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Indian Pediatrics Nov 2018Infantile colic is self-limiting condition but it can be a cause of anxiety for parents and challenge for doctors. The challenge for the doctors lies in correct... (Review)
Review
CONTEXT
Infantile colic is self-limiting condition but it can be a cause of anxiety for parents and challenge for doctors. The challenge for the doctors lies in correct identification of the condition and appropriate management. The objective of this review article is to summarize the pathophysiology, treatment options and outcome in infantile colic so that clinicians can have a fair idea about the condition, recent updates and future prospects.
EVIDENCE
A search of the Cochrane Library, PubMed, and Google Scholar was made using the key words "Infant colic", Infantile colic", "excessive crying in infants". All the materials were analyzed and summarized.
RESULTS
At present, infantile colic is an area of clinical research both in terms of etiology and treatment. Various etiological theories have been proposed but none of them are strong enough to completely describe the condition. Various treatment agents are being tried for colic like counseling and behavioral modification, dietary modification, lactase and probiotic supplementation, pain relieving agents, and chiropathy. Proper counseling of the parents is the first line of management at present. Simethicone has no role in decreasing the symptoms of colic and Dicyclomine is not recommended in children younger than six months. No specific recommendations have been made on the use of pain relieving agents and manipulative therapies in colic. At present strong evidence is lacking regarding the use of probiotics, lactase supplementation and dietary modification.
CONCLUSIONS
Counseling of parents about the benign nature of the condition is considered first line for now until an effective treatment is established. Other treatment options are prescribed on a case-based manner, and based on the parental perception of the condition.
Topics: Behavior Therapy; Colic; Counseling; Crying; Diet Therapy; Humans; Infant; Infant, Newborn; Parasympatholytics
PubMed: 29941700
DOI: No ID Found -
Indian Journal of Pharmacology 2017The study was designed to evaluate possible antihistaminic and anticholinergic activities of . (Comparative Study)
Comparative Study
OBJECTIVE
The study was designed to evaluate possible antihistaminic and anticholinergic activities of .
MATERIALS AND METHODS
Effects of crude ethanolic (Ed.Eth) and effects of crude aqueous (Ed.Aq) extracts of were studied using isolated guinea pig ileum, rabbit jejunum, and rabbit trachea. Tissue responses were recorded using isotonic and isometric transducers, connected with PowerLab data acquisition system.
RESULTS
A dose-dependent (0.1-0.3 mg/ml) rightward shift was demonstrated in histamine concentration-response curves. Whereas a complete relaxation of carbachol (1 μM)-induced contractions in isolated rabbit jejunum (3 mg/ml) and tracheal (10 mg/ml) preparations was observed, similar to dicyclomine at 1 and 3 μM, respectively. However, no significant difference between the effects of Ed.Eth and Ed.Aq was observed.
CONCLUSION
Study provides pharmacological evidence for the presence of antihistaminic and anticholinergic activities in crude extracts of and also highlight its medicinal significance in the management of airway and gastrointestinal disorders.
Topics: Animals; Cholinergic Antagonists; Dicyclomine; Dose-Response Relationship, Drug; Equisetum; Female; Guinea Pigs; Histamine Antagonists; Ileum; Jejunum; Male; Plant Extracts; Rabbits; Trachea
PubMed: 28458431
DOI: 10.4103/0253-7613.201017 -
PloS One 2017We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
We report information about an unpublished 1970s study ("8-way" Bendectin Study) that aimed to evaluate the relative therapeutic efficacy of doxylamine, pyridoxine, and dicyclomine in the management of nausea and vomiting during pregnancy. We are publishing the trial's findings according to the restoring invisible and abandoned trials (RIAT) initiative because the trial was never published.
DESIGN
Double blinded, multi-centred, randomized placebo-controlled study.
SETTING
14 clinics in the United States.
PARTICIPANTS
2308 patients in the first 12 weeks of pregnancy with complaints of nausea or vomiting were enrolled.
INTERVENTIONS
Each patient was randomized to one of eight arms: placebo, doxylamine/pyridoxine/dicylcomine, doxylamine/pyridoxine, dicylomine/pyridoxine, doxylamine, dicyclomine/pyridoxine, pyridoxine and dicyclomine. Each patient was instructed to take 2 tablets at bedtime and 1 additional tablet in the afternoon or morning if needed, for 7 nights.
