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Biomedicines Feb 2023infection (CDI) is an urgent threat and unmet medical need. The current treatments for CDI are not enough to fight the burden of CDI and recurrent CDI (r-CDI). This... (Review)
Review
infection (CDI) is an urgent threat and unmet medical need. The current treatments for CDI are not enough to fight the burden of CDI and recurrent CDI (r-CDI). This review aims to highlight the future drugs for CDI and their related patented applications. The non-patent literature was collected from PubMed and various authentic websites of pharmaceutical industries. The patent literature was collected from free patent databases. Many possible drugs of the future for CDI, with diverse mechanisms of action, are in development in the form of microbiota-modulating agents (e.g., ADS024, CP101, RBX2660, RBX7455, SYN-004, SER-109, VE303, DAV132, MET-2, and BB128), small molecules (e.g., ridinilazole, ibezapolstat, CRS3123, DNV3837, MGB-BP-3, alanyl-L-glutamine, and TNP-2198), antibodies (e.g., IM-01 and LMN-201), and non-toxic strains of CD (e.g., NTCD-M3). The development of some therapeutic agents (e.g., DS-2969b, OPS-2071, cadazolid, misoprostol, ramoplanin, KB109, LFF571, and Ramizol) stopped due to failed clinical trials or unknown reasons. The patent literature reveals some important inventions for the existing treatments of CDI and supports the possibility of developing more and better CDI-treatment-based inventions, including patient-compliant dosage forms, targeted drug delivery, drug combinations of anti-CDI drugs possessing diverse mechanisms of action, probiotic and enzymatic supplements, and vaccines. The current pipeline of anti-CDI medications appears promising. However, it will be fascinating to see how many of the cited are successful in gaining approval from drug regulators such as the US FDA and becoming medicines for CDI and r-CDI.
PubMed: 36830964
DOI: 10.3390/biomedicines11020426 -
AJOG Global Reports Aug 2022The ideal method for induction of labor is still not clearly defined. Recent reports in literature have shown that oral administration of low-dose misoprostol is as...
BACKGROUND
The ideal method for induction of labor is still not clearly defined. Recent reports in literature have shown that oral administration of low-dose misoprostol is as effective as vaginal administration for induction of labor. The use of vaginal misoprostol in combination with Foley catheter has been shown to shorten the period of induction. However, there are limited reports on the use of oral misoprostol in combination with Foley catheter. Given the convenience of oral administration, improved compliance relative to other methods is probable. This study proposed that the combination of oral misoprostol and Foley catheter would be a better means of inducing labor.
OBJECTIVE
To compare the efficacy of combined low-dose oral misoprostol and Foley catheter with oral misoprostol alone for induction of labor at term gestation. The efficacy was compared in terms of the induction-to-delivery interval and the number of women delivering vaginally within 24 hours. The second objective was to document adverse events, if any, of the 2 protocols.
STUDY DESIGN
The study was conducted at a tertiary care center and included 200 patients with indication for induction, randomly allotted to either of the 2 groups: group A (a combination of Foley catheter and 25-µg misoprostol every 2 hours orally) and group B (only 25-µg misoprostol every 2 hours orally), using computer-generated random number sequence. The obstetrical and neonatal outcomes were recorded and compared between the 2 groups. Quantitative variables were compared using unpaired and paired -tests within the groups across follow-ups.
RESULTS
Group A had significantly shorter mean induction-to-active-labor interval (10.67±1.75 vs 16.28±1.69 hours), mean induction-to-full-dilation interval (11.49 vs 19.00 hours), and mean induction-to-delivery interval (16.85 vs 21.90 hours). The proportion of women delivering vaginally within 24 hours was higher in group A (76 vs 57 women). In comparing maternal side effects, the only significant difference between the 2 groups was found in postpartum hemorrhage. A 5-minute Apgar score <7 was significantly more frequent in group B.
CONCLUSION
The combination of oral misoprostol with transcervical Foley catheter reduced the induction-to-delivery interval significantly (=.001). In addition, the proportion of women delivering vaginally within 24 hours was significantly higher. Hence, the use of oral misoprostol with Foley catheter for induction of labor would be beneficial for patients.
