Evening versus morning dosing regimen drug therapy for hypertension.

BACKGROUND: Variation in blood pressure levels display circadian rhythms. Complete 24-hour blood pressure control is the primary goal of antihypertensive treatment and reducing adverse cardiovascular outcomes is the ultimate aim. This is an update of the review first published in 2011. OBJECTIVES: To evaluate the effectiveness of administration-time-related effects of once-daily evening versus conventional morning dosing antihypertensive drug therapy regimens on all-cause mortality, cardiovascular mortality and morbidity, total adverse events, withdrawals from treatment due to adverse effects, and reduction of systolic and diastolic blood pressure in people with primary hypertension. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register via Cochrane Register of Studies (17 June 2022), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6, 2022); MEDLINE, MEDLINE In-Process and MEDLINE Epub Ahead of Print (1 June 2022); Embase (1 June 2022); ClinicalTrials.gov (2 June 2022); Chinese Biomedical Literature Database (CBLD) (1978 to 2009); Chinese VIP (2009 to 7 August 2022); Chinese WANFANG DATA (2009 to 4 August 2022); China Academic Journal Network Publishing Database (CAJD) (2009 to 6 August 2022); Epistemonikos (3 September 2022) and the reference lists of relevant articles. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing the administration-time-related effects of evening with morning dosing monotherapy regimens in people with primary hypertension. We excluded people with known secondary hypertension, shift workers or people with white coat hypertension. DATA COLLECTION AND ANALYSIS: Two to four review authors independently extracted data and assessed trial quality. We resolved disagreements by discussion or with another review author. We performed data synthesis and analyses using Review Manager Web for all-cause mortality, cardiovascular mortality and morbidity, serious adverse events, overall adverse events, withdrawals due to adverse events, change in 24-hour blood pressure and change in morning blood pressure. We assessed the certainty of the evidence using GRADE. We conducted random-effects meta-analysis, fixed-effect meta-analysis, subgroup analysis and sensitivity analysis. MAIN RESULTS: We included 27 RCTs in this updated review, of which two RCTs were excluded from the meta-analyses for lack of data and number of groups not reported. The quantitative analysis included 25 RCTs with 3016 participants with primary hypertension. RCTs used angiotensin-converting enzyme inhibitors (six trials), calcium channel blockers (nine trials), angiotensin II receptor blockers (seven trials), diuretics (two trials), α-blockers (one trial), and ß-blockers (one trial). Fifteen trials were parallel designed, and 10 trials were cross-over designed. Most participants were white, and only two RCTs were conducted in Asia (China) and one in Africa (South Africa). All trials excluded people with risk factors of myocardial infarction and strokes. Most trials had high risk or unclear risk of bias in at least two of several key criteria, which was most prominent in allocation concealment (selection bias) and selective reporting (reporting bias). Meta-analysis showed significant heterogeneity across trials. No RCTs reported on cardiovascular mortality and cardiovascular morbidity. There may be little to no differences in all-cause mortality (after 26 weeks of active treatment: RR 0.49, 95% CI 0.04 to 5.42; RD 0, 95% CI -0.01 to 0.01; very low-certainty evidence), serious adverse events (after 8 to 26 weeks of active treatment: RR 1.17, 95% CI 0.53 to 2.57; RD 0, 95% CI -0.02 to 0.03; very low-certainty evidence), overall adverse events (after 6 to 26 weeks of active treatment: RR 0.89, 95% CI 0.67 to 1.20; I² = 37%; RD -0.02, 95% CI -0.07 to 0.02; I² = 38%; very low-certainty evidence) and withdrawals due to adverse events (after 6 to 26 weeks active treatment: RR 0.76, 95% CI 0.47 to 1.23; I² = 0%; RD -0.01, 95% CI -0.03 to 0; I² = 0%; very low-certainty evidence), but the evidence was very uncertain. AUTHORS' CONCLUSIONS: Due to the very limited data and the defects of the trials' designs, this systematic review did not find adequate evidence to determine which time dosing drug therapy regimen has more beneficial effects on cardiovascular outcomes or adverse events. We have very little confidence in the evidence showing that evening dosing of antihypertensive drugs is no more or less effective than morning administration to lower 24-hour blood pressure. The conclusions should not be assumed to apply to people receiving multiple antihypertensive drug regimens.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION).

