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devastated
#I tried to submit to a publisher that was recommended to me#but their window of submission is only open June 1-June 30#Will I have to wait a WHOLE ASS YEAR now????????#screaming weeping throwing up
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Announcement: 2023 OFIC Press Prize
Submissions for the 2023 OFIC Press Prize are OPEN until 11:59pm EST on June 1, 2023.
The OFIC Press Prize will be awarded to up to 2 novels and up to 3-4 novellas, which will be published in 2024. The prize for a novel is $1000 and a novella $250. Novels will be published as standalone books and novellas will be compiled into an anthology.
We're looking for manuscripts that don't really fit in a traditional publishing category, maybe because they're too romance-y for general or literary fiction, and not romance-y enough for romance. Or maybe there's just a truly tasteless amount of smut. What we value most is an earnest portrayal of character, interesting relationship dynamics, and well-crafted prose that prioritizes clarity and voice.
We can guarantee the winners their prize money, thorough editorial feedback, professional cover design, and digital publication. We plan to run a Kickstarter to fund a physical print and distribution. Should our Kickstarter succeed, you'll also receive 10 copies of your book/anthology. We'll do a print of 100 copies to sell in our online store in addition to the number of Kickstarter contributors.
Rules & Restrictions:
Novellas can be 12,000 to 50,000 words; novels are over 50,000. While we have no upper limit, know that anything over 150k is going to be a really hard sell. We're not opposed, though. If it slaps, it slaps.
Must be written in English.
Author must be 18 or older to submit.
Your work cannot be published or posted anywhere else. If you’ve posted a work on any social platform, even if you take it down, for legal reasons, we cannot accept it. This means you can’t delete a work from AO3 and file off the serial numbers to send to us.
Your work must stand on its own as an original piece, although we of course welcome common fanfiction tropes (or the subversion thereof), and works that feel fanfiction-y but contain original characters and worlds. Again, legal reasons.
We can't publish song lyrics (either within the manuscript or in the title) unless they're public domain.
Manuscript Formatting:
Please provide the following as front matter of your manuscript:
A title page with your contact info. Your AO3 handle/social media can go here if you're comfortable sharing that, as well as if you'd like to publish under a pseud or pen name.
A cover letter with a brief fan history. You can share however much or little you'd like to share, but we're mostly looking for your relationship to fandom and fanfiction: how long you've been in fandom, what fandoms you've been in, community events you've participated in, things like that. If you don't know what "in fandom" means, this is not the press for you.
A synopsis of the story. This doesn't have to be fancy or professional-sounding. In fact the closer it sounds to a tumblr shitpost, the better. Pretend your best friend has just asked, "So what's your book about?" The synopsis would be the long answer/tea spill that follows. It should include all major plot beats (even if that involves major spoilers). No page limit, but it shouldn't be super long, up to 5ish pages, preferably 1-2.
You can format it however you like as long as the font is readable, preferably 12pt Times New Roman or Garamond. Please provide page numbers in the footer of the document. Double-spaced preferred with one inch indentation at the start of paragraphs.
If you have questions or would like clarification on any of the above, email [email protected] or send us an ask. We’re excited to read your work!
site | subscribe | submit | faq
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These aren't late, Valentine's Day and time are social constructs
#hiveworks#oc kiss challenge#comic#original characters#ocs#keen remedy#adrian grey#nigel#I'm submitting to publishers but nothing yet#hiveworks please open submissions again#i love them#they love each other#i love my boys so much!!!#chapter 1 is almost done#stuck together reluctantly to lovers#idiots in love
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At long last! Submissions are finally open!
April 3, 2023 - June 24, 2023
Make sure to read the entirety of the submissions guidelines before you send your pitch. And can’t wait to see what you send!
🌟 wildstarpress.com/pitch-to-us 🌟
#WildStar Press#comics#SUBMISSIONS OPEN#reblog this so someone's comic can find a new home#indie publishing
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cool girls submit to dreamworldgirlzine…
#litmag#poetry#literarymagazine#writing community#dreamcore#y2k#multimedia#girlhood#zine#writing#fiction#art magazine#art#digital magazine#poetrycommunity#onlinemagazine#print magazines#new magazine#art and literature#submissions open#small publishing
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welp, just submitted a story to a lit mag whose response times can apparently be as big as 6 months so, now it's a waiting game to see which side the coin lands on but i should at least be close to the top of the reading pile if they go in order since submissions only opened a little over an hour ago so hopefully the response doesn't take forever.