PubMed: 36276789
DOI: 10.1016/j.xagr.2022.100060 -
BMJ Open Gastroenterology Jun 2024The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The management of non-alcoholic steatohepatitis (NASH) is an unmet clinical need. Misoprostol, a structural analogue of naturally occurring prostaglandin E1, has been reported to decrease proinflammatory cytokine production and may have a potential role in treating NASH. We aimed to evaluate the efficacy and safety of misoprostol in treating patients with NASH.
METHODS
In this phase 2, double-blind, randomised, placebo-controlled trial, patients with NASH were randomly assigned in a 1:1 ratio to receive 200 µg of misoprostol or placebo thrice daily for 2 months. The primary endpoint was an improvement in liver function tests (LFTs), interleukin-6 (IL-6) and endotoxin levels. The secondary endpoint was improvement in insulin resistance, dyslipidaemia, hepatic fibrosis and hepatic steatosis.
RESULTS
A total of 50 patients underwent randomisation, of whom 44 (88%) were males. The age range was 25-64 years (mean±SE of mean (SEM) 38.1±1.4). 19 (38%) patients had concomitant type 2 diabetes mellitus. 32 (64%) patients were either overweight or obese. At the end of 2 months' treatment, a reduction in total leucocyte count (TLC) (p=0.005), alanine aminotransferase (ALT) (p<0.001), aspartate aminotransferase (AST) (p=0.002) and controlled attenuation parameter (CAP) (p=0.003) was observed in the misoprostol group, whereas placebo ensued a decline in ALT (p<0.001), AST (p=0.018), gamma-glutamyl transferase (GGT) (p=0.003), CAP (p=0.010) and triglycerides (p=0.048). There was no diminution in insulin resistance, hepatic fibrosis (elastography) and dyslipidaemia in both groups. However, misoprostol resulted in a significant reduction in CAP as compared with the placebo group (p=0.039). Moreover, in the misoprostol group, pretreatment and post-treatment IL-6 and endotoxin levels remained stable, while in the placebo group, an increase in the IL-6 levels was noted (p=0.049). Six (12%) patients had at least one adverse event in the misoprostol group, as did five (10%) in the placebo group. The most common adverse event in the misoprostol group was diarrhoea. No life-threatening events or treatment-related deaths occurred in each group.
CONCLUSION
Improvement in the biochemical profile was seen in both misoprostol and placebo groups without any statistically significant difference. However, there was more improvement in steatosis, as depicted by CAP, in the misoprostol group and worsening of IL-6 levels in the placebo group.
TRIAL REGISTRATION NUMBER
NCT05804305.
Topics: Humans; Male; Female; Non-alcoholic Fatty Liver Disease; Middle Aged; Double-Blind Method; Adult; Misoprostol; Interleukin-6; Treatment Outcome; Insulin Resistance; Liver Cirrhosis; Liver Function Tests; Liver
PubMed: 38844374
DOI: 10.1136/bmjgast-2023-001342 -
BMJ Open Jan 2021To assess access (availability and affordability) to oxytocin and misoprostol at health facilities in Kenya, Uganda and Zambia to improve prevention and management of...
Access to oxytocin and misoprostol for management of postpartum haemorrhage in Kenya, Uganda and Zambia: a cross-sectional assessment of availability, prices and affordability.
OBJECTIVE
To assess access (availability and affordability) to oxytocin and misoprostol at health facilities in Kenya, Uganda and Zambia to improve prevention and management of postpartum haemorrhage (PPH).
DESIGN
The assessment was undertaken using data from Health Action International (HAI) research on sexual and reproductive health commodities based on a cross-sectional design adapted from the standardised WHO/HAI methodology.
SETTING
Data were collected from 376 health facilities in in Kenya, Uganda and Zambia in July and August 2017.
OUTCOME MEASURES
Availability was calculated as mean percentage of sampled medicine outlets where medicine was found on the day of data collection. Medicine prices were compared with international reference prices (IRP) and expressed as median price ratios. Affordability was calculated using number of days required to pay for a standard treatment based on the daily income of the lowest paid government worker.