PURPOSE: Cancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). METHODS: 110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. RESULTS: Fifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. CONCLUSIONS: Self-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

COVISHIELD vaccine-induced thyroiditis: a case report.

BACKGROUND: The rapid development of coronavirus disease 2019 vaccines during the pandemic has left their long-term effects largely unknown. Instances of autoimmune and subacute thyroiditis showing features of autoimmune/inflammatory syndrome induced by adjuvants have been reported post-vaccination. This case report aims to highlight the autoimmune/inflammatory syndrome induced by adjuvants syndrome after coronavirus disease 2019 vaccination, drawing attention to a possible connection with thyroid dysfunction and urging for further thorough research. CASE PRESENTATION: We present a case of thyroiditis induced by the COVISHIELD vaccine in a 37-year-old Indian woman. An apparently normal and healthy adult woman developed neck pain and easy fatigability 2 weeks after the second dose of COVISHIELD, which gradually increased and was associated with irritability, decreased sleep, excessive sweating, tremor, palpitation, and weight loss. She presented to the outpatient department after 1 week of symptoms and was evaluated with laboratory tests and imaging. She was diagnosed with thyroiditis due to the coronavirus disease 2019 vaccine and was treated with propranolol. CONCLUSION: This case report adds to the growing evidence of coronavirus disease 2019 vaccine-related thyroid issues. The development of thyroiditis is rare and underreported post-coronavirus disease 2019 vaccination; hence, research to evaluate the association of coronavirus disease 2019 vaccines with thyroid dysfunction needs to be done in the future.

Minocycline in depression not responding to first-line therapy: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results in prolonged hospitalization and healthcare costs. Anti-inflammatory drugs have shown promising results in depression not responding to initial therapy. Minocycline has anti-inflammatory properties and crosses the blood-brain barrier. It has demonstrated varied results in several randomized controlled trials (RCTs). METHODS: We assessed the efficacy of minocycline compared to placebo in depression not responding to one first-line antidepressant via a systematic review and meta-analysis. We performed a comprehensive literature search across PubMed, Cochrane, and Scopus for RCTs. We visualized the results using forest plots and drapery plots. We assessed and explored heterogeneity using I2, prediction interval, and meta-regression. Then, we rated the certainty of the evidence. RESULTS: Four RCTs revealed a non-significant difference in depression severity [-3.93; 95% CI: -16.14 to 8.28], rate of response [1.15; 0.33-4.01], and rate of remission [0.94; 0.44-2.01]. However, the reduction in depression severity is significant at a trend of P < .1. The high between-study heterogeneity (I2 = 78%) for depression severity could be answered by meta-regression (P = .02) for the duration of therapy. CONCLUSION: There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy. However, the treatment response varies with treatment duration and patients' neuroinflammatory state. Thus, larger and longer RCTs, especially in diverse disease subgroups, are needed for further insight. This is needed to allow greater precision medicine in depression and avoid elevated healthcare expenditure associated with hit-and-trial regimens. REGISTRATION: CRD42023398476 (PROSPERO).

Are paid tools worth the cost? A prospective cross-over study to find the right tool for plagiarism detection.

Background: The increasing pressure to publish research has led to a rise in plagiarism incidents, creating a need for effective plagiarism detection software. The importance of this study lies in the high cost variation amongst the available options for plagiarism detection. By uncovering the advantages of these low-cost or free alternatives, researchers could access the appropriate tools for plagiarism detection. This is the first study to compare four plagiarism detection tools and assess factors impacting their effectiveness in identifying plagiarism in AI-generated articles. Methodology: A prospective cross-over study was conducted with the primary objective to compare Overall Similarity Index(OSI) of four plagiarism detection software(iThenticate, Grammarly, Small SEO Tools, and DupliChecker) on AI-generated articles. ChatGPT was used to generate 100 articles, ten from each of ten general domains affecting various aspects of life. These were run through four software, recording the OSI. Flesch Reading Ease Score(FRES), Gunning Fog Index(GFI), and Flesch-Kincaid Grade Level(FKGL) were used to assess how factors, such as article length and language complexity, impact plagiarism detection. Results: The study found significant variation in OSI(p < 0.001) among the four software, with Grammarly having the highest mean rank(3.56) and Small SEO Tools having the lowest(1.67). Pairwise analyses revealed significant differences(p < 0.001) between all pairs except for Small SEO Tools-DupliChecker. Number of words showed a significant correlation with OSI for iThenticate(p < 0.05) but not for the other three. FRES had a positive correlation, and GFI had a negative correlation with OSI by DupliChecker. FKGL negatively correlated with OSI by Small SEO Tools and DupliChecker. Conclusion: Grammarly is unexpectedly most effective in detecting plagiarism in AI-generated articles compared to the other tools. This could be due to different softwares using diverse data sources. This highlights the potential for lower-cost plagiarism detection tools to be utilized by researchers.

