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BioRxiv : the Preprint Server For... Aug 2023Despite extensive human use of the inhalation route for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods...
RATIONALE
Despite extensive human use of the inhalation route for ingesting opioids, models in rodents have mostly been limited to parenteral injection and oral dosing. Methods using electronic drug delivery systems (EDDS; "e-cigarettes") have shown efficacy in rodent models but these do not faithfully mimic the most popular human inhalation method of heating heroin to the point of vaporization.
OBJECTIVE
This study was designed to determine if direct volatilization of heroin hydrochloride delivers effective heroin doses to rodents.
METHODS
Middle aged rats were exposed to vapor created by direct heating of heroin HCl powder in a ceramic e-cigarette type atomizer. Efficacy was determined with a warm water tail withdrawal nociception assay, rectal temperature and self-administration.
RESULTS
Ten minutes of inhalation of vaporized heroin slowed response latency in a warm water tail withdrawal assay and increased rectal temperature in male rats, in a dose-dependent manner. Similar antinociceptive effects in female rats were attenuated by the opioid antagonist naloxone (1.0 mg/kg, s.c.). Female rats made operant responses for heroin vapor in 15-minute sessions, increased their response rate when the reinforcement ratio increased from FR1 to FR5, and further increased their responding when vapor delivery was omitted. Anti-nociceptive effects of self-administered volatilized heroin were of a similar magnitude as those produced by the 10-minute non-contingent exposure.
CONCLUSIONS
This study shows that "chasing the dragon" methods of inhalation of heroin can be modeled successfully in the rat. Inhalation techniques may be particularly useful for longer term studies deep into middle age of rat species.
PubMed: 37786688
DOI: 10.1101/2023.08.09.552712 -
International Journal of Colorectal... May 2024A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that... (Observational Study)
Observational Study
BACKGROUND AND AIMS
A high number of topical products are available for the treatment of hemorrhoidal symptoms. Sucralfate-based topical products constitute a new treatment alternative that act as a mechanical barrier to facilitate healing. The aim of this prospective, observational study was to determine patient- and physician-assessed effectiveness and tolerability of rectal ointment and suppositories containing sucralfate for the treatment of hemorrhoidal symptoms in routine clinical practice.
METHODS
Adult patients with diagnosed, mild-to-moderate, symptomatic non-bleeding hemorrhoids treated with rectal ointment or suppositories containing sucralfate were enrolled. Patients were administered treatment twice per day for at least 1 week until symptom resolution and/or for a maximum of 4 weeks. The primary endpoint was patient-assessed effectiveness on a modified Symptom Severity Score (mSSS, range 0 to 14). Physician-assessed effectiveness (9 symptoms, 0 to 5 Likert scale), hemorrhoid grade, and patient satisfaction were also determined.
RESULTS
Five investigators enrolled 60 patients; mean age was 48.4 ± 16.6 years and 72.4% were female. Pain or pressure sensitivity was reported as the most severe symptom by patients, and pressure sensitivity, discharge, soiling, and prolapse by physicians. Mean patient-assessed mSSS at baseline was 6.6 ± 1.9 and was significantly improved overall and in the ointment and suppository groups individually by -4.6 ± 2.0, -4.4 ± 1.8, and -4.8 ± 2.2, respectively (p < 0.0001). Investigator-assessed mean baseline symptom score was 18.1 ± 3.9 and improved by -7.1 ± 4.5, -6.9 ± 5.4, and -7.3 ± 3.5, respectively (p < 0.0001). Investigator-assessed symptoms of pressure sensitivity, swelling, and discharge were improved to the greatest extent. Hemorrhoid grade was improved in 38% of patients at the end of treatment. Compliance with treatment was 97.4% and patient satisfaction with application and onset of action was high (81.3% and 76.2%, respectively). Both the ointment and suppository were well tolerated.
CONCLUSIONS
The effectiveness of topical ointment or suppository containing sucralfate on patient- and investigator-assessed hemorrhoidal symptoms in real-life clinical practice was demonstrated. Patient satisfaction was high and treatments were well tolerated. Larger controlled trials are warranted to confirm the results.
