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Archives of Virology Jun 2023Since May 2022, there has been a global increase in the number of Mpox virus (MPXV) cases in countries that were previously considered non-endemic. In July 2022, the... (Review)
Review
Since May 2022, there has been a global increase in the number of Mpox virus (MPXV) cases in countries that were previously considered non-endemic. In July 2022, the World Health Organization (WHO) declared this outbreak a public health emergency of international concern. The objective of this systematic review is to examine the novel clinical features of Mpox and to assess the available treatment options for managing the disease in patients who are afflicted with it. We conducted a systematic search in several databases, including PubMed, Google Scholar, Cochrane Library, and the grey literature, from May 2022 to February 2023. We identified 21 eligible studies, which included 18,275 Mpox cases, for final qualitative analysis. The majority of cases were reported in men who have sex with men (MSM) and immunocompromised individuals with HIV (36.1%). The median incubation period was 7 days (IQR: 3-21). The novel clinical manifestations include severe skin lesions on the palms, oral and anogenital regions, as well as proctitis, penile edema, tonsillitis, ocular disease, myalgia, lethargy, and sore throat, without any preceding prodromal symptoms or systemic illness. In addition, fully asymptomatic cases were documented, and various complications, including encephalomyelitis and angina, were noted. Clinicians must be familiar with these novel clinical characteristics, as they can aid in testing and tracing such patients, as well as asymptomatic high-risk populations such as heterosexuals and MSM. In addition to supportive care, currently, there are several effective prophylactic and treatment strategies available to combat Mpox, including the vaccines ACAM2000 and MVA-BN7, as well as the immunoglobulin VIGIV and the antivirals tecovirimat, brincidofovir, and cidofovir against severe Mpox infection.
Topics: Male; Humans; Monkeypox virus; Homosexuality, Male; Mpox (monkeypox); Sexual and Gender Minorities
PubMed: 37386209
DOI: 10.1007/s00705-023-05808-4 -
Journal of Crohn's & Colitis Jul 2022Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different...
BACKGROUND
Ulcerative proctitis is a common and often highly symptomatic form of inflammatory bowel disease. We performed a systematic review to assess the efficacy of different therapies in the management of patients with ulcerative proctitis.
METHODS
We identified randomized controlled trials in adults with ulcerative proctitis treated with oral or topical therapies for induction of response or remission, or prevention of relapse.
RESULTS
A total of 32 randomized controlled trials were included [27 induction/2839 participants, five maintenance/334 participants]. Follow-up varied from 3 to 8 weeks for induction, and from 6 to 24 months for maintenance of remission. 5-Aminosalicylic acid [5-ASA] suppository was the most frequently evaluated treatment [14/32, 43.7%], followed by steroid enema [7/32, 21.9%]. Topical 5-ASA demonstrated effectiveness for induction of clinical response or remission and prevention of relapse in several studies. Combined topical steroids and 5-ASA was more effective than topical 5-ASA or topical steroids alone to induce response [100% of patients for combination vs 70% for beclomethasone alone and 76% for 5-ASA alone]. One observational study suggested azathioprine may be effective in patients with ulcerative proctitis. Only two cohort studies evaluated the efficacy of tumour necrosis factor inhibitors in ulcerative proctitis. Small molecules, anti-integrins and anti-interleukin therapies have not been evaluated in isolated ulcerative proctitis.
CONCLUSION
The role of topical 5-ASA as a treatment for ulcerative proctitis has been confirmed in this systematic literature review, for induction and maintenance of remission. Future trials are needed to investigate the efficacy of more recent and upcoming drug classes in patients with ulcerative proctitis.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ulcerative; Humans; Mesalamine; Observational Studies as Topic; Proctitis; Recurrence
PubMed: 34850857
DOI: 10.1093/ecco-jcc/jjab218 -
Journal of Investigative Medicine : the... Feb 2021Several published studies have evaluated the safety and effectiveness of oral and intravenous tacrolimus for the management of patients with inflammatory bowel disease... (Review)
Review
Several published studies have evaluated the safety and effectiveness of oral and intravenous tacrolimus for the management of patients with inflammatory bowel disease (IBD). However, little is known about the effectiveness of topical tacrolimus in this patient population. The aim of this systematic review was to evaluate the current state of literature to evaluate the safety and effectiveness of rectal administration of topical tacrolimus, in the form of suppository, ointment, and/or enema in patients with ulcerative proctitis, perianal Crohn's disease (CD), and chronic refractory pouchitis. Electronic database searches were conducted in international databases since their inception until February 2020. Study subjects were categorized into three groups: topical tacrolimus for patients with proctitis, perianal CD, and chronic refractory pouchitis. The primary end point of this study was the remission rate. Secondary end points were response rate and the incidence of AEs. Eleven studies were included in the final assessment in this systematic review. This provided information from 188 patients. Tacrolimus was administered topically as suppositories, ointment, or enema. Clinical remission was achieved in 57.1%, 57.14%, and 70.0% in patients with proctitis, fistulizing perianal CD, and chronic pouchitis. The most commonly reported side effect was perianal itching and burning. Reversible nephrotoxicity occurred in a single patient. No clear correlation was found between blood levels and clinical outcomes. Topical tacrolimus is effective for a subset of patients with IBD. The adverse effects were minimal and tolerable. Well-designed randomized clinical trials are warranted to establish the appropriate dose and administration method.
