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Expert Opinion on Biological Therapy Aug 2010There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and... (Review)
Review
IMPORTANCE OF THE FIELD
There are currently over thirty million people infected with HIV and there are no vaccines available to prevent HIV infections or disease. The genitourinary, rectal and oral mucosa are the mucosal HIV transmission routes. An effective vaccine that can induce both systemic and local mucosal immunity is generally accepted as a major means of protection against mucosal HIV transmission and AIDS.
WHAT THE READER WILL GAIN
Structure and cells that comprise the oral, vaginal and rectal mucosa pertaining to HIV transmission and vaccination strategies through each mucosal route to prevent mucosal and systemic infection will be discussed.
AREAS COVERED IN THIS REVIEW
Covering publications from 1980s through 2010, mucosal transmission of HIV and current and previous approaches to vaccinations are discussed.
TAKE HOME MESSAGE
Although oral transmission of HIV is far less common than vaginal and rectal transmissions, infections through this route do occur through oral sex as well as vertically from mother to child. Mucosal vaccination strategies against oral and other mucosal HIV transmissions are under intensive research but the lack of consensus on immune correlates of protection and lack of safe and effective mucosal adjuvants and delivery systems hamper progress towards a licensed vaccine.
Topics: AIDS Vaccines; Administration, Intravaginal; Administration, Oral; Administration, Rectal; Animals; Female; HIV Infections; Humans; Immunity, Mucosal; Intestinal Mucosa; Male; Mouth Mucosa; Mucous Membrane
PubMed: 20624114
DOI: 10.1517/14712598.2010.496776 -
The Cochrane Database of Systematic... Feb 2014Primary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Primary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries.
OBJECTIVES
To assess the effectiveness and safety of any intervention used for the treatment of primary PPH.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013).
SELECTION CRITERIA
Randomised controlled trials comparing any interventions for the treatment of primary PPH.
DATA COLLECTION AND ANALYSIS
We assessed studies for eligibility and quality and extracted data independently. We contacted authors of the included studies to request more information.
MAIN RESULTS
Ten randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review.Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41). Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering.Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes.One study compared lower segment compression but was too small to assess impact on primary outcomes.We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics.
AUTHORS' CONCLUSIONS
Clinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit.The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.
Topics: Administration, Rectal; Ergonovine; Female; Humans; Hysterectomy; Maternal Mortality; Misoprostol; Oxytocics; Oxytocin; Postpartum Hemorrhage; Pregnancy; Randomized Controlled Trials as Topic
PubMed: 24523225
DOI: 10.1002/14651858.CD003249.pub3 -
Digestion 2012Due to misunderstandings about their effectiveness and feasibility, topical (or rectal) therapies with aminosalicylates (5-aminosalicylic acid, 5-ASA) and steroids are... (Review)
Review
Due to misunderstandings about their effectiveness and feasibility, topical (or rectal) therapies with aminosalicylates (5-aminosalicylic acid, 5-ASA) and steroids are often underused in patients with ulcerative colitis (UC). However, many of these patients could be treated solely with rectal/topical therapies, or could benefit from them in combination with oral therapies. We review the evidence for topical therapies containing 5-ASA and budesonide in UC and discuss how these therapies can be optimized in daily practice, thereby improving compliance. Finally, we provide a brief summary of studies on the use of other topical treatments in UC, the results of which were both promising and negative.
Topics: Administration, Rectal; Anti-Inflammatory Agents; Budesonide; Colitis, Ulcerative; Drug Therapy, Combination; Enema; Guideline Adherence; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Mesalamine; Patient Compliance; Practice Guidelines as Topic; Suppositories
PubMed: 23051725
DOI: 10.1159/000341947 -
PloS One 2022This study aims to evaluate the efficacy and safety of oxycodone hydrochloride (OxyContin) rectal administration in cancer pain patients. This is geared towards... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to evaluate the efficacy and safety of oxycodone hydrochloride (OxyContin) rectal administration in cancer pain patients. This is geared towards providing the research evidence for a novel route of OxyContin administration.