Topics: Humans; Sucralfate; Hemorrhoids; Female; Suppositories; Male; Middle Aged; Ointments; Prospective Studies; Treatment Outcome; Patient Satisfaction; Adult; Aged; Administration, Rectal
PubMed: 38750150
DOI: 10.1007/s00384-024-04642-7 -
Zhongguo Ying Yong Sheng Li Xue Za Zhi... Dec 2023Mucoadhesive polymers are a new and exciting development in drug delivery systems that have the potential to significantly increase therapeutic efficacy. These polymers... (Review)
Review
Mucoadhesive polymers are a new and exciting development in drug delivery systems that have the potential to significantly increase therapeutic efficacy. These polymers stick to mucosal surfaces, increasing the amount of time that medications stay at the site of absorption and improving their bioavailability. These mechanisms include longer contact times with the mucosal surface, better drug solubility, and defence against enzymatic degradation of pharmaceuticals. Mucoadhesive polymers also provide a number of benefits over traditional drug delivery methods, including less frequent dosage, better patient compliance, and fewer adverse effects. Due to their adaptability, Mucoadhesive polymers may be used in the rectal, vaginal, ophthalmic, nasal, and oral routes of drug delivery. Mucoadhesive polymers have advantages now, but they also have potential for the future of medication delivery. Mucoadhesion offers excellent possibilities for the delivery of a range of substances through the nasal, vaginal, buccal, and ocular routes of administration. Furthermore, mucoadhesion facilitates the achievement of an extended local or systemic pharmacological effect. In this study, we covered the mechanisms behind mucoadhesion, possible uses for Mucoadhesive polymers in drug administration, and techniques for assessing Mucoadhesive drug delivery systems. The goal of current research is to create innovative Mucoadhesive polymers that have better biodegradability, biocompatibility, and adhesive qualities. Moreover, it is anticipated that the effectiveness of Mucoadhesive polymers would be increased when combined with other cutting-edge drug delivery technologies, such as micro particles and nanoparticles.
Topics: Humans; Adhesiveness; Drug Delivery Systems; Mucous Membrane; Polymers
PubMed: 38751344
DOI: 10.62958/j.cjap.2023.005 -
JAMA Surgery Jun 2024Surgical site infections (SSIs)-especially anastomotic dehiscence-are major contributors to morbidity and mortality after rectal resection. The role of mechanical and... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Surgical site infections (SSIs)-especially anastomotic dehiscence-are major contributors to morbidity and mortality after rectal resection. The role of mechanical and oral antibiotics bowel preparation (MOABP) in preventing complications of rectal resection is currently disputed.
OBJECTIVE
To assess whether MOABP reduces overall complications and SSIs after elective rectal resection compared with mechanical bowel preparation (MBP) plus placebo.
DESIGN, SETTING, AND PARTICIPANTS
This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 3 university hospitals in Finland between March 18, 2020, and October 10, 2022. Patients aged 18 years and older undergoing elective resection with primary anastomosis of a rectal tumor 15 cm or less from the anal verge on magnetic resonance imaging were eligible for inclusion. Outcomes were analyzed using a modified intention-to-treat principle, which included all patients who were randomly allocated to and underwent elective rectal resection with an anastomosis.
INTERVENTIONS
Patients were stratified according to tumor distance from the anal verge and neoadjuvant treatment given and randomized in a 1:1 ratio to receive MOABP with an oral regimen of neomycin and metronidazole (n = 277) or MBP plus matching placebo tablets (n = 288). All study medications were taken the day before surgery, and all patients received intravenous antibiotics approximately 30 minutes before surgery.
MAIN OUTCOMES AND MEASURES
The primary outcome was overall cumulative postoperative complications measured using the Comprehensive Complication Index. Key secondary outcomes were SSI and anastomotic dehiscence within 30 days after surgery.
RESULTS
In all, 565 patients were included in the analysis, with 288 in the MBP plus placebo group (median [IQR] age, 69 [62-74] years; 190 males [66.0%]) and 277 in the MOABP group (median [IQR] age, 70 [62-75] years; 158 males [57.0%]). Patients in the MOABP group experienced fewer overall postoperative complications (median [IQR] Comprehensive Complication Index, 0 [0-8.66] vs 8.66 [0-20.92]; Wilcoxon effect size, 0.146; P < .001), fewer SSIs (23 patients [8.3%] vs 48 patients [16.7%]; odds ratio, 0.45 [95% CI, 0.27-0.77]), and fewer anastomotic dehiscences (16 patients [5.8%] vs 39 patients [13.5%]; odds ratio, 0.39 [95% CI, 0.21-0.72]) compared with patients in the MBP plus placebo group.
CONCLUSIONS AND RELEVANCE
Findings of this randomized clinical trial indicate that MOABP reduced overall postoperative complications as well as rates of SSIs and anastomotic dehiscences in patients undergoing elective rectal resection compared with MBP plus placebo. Based on these findings, MOABP should be considered as standard treatment in patients undergoing elective rectal resection.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT04281667.