Efficacy and safety of sufentanil sublingual tablet system in postoperative pain management: a systematic review and meta-analysis.

BACKGROUND: Sufentanil sublingual tablet system (SSTS) is a recently approved formulation for postoperative pain management that has become popular due to its pharmacokinetic properties such as good bioavailability, rapid attainment of equilibrium and elimination without any metabolites, along with its pharmacodynamic properties such as rapid onset and effective pain reduction. It is also relatively well tolerated by patients. OBJECTIVE: This is a quantitative analysis of the efficacy and safety of SSTS in patients with moderate to severe postoperative pain. DESIGN: This is a systematic review and meta-analysis. Databases such as Cochrane Library, MEDLINE and EMBASE were searched for eligible articles. SETTINGS: Randomised controlled trials published after 2000 in English language and which assessed at least one of the outcome measures of interest with pain intensity difference between 12 hours and a maximum of 96 hours. PARTICIPANTS: Adults with moderate to severe postoperative pain and taking SSTS for pain management. METHODS: Data were analysed using Review Manager (RevMan) V.5.3. Risk of bias (RoB) assessment was done using RoB-2 scale, and overall grading of evidence of each outcome was done using GRADEpro Guideline Development Tool. RESULTS: Analysis of SSTS versus control indicates a statistically significant reduction in summed pain intensity difference at 12 hours (mean difference (MD)=-12.33 (95% CI -15.5 to -9.17), p<0.00001), summed pain intensity difference at 48 hours (MD=-43.57 (95% CI -58.65 to -28.48), p<0.00001), time-weighted total pain relief over 12 hours (MD=-4.77 (95% CI -6.28 to -3.27), p<0.00001) and pain intensity difference (MD=-0.73 (95% CI -1.00 to -0.46), p<0.00001) with SSTS, alongside high quality of evidence. Success of treatment as assessed by Patient Global Assessment (OR=4.01 (95% CI 2.74 to 5.89), p<0.00001) and Healthcare Professional Global Assessment (OR=4.46 (95% CI 3.03 to 6.56), p<0.00001) scoring at 72 hours was observed in a significantly high number of individuals using SSTS, with high quality of evidence. There was no difference in adverse events except for dizziness (RR=1.90, 95% CI 1.02 to 3.52). There was a significantly higher number of total adverse events in orthopaedic surgery in the SSTS group than in the comparator. CONCLUSION: SSTS is effective in postoperative pain management in patients with moderate to severe pain. It also has good tolerability and high patient satisfaction. PROSPERO REGISTRATION NUMBER: CRD42018115458.

Rationality, Efficacy, Tolerability of Empagliflozin Plus Linagliptin Combination for the Management of Type 2 Diabetes Mellitus: A Systematic Review of Randomized Controlled Trials and Observational Studies.