PubMed: 33622709
DOI: 10.1136/jim-2020-001699 -
Journal of Medical Virology Apr 2023Currently, many cases of mpox patients living with the human immunodeficiency virus (HIV) have been reported. Immunocompromised mpox patients, including those living... (Meta-Analysis)
Meta-Analysis
Currently, many cases of mpox patients living with the human immunodeficiency virus (HIV) have been reported. Immunocompromised mpox patients, including those living with HIV are noted for an increased risk for severe symptoms; however, existing studies did not focus on the statistical comparison of mpox outcomes associated with HIV. Thus, we conducted a systematic review and meta-analysis to evaluate and compare the clinical manifestations of mpox in people living with HIV (PLWH) and people without HIV. In this systematic review and meta-analysis, PubMed/MEDLINE, Embase, and Google Scholar were searched up to March 7, 2023. A random effects model was used to calculate the pooled prevalence along with the 95% confidence intervals (CI), and the odds ratio and its corresponding 95% CIs were calculated to elucidate the significance of each clinical feature for mpox patients with and without HIV. In this study, we included 99 published papers with 2413 patients with mpox (median age, 35.5 years; PLWH n = 1151) from 27 countries across six continents. The odds ratio of the mpox outcomes with PLWH in comparison to patients without HIV was found to be significant for skin rash (1.24, 95% CI: 1.01-1.53), proctitis (2.03, 95% CI: 1.36-3.04), cough (0.57, 95% CI: 0.33-0.98), and diarrhea (3.85, 95% CI: 1.24-11.98). The odds ratio of mpox patients with HIV for historical infections of syphilis was 2.14 (95% CI: 1.38-3.32), compared with those without HIV. This is the first international and comprehensive study that performed a systematic review and meta-analysis to statistically measure mpox manifestations according to HIV status. As clinical features related to mucosal contact were characteristically pronounced in PLWH, our systematic review provides insight that the primary invasion site of infection strongly relates to the outcomes of mpox.
Topics: Humans; Adult; HIV Infections; HIV; Mpox (monkeypox)
PubMed: 36991570
DOI: 10.1002/jmv.28713 -
Health Science Reports Oct 2023The 2022-mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited....
BACKGROUND AND AIMS
The 2022-mpox outbreak has spread worldwide in a short time. Integrated knowledge of the epidemiology, clinical characteristics, and transmission of mpox are limited. This systematic review of peer-reviewed articles and gray literature was conducted to shed light on the epidemiology, clinical features, and transmission of 2022-mpox outbreak.
METHODS
We identified 45 peer-reviewed manuscripts for data analysis. The standards of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration were followed for conducting the study.
RESULTS
The case number of mpox has increased about 100 times worldwide. About 99% of the cases in 2022 outbreak was from non-endemic regions. Men (70%-98% cases) were mostly infected with homosexual and bisexual behavior (30%-60%). The ages of the infected people ranged between 30 and 40 years. The presence of HIV and sexually transmitted infections among 30%-60% of cases were reported. Human-to-human transmission via direct contact and different body fluids were involved in the majority of the cases (90%-100%). Lesions in genitals, perianal, and anogenital areas were more prevalent. Unusually, pharyngitis (15%-40%) and proctitis (20%-40%) were more common during 2022 outbreak than pre-2022 outbreaks. Brincidofovir is approved for the treatment of smallpox by FDA (USA). Two vaccines, including JYNNEOSTM and ACAM2000®, are approved and used for pre- and post-prophylaxis in cases. About 100% of the cases in non-endemic regions were associated with isolates of IIb clade with a divergence of 0.0018-0.0035. Isolates from B.1 lineage were the most predominant followed by B.1.2 and B.1.10.