OUTCOMES
Reported outcomes included the number of hours of nausea reported by patients, the frequency of vomiting reported by patients and the overall efficacy of medication as judged by physicians.
RESULTS
Data from 1599 (69% of those randomized) participants were analyzed. Based on the available summary data of physician evaluation of symptoms and ignoring missing data and data integrity issues, the proportion of participants who were "evaluated moderate or excellent" was greater in each of the seven active treatment groups when compared with placebo (57%): doxylamine/pyridoxine/dicylcomine (14% absolute difference versus placebo; 95% CI: 4 to 24), doxylamine/pyridoxine (21; 95% CI 11 to 30), dicylomine/pyridoxine (21; 95% CI 11 to 30), doxylamine (20; 95% CI 10 to 29), dicyclomine/pyridoxine (4; 95% CI -6 to 14), pyridoxine (9; 95% CI -1 to 19) and dicyclomine (4; 95% CI -6 to 14). Based on incomplete information, the most common adverse events were apparently drowsiness and fatigue. There is a high risk of bias in these previously unpublished results given the high attrition rate in a 7 day trial, the lack of prespecified outcomes or analyses, and the exclusion of some data because of questionable data integrity.
CONCLUSION
The available information about this "8-way Bendectin" trial indicates it should not be used to support the efficacy of doxylamine, pyridoxine or dicyclomine for the treatment of nausea and vomiting during pregnancy because of a high risk of bias.
TRIAL REGISTRATION
Not registered.
Topics: Cooperative Behavior; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Nausea; Physicians; Placebos; Pregnancy; Pregnancy Complications; Publication Bias; Publications; Pyridoxine; Research Report; Risk; Vomiting
PubMed: 28052111
DOI: 10.1371/journal.pone.0167609 -
Physiology & Behavior Feb 2017Several studies have investigated the transition of consolidation of recent memory to remote memory in aversively motivated tasks, such as contextual fear conditioning...
Several studies have investigated the transition of consolidation of recent memory to remote memory in aversively motivated tasks, such as contextual fear conditioning (CFC) and inhibitory avoidance (IA). However, the mechanisms that serve the retrieval of remote memories, has not yet been fully understood. Some evidences suggest that the central cholinergic system appears be involved in the modulation of these processes. Therefore, the present study aimed to investigate the effects of a pre-test administration of dicyclomine, a high-affinity M1 muscarinic receptor antagonist, on the retrieval of remote memories in fear conditioning and IA tasks. Male Wistar rats were trained, and after 1 or 28days, the rats received dicyclomine (16 or 32mg/kg, intraperitoneally, i.p.) and were tested in CFC, tone fear conditioning (TFC) and IA tasks. At both time intervals, 32mg/kg dicyclomine induced impairment of CFC. In TFC task only the performance of the rats 28days after training was impaired. The IA task was not affected in any of the studied intervals. These findings suggest a differential contribution of muscarinic receptors on recent and remote memories retrieval revealing a more generalized role in remote memory.
Topics: Acoustic Stimulation; Analysis of Variance; Animals; Avoidance Learning; Conditioning, Classical; Dicyclomine; Dose-Response Relationship, Drug; Fear; Male; Mental Recall; Muscarinic Antagonists; Rats; Rats, Wistar; Receptor, Muscarinic M1; Time Factors
PubMed: 27940145
DOI: 10.1016/j.physbeh.2016.12.008 -
BMC Pregnancy and Childbirth Nov 2016Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting mothers. In April 2013 the FDA approved the delayed-release combination of doxylamine succinate and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Nausea and vomiting of pregnancy (NVP) affects up to 80% of expecting mothers. In April 2013 the FDA approved the delayed-release combination of doxylamine succinate and pyridoxine hydrochloride (Diclegis®) for NVP, based in part, on the results of a phase III randomized trial demonstrating the efficacy of this drug combination [study drug marketed under the trade name Diclectin® in Canada and Diclegis® in the United States] compared to placebo in pregnant women. Study drug dosing occurred for 14 days, which is substantially longer than what has been performed in similar studies. The objective of this study was to evaluate, through secondary analysis, whether the primary measure of efficacy can be demonstrated after five days of treatment.
METHODS
Women suffering from NVP were randomized to receive Diclegis® (n = 131) or placebo (n = 125) for 14 days at doses ranging from two to four tablets a day, based on a pre-specified titration protocol. The primary efficacy endpoint was the change in the validated Pregnancy-Unique Quantification of Emesis (PUQE) score at baseline versus Day 15 between Diclegis®-treated and placebo-treated women. For the present study, the change in PUQE score between baseline and Day 15 (end of the study) was compared to the changes observed for Days 3, 4, and 5.
