Atomized Intranasal Ketorolac Versus Intravenous Ketorolac for the Treatment of Severe Renal Colic in the Emergency Department: A Double-Blind, Randomized Controlled Trial.

STUDY OBJECTIVE: Atomized intranasal (IN) drug administration offers an alternative to the intravenous (IV) route. We aimed to evaluate the analgesic efficacy of IN versus IV ketorolac in emergency department patients with acute renal colic. METHODS: We conducted a double-blind, randomized controlled trial on adult patients (aged 18 to 64 years) with severe renal colic and numerical rating scale pain ratings ≥7.0. They were randomly assigned (1:1) to receive single doses of either IN or IV ketorolac. Our main outcomes were differences in numerical rating scale reduction at 30 and 60 minutes. A 95% confidence interval (CI) was calculated for each mean difference, with a minimum clinically important difference set at 1.3 points. Secondary outcomes included treatment response, adverse events, rescue medications, and emergency department revisits. We analyzed using intention-to-treat. RESULTS: A total of 86 and 85 patients with similar baseline characteristics were allocated to the IV and IN groups, respectively. Mean numerical rating scale scores were 8.52 and 8.65 at baseline, 3.85 and 4.67 at 30 minutes, and 2.80 and 3.04 at 90 minutes, respectively. The mean numerical rating scale reduction differences between the IV and IN groups were 0.69 (95% CI -0.08 to 1.48) at 30 minutes and 0.10 (95% CI -0.85 to 1.04) at 60 minutes. There were no differences in secondary outcomes. CONCLUSION: Neither IN or IV ketorolac was superior to the other for the treatment of acute renal colic, and both provided clinically meaningful reductions in pain scores at 30 to 60 minutes.

Ultrasonographic Assessment of Small Intestinal Motility Following Hyoscine Butylbromide Administration in Horses: A Pilot Study.

Horses commonly receive hyoscine butylbromide (HB) prior to hospital admission for colic. This could alter the appearance of the small intestine (SI) on ultrasound scan and affect clinical decision making. The aim of this study was to assess the impact of HB on ultrasonographically assessed SI motility and heart rate. Six horses hospitalised for medical colic with no significant abnormalities on baseline abdominal ultrasound examination were included. Ultrasound was performed in three locations (right inguinal, left inguinal and hepatoduodenal window) before and at 1, 5, 15, 30, 45, 60, 90, and 120 minutes after intravenous injection of 0.3 mg/kg HB. Three blinded reviewers assessed SI motility using a subjective grading scale from 1 to 4, one being normal motility and four being no motility. Moderate interindividual and interobserver variability was observed, but none of the included horses developed dilated turgid loops of SI. Hyoscine butylbromide did not significantly reduce SI motility grade in any location (P = .60 left inguinal, P = .16 right inguinal, P = .09 duodenum). Heart rate (mean ± SD) was 33 ± 3 prior to HB injection and peaked at 71.3 ± 9 one-minute postinjection. Heart rate was significantly increased until 45 minutes (48 ± 9) after HB administration (P = .04). The appearance of dilated turgid SI loops common with strangulating intestinal lesions did not appear to develop following HB administration. Hyoscine butylbromide administered shortly before abdominal ultrasound examination would not be expected to affect clinical decision making in horses without small intestinal disease.

A real-world evaluation of an herbal treatment for infantile colic reported by 1218 parents in Israel.

PURPOSE: Infantile colic (IC) or fussing and crying behavior of unknown cause, affects up to 20% of the infant population and is one of the major reasons for parents to seek medical advice. Therapeutic options are limited and the key component for IC management is parental support. Fennel-based herbal treatments were shown to significantly reduce crying time. The current study was designed to evaluate the parent perception of effectiveness of a fennel-based commercially-available herbal treatment for IC (BabyCalm, Hisunit Ltd., Israel) using a retrospective online survey. DESIGN AND METHODS: This was a real-world observational, case-control retrospective study. Parents of babies with IC symptoms, who either used the herbal product for their baby or did not use any product were invited to participate in an online survey during August-December 2019. The primary outcome was the perceived level of treatment success and symptom improvement. RESULTS: 1218 parents of IC babies (48% females, 90% up to 3 months of age, 58% exclusively breast-fed) responded to the survey of whom 771 used the treatment. Significantly fewer IC-related symptoms were reported by parents who used the product compared to those that did not. Parents perceived the treatment as successful in 65% of the cases, reporting meaningful improvements within 30 min for 69%-79% of the symptoms. CONCLUSIONS: The majority of parents perceived the herbal treatment as effective in rapid symptom reduction suggesting that this may provide a satisfactory solution for IC in the community.