Topics: Humans; Male; Female; Double-Blind Method; Middle Aged; Surgical Wound Infection; Aged; Anti-Bacterial Agents; Rectal Neoplasms; Administration, Oral; Antibiotic Prophylaxis; Preoperative Care; Neomycin; Cathartics; Metronidazole; Proctectomy; Rectum; Surgical Wound Dehiscence; Elective Surgical Procedures
PubMed: 38506889
DOI: 10.1001/jamasurg.2024.0184 -
PloS One 2024The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the...
Testing for extragenital Neisseria gonorrhoeae and Chlamydia trachomatis: At-home pharyngeal and rectal self-swabs are non-inferior to those completed in healthcare settings.
INTRODUCTION
The rates of gonorrhea and chlamydia have been increasing in the years preceding the COVID19 pandemic. Because most gonorrhea and chlamydia infections are located in the oropharynx and rectum for men who have sex with men (MSM), and because at-home self-collected swabs for these infections are not licensed by Health Canada or the United States Food and Drug Administration, decreased accessed to in-person care during and since the COVID19 pandemic potentially means missed case findings.
OBJECTIVES
To evaluate the performance of at-home self-collected pharyngeal and rectal swabs for gonorrhea and chlamydia nucleic acid amplification testing.
METHODOLOGY
All persons who contacted our Sexual Health Clinic and who had a clinical indication to complete oral and/or rectal swabs for gonorrhea and chlamydia were invited to complete at-home swabs in advance of their scheduled appointments. We mailed swabs and instructions to those who consented. Participants brought these swabs to their scheduled in clinic appointments, where we repeated the same swabs. All matching swabs were sent to the laboratory for analysis to determine concordance.
RESULTS
From September 8, 2022 to July 18, 2023, we enrolled 296 eligible participants who provided 1184 swabs. For analysis, cancelled specimens and specimens with invalid results were excluded, leaving 1032 swabs for comparison. We identified 66 STI diagnoses in 47 unique participants. Overall accuracy was high (exceeding 99%), except for rectal chlamydia, which was 96.0%. While the performance of self-swabs for chlamydia was lower compared to gonorrhea, at-home swabs identified six chlamydia infections that were missed by in-clinic collected swabs (two pharyngeal, four rectal). Removing these six cases as "false positives" increased overall accuracy for chlamydia detection to 99.7% (pharyngeal) and 97.8% (rectal).
CONCLUSION
Self-collected at-home swabs had good performance acceptable for gonorrhea and chlamydia nucleic acid amplification testing.
Topics: Humans; Chlamydia trachomatis; Chlamydia Infections; Gonorrhea; Male; Neisseria gonorrhoeae; Rectum; Pharynx; Specimen Handling; Adult; Female; Nucleic Acid Amplification Techniques; Homosexuality, Male; Middle Aged; Self Care; Young Adult
PubMed: 38768150
DOI: 10.1371/journal.pone.0302785 -
Journal of Cancer Research and... Oct 2023The incidence of colorectal cancer in young adults is on an increasing trend. It is observed that this subgroup of patients has an aggressive disease and carries a...
INTRODUCTION
The incidence of colorectal cancer in young adults is on an increasing trend. It is observed that this subgroup of patients has an aggressive disease and carries a poorer prognosis compared to its older counterpart. This study aimed to analyze the incidence, treatment outcome, and prognostic factors in adolescents and young adults with rectal cancer attending a tertiary cancer center in North India.
MATERIALS AND METHODS
We retrospectively analyzed 50 patients of histologically proven rectal cancer, aged up to 30 years, treated at our center between 2015 and 2019. The clinical, demographic, and pathological parameters were studied in all these patients. Kaplan-Meier survival analysis was used to find out survival. Univariate analysis was performed to assess prognostic factors.
RESULTS
The incidence was 26.4% at our center with a median age of 28 years. Bleeding per rectum was the commonest complaint. Most of them had signet ring cell histology (26%). The median overall survival was 16 months. Survival was significantly better in patients having bleeding per rectum as an initial complaint (P = 0.009), absence of lymphovascular invasion (LVI) (P = 0.005), and perineural invasion (PNI) (P = 0.002), who received complete planned treatment compared to patients who could not receive either of the modality (P < 0.001). Patients who did not receive radiotherapy (RT) had the worst outcomes compared to those who received RT in any form. RT dose of 50.4 Gy was found to be superior as compared to other schedules. There was no significant difference in survival with gender, tumor stage, grade, type of surgery, or chemotherapy regimen.
CONCLUSION
The majority of patients presented in an advanced stage. Therefore, bleeding per rectum should be properly and timely investigated in all these young patients. Early detection and complete treatment are paramount to improving the outcome.