#james talks#i reread it and deeply wanted to rewrite the whole thing but i knew there was simply no time since submissions were only open for 6 days--#and i would just edit out all of my voice if i rewrote or re-edited it so i made a few minor word choice changes and submitted it#nothing to do now but worry incessantly and wait to hear back#it's a horror short btw but i don't wanna say too much rn#anyway just shaking a little bit rn although it's hard to tell if that's the anxiety or the coffee or both#just gonna try not to think about it until i get any sort of email ig.#the magazine features so many cool shorts i doubt i'm getting selected but if i do it would be fun to call myself a published author#anyway i'm gonna go try to sleep now although we all know i'm not going to be able to actually sleep lol#james writes stuff
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DAMN WHAT THE HELL BARIQHRIQRHAUSHASHW !?!?!?!!?!?!!!!!!!!!!!!
#oh my god. anyways fun thing about college there are so many new ways that it can compliment you?????#anyways got the grade for my english paper back which like 💪💪💪💪 yeah i got the A. 😎😎😎 honestly i didnt i would have been pissed bc#that shit WAS brilliant actually but THEN my professor was like in the comments hey if you wanted you could edit this and submit it to this#fuckin. peer reviewed journal and shit like i thought it was really good“ like SIR?!?!?!?!?!? SIR!?!?!?!?!?!#its an undergrad one obviously but this is insane to me wth#he said submission closes next week but the site says thats when its opening so ill probably wait and#decide over break after talking to my parents#but thats absolutely wild#also the complements thing is crazy#like in hs its me: does smth smart someone: oh thats so smart#but then in COLLEGE i do smth smart and people start asking me to TA and submit to academic publications ahfiahdhahs#wild. anyways i need to turn in this other paper now which is what i was SUPPOSED TO BE DOING before i checked my email. anyways thats wild#i may honestly submit if i can becaused seeing if i could get published would be SICK#and would look fucking awesome on my resume. also bragging rights and the ego boost bc lets be real#esp at 18 thats wild teehee. anyways need to do real work not theoretical work atm so yeah ✌️ bye#blah
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next redraw poll will be like , official art of various media as options I PROMMMYYY
#also i think my submissions r open if yall have ideas#so official art from published media think like ace attorney official arts#comic panels/ manga panels#anime /cartoon/show screencaps#official art or renders from popup shops#ect
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actually just had the silly idea to try and edit down my 940 words flash piece to micro or near micro level and i think i'm going to hate every minute of attempting that at first but i remember when i was first drafting it i finished the opening paragraph and thought "this already feels like a full arc" but i was naïve and silly and was like noooo i have to expand and elaborate on it and now i have a 940 word beast that really does not need to be 940 words. so
#magazine i want to submit it to opens submissions in september so#said magazine published one of my fave micros of all time so i wanna be like heyyyyyyyy#sometimes when im editing my older flash pieces my approach is like. i dont think you deserved this amount of words#i only have one flash piece near 1000 words where i feel like the story suits being near 1000 words#i am soooo becoming a 500-700 words range girly#want to get my ass to 200-400 words
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Kinda related to the DNI stuff sort of. So I don't have a DNI or plan on adding one, but I do allow ppl to draw their OCs with my OCs.
BUT there are a few fandoms I'm not comfortable with for reasons and I don't want ppl to draw their fandom OCs with my OCs. So maybe I should do a DNI for that??
.
#artfight#art fight#artfight2023#submission#held back on publishing these asks for a while#because it's gonna open a can of worms lol
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Checking in!
It has been brought to our attention that our entire Mulberry Literary blog has been entirely swept clean except for one Feb post... Not sure why!
Nevertheless, we wanted to let you all know that our submissions are still open until July 15th for:
Poetry
Prose (submissions are closed since we reached our maximum!)
Art
There's no fee to submit your work, and you'll be entered to win a cash prize with publication. Full submission guidelines are on our website!
www.mulberryliterary.com
And in light of the recent work we'll have to put in to get our blog back to normal, we'll update our theme and icon ;)
#mulberrylitmag#mulberry literary#indie publishing#open call#call for submissions#call for poetry#call for writing#writing contest
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AUTHOR-CENTRIC PUBLISHER SEEKING MANUSCRIPT SUBMISSIONS!
Who we are: An author-centric traditional publisher based in Athens, GA.
What we’re looking for: Experimental stories and new voices in the genres of low-fantasy, cozy fantasy, high fantasy romance, and space opera.