CONCLUSION
This study will add integrated knowledge of the epidemiology, clinical features, and transmission of mpox.
PubMed: 37808926
DOI: 10.1002/hsr2.1603 -
Brachytherapy 2021To describe technical challenges and complications encountered during and after high-dose-rate prostate brachytherapy (HDR-BT) and review management of these...
PURPOSE
To describe technical challenges and complications encountered during and after high-dose-rate prostate brachytherapy (HDR-BT) and review management of these complications.
METHODS AND MATERIALS
The authors performed a systematic review of the literature on toxicities encountered after prostate HDR-BT +/- external beam radiotherapy. A total of 397 studies were identified, of which 64 were included. A focused review of literature regarding the management of acute and late toxicities also performed.
RESULTS
Most acute toxicities include grade 0-2 genitourinary and gastrointestinal toxicity. Overall, Grade 3+ Common Terminology Criteria for Adverse Events toxicity after HDR-BT was low [genitourinary: 0-1%; gastrointestinal 0-3%]. Rates of fistula formation were <1%, and radiation cystitis/proctitis were <14% and more commonly reported in cohorts treated with HDR-BT boost and external beam radiotherapy.
CONCLUSIONS
HDR-BT both as monotherapy or combined with external beam radiotherapy for prostate cancer is well tolerated. Serious complications are rare.
Topics: Brachytherapy; Humans; Male; Prostatic Neoplasms; Radiation Injuries; Urogenital System
PubMed: 33612395
DOI: 10.1016/j.brachy.2020.10.007 -
Journal of Crohn's & Colitis Jan 2023Treatment options for proctitis are limited. To assist trial design for novel therapeutics, we conducted a systematic review and meta-analysis of proctitis randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Treatment options for proctitis are limited. To assist trial design for novel therapeutics, we conducted a systematic review and meta-analysis of proctitis randomized controlled trials [RCTs] to quantify placebo rates and identify factors influencing them.
METHODS
We searched MEDLINE, EMBASE and CENTRAL from inception to June 2021. Placebo-controlled trials of pharmacological interventions for proctitis were eligible. Placebo clinical response and remission rates for induction and maintenance trials were extracted and pooled using a random-effects model. Mixed-effects meta-regression was used to evaluate the impact of patient and study-level characteristics.
RESULTS
Twenty RCTs [17 induction and four maintenance phases] were included. The most common intervention was aminosalicylates and most studies investigated topical medications. The pooled placebo clinical response and remission rates for induction trials were 28% (95% confidence interval [CI] 22-35%; n = 17) and 20% [95% CI 12-32%; n = 9], respectively. Pooled placebo endoscopic response and remission rates were 32% [95% CI 26-39%, n = 12] and 18% [95% CI 9-33%, n = 6], respectively. For maintenance trials, the pooled placebo clinical remission rate was 29% [95% CI 16-46%, n = 17]. Trials published after 2005 and trials with a longer duration of follow-up were associated with significantly lower placebo response rates. Nineteen of 20 studies were assessed as having an unclear risk of bias, reflecting the historical nature of trials.
CONCLUSIONS
Placebo response and remission rates in proctitis trials are influenced by trial phase and the endpoint being assessed. These contemporary rates will inform trial design for novel therapeutics for treatment of proctitis, which is a large unmet need.
Topics: Humans; Randomized Controlled Trials as Topic; Remission Induction; Induction Chemotherapy; Proctitis; Placebo Effect
PubMed: 35930405
DOI: 10.1093/ecco-jcc/jjac109 -
Journal of Medical Virology Feb 2023Monkeypox is a zoonotic disease, endemic in central and west African regions, and has re-emerged, currently causing an outbreak as of May 2022. In this systematic... (Review)
Review
A systematic review and clinical atlas on mucocutaneous presentations of the current monkeypox outbreak: With a comprehensive approach to all dermatologic and nondermatologic aspects of the new and previous monkeypox outbreaks.
