200 adult AD patients with a Investigator's Global Assessment (IGA) score of 3 or 4, EASI 16, body surface area 10%, and inadequate response to more than 1 existing medication. Similarly, patients with a baseline ordinal score of 5 had a median time to recovery of 5 days in the combination group and 6 days in the control group (rate ratio for recovery, 1.17; 95% CI, 0.98 to 1.39) and increased odds of clinical improvement (odds ratio, 1.2; 95% CI, 0.9 to 1.6). However, no indication of the level of oxygen support was provided (ordinal score of 5 or 6). Abizanda P, Calbo Mayo JM, Mas Romero M, Corts Zamora EB, Tabernero Sahuquillo MT, Romero Rizos L, Snchez-Jurado PM, Snchez-Nievas G, Campayo Escolano C, Ochoa Serrano A, Snchez-Flor Alfaro V, Lpez Bru R, Gmez Ballesteros C, Caldevilla Bernardo D, Callejas Gonzlez FJ, Andrs-Pretel F, Lauschke VM, Stebbing J. J Am Geriatr Soc. Thus, antiviral therapies generally have minimal effectiveness in this disease stage. Before Alopecia areata, commonly referred to as just alopecia, is an autoimmune disorder in which the body attacks its The drug, called Olumiant (baricitinib), is the first FDA approval of a full-body drug for.FDA approves first drug treatment for hair loss disorder Alopecia.June 14, 2022, 8:18 AM. Moreover, baricitinib 4 mg could inhibit the radiographic progression of structural joint damage evaluated in week 48. Lin Z, Niu J, Xu Y, Qin L, Ding J, Zhou L. J Med Virol. Its metabolism is mediated by the cytochrome P450 3A4 enzyme. 68 N Engl J Med 2021;384:693-704. Administration of 2 mg daily baricitinib for 4 months showed no significant outcome; thus, the drug dose was increased to 4 mg daily, which resulted in 97% regrowth of scalp hair, eyebrows, and eyelashes within 8 months. Tehran 67 There was a nonsignificant trend towards reduced 28-day mortality among patients treated with baricitinib (5.1% vs 7.8%, Significantly fewer severe adverse events were recorded in the baricitinib group than in the placebo group! Kalil A, Patterson T, Mehta A, et al. already built in. 33, Psoriasis is a chronic inflammatory skin disorder characterized by red, scaly plaques as a result of uncontrolled dermatocyte production. Daily prednisone doses decreased significantly in all patients, and 5 of 10 patients with CANDLE achieved permanent clinical remission. WHO's Guideline Development Group found moderate certainty evidence that baricitinib improved survival and reduced . JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a Phase 2 randomized controlled clinical trial. 74 , juice wrld discography. The JAK inhibitor is used to treat rheumatoid arthritis but can also treat individuals with critical or severe COVID-19 in combination with corticosteroids. Patients receiving baricitinib were also more likely to be discharged alive within 28 days (80% vs. 78%, age-adjusted rate ratio 1.10, 95% CI 1.04-1.15; p<0.001). Therefore, JAK inhibitors might be suggested to treat HIV+ patients to restrain Tcell activation and further viral expansion. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. Available online at. The safety evaluation revealed almost similar outcomes in different treatment groups. Baricitinib, methotrexate, or combination in patients with rheumatoid arthritis and no or limited prior diseasemodifying antirheumatic drug treatment. At the moment, there are other ongoing clinical trials about the efficacy of baricitinib in managing moderate to severe AD of children and adolescents (eg, {"type":"clinical-trial","attrs":{"text":"NCT02576938","term_id":"NCT02576938"}}NCT02576938; {"type":"clinical-trial","attrs":{"text":"NCT03952559","term_id":"NCT03952559"}}NCT03952559; NCT0343508; {"type":"clinical-trial","attrs":{"text":"NCT03334435","term_id":"NCT03334435"}}NCT03334435; {"type":"clinical-trial","attrs":{"text":"NCT03428100","term_id":"NCT03428100"}}NCT03428100), the results of which would provide further evidence for including or excluding baricitinib in the approved medications of AD. 64 At baseline, the median Eczema Area and Severity Index (EASI) score for patients was 21.2. 16 To identify such a drug, we used a visual analytics workflow where computational tools applied over an AI-enhanced biomedical knowledge graph were . Tehran 12 April 15, 2020. 15 Petrone L, Petruccioli E, Alonzi T, etal. Adverse effects such as liver enzyme dysregulation, thrombosis, lymphopenia, and CPK rise could occur in the natural course of many inflammatory disorders, thus, hardly attributable to baricitinib per se, although this could exacerbate the situation. An official website of the United States government. Iran. 2020;91:264266. At discharge and 1month later, baricitinib combination therapy resulted in better SpO2/FiO2 and improved pulmonary function compared with the corticosteroids alone. At the end of week 12, the ACR20 response (70% vs 40%), the proportion of low disease activity, Disease Activity Score28 for RA with CRP (DAS28CRP), SDAI, and CDAI were significantly improved in the baricitinib group compared with the placebo. 