What sets us apart: Our commitment to the time-honored traditional publishing experience– without the traditional constraints. Through innovative uses of modern technologies and resources for crowdfunding and grassroots efforts, we mitigate the initial costs of publishing. We, as the publisher, bear the upfront costs, thereby ensuring our authors are free from financial burdens.
By reimagining the traditional model, SkyShark Publishers is able to invest in literature that resonates with depth and diversity, championing authors every step of the way—from the first draft to the final print.
We would love to hear from you. Click here to see our submission guidelines, or scan the QR code in the graphic.
Thank you for your time!
#writeblr#booklr#calls for submission#fantasy#space opera#writers on tumblr#authors of tumblr#low fantasy#cozy fantasy#high fantasy#new authors#submissions open#traditional publishing#traditional publisher
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Your first pages - 4 more book openings critiqued at @Litopia by literary agent @agentpete, author Jon Duffy and me!
I’ve just guested again at Litopia, the online writers’ colony and community. Each week they have a YouTube show, Pop-Up Submissions, where four manuscripts are read and critiqued live on air by literary agent Peter Cox @agentpete and a guest, or sometimes two. This time the other guest was longtime Litopian and author Jon Duffy. The format is simple. Four manuscripts, each with a short blurb.…
View On WordPress
#beginnings#blurbs#how to get your book published#literary agents#Litopia#opening pages#Pop-Up Submissions#publishing#show not tell#titles#writing style#your first pages
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Lupine Publishers | The Early Treatment of a Bodybuilder with Symptomatic Chronic Renal Failure with Intestinal Dialysis: A New Recommendation for Intestinal Dialysis Enhancement
Abstract
Background: Dietary therapy aiming primarily at reducing the generation and accumulation of urea through protein restriction is the most important non-dialytic therapeutic intervention in the management of chronic renal failure. The use of a urea lowering agent “acacia gum” with protein restriction has been increasingly used as a new form of dietary dialysis which has been increasingly known as intestinal dialysis. Just like in other forms of dialysis, the use of conservative dietary and pharmacological measures is also necessary in intestinal dialysis.
Patients and methods: The early treatment of a bodybuilder with symptomatic chronic renal failure with intestinal dialysis is described, and the relevant literatures were reviewed with the primary of identifying the evidence that can contribute to enhancing intestinal dialysis.
Results: At about the age of 50 years (March, 2022), a professional bodybuilder who presented with progressive symptomatic uremia associated with nausea, vomiting, pruritus, and mild anemia. His weight was about 100 Kg, and before his current illness he reported that his bench press single maximum repetition was 140Kg. On the 19th of March, blood urea level was 162 mg /dL and serum creatinine was 6.2 mg /dL. Renal ultrasound confirmed the chronicity of renal failure and showed small kidneys. The conservative dietary (Acacia gum supplementation plus very low protein diet) and pharmacological managements were prescribed according to the latest published intestinal dialysis guidelines and included oral iron and folic acid capsule, and calcium carbonate. After two weeks, the patient was asymptomatic and blood urea was lowered to 126.4 mg/dL, and the hemoglobin was increased to 11g/d.
Conclusion: This is just another case to demonstrate that intestinal dialysis is effective in lowering blood urea level and improving symptoms in symptomatic chronic renal failure. There is a convincing evidence to support that the addition of essential amino acids and ketoanalogues in the management of chronic renal failure with intestinal dialysis can contribute to its enhancement.
Keywords: Symptomatic uremia; Intestinal dialysis; Ketoanalogues of essential amino acids.
Introduction
Dietary therapy aiming primarily at reducing the generation and accumulation of urea through protein restriction is the most important non-dialytic therapeutic intervention in the management of chronic renal failure. The use of a urea lowering agent “acacia gum” with protein restriction has been increasingly used as a new form of dietary dialysis which has been increasingly known as intestinal dialysis. Just like in other forms of dialysis, the use of conservative dietary and pharmacological measures is also necessary in intestinal dialysis [1-14].
Patients and methods
The early treatment of a bodybuilder with symptomatic chronic renal failure with intestinal dialysis is described, and the relevant literatures were reviewed with the primary of identifying the evidence that can contribute to enhancing intestinal dialysis.