RESULTS
Availability of either oxytocin or misoprostol at health facilities was high; 81% in Kenya, 82% in Uganda and 76% in Zambia. Oxytocin was more available than misoprostol, and it was most available in the public sector in the three countries. Availability of misoprostol was highest in the public sector in Uganda (88%). Oxytocin and misoprostol were purchased by patients at prices above IRP, but both medicines cost less than a day's wages and were therefore affordable. Availability of misoprostol was poor in rural settings where it would be more preferred due to lack of trained personnel and cold storage facilities required for oxytocin.
CONCLUSION
Availability and affordability of either oxytocin or misoprostol at health facilities met the WHO benchmark of 80%. However, countries with limited resources should explore mechanisms to optimise management of PPH by improving access to misoprostol especially in rural areas.
Topics: Costs and Cost Analysis; Cross-Sectional Studies; Drugs, Essential; Female; Health Services Accessibility; Humans; Kenya; Misoprostol; Oxytocin; Postpartum Hemorrhage; Pregnancy; Private Sector; Uganda; Zambia
PubMed: 33414148
DOI: 10.1136/bmjopen-2020-042948 -
PloS One 2020Misoprostol is listed in the WHO essential medicines list and can be used for induction of labour, for prevention and treatment of post-partum haemorrhage, and for...
Misoprostol is listed in the WHO essential medicines list and can be used for induction of labour, for prevention and treatment of post-partum haemorrhage, and for abortions. The compound is unstable, and substandard misoprostol preparations have been detected in low- and middle-income countries. We now investigated the stability of misoprostol tablets according to the international guidelines for stability testing of pharmaceutical products. Three brands (four batches) of misoprostol tablets were collected in Malawi and Rwanda: the originator product, a WHO-prequalified product, and a generic product without WHO prequalification. A further batch of the originator product was collected in Germany. To investigate the effect of damage to the primary packaging, additional blister strips of one sample were intentionally damaged with a needle and investigated in parallel. Samples were placed in stability chambers for six months at 40°C/75% relative humidity (RH) and at 25°C/60% RH. After 0, 1, 2, 3 and 6 months, misoprostol content was determined according to the International Pharmacopeia. At 40°C/75% RH, all samples showed a decline of misoprostol content, but four of the batches still remained within the pharmacopeial specifications, while one of the two batches of the generic product without WHO-prequalification showed a final content of 86.2% which is out of specifications. Damage to the primary packaging greatly decreased stability, resulting in a final content of only 48.2% of the declared misoprostol amount. At 25°C/60% RH all samples remained in specifications for six months, even the sample with the damaged blister. Dissolution of misoprostol remained in specifications of the pharmacopoeia for six months for all batches, except for the sample with damaged blisters stored at 40°C/75% RH. This study confirms that the stability of misoprostol tablets must be ensured by intact, good-quality primary packaging. Careful supplier qualification is required in the procurement process.
Topics: Chromatography, High Pressure Liquid; Drug Packaging; Drug Stability; Humidity; Malawi; Misoprostol; Rwanda; Tablets; Temperature
PubMed: 32877459
DOI: 10.1371/journal.pone.0238628 -
BMC Pregnancy and Childbirth Nov 2019Early pregnancy failure (EPF) is a common complication of pregnancy. If women do not abort spontaneously, they will undergo medical or surgical treatment in order to... (Comparative Study)
Comparative Study
Mifepristone and misoprostol versus misoprostol alone for uterine evacuation after early pregnancy failure: study protocol for a randomized double blinded placebo-controlled comparison (Triple M Trial).
BACKGROUND
Early pregnancy failure (EPF) is a common complication of pregnancy. If women do not abort spontaneously, they will undergo medical or surgical treatment in order to remove the products of conception from the uterus. Curettage, although highly effective, is associated with a risk of complications; medical treatment with misoprostol is a safe and less expensive alternative. Unfortunately, after 1 week of expectant management in case of EPF, medical treatment with misoprostol has a complete evacuation rate of approximately 50%. Misoprostol treatment results may be improved by pre-treatment with mifepristone; its effectiveness has already been proven for other indications of pregnancy termination. This study will test the hypothesis that, in EPF, the sequential combination of mifepristone with misoprostol is superior to the use of misoprostol alone in terms of complete evacuation (primary outcome), patient satisfaction, complications, side effects and costs (secondary outcomes).