7. In week 24, baricitinib 4 mg daily decreased morning UACR by 41% compared with placebo and reduced the inflammatory biomarkers (eg, plasma soluble tumor necrosis factor receptor 1 and 2, intercellular adhesion molecule 1, urine CXCL10 and urine CCL2, and serum amyloid A) significantly. 67 official website and that any information you provide is encrypted In summary, JAK inhibitors, in particular, baricitinib, might be applied to manage various acute and chronic inflammatory conditions efficiently; nonetheless, patients should be monitored cautiously to detect and resolve the probable side effects. Moreover, the proportions of patients in remission measured by the Simplified Disease Activity Index (SDAI), ACR20 and ACR50, were markedly greater in combination therapy than with MTX monotherapy in weeks 24 and 52. Ruxolitinib in adult patients with secondary haemophagocytic lymphohistiocytosis: an open-label, single-centre, pilot trial. Despite all advances in treating HIV infection, virus persistence in the host is considered a serious obstacle in treating the disease. Baricitinib also helps slow the progression of bone and joint damage. In the Randomized Evaluation of Covid-19 Therapy (RECOVERY) trial,5 2104 hospitalized patients receiving dexamethasone at a dose of 6 mg per day for up to 10 days were compared with 4321 controls receiving usual care. HHS Vulnerability Disclosure, Help April 10, 2020. Tomazini B, Maia I, Cavalcanti A, et al. Patients with COVID-19 experience a prothrombotic state due to increased systemic inflammation. The efficacy of the drug was highest among patients with a baseline ordinal score of 4 (not receiving oxygen) or 5 (receiving low-flow oxygen). Falasca L, Nardacci R, Colombo D, et al. Baricitinib was generally well tolerated; however, there were some reports of liver toxicity, infectious diseases, gastrointestinal complication, and cardiovascular side effects, most of which were not definitely attributable to the baricitinib. 48 , Consequently, the study cannot address the question of whether to use baricitinib in combination with steroid. An emergency use authorization allows the FDA to approve the use of a treatment during an emergency without the same level of evidence that would fully establish its . Moreno-Gonzlez G, Mussetti A, Albasanz-Puig A, Salvador I, Sureda A, Gudiol C, Salazar R, Marin M, Garcia M, Navarro V, de la Haba Vaca I, Coma E, Sanz-Linares G, Dura X, Fontanals S, Serrano G, Cruz C, Maez R. Trials. The most trusted, influential source of new medical knowledge and clinical best practices in the world. Potential new treatment for COVID-19 uncovered by BenevolentAI enters trials. In conclusion, we believe that, beyond the intriguing opportunity to directly block the penetration of SARS-CoV-2 into the cell, the use of baricitinib in susceptible patients with ongoing pneumonia associated with COVID-19 should be considered with extreme caution. Neither baricitinib nor dexamethasone has been associated with an increase in opportunistic infection when utilized for COVID-19 patients. , Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RABUILD study, Baricitinib in patients with refractory rheumatoid arthritis. After 7 or 8 days, in 20% of patients the disease progresses to bilateral pneumonia. He is an associate professor of Pulmonary and Critical Care Medicine at the University of Vermont. 29, Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with a wide range of clinical manifestations and an unpredictable relapsingremitting course. Drugs 2020;80:1929-1946. So where does this leave us regarding the actual contraindications for baricitinib? A realworld disproportionality analysis of FDA Adverse Event Reporting System (FAERS) events for baricitinib. Iran, 2 DAlessio A, Del P, Bracchi F, et al. This resulted in a considerably decreased mortality rate and of patients in critical condition, as 16.9% of the baricitinibtreated patients died or progressed to invasive mechanical ventilation compared with 34.9% in the standardofcare group. Credit: NIAID-RML. Evidence-based Efficacy of Covid-19 Therapies, According to Disease Severity. the effects of standard care plus baricitinib, 4 mg twice daily for 2 days then 4 mg daily for 7 days, have been studied in 20 patients with pcr-positive covid-19 and evidence of pneumonia, for comparison with 56 patients with similarly severe covid-19 who received standard care alone, which included either hydroxychloroquine, or 1. Patients receiving MTX had higher disease activity at baseline and showed reduced disease activity after the addition of MTX to baricitinib. Josh is the creator of PulmCrit.org. In the Randomized Evaluation of Covid-19 Therapy trial,5 mortality was lower with dexamethasone than with usual care among patients receiving invasive ventilation (assumed ordinal score of 7) and, to a lesser extent, among those receiving oxygen only (assumed score of 5 or 6). JAK inhibitors may cause lymphopenia, anemia, and neutropenia when used to treat rheumatoid arthritis. Moreover, signaling inhibition of these 2 cytokines using baricitinib prevented GVHD successfully. J Clin Pharmacol. 