Phloroglucinol-Derived Medications are Effective in Reducing Pain and Spasms of Urinary and Biliary Tracts: Results of Phase 3 Multicentre, Open-Label, Randomized, Comparative Studies of Clinical Effectiveness and Safety.

INTRODUCTION: Pain and spasms of urinary and biliary tracts are conditions causing poor quality of life. Treatment with analgesic drugs such as non-steroidal anti-inflammatory drugs and modulators of the parasympathetic system are not always tolerated, and often additional therapeutic options are necessary. The present analysis aimed to evaluate the pharmacokinetics and effectiveness of oral and parenteral preparations based on phloroglucinol in reducing pain and spasms associated with renal or biliary colic in phase 3, multicentre, open-label, randomized, comparative studies on clinical effectiveness and safety. METHODS: Pharmacokinetic and pharmacodynamic studies were carried out. Four phase 3 multicentre, open-label, randomized, comparative studies were conducted to evaluate the clinical effectiveness and safety in patients with pain and spasms of urinary or biliary tracts. Eligible patients randomly received either phloroglucinol orally or via intramuscular (IM)/intravenous (IV) administration and reference drug, dexketoprofen for urinary spasms and pain, the non-steroidal anti-inflammatory drug metamizole or scopolamine-based reference drug for biliary colic. The primary outcomes were symptoms and observed frequency of spasms, while the secondary outcome was the duration of improvement or the time between the drug administration and the recurrence of symptoms. Comparison of groups by quantitative characteristics was performed using the T-test for independent samples or the Mann-Whitney test. Intragroup comparisons were performed using the Wilcoxon test, or the T-test for linked samples. Qualitative signs were analysed using the Pearson's χ2 test and Fisher's exact test. RESULTS: The pharmacokinetic studies showed that (i) most of the phloroglucinol (> 80% for IV and per os formulations) was eliminated in the first 6 h after dosing, (ii) the drug was eliminated in urine as unchanged phloroglucinol (1,3,5-trihydroxybenzene) in a small proportion (< 3% of the dose) and (iii) a considerable amount of the drug was detected after enzymatic deconjugation with ß-glucoronidase/arylsulfatase from Helix pomatia. As for the pharmacokinetic study, a total of 364 patients were enrolled, divided in four studies: two designed to test the effectiveness of oral and IM/IV preparations in biliary colic and two in urinary colic. Baseline characteristics between groups were similar. Phloroglucinol oral or IV/IM showed an effectiveness comparable to the reference drug in reducing pain and spasms associated with both urinary and biliary colic. There was no difference between all groups by survival analysis. CONCLUSION: Oral and parenteral preparations based on phloroglucinol are as effective in reducing pain and spasms associated with renal or biliary colic as current therapeutic options. Therefore, phloroglucinol may be considered as useful to treat pain and spasms associated with urinary and biliary colic.

Probiotics in the treatment of infantile colic: a meta-analysis of randomized controlled trials.

Introduction: Introduction: infantile colic has always been a problem for caregivers, and research on probiotics in treating and preventing infant colic is still controversial. Material and methods: trials were performed before November 2021 and retrieved from the PubMed, Web of Science, The Cochrane Library, Medline, and Google Scholar databases. Data extraction and quality evaluation of the trials were performed independently by two investigators. A meta-analysis was performed using Review Manager 5.3. It includes nine randomized controlled trials in 587 infants with colic. Results: eight of these experiments described probiotics for the prevention and treatment of intestinal colic in infants, with 228 in the probiotics group and 227 in the placebo group, with a total effective rate (RR = 1.88, 95 % CI: 1.61 to 2.19, p < 0.00001). Conclusion: probiotics may improve therapeutic and preventive effects, especially within four weeks of probiotic treatment.

Introducción: Introducción: el cólico infantil siempre ha sido un problema para los cuidadores y la investigación sobre los probióticos para tratar y prevenir el cólico infantil sigue siendo controvertida. Material y métodos: los ensayos se realizaron antes de noviembre de 2021 y se recuperaron de las bases de datos PubMed, Web of Science, The Cochrane Library, Medline y Google Scholar. Dos investigadores realizaron de forma independiente la extracción de datos y la evaluación de la calidad de los ensayos. Se realizó un metaanálisis utilizando Review Manager 5.3. Incluye nueve ensayos controlados aleatorios en 587 lactantes con cólicos. Resultados: ocho de estos experimentos describieron probióticos para la prevención y el tratamiento del cólico intestinal en lactantes, con 228 en el grupo de probióticos y 227 en el grupo de placebo, con una tasa efectiva total (RR = 1,88, IC del 95 %: 1,61 a 2,19, p < 0,00001). Conclusión: los probióticos pueden mejorar los efectos terapéuticos y preventivos, especialmente dentro de las cuatro semanas posteriores al tratamiento con los mismos.