RESULTS
The use of delayed-release doxylamine succinate and pyridoxine hydrochloride tablets show improved NVP symptom control as compared to placebo on Days 3,4 and 5, with sustained efficacy until the end of the trial.
CONCLUSION
A four day study drug dosing trial with Diclegis® is sufficient to document efficacy, as the results are similar to those achieved after 14 study drug dosing days. The benefit seen at the earlier time validates drug efficacy and minimizes the natural course of improvement.
TRIAL REGISTRATION
CTR No. NCT006 14445 2007.
Topics: Antiemetics; Delayed-Action Preparations; Dicyclomine; Doxylamine; Drug Combinations; Female; Humans; Morning Sickness; Pregnancy; Pyridoxine; Time Factors
PubMed: 27881103
DOI: 10.1186/s12884-016-1172-9 -
The Cochrane Database of Systematic... Sep 2016Infantile colic is a common disorder in the first months of life, affecting somewhere between 4% and 28% of infants worldwide, depending on geography and definitions... (Review)
Review
BACKGROUND
Infantile colic is a common disorder in the first months of life, affecting somewhere between 4% and 28% of infants worldwide, depending on geography and definitions used. Although it is self limiting and resolves by four months of age, colic is perceived by parents as a problem that requires action. Pain-relieving agents, such as drugs, sugars and herbal remedies, have been suggested as interventions to reduce crying episodes and severity of symptoms.
OBJECTIVES
To assess the effectiveness and safety of pain-relieving agents for reducing colic in infants younger than four months of age.
SEARCH METHODS
We searched the following databases in March 2015 and again in May 2016: CENTRAL, Ovid MEDLINE, Embase and PsycINFO, along with 11 other databases. We also searched two trial registers, four thesis repositories and the reference lists of relevant studies to identify unpublished and ongoing studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of pain-relieving agents given to infants with colic.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures of The Cochrane Collaboration.
MAIN RESULTS
We included 18 RCTs involving 1014 infants. All studies were small and at high risk of bias, often presenting major shortcomings across multiple design factors (e.g. selection, performance, attrition, lack of washout period).Three studies compared simethicone with placebo, and one with Mentha piperita; four studies compared herbal agents with placebo; two compared sucrose or glucose with placebo; five compared dicyclomine with placebo; and two compared cimetropium - one against placebo and the other at two different dosages. One multiple-arm study compared sucrose and herbal tea versus no treatment. Simethicone. Comparison with placebo revealed no difference in daily hours of crying reported for simethicone at the end of treatment in one small, low-quality study involving 27 infants. A meta-analysis of data from two cross-over studies comparing simethicone with placebo showed no difference in the number of of infants who responded positively to treatment (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.73 to 1.23; 110 infants, low-quality evidence).One small study (30 participants) compared simethicone with Mentha piperita and found no difference in crying duration, number of crying episodes or number of responders. Herbal agents. We found low-quality evidence suggesting that herbal agents reduce the duration of crying compared with placebo (mean difference (MD) 1.33, 95% CI 0.71 to 1.96; three studies, 279 infants), with different magnitude of benefit noted across studies (I² = 96%). We found moderate-quality evidence indicating that herbal agents increase response over placebo (RR 2.05, 95% CI 1.56 to 2.70; three studies, 277 infants). Sucrose. One very low-quality study involving 35 infants reported that sucrose reduced hours spent crying compared with placebo (MD 1.72, 95% CI 1.38 to 2.06). Dicyclomine. We could consider only one of the five studies of dicyclomine (48 infants) for the primary comparison. In this study, more of the infants given dicyclomine responded than than those given placebo (RR 2.50, 95% CI 1.17 to 5.34). Cimetropium bromide. Data from one very low-quality study comparing cimetropium bromide with placebo showed reduced crying duration among infants treated with cimetropium bromide (MD -30.20 minutes per crisis, 95% CI -39.51 to -20.89; 86 infants). The same study reported that cimetropium increased the number of responders (RR 2.29, 95% CI 1.44 to 3.64).No serious adverse events were reported for all of the agents considered, with the exception of dicyclomine, for which two of five studies reported relevant adverse effects (longer sleep 4%, wide-eyed state 4%, drowsiness 13%).