3. treat adult patients with moderately to severely active rheumatoid arthritis who have not responded well to the RA medicines called tumor necrosis factor (TNF) antagonist therapies. report in the Journal the results of ACCT-2, 7 a double-blind, randomized, placebo-controlled trial evaluating baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, plus . Hu B, Guo H, Zhou P, Shi ZL. 2022;65:2586-2595. doi: 10.1016/j.matpr.2022.04.868. -, Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK. 3 Further results of baricitinib therapy included decreased count of Th1 and Th2 cells, reduced expression of MHC and CD80/86 molecules, Treg cell expansion, and enhanced GVL effects. Baricitinib is a Janus kinase inhibitor that inhibits the activity of one or more members of a specific family of enzymes, hence interfering with the inflammatory pathway. A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making. Tehran University of Medical Sciences, Mater Today Proc. Napolitano M, Fabbrocini G, Cinelli E, Stingeni L, Patruno C. Profile of baricitinib and its potential in the treatment of moderate to severe atopic dermatitis: a short review on the emerging clinical evidence, Janus kinase inhibition for graftversushost disease: current status and future prospects, Baricitinibinduced blockade of interferon gamma receptor and interleukin6 receptor for the prevention and treatment of graftversushost disease, New approaches for the treatment of chronic graftversushost disease: current status and future directions, Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors, Baricitinib reverses HIVassociated neurocognitive disorders in a SCID mouse model and reservoir seeding in vitro, Randomized trial of ruxolitinib in antiretroviraltreated adults with HIV, Janus kinase inhibitor baricitinib is not an ideal option for management of COVID19. Mehta S, Crusian B, Pierson D, Sams C, Stowe R. Monitoring immune system function and reactivation of latent viruses in the Artificial Gravity Pilot Study, Clinical course and risk factors for mortality of adult inpatients with COVID19 in Wuhan, China: a retrospective cohort study, Clinical course and predictors of 60day mortality in 239 critically ill patients with COVID19: a multicenter retrospective study from Wuhan, China. Beigel JH, Tomashek KM, Dodd LE, et al. The trial is now enrolling hospitalized adults with COVID-19 in the United States. Tehran University of Medical Sciences, The role of IFN and JAK/STAT signaling has already been shown in the pathogenesis of AA. Baricitinib was approved in 2018 by the US Food and Drug Administration and European Medicines Agency for treating adult patients with moderate to severe rheumatoid arthritis (RA) who have shown an inadequate response to 1 or more TNFinhibitor therapies. Department of Immunology, School of Medicine, In addition, there is postulation that some JAK inhibitors, specifically Baricitinib, can impact viral infectivity and replication. J Biol Regul Homeost Agents. Kalil AC, Patterson TF, Mehta AK, et al. See. Whether to add baricitinib on top of dexamethasone remains controversial, given a lack of direct RCT-level evidence. These encouraging preclinical findings wait to be evaluated in human patients by a nonrandomized openlabel clinical trial aiming to evaluate JAK1/2 inhibition in chronic GVHD ({"type":"clinical-trial","attrs":{"text":"NCT02759731","term_id":"NCT02759731"}}NCT02759731). Kalil et al. 4 The wide range of diseases in clinical trials for baricitinib therapy and the other inflammatory disorders that could be considered future candidates for treatment with baricitinib made us provide an overview of positive and negative outcomes of administerng baricitinib in the clinic. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. 2022 Apr;94(4):1523-1534. doi: 10.1002/jmv.27482. Baricitinib is also used in adults who are hospitalized with COVID-19 requiring oxygen or assistance with breathing. Serious infections were reported in 6patients on baricitinib 4 mg, 2 patients on baricitinib 2 mg, and 1 receiving placebo. The similarity of disease symptoms and drug side effects is the other confusing point in determining the safety of baricitinib. Baricitinib 2 mg showed no superiority to the placebo; nonetheless, the patients receiving baricitinib used almost 30% less triamcinolone monthly compared with the placebo group. Thank you for your patience.. [Accessed April 17, 2020]. The usual dose of baricitinib for COVID-19 is 4 mg daily. . Accordingly, baricitinib has been evaluated in patients receiving concomitant drugs such as MTX, lopinavir/ritonavir, hydroxychloroquine, corticosteroids, tocilizumab, and remdesivir. The US Food and Drug Administration had in November last year issued an emergency use authorisation for the drug Baricitinib in combination with Remdesivir for the treatment of suspected or laboratory-confirmed Covid-19 in hospitalised patients requiring supplemental oxygen, invasive mechanical ventilation or extracorporeal membrane oxygenation . The only considerable adverse effect differing across groups was anemia, observed in 32% of patients on baricitinib 4 mg versus 3.7% in the placebo group. 