Results
At about the age of 50 years (March, 2022), a professional bodybuilder who presented with progressive symptomatic uremia associated with nausea, vomiting, pruritus, and mild anemia. He was not havening reduction in urine output, edema or hypertension. His weight was about 100 Kg, and before his current illness he reported that his bench press single maximum repetition was 140Kg. On the 19th of March, blood urea level was 162 mg / dL and serum creatinine was 6.2 mg /dL. Urinalysis showed 2 plus albuminuria and one plus amorphous urate. Blood calcium and serum electrolytes were within normal ranges, but he had mild hyperphosphatemia with serum phosphorus of 4.9 mg/dL (Normal range 2.4-4.4mg/dL). Hemoglobin was 10.7 mg/dL (Normal ranges: 11.5-16.5 g/dL). Liver function tests were normal (Total serum bilirubin 0.8 mg/dL, Aspartate aminotransferase (SGOT) 25 iu/L, alanine aminotransferase (SPOT) 21 iu/L, alkaline phosphatase 284 iu/L).
He reported history of episodes of hyperglycemia that in the case of bodybuilders is generally attributed to growth hormone administration in excessive doses. However, the patient was reluctant to provide details about the performance enhancing medications such as anabolic steroids and growth hormone, and he was not confirming or denying the use of such agent. He was simply saying that he was taking protein supplements. Renal ultrasound (Figure 1) confirmed the chronicity of renal failure and showed small kidneys (RK: 8 x 4, cortex 6 mm, LK: 8.2 x 4, cortex 6 mm). The kidneys had hyper-echoic texture with reduced cortical thickness and loss of the cortico-medullary differentiation. There were small cysts on both kidneys, not more than 1.5 cm in diameter. Abdominal ultrasound also showed small polyp in the gall bladder and mild enlargement of the prostate with a volume of 27 cm3 (Normally up to 25). The patient initially required oral prochorperazine 5 mg for two days control the nausea and vomiting, and oral antihistamine plus topical crotamiton 10% to control pruritus. The conservative dietary (Acacia gum supplementation plus very low protein diet) and pharmacological managements were prescribed according to the latest published intestinal dialysis guidelines and included oral iron and folic acid capsule, and calcium carbonate. He also received oral finasteride 5 mg daily for the prostatic enlargement. After two weeks, the patient was asymptomatic and blood urea was lowered to 126.4 mg/dL and the hemoglobin was increased to 11g/d. Ultrasound showed normal prostate size of 20 cm3. Literature review suggested that the addition of essential amino acids and ketoanalogues in the management of chronic renal failure with intestinal dialysis can contribute to its enhancement. Therefore, Ketosteril (Fresenius), was prescribed in a low initial dose of three tablets, and was ordered to be brought to the patient from Turkey.
Discussion
Until now, there is no evidence to support that high protein diet per se can cause chronic renal failure. However, nephrocalcinosis caused exogenous vitamin D intoxication was reported to cause renal failure in a bodybuilder athlete [15]. Therefore, an accurate causation of the chronic renal failure cannot be determined. Carrero et al (2020) emphasized the importance and benefits of fruits and vegetables in patients with chronic renal failure. The intake of fruits and vegetables is associated with a higher fiber intake which can cause a shift in the gut microbiota towards reduced production of uremic toxins. The intake of fruits and vegetables is also associated with lower intake phosphorus, and thus help in controlling hyperphosphataemia [16]. However, the latest published intestinal dialysis guidelines have already suggested intake of fruits and vegetables [17]. The use of Keto-analogues of essential amino acids in the management of chronic renal failure has been reported as early as the 1970s (Walser, 1978; Bauerdick and colleagues, 1978, Giovannetti et al, 1980) [18]. Bauerdick and colleagues (1978) reported the use of nitrogen-free hydroxy and keto precursers of amino acids in the treatment of patients with chronic renal failure with essential amino acid and a low-protein diet was associated with a more positive nitrogen balance [19]. In 1980, Giovannetti et al treated twenty patients with advanced chronic renal failure with a low protein diet (0.2 g/kg/day hour vegetable proteins) and essential aminoacids and ketoanalogues. They reported that treatment was associated with a favorable outcome [20]. In 1981, Barsotti et al emphasized that treatment of chronic renal failure a very low protein diet plus essential amino acids and ketoanalogues is not associated with reduction of creatinine clearance, while treatment with hemodialysis and free protein intake is associated with reduction of creatinine clearance. They treated thirty-one patients with a conventional low-protein diet, and treatment was associated with a linear reduction of creatinine clearance. A thirteen patient treated with hemodialysis experienced significantly accelerated decline of creatinine clearance. However, only one of a twelve patients treated with a very low protein diet supplemented plus essential amino acids and ketoanalogues, experienced continued a continued reduction in creatinine clearance [21].