Monkeypox is a zoonotic disease, endemic in central and west African regions, and has re-emerged, currently causing an outbreak as of May 2022. In this systematic review, we aimed to characterize the current face of the disease, with a detailed categorization of mucocutaneous, as well as systemic symptoms of the disease. We searched four main online databases with the keywords "monkeypox" and "Orthopoxvirus". A total of 46 articles were included, with a cumulative number of 1984 confirmed cases. Patients were predominantly men who have sex with men, who were mostly in their 30s, with a history of unprotected sexual contact or international travel. Among mucocutaneous manifestations, anogenital lesions were the most commonly observed, followed by lesions on the limbs, face, trunk, and palms or soles. Among lesion types, vesiculopustular, pustular or pseudo-pustular, vesicular-umbilicated and papular lesions were the most common, mainly presenting asynchronously, with less than 10 lesions on each patient. Almost all patients also reported systemic manifestations, namely fever, lymphadenopathy, fatigue, myalgia, headaches, pharyngitis, and proctitis. Sexual contact is the main pathway of transmission in the current outbreak, with viral shedding in bodily fluids playing a key role. We've compared these idiosyncratic findings of the new outbreak with previous outbreaks. We've also gathered and categorized images from our included studies to make a "clinical atlas" for this "new" face of monkeypox, which can be of utmost importance for clinicians to be familiarized with, and have a clear picture of monkeypox for their differential diagnoses.
Topics: Male; Animals; Humans; Female; Homosexuality, Male; Sexual and Gender Minorities; Disease Outbreaks; Mpox (monkeypox); Zoonoses
PubMed: 36254380
DOI: 10.1002/jmv.28230 -
The Cochrane Database of Systematic... Apr 2022There are a limited number of treatment options for people with corticosteroid-refractory ulcerative colitis. Animal models of inflammatory bowel disease and... (Review)
Review
BACKGROUND
There are a limited number of treatment options for people with corticosteroid-refractory ulcerative colitis. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that tacrolimus may be an effective treatment for ulcerative colitis.
OBJECTIVES
To evaluate the efficacy and safety of tacrolimus for induction of remission in people with corticosteroid-refractory ulcerative colitis.
SEARCH METHODS
We searched the Cochrane Gut group specialised register, CENTRAL, MEDLINE (PubMed), Embase, Clinicaltrials.gov and WHO ICTRP from inception to October 2021 to identify relevant randomised controlled trials (RCT).
SELECTION CRITERIA
Two review authors independently selected potentially relevant studies to determine eligibility based on the prespecified criteria.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and analysed them using Review Manager Web. The primary outcomes were induction of remission and clinical improvement, as defined by the studies and expressed as a percentage of the participants randomised (intention-to-treat analysis).
MAIN RESULTS
This review included five RCTs with 347 participants who had active ulcerative colitis or ulcerative proctitis. The duration of intervention varied between two weeks and eight weeks. Tacrolimus versus placebo Tacrolimus (oral and rectal) may be superior in achieving clinical remission compared to placebo (oral and rectal) (14/87 participants with tacrolimus versus 1/61 participants with placebo; risk ratio (RR) 3.76, 95% confidence interval (CI) 1.03 to 13.73; 3 studies). These results are of low certainty due to imprecision and risk of bias. Tacrolimus (oral and rectal) may be superior for clinical improvement compared to placebo (oral and rectal) (45/87 participants with tacrolimus versus 7/61 participants with placebo; RR 4.47, 95% CI 2.15 to 9.29; 3 studies). These results are of low certainty due to imprecision and risk of bias. The evidence is very uncertain about the effects of tacrolimus (oral and rectal) on serious adverse events compared to placebo (oral and rectal) (2/87 participants with tacrolimus versus 0/61 participants with placebo; RR 2.44, 95% CI 0.12 to 48.77; 3 studies). These results are of very low certainty due to high imprecision and risk of bias. Tacrolimus versus ciclosporin One study compared oral tacrolimus to intravenous ciclosporin, with an intervention lasting two weeks and 113 randomised participants. The evidence is very uncertain about the effect of tacrolimus on achievement of clinical remission compared to ciclosporin (15/33 participants with tacrolimus versus 24/80 participants with ciclosporin; RR 1.52, 95% CI 0.92 to 2.50). The results are of very low certainty due to risk of bias and high imprecision. The evidence is very uncertain about the effect of tacrolimus on clinical improvement compared to intravenous ciclosporin (23/33 participants with tacrolimus versus 62/80 participants with ciclosporin; RR 0.90, 95% CI 0.70 to 1.16). The results are of very low certainty due to risk of bias and imprecision. Tacrolimus versus beclometasone One study compared tacrolimus suppositories with beclometasone suppositories in an intervention lasting four weeks with 88 randomised participants. There may be little to no difference in achievement of clinical remission (16/44 participants with tacrolimus versus 15/44 participants with beclometasone; RR 1.07, 95% CI 0.60 to 1.88). The results are of low certainty due to high imprecision. There may be little to no difference in clinical improvement when comparing tacrolimus suppositories to beclometasone suppositories (22/44 participants with tacrolimus versus 22/44 with beclometasone; RR 1.00, 95% CI 0.66 to 1.52). The results are of low certainty due to high imprecision. There may be little to no difference in serious adverse events when comparing tacrolimus suppositories to beclometasone suppositories (1/44 participants with tacrolimus versus 0/44 with beclometasone; RR 3.00, 95% CI 0.13 to 71.70). These results are of low certainty due to high imprecision. There may be little to no difference in total adverse events when comparing tacrolimus suppositories to beclometasone suppositories (21/44 participants with tacrolimus versus 14/44 participants with beclometasone; RR 1.50, 95% CI 0.88 to 2.55). These results are of low certainty due to high imprecision. No secondary outcomes were reported for people requiring rescue medication or to undergo surgery.