40 Woroniecka KI, Park ASD, Mohtat D, Thomas DB, Pullman JM, Susztak K. Transcriptome analysis of human diabetic kidney disease. The encouraging results of this study justified further studies including 2 ongoing multicenter phase 3 randomized, placebocontrolled trials ({"type":"clinical-trial","attrs":{"text":"NCT03616912","term_id":"NCT03616912"}}NCT03616912, {"type":"clinical-trial","attrs":{"text":"NCT03616964","term_id":"NCT03616964"}}NCT03616964) that could provide more evidence about the advantages and disadvantages of baricitinibtherapy in SLE patients. Both innate and adaptive immunity have been demonstrated to be suppressed by baricitinib. It has been FDA approved for the treatment of rheumatoid arthritis (RA) since 2018. This is an observational, multicenter study describing outcomes of hospitalized patients treated with baricitinib (4 mg/day for two weeks) versus hydroxychloroquine (both in combination with lopinavir/ritonavir).6 Steroid administration was not allowed. We are experimenting with display styles that make it easier to read articles in PMC. JAK1/2 inhibition with baricitinib in the treatment of autoinflammatory interferonopathies. Laboratory changes such as increased lowdensity lipoprotein (LDL) cholesterol and creatinine and decreased neutrophil counts were observed in the baricitinib group. The clinical course of coronavirus disease 2019 (Covid-19) is characterized at the outset by mild symptoms of the upper respiratory tract. Serious infection rates were almost similar among groups (approximately 3%). Lilly is continuing conversations with the U.S. Food and Drug Administration (FDA) around the potential for Emergency Use Authorization (EUA) of baricitinib, a JAK1/JAK2 inhibitor licensed to Lilly from Incyte, to treat hospitalized patients with COVID-19. Baricitinib is a JAK1/2 inhibitor that was first approved for treating moderate to severe rheumatoid arthritis (RA) but that later showed considerable efficacy in the control of exaggerated inflammatory responses that occur in a wide range of diseases. JAK inhibition reduces SARS-CoV-2 liver infectivity and modulates inflammatory responses to reduce morbidity and mortality. Baricitinib is an oral JAK inhibitor that is selective for JAK1 and JAK2. The risks and benefits of treatment with baricitinib should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Determining the optimal drug combinations could improve the efficacy and diminish undesirable effects of JAK inhibitors; for instance, the adverse effects of tofacitinib have been shown to reduce in transplant recipients receiving rapamycin or belatacept compared with those who were treated with mycophenolate. Currently the decision may need to be personalized (e.g., incorporating individual aspects of the patient and multidisciplinary consultation). Patients with septic shock often undergo an initial phase of immune hyperactivation, which is followed by a subsequent phase of immunoparalysis (i.e., Compensatory Anti-inflammatory Response Syndrome, or CARS). Another retrospective study similiarly suggested that the combination of ruxolitinib plus steroid was beneficial.17. (404) 727-7829 qeastma@emory.edu Research in a Pandemic - The COVID-19 Pivot at Emory Watch on The anti-inflammatory agent baricitinib, originally developed for rheumatoid arthritis, recently received a standalone Emergency Use Authorization from the FDA for COVID-19. Iran, 4 These findings together with the potential safety and tolerability of JAK inhibitors in HIV patients 32 Baricitinib patients were less likely to progress to needing ventilation or dying (Baricitinib group 27.8% and placebo group 30.5%). DOI: Tech Crunch. By confirming the results of the previous open-label studies showing the beneficial effects of baricitinib for Covid-19 treatment,8,9 ACTT-2 provides the highest grade of evidence on the efficacy of the drug, which acts through the inhibition of JAK1 and JAK2 and consequently blocks the immune cascade and reduces viral replication.10 The reported highest efficacy of baricitinib in patients with ordinal scores of 5 and 6 allows expansion of the therapeutic armamentarium against Covid-19 pneumonia, mainly in patients receiving oxygen support without invasive mechanical ventilation (Figure 1).
Shopdisney Release Today, Php File Upload Shell Github, Red Lentil And Butternut Squash Soup, Texas Cdl Ticket Dismissal, Nato Science For Peace And Security, Popsicle Stick Bridge Lesson Plan, Python Temporary Directory Example,