Topics: Young Adult; Humans; Adolescent; Aged; Adult; Retrospective Studies; Treatment Outcome; Rectal Neoplasms; Administration, Rectal; Gastrointestinal Hemorrhage
PubMed: 38376310
DOI: 10.4103/jcrt.jcrt_319_22 -
Gut Microbes 2024With an increasing interest in dietary fibers (DFs) to promote intestinal health and the growth of beneficial gut bacteria, there is a continued rise in the...
With an increasing interest in dietary fibers (DFs) to promote intestinal health and the growth of beneficial gut bacteria, there is a continued rise in the incorporation of refined DFs in processed foods. It is still unclear how refined fibers, such as guar gum, affect the gut microbiota activity and pathogenesis of inflammatory bowel disease (IBD). Our study elucidated the effect and underlying mechanisms of guar gum, a fermentable DF (FDF) commonly present in a wide range of processed foods, on colitis development. We report that guar gum containing diet (GuD) increased the susceptibility to colonic inflammation. Specifically, GuD-fed group exhibited severe colitis upon dextran sulfate sodium (DSS) administration, as evidenced by reduced body weight, diarrhea, rectal bleeding, and shortening of colon length compared to cellulose-fed control mice. Elevated levels of pro-inflammatory markers in both serum [serum amyloid A (SAA), lipocalin 2 (Lcn2)] and colon (Lcn2) and extensive disruption of colonic architecture further affirmed that GuD-fed group exhibited more severe colitis than control group upon DSS intervention. Amelioration of colitis in GuD-fed group pre-treated with antibiotics suggest a vital role of intestinal microbiota in GuD-mediated exacerbation of intestinal inflammation. Gut microbiota composition and metabolite analysis in fecal and cecal contents, respectively, revealed that guar gum primarily enriches Actinobacteriota, specifically . Guar gum also altered multiple genera belonging to phyla Bacteroidota and Firmicutes. Such shift in gut microbiota composition favored luminal accumulation of intermediary metabolites succinate and lactate in the GuD-fed mice. Colonic IL-18 and tight junction markers were also decreased in the GuD-fed group. Importantly, GuD-fed mice pre-treated with recombinant IL-18 displayed attenuated colitis. Collectively, unfavorable changes in gut microbiota activity leading to luminal accumulation of lactate and succinate, reduced colonic IL-18, and compromised gut barrier function following guar gum feeding contributed to increased colitis susceptibility.
Topics: Animals; Mice; Gastrointestinal Microbiome; Interleukin-18; Inflammation; Colitis; Dietary Fiber; Lactic Acid; Succinates; Galactans; Mannans; Plant Gums
PubMed: 38630030
DOI: 10.1080/19490976.2024.2341457 -
World Journal of Clinical Pediatrics Mar 2024Fever is a common cause of medical consultation and hospital admission, particularly among children. Recently, the United Kingdom's National Institute for Health and...
BACKGROUND
Fever is a common cause of medical consultation and hospital admission, particularly among children. Recently, the United Kingdom's National Institute for Health and Care Excellence (NICE) updated its guidelines for assessing fever in children under five years of age. The efficient assessment and management of children with fever are crucial for improving patient outcomes.
AIM
To evaluate fever assessment in hospitalized children and to assess its adherence with the NICE Fever in under 5s guideline.
METHODS
We conducted a retrospective cohort review of the electronic medical records of children under five years of age at the Department of Pediatrics, Salmaniya Medical Complex, Bahrain, between June and July 2023. Demographic data, vital signs during the first 48 h of admission, route of temperature measurement, and indications for admission were gathered. Fever was defined according to the NICE guideline. The children were divided into five groups according to their age (0-3 months, > 3-6 months, > 6-12 months, > 12-36 months, and > 36-60 months). Patients with and without fever were compared in terms of demography, indication for admission, route of temperature measurement, and other vital signs. Compliance with the NICE Fever in the under 5s guideline was assessed. Full compliance was defined as > 95%, partial compliance as 70%-95%, and minimal compliance as ≤ 69%. Pearson's , Student's test, the Mann-Whitney test, and Spearman's correlation coefficient (r) were used for comparison.