BACKGROUND: Treatment of diabetes mellitus includes more than one drug of different groups, which may lead to a high pill burden and non-adherence to drugs. We have aimed to systematically analyze the clinical efficacy, safety, and pharmacoeconomic cost-effectiveness of the fixed-dose combination of empagliflozin plus a linagliptin in Type-2 Diabetes mellitus (T2DM) patients. METHODS: A literature search of PubMed/MEDLINE, SCOPUS, Google Scholar, and EMBASE was performed using the MeSH terms and/or keywords"((Single-pill combination) OR ((Fixeddose combination) OR (Combination therapy)) AND (Empagliflozin add on-to Linagliptin) OR (Empagliflozin combined with Linagliptin) OR ((Combination of Empagliflozin and Linagliptin)" from the inception to February 2021. RESULTS: Search results were found in a total of 13 clinical studies. After removing duplicates and studies not according to inclusion criteria, a total of eight clinical studies (Randomized controlled trials: 7; Observational cohort studies: 1) were included (n=7491). A significant reduction in the primary endpoint, the mean changes in baseline HbA1c at the end of 24 weeks and/or 52 weeks was found in the empagliflozin plus a linagliptin combination group in all included studies. In addition, significant efficacy was seen in decreasing the secondary endpoints such as the mean change in the fasting plasma glucose, systolic and diastolic blood pressure (DBP), and body weight with fewer adverse events than the adverse effects with either drug alone. CONCLUSION: After reviewing findings from the available clinical studies of the combination of empagliflozin plus linagliptin, we conclude that the combination is effective, safe, tolerable, and rationale cost effective compared to placebo and either drug alone for the management of T2DM in patients with inadequate glycemic control with metformin alone, patients with intolerance to metformin, increased baseline HbA1c, patients with overweight or obesity and diabetic hypertensive, CHF, atherosclerotic cardiovascular disease, and renal dysfunction patients. Future randomized controlled trials in a larger number of T2DM patients with or without CHF and renal failure patients are recommended.

Assessment of Caregiving Burden of Family Caregivers of Advanced Cancer Patients and Their Satisfaction with the Dedicated Inpatient Palliative Care Provided to Their Patients: A Cross-Sectional Study from a Tertiary Care Centre in South Asia.

BACKGROUND AND OBJECTIVES: Family Caregivers (FCs) of advanced cancer patients often suffer from caregiving burden due to stress arising from the responsibility of caregiving. During the course of their patients palliative therapy, FCs quality of life seems to be influenced by their satisfaction with the quality of patient care. In this study, caregiving burden of FCs and their satisfaction with dedicate Inpatient palliative care (IPC) services provided to their patients  were studied. MATERIAL AND METHODS: This cross-sectional study assessed 211 FCs of advanced cancer patients. Caregiving burden of FCs and their satisfaction with IPC were studied through Zarith Burden Interview (ZBI-12 version) and Family Carer Satisfaction with Palliative Care scale (FAMCARE-2)  questionnaires, respectively. Descriptive and correlation analyses were deployed for data analysis. RESULTS: The summative mean ZBI-12 score for FCs was 20.26±5.92, suggesting moderate to high caregiving burden among FCs. Significantly higher scores were observed among FCs who belonged to below poverty line (BPL) families(p=0.025), revealing higher caregiving burden among this lower income group. FCs who were male, unmarried, unemployed, and residing in rural experienced higher caregiving burden. However, it did not lead to a statistically significant difference. The summative mean FAMCARE-2 scale scores was 74.01±4.34, which suggested FCs high satisfaction with the palliative care services provided to their patients. FAMCARE-2 scale scores were lower for BPL families, but it was not statistically significant. CONCLUSION: FCs from lower-income groups experienced higher caregiving burden. It seems that IPC unit provided satisfactory services to advanced cancer patients, leading to enhancement of FCs satisfaction and consequently quality of life. 
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Toxicoepidemiology of poisoning exhibited in Indian population from 2010 to 2020: a systematic review and meta-analysis.

OBJECTIVE: To determine the prevalence of pesticide, corrosive, drugs, venom and miscellaneous poisoning in India. SETTING: Systematic literature search was done in PubMed Central, Cochrane and Google Scholar databases for studies that satisfied the inclusion criteria. Systematic review and meta-analyses of all observational studies published in the English language from January 2010 to May 2020 were included in this review. PARTICIPANTS: Patients exposed to poisoning reported to hospitals were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The prevalence of pesticide poisoning was analysed. The prevalence of poisoning due to corrosives, venom, drugs and miscellaneous agents, along with subgroup analysis based on age and region, was also determined. The percentage of persons with poisoning along with 95% CI was analysed. RESULTS: Pooled analysis of studies revealed that pesticides were the main cause of poisoning in adults, with an incidence of 63% (95% CI 63% to 64%), while miscellaneous agents were the main cause of poisoning in children, with an incidence of 45.0% (95% CI 43.1% to 46.9%), among those presenting to hospitals. Pesticide poisoning was the most prevalent in North India (79.1%, 95% CI 78.4% to 79.9%), followed by South (65.9%, 95% CI 65.3% to 66.6%), Central (59.2%, 95% CI 57.9% to 60.4%), West (53.1%, 95% CI 51.9% to 54.2%), North East (46.9%, 95% CI 41.5% to 52.4%) and East (38.5%, 95% CI 37.3% to 39.7%). The second most common cause of poisoning was miscellaneous agents (18%, 95% CI 18% to 19%), followed by drugs (10%, 95% CI 10% to 10%), venoms (6%, 95% CI 6% to 6%) and corrosives (2%, 95% CI 1% to 2%). CONCLUSIONS: Pesticide poisoning is the most common type of poisoning in adults, while miscellaneous agents remain the main cause of poisoning in children. PROSPERO REGISTRATION NUMBER: CRD42020199427.