Mitch and colleagues (1982) described the treatment of 9 patients who severe chronic renal failure (mean glomerular filtration rate 4.8 ml/min; mean serum creatinine 11.3 mg/dl). They were treated with protein restriction (22.5 g daily of mixed quality protein) plus essential amino acids and keto-analogues of essential amino acids including tyrosine, ornithine, and a high proportion of branched-chain ketoacids, and very little methionine. Phenylalanine and tryptophan were not provided. One month of treatment was associated with significant lowering of serum urea nitrogen. Hyperphosphatemia which was observed in three patients, improved. Treatment was not associated with side effects. The treatment precluded the need for dialysis in patients with severe chronic renal failure who would otherwise need dialysis [22]. In 1983, Barsotti et al described the treatment of 48 patients with chronic uraemia for a maximum of 36 months with low protein diet plus essential amino acids and keto-analogues. Ten patients experienced reduction of renal function and required dialysis.
Eight patients experienced difficulties in complying with treatment and also required dialysis. Three died for causes that are not directly related to renal failure. 27 patients continued with treatment without important reduction in renal function, and enjoyed satisfactory subjective and objective states without evidence of protein malnutrition or unwanted effects [23]. In 1985, Barsotti et al reported that the treatment of men who had uremia with a low protein diet plus essential amino acids and ketoanalogues was associated with restoration of testosterone levels in blood [24]. In 1985, Ciardella et al described the treatment of eighty-five patients with chronic renal failure with a vegetarian low-protein, low-phosphorus diet plus essential amino acids and ketoanalogues. Treatment was associated with marked reduction of serum triglycerides in the 61 men, but the reduction was not significant in woman. When the patients were later treated by maintenance hemodialysis without dietary restrictions, the experienced elevations in serum triglycerides levels which was attributed to the loss of the effect of the dietary restriction on uremic male hypogonadism [25].
Conclusion
This is just another case to demonstrate that intestinal dialysis is effective in lowering blood urea level and improving symptoms in symptomatic chronic renal failure. There is a convincing evidence to support that the addition of essential amino acids and ketoanalogues in the management of chronic renal failure with intestinal dialysis can contribute to its enhancement.
Conflict of interest
None.
For more Lupine Journals please click here: https://lupinepublishers.com/index.php
For more Journal of Urology & Nephrology Studies articles please click here: https://lupinepublishers.com/urology-nephrology-journal/index.php
#lupine publishers#articles#urology#submission#lupine journals#journal of urology & nephrology studies#open access journals#nephritis#nephrology#juns
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Lupine Publishers | The Risk of Hospitalization due to COVID-19 in Patients with Inflammatory Bowel Disease
Abstract
Objectives: The novel coronavirus SARS-CoV2 became a worldwide pandemic in 2020. It is known that patients with inflammatory bowel disease (IBD) are at an increased risk of infection, particularly when on immunosuppressive therapy. The outcomes of COVID-19 in IBD patients remain somewhat unclear.
Methods: This Finnish retrospective observational cohort study enrolled 74 patients with an established IBD diagnosis and a confirmed COVID-19 infection. Patient data (age, sex, body mass index, IBD type, biochemical and clinical activity, comorbidities [Charlson comorbidity index [CCI]) and symptoms of COVID-19 were compared with hospitalization due to the COVID-19 infection.
Results: We found that older age (p < 0.01) and comorbidities (CCI score higher than one [p < 0.01]) were associated with hospitalization due to COVID-19 infection. In contrast, none of the studied pharmacological treatments for IBD, IBD type or disease activity were associated with a higher risk of hospitalization.
Conclusion: Our study shows that comorbidities and older age are associated with hospitalization due to COVID-19. On the other hand, different pharmacological treatments for IBD were not linked to a higher risk of hospitalization.
Keywords:Inflammatory bowel diseases; Crohn’s disease; Ulcerative Colitis; COVID-19; Immunosuppressive Treatment
Introduction
The coronavirus pandemic is a worldwide health crisis brought on by severe acute respiratory syndrome coronavirus 2 (SARS CoV 2), which causes a COVID-19 (coronavirus disease 2019) infection [1]. The disease has continued to spread globally and was classified as a pandemic on 11 March 2020, by the World Health Organization [2]. Clinical symptoms in COVID-19 vary between patients, but most individuals have a mild form of the disease with no or flu-like symptoms, including a dry cough, fever, runny nose and fatigue. Additional symptoms may comprise shivering, throat pain, anosmia, headache, joint pain, nausea and diarrhoea [3,4]. In more severe forms of the disease, marked inflammation and progressive pneumonia occur, leading to difficulties in breathing. A COVID-19 infection has often proved to be more severe in patients over 60 years of age. Furthermore, most patients with COVID-19 requiring hospitalization or intensive care unit (ICU) admission have been shown to have at least one comorbidity, such as chronic lung or heart disease, diabetes or conditions that affect their immune system [5]. In addition, smokers have been suggested to develop more severe symptoms of COVID-19 and are more likely to be admitted to intensive care, to need mechanical ventilation or to die than to non-smokers [6].