METHODS
The trial will be performed multi-centred, prospectively, two-armed, randomised, double-blinded and placebo-controlled. Women with confirmed EPF by ultrasonography (6-14 weeks), managed expectantly for at least 1 week, can be included and randomised to pre-treatment with oral mifepristone (600 mg) or oral placebo (identical in appearance). Randomisation will take place after receiving written consent to participate. In both arms pre-treatment will be followed by oral misoprostol, which will start 36-48 h later consisting of two doses 400 μg (4 hrs apart), repeated after 24 h if no tissue is lost. Four hundred sixty-four women will be randomised in a 1:1 ratio, stratified by centre. Ultrasonography 2 weeks after treatment will determine short term treatment effect. When the gestational sac is expulsed, expectant management is advised until 6 weeks after treatment when the definitive primary endpoint, complete or incomplete evacuation, will be determined. A sonographic endometrial thickness < 15 mm using only the allocated therapy by randomisation is considered as successful treatment. Secondary outcome measures (patient satisfaction, complications, side effects and costs) will be registered using a case report form, patient diary and validated questionnaires (Short Form 36, EuroQol-VAS, Client Satisfaction Questionnaire, iMTA Productivity Cost Questionnaire).
DISCUSSION
This trial will answer the question if, in case of EPF, after at least 1 week of expectant management, sequential treatment with mifepristone and misoprostol is more effective than misoprostol alone to achieve complete evacuation of the products of conception.
TRIAL REGISTRATION
Clinicaltrials.gov (d.d. 02-07-2017): NCT03212352. Trialregister.nl (d.d. 03-07-2017): NTR6550. EudraCT number (d.d. 07-08-2017): 2017-002694-19. File number Commisie Mensgebonden Onderzoek (d.d. 07-08-2017): NL 62449.091.17.
Topics: Abortifacient Agents, Nonsteroidal; Abortifacient Agents, Steroidal; Abortion, Incomplete; Adolescent; Adult; Cost-Benefit Analysis; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Multicenter Studies as Topic; Patient Satisfaction; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Randomized Controlled Trials as Topic; Ultrasonography; Watchful Waiting; Young Adult
PubMed: 31775677
DOI: 10.1186/s12884-019-2497-y -
BMC Pregnancy and Childbirth Sep 2022Various methods are used for cervical ripening during the induction of labor. Mechanical and pharmacological methods are commonly used for cervical ripening. A... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Various methods are used for cervical ripening during the induction of labor. Mechanical and pharmacological methods are commonly used for cervical ripening. A double-balloon catheter was specifically developed to ripen the cervix and induce labor; however, the efficacy of the double-balloon catheter in cervical ripening compared to other methods is unknown.
METHODS
We searched five databases and performed a Bayesian network meta-analysis. Six interventions (double-balloon catheter, Foley catheter, oral misoprostol, vaginal misoprostol, dinoprostone, and double-balloon catheter combined with oral misoprostol) were included in the search. The primary outcomes were cesarean delivery rate and time from intervention-to-birth. The secondary outcomes were as follows: Bishop score increment; achieving a vaginal delivery within 24 h; uterine hyperstimulation with fetal heart rate changes; need for oxytocin augmentation; instrumental delivery; meconium staining; chorioamnionitis; postpartum hemorrhage; low Apgar score; neonatal intensive care unit admission; and arterial pH.
RESULTS
Forty-eight randomized controlled trials involving 11,482 pregnant women were identified. The cesarean delivery rates of the cervical ripening with a double-balloon catheter and oral misoprostol, oral misoprostol, and vaginal misoprostol were significantly lower than cervical ripening with a Foley catheter (OR = 0.48, 95% CI: 0.23-0.96; OR = 0.74, 95% CI: 0.58-0.93; and OR = 0.79, 95% CI: 0.64-0.97, respectively; all P < 0.05). The time from intervention-to-birth of vaginal misoprostol was significantly shorter than the other five cervical ripening methods. Vaginal misoprostol and oral misoprostol increased the risk of uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter. A double-balloon catheter with or without oral misoprostol had similar outcomes, including uterine hyperstimulation with fetal heart rate changes compared to a Foley catheter.