METHODS
Relevant randomized controlled trials (RCTs) were searched in electronic databases, including PubMed, Cochrane Library, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP database), Wanfang Data Knowledge Service Platform, and Chinese Biomedical Literature Database (CBM). Moreover, unpublished academic data were obtained by contacting the colleague, professor, or Institute of Traditional Chinese Medicine. The RCTs of transrectal Oxycodone administration of sustained-release tablets for moderate and severe pain patients were searched in the databases from inception to December 2020.
RESULTS
According to the inclusion criteria, a total of 8 RCTs were included, with a total of 648 patients. Meta analysis results showed that there was no statistically significant difference in the efficacy of moderate to severe pain control between the rectal administration group and the oral administration group (RR = 1.04, 95%CI: 0.99-1.10, p = 0.13>0.05). At the same time, the incidence of adverse reactions in the rectal administration group was low. In terms of constipation, the rectal administration group was less than the oral administration group, with a statistically significant difference (RR = 0.43, 95%CI: 0.31-0.58, p< 0.00001). In terms of nausea and vomiting, the rectal administration group was less than the oral administration group, and the difference was statistically significant(RR = 0.30, 95%CI: 0.21-0.42, p<0.00001). In terms of sleepiness, there was no significant difference between the two groups(RR = 0.54, 95%CI: 0.26-1.15, p = 0.11>0.05). In terms of dizziness, there was no statistically significant difference between the two groups (RR = 0.43, 95%CI:0.27-0.68, p = 0.31>0.05). In terms of dyuria, there was no statistically significant difference between the two groups (RR = 0.37, 95%CI: 0.02-7.02, p = 0.51>0.05). In terms of KPS scores there was no significant difference was noted between the rectal and oral administration groups (RR = 1.04, 95%CI: 0.89-1.21, p = 0.63>0.05).
CONCLUSION
In summary, we found no significant differences in efficacy between rectal administration of OxyContin and oral administration. Thus, rectal administration should be considered in managing cancer pain among patients with difficulty in oral OxyContin administration.
PROSPERO REGISTRATION NUMBER
CRD42021209660.
Topics: Administration, Rectal; Cancer Pain; Delayed-Action Preparations; Humans; Oxycodone; Pain
PubMed: 35759471
DOI: 10.1371/journal.pone.0266754 -
Drug Delivery and Translational Research Dec 2017Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e.,... (Review)
Review
Sexual intercourse (vaginal and anal) is the predominant mode of human immunodeficiency virus (HIV) transmission. Topical microbicides used in an on-demand format (i.e., immediately before or after sex) can be part of an effective tool kit utilized to prevent sexual transmission of HIV. The effectiveness of prevention products is positively correlated with adherence, which is likely to depend on user acceptability of the product. The development of an efficacious and acceptable product is therefore paramount for the success of an on-demand product. Acceptability of on-demand products (e.g., gels, films, and tablets) and their attributes is influenced by a multitude of user-specific factors that span behavioral, lifestyle, socio-economic, and cultural aspects. In addition, physicochemical properties of the drug, anatomical and physiological aspects of anorectal and vaginal compartments, issues relating to large-scale production, and cost can impact product development. These factors together with user preferences determine the design space of an effective, acceptable, and feasible on-demand product. In this review, we summarize the interacting factors that together determine product choice and its target product profile.
Topics: Administration, Rectal; Administration, Topical; Anti-Infective Agents; Clinical Trials as Topic; Female; HIV Infections; Humans; Male; Patient Compliance; Patient Preference; Sexual Behavior; Vaginal Creams, Foams, and Jellies
PubMed: 28589452
DOI: 10.1007/s13346-017-0385-4 -
Drug Testing and Analysis Nov 2022The rectal administration of glucocorticoids, as well as any injectable, and oral ones, is currently prohibited by the World Anti-Doping Agency when occurs "in...