AUTHORS' CONCLUSIONS
There is low-certainty evidence that tacrolimus may be superior to placebo for achievement of clinical remission and clinical improvement in corticosteroid-refractory colitis or corticosteroid-refractory proctitis. The evidence is very uncertain about the effect of tacrolimus compared to ciclosporin for achievement of clinical remission or clinical improvement. There may be no difference between tacrolimus and beclometasone for inducing clinical remission or clinical improvement. The cohorts studied to date were small, with missing data sets, offered short follow-up and the clinical endpoints used were not in line with those suggested by regulatory bodies. Therefore, no clinical practice conclusions can be made. This review highlights the need for further research that targets the relevant clinical questions, uses appropriate trial methodology and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration so as to capture the efficacy and effectiveness of tacrolimus in the medium to long term. Well-structured efficacy studies need to be followed up by long-term phase 4 extensions to provide key outputs and inform in a real-world setting.
Topics: Adrenal Cortex Hormones; Beclomethasone; Colitis, Ulcerative; Cyclosporine; Humans; Proctitis; Remission Induction; Suppositories; Tacrolimus
PubMed: 35388476
DOI: 10.1002/14651858.CD007216.pub2 -
Journal of Medical Virology Apr 2023Since early May 2022, outbreaks of Monkeypox (Mpox) cases have emerged and become a global concern. Studies exploring the gastrointestinal symptoms and/or liver injury... (Meta-Analysis)
Meta-Analysis
Since early May 2022, outbreaks of Monkeypox (Mpox) cases have emerged and become a global concern. Studies exploring the gastrointestinal symptoms and/or liver injury of Mpox are still very limited. This systematic review and meta-analysis is the first to summarize the gastrointestinal symptoms reported by Mpox patients. We searched for Mpox studies published until October 21, 2022, in MEDLINE, EMBASE, SCOPUS, and organization websites. Mpox studies were observational studies that reported at least one of either gastrointestinal symptoms and/or liver injury in Mpox patients. Meta-analysis was done to obtain the pooled prevalence of gastrointestinal symptoms in Mpox patients. Subgroup analyses were done based on the study location, age groups, and Mpox Clades. The quality of included studies was assessed using the NIH Quality Assessment Tool. Overall, 31 studies that reported gastrointestinal symptoms and/or liver injury in Mpox patients were included. The reported gastrointestinal symptoms were abdominal pain, anorexia, diarrhea, nausea, and vomiting. There is a lack of reporting for liver injury. The most prevalent gastrointestinal symptoms in Mpox patients were anorexia (47%; 95% confidence interval [CI] 41%-53%), followed by vomiting (12%; 95% CI 11%-13%), nausea (10%; 95% CI 9%-11%), abdominal pain (9%; 95% CI 8%-10%), and diarrhea (5%; 95% CI 4%-6%). Additionally, the prevalence of proctitis, rectal/anal pain, and rectal bleeding were 11% (95% CI 11%-12%), 25% (95% CI 24%-27%), and 12% (95% CI 11%-13%), respectively. Anorexia was the most frequently reported gastrointestinal symptom in Mpox patients, followed by vomiting, nausea, abdominal pain, and diarrhea. Proctitis is a novel presentation of Mpox in the 2022 outbreak.
Topics: Humans; Mpox (monkeypox); COVID-19; Anorexia; Gastrointestinal Diseases; Vomiting; Diarrhea; Nausea; Abdominal Pain; Proctitis
PubMed: 36975777
DOI: 10.1002/jmv.28709