The treatment of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), frequently includes immunosuppressant medications [7-10]. The immunomodulators commonly used in IBD are corticosteroids, thiopurines, methotrexate, calcineurin inhibitors, anti-tumour necrosis factor agents or other biologicals. Their modes of action differ from each other, but they all compromise, to some extent, the patient’s immune response [11]. This may increase the patient’s risk of viral and bacterial infections and adverse outcomes of COVID-19 [12,13]. However, published data on possible associations of immunosuppressive therapy with severe COVID-19 remain inconsistent. Data extracted from the international registry Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD; 1,439 cases, 112 with severe COVID-19) suggest an increased risk with thiopurines either combined with biologicals or as a monotherapy [14], whereas data from the French national health system (268,185 IBD patients, 600 hospitalizations) indicate no such association [15]. So far, there is no clear evidence for an increased risk of more severe outcomes in patients with IBD in the context of COVID-19. This study aimed to describe how COVID-19 presents and evolves in patients with IBD and to identify potential risk factors that may predict the severity and outcomes of a COVID-19 infection in IBD patients.
Methods
This was a retrospective, observational cohort study. All eligible patients were adults (18 years and older) with an established diagnosis of CD or UC and a confirmed diagnosis of COVID-19, which was defined as the PCR-confirmed presence of the SARS-CoV-2 genome in a nasopharyngeal swab. The Hospital District of Helsinki and Uusimaa is the largest hospital district in Finland, covering a population of more than 1.7 million. The IBD registry is an integrated platform of the hospital patient data system and comprises 5,194 secondary or tertiary care patients with an IBD diagnosis, treated mostly with immunosuppressants and biologicals. We identified IBD patients with a COVID-19 diagnosis by performing a search combining the hospital district’s COVID-19 registry and the IBD registry. The more detailed patient and disease data were collected retrospectively from the patient electronic charts in April 2021. For all eligible patients, we collected the following data: age, sex, ethnicity, pregnancy, body mass index, IBD type, IBD duration, surgical IBD treatment, pharmacological IBD treatment, other comorbidities (expressed with the Charlson Comorbidity Index [CCI] [16] signs and symptoms of COVID-19 (fever, cough, dyspnoea, dysosmia/dysgeusia, pharyngitis, diarrhoea, arthralgia-myalgia/ asthenia, rhinitis, dysphonia, headache, abdominal pain, nausea/ vomiting, thrombosis), antibiotic and anticoagulant therapies for COVID-19, COVID-19 outcomes (hospitalization on a regular ward and in an ICU as well as death), and smoking status.
Data on faecal calprotectin (FC) as a surrogate marker of inflammation were recorded 0–6 months before the COVID-19 infection, during the COVID-19 infection and after the COVID-19 infection. Values considered to be normal for FC were < 200 μg/g [17,18]. The last registration on clinical activity of IBD was assessed based on patient charts. Clinical disease activity was determined according to the presence or absence of symptoms due to IBD (number of bowel movements, presence or absence of abdominal pain and presence of blood on defecation). The Charlson Comorbidity Index (CCI) is a validated and easily applicable method of estimating the disease severity and the risk of death from a comorbid disease. It has also been shown that a higher mean CCI score is significantly associated with mortality and disease severity in COVID-19 patients [19].
Statistical analysis
Statistical analysis was performed using the R software environment (version R-3.6.2). Differences in the hospitalization status and the studied variables were tested for significance using logistic regression, where the age and BMI of the patients served as confounding factors. Statistical significance was set at p < 0.05. The values are presented as numeric with percentage or as mean with SD.
Ethical considerations
Permission to conduct the study was received from the institutional review board of Helsinki University Hospital. As this was a retrospective, non-interventional patient records review study, no ethics committee approval was required.