AUTHORS' CONCLUSIONS
At the present time, evidence of the effectiveness of pain-relieving agents for the treatment of infantile colic is sparse and prone to bias. The few available studies included small sample sizes, and most had serious limitations. Benefits, when reported, were inconsistent.We found no evidence to support the use of simethicone as a pain-relieving agent for infantile colic.Available evidence shows that herbal agents, sugar, dicyclomine and cimetropium bromide cannot be recommended for infants with colic.Investigators must conduct RCTs using standardised measures that allow comparisons among pain-relieving agents and pooling of results across studies. Parents, who most often provide the intervention and assess the outcome, should always be blinded.
PubMed: 27631535
DOI: 10.1002/14651858.CD009999.pub2 -
Cancer Management and Research 2016Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity...
Anaplastic lymphoma kinase (ALK) gene fusions occur in 3%-7% of non-small-cell lung cancer (NSCLC) cases. Ceritinib, a once-daily, oral ALK inhibitor, has activity against crizotinib-resistant and crizotinib-naïve NSCLC, including brain metastases. Ceritinib (Zykadia™) was granted accelerated approval by the US Food and Drug Administration in 2014 for treating crizotinib-resistant ALK-positive NSCLC. Adverse events (AEs), particularly gastrointestinal (GI) AEs, are commonly experienced at the recommended dose of 750 mg/d and ∼38% of patients require dose interruption or reduction for GI AEs. This case study details our experience with the use of proactive GI AE management regimens in patients treated with ceritinib (750 mg/d) across two study sites. Proactive Regimens A and B were implemented in patients with metastatic ALK-positive NSCLC treated with ceritinib to manage drug-related GI AEs. Regimen A comprised ondansetron and diphenoxylate/atropine or loperamide, taken 30 minutes prior to ceritinib dose. Regimen B included dicyclomine (taken with the first ceritinib dose), ondansetron (taken 30 minutes prior to ceritinib dose for the first seven doses), and loperamide (taken as needed with the onset of diarrhea). The proactive medications were tapered off depending on patient tolerability to ceritinib. Nine patient cases are presented. Starting Regimens A or B before the first dose of ceritinib, or as soon as GI symptoms were encountered, prevented the need for dose reduction due to GI toxicity in eight of the nine patients. Using these regimens, 78% of patients were able to remain on 750 mg/d fasting. Two patients received 23 months and 16 months of therapy and remain on ceritinib 750 mg/d and 600 mg/d, respectively. Although not currently recommended or implemented in clinical studies, based on the patients evaluated here, upfront or proactive treatment plans that address AEs early on can allow the majority of patients to remain on the approved 750 mg/d ceritinib dose.
PubMed: 27069372
DOI: 10.2147/CMAR.S96471 -
American Family Physician Oct 2015Infantile colic is a benign process in which an infant has paroxysms of inconsolable crying for more than three hours per day, more than three days per week, for longer...
Infantile colic is a benign process in which an infant has paroxysms of inconsolable crying for more than three hours per day, more than three days per week, for longer than three weeks. It affects approximately 10% to 40% of infants worldwide and peaks at around six weeks of age, with symptoms resolving by three to six months of age. The incidence is equal between sexes, and there is no correlation with type of feeding (breast vs. bottle), gestational age, or socioeconomic status. The cause of infantile colic is not known; proposed causes include alterations in fecal microflora, intolerance to cow's milk protein or lactose, gastrointestinal immaturity or inflammation, increased serotonin secretion, poor feeding technique, and maternal smoking or nicotine replacement therapy. Colic is a diagnosis of exclusion after a detailed history and physical examination have ruled out concerning causes. Parental support and reassurance are key components of the management of colic. Simethicone and proton pump inhibitors are ineffective for the treatment of colic, and dicyclomine is contraindicated. Treatment options for breastfed infants include the probiotic Lactobacillus reuteri (strain DSM 17938) and reducing maternal dietary allergen intake. Switching to a hydrolyzed formula is an option for formula-fed infants. Evidence does not support chiropractic or osteopathic manipulation, infant massage, swaddling, acupuncture, or herbal supplements.
Topics: Colic; Education, Medical, Continuing; Female; Gastrointestinal Agents; Humans; Infant; Infant, Newborn; Male; Pediatrics; Practice Guidelines as Topic; Probiotics; United States
PubMed: 26447441
DOI: No ID Found