RESULTS
Of the 136 patients reviewed, 80 (58.8%) were boys. The median age at admission was 14.2 [interquartile range (IQR): 1.7-44.4] months, with the most common age group being 36-60 months. Thirty-six (26.4%) patients had fever, and 100 (73.6%) were afebrile. The commonest age group for febrile patients (> 12-36 months) was older than the commonest age group for afebrile patients (0-3 months) ( 0.027). The median weight was 8.3 (IQR: 4.0-13.3) kg. Patients with fever had higher weight than those without fever [10.2 (IQR: 7.3-13.0) 7.1 (IQR: 3.8-13.3) kg, respectively] ( = 0.034). Gastrointestinal disease was the leading indication for hospital admission ( = 47, 34.6%). Patients with central nervous system diseases and fever of unknown etiology were more likely to be febrile ( = 0.030 and = 0.011, respectively). The mean heart rate was higher in the febrile group than the afebrile group (140 ± 24 126 ± 20 beats per minute, respectively) [ = 0.001 (confidence interval: 5.8-21.9)] with a positive correlation between body temperature and heart rate, = 0.242, = 136, = 0.004. A higher proportion of febrile patients received paracetamol ( = 35, 81.3%) compared to the afebrile patients ( = 8, 18.6%) ( < 0.001). The axillary route was the most commonly used for temperature measurements ( = 40/42, 95.2%), followed by the rectal route ( = 2/42, 4.8%). The department demonstrated full compliance with the NICE guideline for five criteria: the type of thermometer used, route and frequency of temperature measurement, frequency of heart rate measurement, and use of antipyretics as needed. Partial compliance was noted for two criteria, the threshold of fever at 38 °C or more, and the respiratory rate assessment in febrile patients. Minimal compliance or no record was observed for the remaining three criteria; routine assessment of capillary refill, temperature reassessment 1-2 h after each antipyretic intake, and refraining from the use of tepid sponging.
CONCLUSION
This study showed that fever assessment in hospitalized children under five years of age was appropriate, but certain areas of adherence to the NICE guideline still need to be improved.
PubMed: 38596442
DOI: 10.5409/wjcp.v13.i1.88864 -
Animal : An International Journal of... Feb 2024In newborn ruminants, transfer of passive immunity is essential to obtain protection against pathogens. This study aimed to increase the permeability of the blood-milk...
In newborn ruminants, transfer of passive immunity is essential to obtain protection against pathogens. This study aimed to increase the permeability of the blood-milk barrier using intramammary lipopolysaccharides (LPS) in goats at parturition to modulate colostrum composition. Twenty multiparous Majorera dairy goats were randomly allocated in one of the two experimental groups. The LPS group (n = 10) received an intramammary administration (IA) of saline (2 mL) containing 50 µg of LPS from Escherichia coli (O55:B5) in each half udder at parturition. The control group (n = 10) received an IA of saline (2 mL). Rectal temperature (RT) was recorded, and a blood sample was collected at parturition (before IA). In addition, RT was measured, and blood and colostrum/milk samples were collected on day (d) 0.125 (3 hours), 0.5 (12 hours), 1, 2, 4, 7, 15 and 30 relative to the IA. Goat plasma immunoglobulin G (IgG) and M (IgM) and serum β-hydroxybutyrate, glucose, calcium, free fatty acids, lactate dehydrogenase and total protein concentrations were determined. Colostrum and milk yields as well as chemical composition, somatic cell count (SCC), IgG and IgM concentrations were measured. The MIXED procedure (SAS 9.4) was used, and the model included the IA, time, and the interaction between both fixed effects. Statistical significance was set as P < 0.05. Goats from the LPS group showed higher RT on d 0.125, 0.5 and 4 relative to the IA compared to the control group (P = 0.007). Goat serum biochemical variables and plasma IgG and IgM concentrations were not affected by the IA. Colostrum and milk yield as well as chemical composition were not affected by the IA, except for milk lactose percentage that was lower in the LPS group compared to the control group (4.3 ± 0.08 and 4.6 ± 0.08%, respectively P = 0.026). Colostrum SCC was higher in the LPS group than in the control group (3.5 ± 0.09 and 3.1 ± 0.09 cells × 10/mL, respectively; P = 0.011). Similarly, milk SCC increased in the LPS group compared to the control group (P = 0.004). The LPS group showed higher IgG (P = 0.044) and IgM (P = 0.037) concentrations on colostrum than the control group (31.9 ± 4.8 and 19.0 ± 4.8 mg/mL, 0.8 ± 0.08 and 0.5 ± 0.08 mg/mL, respectively). No differences in milk IgG and IgM concentrations between groups were observed. In conclusion, the IA of LPS at parturition increases RT, SCC and IgG and IgM concentrations in colostrum without affecting either yield or chemical composition.
Topics: Pregnancy; Female; Animals; Colostrum; Lipopolysaccharides; Goats; Lactation; Parturition; Milk; Immunoglobulin G; Immunoglobulin M
PubMed: 38320347
DOI: 10.1016/j.animal.2024.101082