Results
Study population
Between 29 January 2020 and 15 April 2021, 74 patients with IBD (CD n = 32 [43%], UC n = 42 [57%]) had been diagnosed with a COVID-19 infection. The patients’ baseline characteristics are shown in (Table 1). Within the six months prior to the COVID-19 infection, 18% (n = 13) of the CD patients and 18% (n = 13) of UC patients had an active IBD. Based on the available data, 22% (n = 7) of the CD and 24% (n = 10) of the UC patients had a biochemically active disease, whereas 28% (n = 9) of the CD and 19% (n = 8) of the UC patients had a clinically active disease. Six percent (n = 2) of the CD patients and 19% (n = 8) of the UC patients were not on any pharmacological treatment for IBD at the time of COVID-19 diagnosis. At the time of COVID-19 diagnosis, three patients (4%) were on systemic corticosteroid and thiopurine combination therapy; of these, only one UC patient was hospitalized on a regular ward and did not require ICU admission. We identified only one patient who was on concomitant medication with systemic corticosteroids, thiopurine and biologicals, and this patient was not hospitalized. Seven CD patients (22%) and eight UC patients (19%) were treated with thiopurine and biologicals, of these, one patient with CD and one with UC were hospitalized on a regular ward. Overall, two patients were pregnant, and neither of them was hospitalized. Nearly threequarters (72%, n = 23) of the CD patients and two-thirds (60%, n = 25) of the UC patients had no significant comorbidities (CCI 0). One comorbidity was present in 22% (n = 7) of the CD patients and in 19% (n = 8) of the UC patients. Hence, only 15% of all patients had two or more comorbidities. Seven patients (9%) had asthma, while none had been diagnosed with chronic obstructive pulmonary disease. For 36 patients, an FC value determined 0–6 months prior to the COVID-19 infection was available: the average value for CD patients was 279 μg/g and for UC patients 421 μg/g (FC range in all patients 5–1,600 μg/g, SD 482 μg/g). During the study period, 13 (18%) patients were hospitalized, four (5%) were admitted to an intensive care unit, and one patient died (Table 2). Except for the patient who eventually died, no-one needed mechanical ventilation. Among all hospitalized patients, the average number of days spent on a regular ward due to COVID-19 was 3.7 for CD, 6.3 for UC and 5.7 for all patients. Most patients (n = 62, 84%) were not on antibiotic therapy at the time of the COVID-19 infection. After the COVID-19 diagnosis had been established, 43% (n = 32) of all patients and 100% of those hospitalized received thrombosis prophylaxis.
COVID-19 symptoms
The most common COVID-19 symptoms, presented in Table 2, were cough (56%), rhino-pharyngitis (51%), fever (46%), headache (34%), dyspnoea (26%), diarrhoea (24%), arthralgia/myalgia (16%), dysosmia/dysgeusia (15%), flu-like symptoms (13%), abdominal pain (12%) and nausea/vomiting (9%). Five percent did not develop any symptoms due to the COVID-19 infection. No thromboembolic complications were diagnosed.
Factors predicting hospitalization
In all statistical analyses age, body mass index (BMI) and sex were examined simultaneously with the variable, and each variable was also examined alone. Increasing age was associated with a higher risk of hospitalization (p < 0.01), presented in (Figure 1A). With a CCI of two or more, the risk of hospitalization was significantly increased (p < 0.01 vs CCI 0–1), as seen in (Figure 1B). When the points for age were omitted from the CCI score, patients who had points due to an underlying medical condition were still more likely to be hospitalized (p < 0.01 vs no underlying medical condition).
Factors not predicting hospitalization
We could not demonstrate any significant association between BMI and risk of hospitalization, although there was a trend towards such a risk (p = 0.09). Interestingly, there was a significant association between BMI and hospitalization when one patient with a BMI of 54 was removed as an outlier (p = 0.02) (Figure 1C). Neither sex nor IBD type (UC or CD) had a significant impact on COVID-19 outcomes. There was no significant difference in hospitalizations among patients on biological medication, thiopurines or systemic corticosteroids, nor among patients who were taking any of the said medications as a combined therapy.