CONCLUSION
Double-balloon catheter did not show superiority when compared with other single method in primary and secondary outcomes of labor induction. The combination of double-balloon catheter with oral misoprostol was significantly reduced the rate of cesarean section compared to Foley catheter without increased risk of uterine hyperstimulation with fetal heart rate changes, which was shown in oral or vaginal misoprostol.
Topics: Administration, Intravaginal; Bayes Theorem; Cervical Ripening; Cesarean Section; Female; Humans; Infant, Newborn; Labor, Induced; Misoprostol; Network Meta-Analysis; Oxytocics; Pregnancy; Randomized Controlled Trials as Topic; Urinary Catheters
PubMed: 36068489
DOI: 10.1186/s12884-022-04988-2 -
BMC Pregnancy and Childbirth Nov 2019Community distribution of misoprostol to pregnant women in advance of labor is one of the compelling strategies for preventing postpartum hemorrhage. Concerns have been... (Review)
Review
INTRODUCTION
Community distribution of misoprostol to pregnant women in advance of labor is one of the compelling strategies for preventing postpartum hemorrhage. Concerns have been reported that misoprostol distribution could reduce facility delivery or lead to misuse of the medication. This scoping review was conducted to synthesize the evidence on the effect of community-based misoprostol distribution on rates of facility delivery, and to assess the frequency of mothers taking distributed misoprostol before delivery, and any harmful outcomes of such misuse.
METHODS
We included peer-reviewed articles on misoprostol implementation from PubMed, Cochrane Review Library, Popline, and Google Scholars. Narrative synthesis was used to analyze and interpret the findings, in which quantitative and qualitative syntheses are integrated.
RESULTS
Three qualitative studies, seven observational studies, and four experimental or quasi-experimental studies were included in this study. All before-after household surveys reported increased delivery coverage after the intervention: ranging from 4 to 46 percentage points at the end of the intervention when compared to the baseline. The pooled analysis of experimental and quasi-experimental studies involving 7564 women from four studies revealed that there was no significant difference in rates of facility delivery among the misoprostol and control groups [OR 1.011; 95% CI: 0.906-1.129]. A qualitative study among health professionals also indicated that community distribution of misoprostol for the prevention of postpartum hemorrhage is acceptable to community members and stakeholders and it is a feasible interim solution until access to facility birth increases. In the community-based distribution of misoprostol programs, self-administration of misoprostol by pregnant women before delivery was reported in less than 2% of women, among seven studies involving 11,108 mothers. Evidence also shows that most women who used misoprostol pills, used them as instructed. No adverse outcomes from misuse in either of the studies reviewed.
CONCLUSIONS
The claim that community-based distribution of misoprostol would divert women who would have otherwise had institutional deliveries to have home deliveries and promote misuse of the medication are not supported with evidence. Therefore, community-based distribution of misoprostol can be an appropriate strategy for reducing maternal deaths which occur due to postpartum hemorrhages, especially in resource-limited settings.
Topics: Delivery of Health Care; Female; Global Health; Humans; Incidence; Labor, Obstetric; Misoprostol; Oxytocics; Postpartum Hemorrhage; Pregnancy; Risk Factors; Survival Rate
PubMed: 31694580
DOI: 10.1186/s12884-019-2539-5 -
American Journal of Obstetrics and... Jun 2024A cesarean scar pregnancy is an iatrogenic consequence of a previous cesarean delivery. The gestational sac implants into a niche created by the incision of the previous... (Comparative Study)
Comparative Study
BACKGROUND
A cesarean scar pregnancy is an iatrogenic consequence of a previous cesarean delivery. The gestational sac implants into a niche created by the incision of the previous cesarean delivery, and this carries a substantial risk for major maternal complications. The aim of this study was to report, analyze, and compare the effectiveness and safety of different treatments options for cesarean scar pregnancies managed in the first trimester through a registry.
OBJECTIVE
This study aimed to evaluated the ultrasound findings, disease behavior, and management of first-trimester cesarean scar pregnancies.