The rectal administration of glucocorticoids, as well as any injectable, and oral ones, is currently prohibited by the World Anti-Doping Agency when occurs "in competition." A reporting level of 100 ng/ml for prednisolone and 300 ng/ml for prednisone was established to discriminate the allowed and the prohibited administration. Here, the urinary excretion profiles of prednisone and prednisolone were evaluated in five volunteers in therapy with glucocorticoid-based rectal formulations containing prednisone or prednisolone caproate. The urinary levels of the excreted target compounds were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following the procedure validated and currently in use in our laboratory to detect and quantitate glucocorticoids in urine. Predictably, the excretion trend of the analytes of interest were generally comparable with those obtained after oral administration, even if the excretion profile showed a broad interindividual variability, with the absorption rate and the systemic bioavailability after rectal administration being strongly influenced by the type of formulations (suppository or rectal cream, in our case) as well as the physiological conditions of the absorption area. Results showed that the target compounds were detectable for at least 30 h after drug administration. After suppository administration, prednisolone levels reached the maximum after 3 h from drug administration and then dropped below the reporting level after 15-21 h; prednisone reached the maximum after 3 h from drug administration, and then dropped below the reporting level after 12-15 h. After cream administration, both prednisone and prednisolone levels remained in a concentration below the reporting level throughout the entire monitored period.
Topics: Humans; Prednisolone; Prednisone; Chromatography, Liquid; Administration, Rectal; Tandem Mass Spectrometry; Glucocorticoids; Administration, Oral
PubMed: 35921255
DOI: 10.1002/dta.3352 -
The Cochrane Database of Systematic... May 2014Severe or complicated malaria is a medical emergency and people die as a result of delays in starting treatment. Most patients need parenteral treatment, and in primary... (Review)
Review
BACKGROUND
Severe or complicated malaria is a medical emergency and people die as a result of delays in starting treatment. Most patients need parenteral treatment, and in primary healthcare facilities, where intravenous therapy is not available but intramuscular injections can be given, intramuscular quinine, artesunate, and artemether have been used before transporting patients to hospital.However, in rural settings with limited access to health care, intramuscular injections may also be unavailable. In these situations, rectal artesunate given prior to transfer to hospital by volunteers with little medical training, may be a feasible option.
OBJECTIVES
To evaluate the effects of pre-referral treatment with rectal artesunate on mortality and morbidity in people with severe malaria.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) published in The Cochrane Library; MEDLINE; EMBASE and LILACS up to 21 May 2014. We also searched the WHO clinical trial registry platform and the metaRegister of Controlled Trials (mRCT) for ongoing trials.
SELECTION CRITERIA
Individual or cluster-randomized controlled trials comparing pre-referral rectal artesunate with placebo or injectable antimalarials in children and children with severe malaria.
DATA COLLECTION AND ANALYSIS
Two authors independently screened titles and abstracts for potentially eligible trials, and extracted data from the included trials. Dichotomous outcomes were summarized using risk ratios (RR) and presented with 95% confidence intervals (95% CI). Where data allowed, we conducted subgroup analyses by age, trial region and whether participants were included in the trial analysis. We assessed the quality of evidence for the most important outcomes using the GRADE approach.
MAIN RESULTS
One trial met the inclusion criteria; a placebo-controlled trial of 17,826 children and adults living in rural villages in Ghana and Tanzania (Africa) and Bangladesh (Asia). Villagers with no previous medical training were trained to recognize the symptoms of severe malaria, administer rectal artesunate and refer patients to hospital. The trained villagers were supervised during the trial period. In the African sites only children aged 6 to 72 months were enrolled, whereas in Bangladesh, older children and adults were also enrolled.In young children (aged 6 to 72 months) there were fewer deaths following rectal artesunate than with placebo (RR 0.74; 95% CI 0.59 to 0.93; one trial; 8050 participants; moderate quality evidence), while in older children and adults there were more deaths in those given rectal artesunate (RR 2.21; 95% CI 1.18 to 4.15; one trial; 4018 participants; low quality evidence).In Africa, only 56% of participants reached a secondary healthcare facility within six hours compared to over 90% in Asia. There were no differences between the intervention and control groups in the proportion of participants reaching a healthcare facility within six hours (RR 0.99; 95% CI 0.98 to 1.01; 12,068 participants), or in the proportion with parasitaemia (RR 1.00; 95% CI 0.98 to 1.02; 17,826 participants), or with coma or convulsions on arrival (RR 1.01; 95% CI 0.90 to 1.14; 12,068 participants).There are no existing trials that compare rectal versus intramuscular artesunate.