Discussion
Our study, which aimed at identifying risk factors for COVID-19 in IBD patients confirms previous findings indicating an association between hospitalization and both comorbidities and older age. Importantly, the use of any medication as maintenance therapy for IBD was not associated with an increased risk of a more severe COVID-19 infection or an undesirable outcome. The data of SECURE-IBD are likely to drive treatment recommendations for IBD during the COVID-19 pandemic. Immunosuppressive medications, especially thiopurines, used to treat IBD may result in a degree of immunosuppression, which has been hypothesized to lead to a more severe COVID-19 infection. Most of the patients in the IBD registry were on immunosuppressive treatment and were therefore thought to be at a higher risk of a severe COVID-19 infection. A recently published review article by Al-Ani and colleagues encourages the continuing of usual maintenance medications and highlights the importance of avoiding corticosteroids [20]. The finding of our study are in line with previous studies. In the case of an IBD flare-up, the risks and benefits of the treatments should be carefully discussed with the patient. More severe COVID-19 has been associated with older age and obesity [21-24]. Moreover, earlier studies have shown male sex to be a risk factor for more severe COVID-19 [25,26]. In the present study no significant association between sex and a higher risk of hospitalization was found. In the context of obesity, it is believed that the excess amount of adipose tissue causes inflammation and an impairment in the immune response. However, no significant correlation between BMI and the risk of hospitalization was found in our study. On the other hand, we found a significant association between age and hospitalization. It has been previously reported in studies of the general population that patients with comorbidities have a higher risk of more severe COVID-19 symptoms [27,28]. This was also seen in our population of IBD patients. Brenner and colleagues have found that increased age, comorbidities and, contrary to our study, also systemic corticosteroids are associated with severe COVID-19 in IBD patients [29].
Between 29 January 2020, when the first COVID-19 case in Finland was confirmed, and 15 April 2021, a total of 48,438 cases had been reported in the Hospital District of Helsinki and Uusimaa, which constitutes 2.8% of the population of 1.7 million [30]. In the present study, we identified 74 (1.4%) out of 5,194 patients in the IBD registry with a confirmed COVID-19 diagnosis since the beginning of the pandemic. The proportion of IBD patients with confirmed COVID-19 is less than half of the corresponding proportion of the general population of the same geographical area. Earlier studies have indicated that patients with IBD are at risk of serious opportunistic infections, particularly when they are treated with immunosuppressive medication. However, the findings of our study suggest that patients with IBD are not at a higher risk of contracting the SARS-COV-2 than the general population. This could be partly explained by a more rigorous hygiene routine. The patients in the Uusimaa Region have received detailed hygiene and health instructions from the specialized IBD nurses since the beginning of the pandemic. In the future, more data are needed on the social impact that the pandemic may have had on these immunocompromised patients. This study has some limitations. Firstly, the number of patients was limited as the incidence of COVID-19 in Finland has remained relatively low. Secondly, the lack of data in the patient records made it challenging to find variables associated with an unfavorable outcome and a higher risk of hospitalization. Additionally, during the pandemic, patients have tended not to attend scheduled laboratory follow-up tests, resulting in missing data. Despite these limitations, we believe that this study reflects well the real-life situation in clinical practice and provides important data on the COVID-19 infection in the IBD population.
The present study also has several strengths. Firstly, as the COVID-19 registry of the hospital district covers all reported cases in the region, it is extremely unlikely that a COVID-19-positive patient included in the IBD registry would have been missed in our search. Secondly, this study was performed in a country with a high IBD prevalence of one percent of the population [31] and with, consistent IBD treatment patterns and active patient organization counselling in place. All patients have equal access to treatment, and most hospital districts have specialized nurses who are trained to treat patients with IBD and advise them on travelling, vaccinations and hygiene. The observation period of this study mainly took place before the national vaccinations against COVID-19 started. Although no vaccine data is available for this study population, the number of COVID-19-vaccinated patients can be neglected, as IBD patients on immunosuppressive therapy were among the groups to receive the vaccine, starting from mid-April 2021. Some of the newest COVID-19 strains that have emerged after the data collection for this study have been found to be more infectious and linked to a higher mortality rate. Future studies will show whether the outcome of COVID-19 will differ from today’s studies.
Conclusion
This is the first report on the characteristics and outcomes of COVID-19 in patients with IBD in Finland, a country with a high prevalence of IBD and low prevalence of COVID-19. We found that comorbidities and older age were associated with a negative COVID-19 outcome such as hospitalization. On the other hand, immunosuppressive treatment for IBD was not associated with the risk of hospitalization or death. The lower incidence of COVID-19 infections among IBD patients in comparison to the general population may be explained by the rigorous hygiene measures undertaken particularly by patients on immunosuppressive therapy.
Author Contributions
Statement of authorship: study design (MK, PM, Ca B, PA), statistical analysis (JJ, JA), initial manuscript drafting (MK), critical revision and final approval (all authors).
Funding
The authors received no specific grant for this research. Patient involvement and patient consent for publication. Patients were not involved in the design, conduct reporting or dissemination plans of this research. Patient consent was not required.
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