STUDY DESIGN
We created an international registry of cesarean scar pregnancy cases to study the ultrasound findings, disease behavior, and management of cesarean scar pregnancies. The Cesarean Scar Pregnancy Registry collects anonymized ultrasound and clinical data of individual patients with a cesarean scar pregnancy on a secure, digital information platform. Cases were uploaded by 31 participating centers across 19 countries. In this study, we only included live and failing cesarean scar pregnancies (with or without a positive fetal heart beat) that received active treatment (medical or surgical) before 12+6 weeks' gestation to evaluate the effectiveness and safety of the different management options. Patients managed expectantly were not included in this study and will be reported separately. Treatment was classified as successful if it led to a complete resolution of the pregnancy without the need for any additional medical interventions.
RESULTS
Between August 29, 2018, and February 28, 2023, we recorded 460 patients with cesarean scar pregnancies (281 live, 179 failing cesarean scar pregnancy) who fulfilled the inclusion criteria and were registered. A total of 270 of 460 (58.7%) patients were managed surgically, 123 of 460 (26.7%) patients underwent medical management, 46 of 460 (10%) patients underwent balloon management, and 21 of 460 (4.6%) patients received other, less frequently used treatment options. Suction evacuation was very effective with a success rate of 202 of 221 (91.5%; 95% confidence interval, 87.8-95.2), whereas systemic methotrexate was least effective with only 38 of 64 (59.4%; 95% confidence interval, 48.4-70.4) patients not requiring additional treatment. Overall, surgical treatment of cesarean scar pregnancies was successful in 236 of 258 (91.5%, 95% confidence interval, 88.4-94.5) patients and complications were observed in 24 of 258 patients (9.3%; 95% confidence interval, 6.6-11.9).
CONCLUSION
A cesarean scar pregnancy can be managed effectively in the first trimester of pregnancy in more than 90% of cases with either suction evacuation, balloon treatment, or surgical excision. The effectiveness of all treatment options decreases with advancing gestational age, and cesarean scar pregnancies should be treated as early as possible after confirmation of the diagnosis. Local medical treatment with potassium chloride or methotrexate is less efficient and has higher rates of complications than the other treatment options. Systemic methotrexate has a substantial risk of failing and a higher complication rate and should not be recommended as first-line treatment.
Topics: Humans; Female; Pregnancy; Cicatrix; Cesarean Section; Pregnancy Trimester, First; Pregnancy, Ectopic; Registries; Adult; Abortifacient Agents, Nonsteroidal; Methotrexate; Ultrasonography, Prenatal; Vacuum Curettage; Misoprostol; Uterine Artery Embolization
PubMed: 37865390
DOI: 10.1016/j.ajog.2023.10.028 -
Journal of Family Medicine and Primary... Sep 2022Over-the-counter (OTC) sale of medical abortion (MA) inducing drugs is a common practice. Exploring its impact on women's health and the barriers to avail free MA...
BACKGROUND
Over-the-counter (OTC) sale of medical abortion (MA) inducing drugs is a common practice. Exploring its impact on women's health and the barriers to avail free MA services at hospital by these women is essential to improve upon policy decision.
METHODS
A prospective observational study included 112 women following ingestion of MA drugs from nonformal providers. Demography, clinical details, and reasons for not availing free abortion services at hospital were recorded.
RESULTS
Among 112 women, mean age was 28.63 (SD 4.7) years. Seventy one (63.39%) women were from rural region; 70.54% were educated below high school; 44 (39.28%) had prior induced abortion; 62.5% had never used any contraception. Majority (101; 90%) took two drugs (Mifepristone and Misoprostol), 28 (25%) used correct dosage. Drugs were consumed beyond 9 weeks of gestation by 25 (22.4%) women. Abnormal vaginal bleeding was commonest 105 (93.75%) presentation. Haemorrhagic shock was noted in 21 (18.75%) women, while 21 (18.7%) women required blood transfusion. "Easy and quick availability of these drugs OTC" was the commonest statement for not attending hospital.
CONCLUSION
Easy and quick availability of OTC drugs, distance to hospital were major barriers. Incorrect dosage and lack of gestational age calculation were two most common errors in the risk assessment protocol. Expanding provider base, by training midlevel providers, can overcome these and unmask the full potential of MA to make abortion safer.
PubMed: 36505611
DOI: 10.4103/jfmpc.jfmpc_86_22