AUTHORS' CONCLUSIONS
In rural areas without access to injectable antimalarials rectal artesunate provided before transfer to a referral facility probably reduces mortality in severely ill young children compared to referral without treatment. However, the unexpected finding of possible higher mortality in older children and adults has to be taken into account in forming any national or local policies about pre-referral rectal artesunate.
Topics: Administration, Rectal; Adult; Age Factors; Antimalarials; Artemisinins; Artesunate; Bangladesh; Child; Child, Preschool; Emergency Medical Services; Ghana; Humans; Infant; Malaria; Rural Health; Tanzania
PubMed: 24869943
DOI: 10.1002/14651858.CD009964.pub2 -
Epilepsia Mar 2020The study assesses the bioavailability of diazepam after intranasal administration (diazepam nasal spray) in healthy volunteers. Comparative agents were diazepam rectal... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The study assesses the bioavailability of diazepam after intranasal administration (diazepam nasal spray) in healthy volunteers. Comparative agents were diazepam rectal gel, which served as the regulatory reference product; and oral diazepam, a product with decades of clinical use. Tolerability of diazepam nasal spray was also assessed.
METHODS
This was a phase 1, open-label, randomized, single-dose, three-treatment, three-period, six-sequence crossover study in 48 healthy adult subjects that consisted of a screening period, a baseline period, and an open-label treatment period. Interperiod intervals were at least 28 days.
RESULTS
Forty-eight healthy volunteer subjects were enrolled, two of whom discontinued before receiving study medication. For all routes of administration, the onset of diazepam absorption was rapid, with measurable concentrations of drug present by the first sample time point. The t (time to reach maximum plasma concentration) was similar for diazepam nasal spray and diazepam rectal gel, both of which were slower than oral diazepam in fasted individuals. Variability (as defined by % coefficient of variation of geometric mean) in peak plasma concentration and area under the curve was lowest with oral diazepam, followed by diazepam nasal spray, with diazepam rectal gel showing the greatest variability. Overall, 131 treatment-emergent adverse events (TEAEs) were considered mild (42 subjects, 91.3%), four TEAEs were considered moderate (four subjects, 8.3%), and no TEAEs were considered severe. The most commonly reported TEAE was somnolence at 56.5% (26/46) during diazepam nasal spray treatment, 89.1% (41/46) with the rectal diazepam gel treatment, and 82.6% (38/46) with oral diazepam treatment. No nasal irritation was observed for the majority of the subjects at any time point after administration, with no score higher than 2 ("minor bleeding that stops within 1 minute").
SIGNIFICANCE
Diazepam nasal spray shows predicable pharmacokinetics and represents a potential novel therapeutic approach to control bouts of increased seizure activity (cluster seizures, acute repetitive seizures).
Topics: Administration, Intranasal; Administration, Oral; Administration, Rectal; Adolescent; Adult; Biological Availability; Diazepam; Female; Gels; Healthy Volunteers; Humans; Male; Middle Aged; Nasal Sprays; Sleepiness; Young Adult
PubMed: 32065672
DOI: 10.1111/epi.16449 -
The Cochrane Database of Systematic... Feb 2012Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Migraine is a highly disabling condition for the individual and also has wide-reaching implications for society, healthcare services, and the economy. Sumatriptan is an abortive medication for migraine attacks, belonging to the triptan family. Rectal administration may be preferable to oral for individuals experiencing nausea and/or vomiting.
OBJECTIVES
To determine the efficacy and tolerability of rectal sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, online databases, and reference lists for studies through 13 October 2011.
SELECTION CRITERIA
We included randomised, double-blind, placebo- and/or active-controlled studies using rectally administered sumatriptan to treat a migraine headache episode, with at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. We used numbers of participants achieving each outcome to calculate relative risk (or 'risk ratio') and numbers needed to treat to benefit (NNT) or harm (NNH) compared to placebo or a different active treatment.