The Satisfaction Level of Undergraduate Medical and Nursing Students Regarding Distant Preclinical and Clinical Teaching Amidst COVID-19 Across India.

BACKGROUND: The COVID-19 pandemic has disrupted the educational system and led to a drastic shift of professional undergraduate teaching for medical and nursing students into online mode. METHODS: This was a cross-sectional, observational questionnaire-based study to assess the satisfaction level of the students. The questionnaire had 25 items of which 23 were questions with responses on the Likert scale and two items on views and suggestions were open-ended. The online questionnaire was shared through various messaging/mailing platforms. Overall satisfaction was assessed, and a satisfaction index was calculated for each item. Data are presented in frequencies and percentages, and SPSS was used to analyze the data. RESULTS: A total of 1068 students participated in the study. The majority were from the age group 21-23 years (54%) and there was almost the same number of participants from both genders. The majority of the students were medical undergraduates (n=919), were in their second year (n=669), belonged to a government institution (n=897) and used a mobile phone for their online classes (n = 871). The majority of the students were dissatisfied (42%) with no significant difference between medical and nursing students (p = 0.192). First-year students were significantly dissatisfied compared with other senior students (p = 0.005). The maximum satisfaction index (78.23%) was observed with faculties being supportive and responsive in resolving the queries and the minimum (46.39%) was observed with issues related to communication and discussion with peer students. There were 662 responses as views which mostly contained negative comments regarding interaction and focus, practical learning, teaching content, and technological/infrastructural flaws. There was major dissatisfaction regarding the practical and clinical learning. CONCLUSION: Online learning is essential at current times but is not an effective alternative for medical and nursing education. Face-to-face classes and practical sessions along with online learning can be a viable option.

Renal Histopathological Changes in Coronavirus Disease 2019 Patients: A Systematic Review and Meta-analysis of Individual Patient Data.

The major targets of coronavirus disease 2019 (COVID-19) are the respiratory and immune systems. However, a significant proportion of hospitalized patients had kidney dysfunction. The histopathological surveys have principally focused on respiratory, hematopoietic, and immune systems, whereas histopathologic data of kidney injury are lacking. Our study aimed to summarize the renal histopathological findings in COVID-19 from the published case report and case series. We conducted a systematic searching of databases such as MEDLINE, EMBASE, and Cochrane Library for published reports of COVID-19 patients with renal histopathological changes from autopsy studies and from "for cause" indication biopsies. Included in our study are case reports and case series with extractable quantitative data on patient demographics such as age, sex, ethnicity, as well as data on renal function tests, their comorbidities, and biopsy to study the histopathological changes. Data were analyzed with Microsoft Excel. To evaluate the methodological quality, we chose the framework for appraisal, synthesis, and application of evidence suggested by Murad et al. Systematic searches of literature found 31 studies that fulfilled the eligibility criteria. These studies included a total of 139 cases, where individual case details including clinical and histopathological findings were available. The median age of the cases was 62 years with a male:female ratio of 2.5:1. Associated comorbidities were noted in 78.4% of cases. The majority of the cases had renal dysfunction with proteinuria which was documented in more than two-thirds of the cases. The histopathological findings observed the frequent tubular involvement manifested by acute tubular injury. Regarding glomerular pathology, collapsing glomerulopathy emerged as a distinct lesion in these patients and was noted among 46.8% of cases with glomerular lesions. A small subset of cases (4.3%) had thrombotic microangiopathy. Collapsing glomerulopathy emerged as a hallmark of glomerular changes among COVID-19 patients. Tubular damage is common and is linked to multiple factors including ischemia, sepsis among others. In the form of thrombotic microangiopathy seen in a subset of patients, vascular damage hints toward the hyper-coagulable state associated with the infection. The demonstration of viral particles in renal tissue remains debatable and requires further study.