MAIN RESULTS
Three studies (866 participants) compared rectally administered sumatriptan with placebo or an active comparator. Most of the data were for the 12.5 mg and 25 mg doses. For the majority of efficacy outcomes, sumatriptan surpassed placebo. For sumatriptan 12.5 mg versus placebo the NNTs were 5.2 and 3.2 for headache relief at one and two hours, respectively. Results for the 25 mg dose were similar to the 12.5 mg dose, and there were no significant differences between the two doses for any of the outcomes analysed. The NNTs for sumatriptan 25 mg versus placebo were 4.2, 3.2, and 2.4 for pain-free at two hours, headache relief at one hour, and headache relief at two hours, respectively.Relief of functional disability was greater with sumatriptan than with placebo, with NNTs of 8.0 and 4.0 for the 12.5 mg and 25 mg doses, respectively. For the most part, adverse events were transient and mild and were more common with sumatriptan than with placebo, but there were insufficient data to perform any analyses.Direct comparison of sumatriptan with active treatments was limited to one study comparing sumatriptan 25 mg with ergotamine tartrate 2 mg + caffeine 100 mg.
AUTHORS' CONCLUSIONS
Based on limited amounts of data, sumatriptan 25 mg, administered rectally, is an effective treatment for acute migraine attacks, with participants in these studies experiencing a significant reduction in headache pain and functional disability within two hours of treatment. The lack of data on relief of headache-associated symptoms or incidence of adverse events limits any conclusions that can be drawn.
Topics: Acute Disease; Administration, Rectal; Adult; Caffeine; Ergotamine; Female; Humans; Male; Migraine Disorders; Pain Management; Randomized Controlled Trials as Topic; Serotonin 5-HT1 Receptor Agonists; Sumatriptan
PubMed: 22336868
DOI: 10.1002/14651858.CD009664 -
American Journal of Veterinary Research Sep 2020To determine the pharmacokinetics and efficacy of trazodone following rectal administration of a single dose to healthy dogs.
OBJECTIVE
To determine the pharmacokinetics and efficacy of trazodone following rectal administration of a single dose to healthy dogs.
ANIMALS
6 healthy adult dogs.
PROCEDURES
Each dog received a single dose of trazodone (approx 8 mg/kg) per rectum. Trazodone tablets were crushed into a powder, mixed with 5 mL of tap water, and injected into the rectum via a red rubber catheter. Sedation scores were assigned, and blood samples were collected for determination of plasma trazodone concentration at predetermined times before and after drug administration. Pharmacokinetic parameters were estimated by noncompartmental analysis.
RESULTS
Plasma trazodone concentration remained below the detection limit for 1 dog even though it became moderately sedate. Median (interquartile [25th to 75th percentile] range [IQR]) maximum plasma trazodone concentration and volume of distribution and clearance corrected for bioavailability were 1.00 μg/mL (0.66 to 1.40 μg/mL), 10.3 L/kg (7.37 to 14.4 L/kg), and 639 mL/kg/h (594 to 719 mL/kg/h), respectively. Median time to maximum plasma trazodone concentration and elimination half-life were 15 minutes (range, 15 to 30 minutes) and 12 hours (IQR, 7.99 to 12.7 hours), respectively. All dogs became mildly or moderately sedate, and the extent of sedation was maximal at a median of 30 minutes (IQR, 30 to 60 minutes) after trazodone administration. No adverse effects were observed.
CONCLUSIONS AND CLINICAL RELEVANCE
Rectal administration of trazodone may be a viable option for sedation and treatment of anxiety in dogs for which administration of sedatives and anxiolytics by other routes is contraindicated. Further research is necessary to better elucidate the pharmacokinetics and efficacy of trazodone following rectal administration and determine optimal dosing.
Topics: Administration, Oral; Administration, Rectal; Animals; Anti-Anxiety Agents; Area Under Curve; Dogs; Half-Life; Trazodone
PubMed: 33112166
DOI: 10.2460/ajvr.81.9.739