Efficacy of green tea, its polyphenols and nanoformulation in experimental colitis and the role of non-canonical and canonical nuclear factor kappa beta (NF-kB) pathway: a preclinical in-vivo and in-silico exploratory study.

NF-kB plays a major role in the aetiopathogenesis of inflammatory-colitis. In this study, we evaluated the efficacy of green tea and its polyphenols and their nanoformulation in Tri-Nitro Benzene Sulfonic acid (TNBS) induced colitis in in-vivo system (Rat) and the involvement of non-canonical and canonical NF-kB pathway in green tea mediated protection (in-silico platform). We used the Wister rat model of TNBS-induced colitis. Rats were grouped into eleven groups (six animals each) and administered vehicle (ethanol), TNBS, Epicatechin (EC), Epigallocatechin (EGC), Epicatechin-gallate (ECG), Epigallocatechin-gallate (EGCG), sulfasalazine, green tea, EGCG + sulfasalazine, nano-EGCG and nano-EGCG + sulfasalazine for 14 days after induction of colitis. Colonic tissue was evaluated for the level of malondialdehyde, myeloperoxidase activity, catalase, reduced glutathione, glutathione peroxidase, IL-6, TNF-α, IL-1ß, NF-κB and morphological and histopathological evidence of damage. In the in-silico part, molecular docking and dynamic simulation study of EGCG was done against different targets in NF-kB for detailed evaluation of the role of non-canonical and canonical NF-KB pathway. In our study, EGCG reduced colonic inflammation, markers of oxidative stress, TNF-α, NF-κB, IL-1ß and IL-6. Nano-EGCG + sulfasalazine was more efficacious when compared to EGCG + sulfasalazine. In molecular docking and molecular dynamic simulation studies, EGCG showed a good binding profile to the inhibitor binding sites of IKK-beta, IKK-alpha and NIK. Thus, it can be concluded that EGCG showed protective action in experimental colitis acting through both non-canonical and canonical NF-kB pathway. Nano-EGCG + sulfasalazine combination showed better protection than nano-EGCG alone. Communicated by Ramaswamy H. Sarma.

Efficacy and safety of Risankizumab in moderate to severe psoriasis: A systematic review and meta-analysis.

Monoclonal antibodies are explored for their therapeutic potential in Psoriasis. To evaluate Risankizumab in the moderate to severe psoriasis with regard to efficacy, tolerability, and safety PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) and clinicaltrials.gov, databases were searched for relevant RCTs. The reference lists of relevant publications were also scanned manually to identify any further studies not indexed in the searched databases. Only RCT aiming to evaluate the role of Risankizumab in the treatment of moderate to severe psoriasis were considered eligible for this systematic review. Intervention group was patients taking Risankizumab and placebo or other monoclonal antibody was considered as control group. Cochrane review manager 5 (RevMan) version 5.3 was used for data synthesis and meta-analysis. Quality assessment of included randomized controlled trials was done with Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). Overall Grading of evidence for study objectives was performed with GRADE Pro GDT software. A total of seven studies were included in analysis with total of 1533 and 710 patients in Risankizumab and standard care groups, respectively. Statistically significant increase in percentage of individual achieving PASI90 (OR = 11.01 (95% CI = 8.67-13.99), DLQI-01 (OR = 6.95 (95% CI = 5.53-8.75), sPGA-01 (OR = 14.22 (95% CI = 11.10-18.22); sPGA-0 (OR = 6.39 (95% CI = 4.79-8.54) in risankizumab group as compared with control, with high quality of evidence. Increased risk of infections with risankizumab as compared with placebo (OR = 1.44 [95% CI = 1.13-1.83], high quality evidence), while no difference in SAE among two groups. Analysis of all outcome data from RCTs. In the light of evidence from systematic review on effectiveness of Risankizumab, we propose treatment with risankizumab for psoriasis patients not responding to available treatment.

Target/therapies for chronic recurrent erythema nodosum leprosum.

A Type 2 lepra reaction or erythema nodosum leprosum is an anticipated complication in the lepromatous spectrum of leprosy cases. It is an example of an immune complex-mediated complement activated disease (Type III hypersensitivity reaction). Hence, we tried to target the inflammatory mediators and the mental stressors for the possible management strategies.