Oral lactase for infantile colic: a randomized double-blind placebo-controlled trial.

BACKGROUND: Infantile colic is a common problem during the first three months of life. This randomized, double-blind, placebo-controlled trial conducted in an urban hospital in Delhi, India evaluated the efficacy and safety of oral lactase in management of infantile colic. METHODS: One hundred sixty-two clinically healthy infants aged < 5 months age [mean (SD) = 63.5 (30.5) days] fulfilling the Rome-IV diagnostic criteria for infantile colic were enrolled. Eligible children were randomly allocated to receive 5 drops of lactase (600 FCC units/mL) (n = 80) or placebo (n = 82) mixed with breast milk or formula feed four times a day for a duration of 4 weeks. Primary outcomes were duration of crying or fussing (min/d), and number of days with colic lasting > 3 h/d; secondary outcomes were parental satisfaction and adverse events. RESULTS: At the end of four weeks, mean (SD) crying or fussing time (min/d) was significantly shorter in infants receiving lactase in comparison to placebo [89.9 (115.2) vs.178.5 (153.2); P = 0.001]. The mean (SD) number of days with colic was also significantly less in the lactase group as compared to placebo group at the end of the treatment [12.1 (7.8) vs 17.6 (8.4); P < 0.001]. By the end of 4th week, parental satisfaction in terms of infant's mood, activity, alertness, comfort and oral intake was better in intervention group. The adverse event profile was comparable between two groups. CONCLUSIONS: Oral lactase treatment in infantile colic results in symptomatic relief in terms of shortening of duration of crying or fussing, and better parental satisfaction. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2017/12/010930) registered on 20/12/2017.

Predicting the likelihood of successful medical treatment of early pregnancy loss: development and internal validation of a clinical prediction model.

STUDY QUESTION: What are clinical predictors for successful medical treatment in case of early pregnancy loss (EPL)? SUMMARY ANSWER: Use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start are predictors for successful medical treatment in case of EPL. WHAT IS KNOWN ALREADY: Success rates of medical treatment for EPL vary strongly, between but also within different treatment regimens. Up until now, although some predictors have been identified, no clinical prediction model has been developed yet. STUDY DESIGN, SIZE, DURATION: Secondary analysis of a multicentre randomized controlled trial in 17 Dutch hospitals, executed between 28 June 2018 and 8 January 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a non-viable pregnancy between 6 and 14 weeks of gestational age, who opted for medical treatment after a minimum of 1 week of unsuccessful expectant management. Potential predictors for successful medical treatment of EPL were chosen based on literature and expert opinions. We internally validated the prediction model using bootstrapping techniques. MAIN RESULTS AND THE ROLE OF CHANCE: 237 out of 344 women had a successful medical EPL treatment (68.9%). The model includes the following variables: use of mifepristone, BMI, number of previous uterine aspirations and the presence of minor clinical symptoms (slight vaginal bleeding or some abdominal cramps) at treatment start. The model shows a moderate capacity to discriminate between success and failure of treatment, with an AUC of 67.6% (95% CI = 64.9-70.3%). The model had a good fit comparing predicted to observed probabilities of success but might underestimate treatment success in women with a predicted probability of success of ∼70%. LIMITATIONS, REASONS FOR CAUTION: The vast majority (90.4%) of women were Caucasian, potentially leading to less optimal model performance in a non-Caucasian population. Limitations of our model are that we have not yet been able to externally validate its performance and clinical impact, and the moderate accuracy of the prediction model of 0.67. WIDER IMPLICATIONS OF THE FINDINGS: We developed a prediction model, aimed to improve and personalize counselling for medical treatment of EPL by providing a woman with her individual chance of complete evacuation. STUDY FUNDING/COMPETING INTEREST(S): The Triple M Trial, upon which this secondary analysis was performed, was funded by the Healthcare Insurers Innovation Foundation (project number 3080 B15-191). TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT03212352.

Antispasmodic activity and mechanism of action of polyherbal formulation DCD-684 on rabbit jejunum.

Digas colic drops (DCD-684) is a polyherbal formulation containing decoctions of five medicinal plants namely Carum carvi L., Foeniculum vulgare Mill, Mentha arvensis L., Mentha piperita L. and Zingiber officinale Roscoe. These plants have been extensively used in traditional medicine for the treatment of various gastrointestinal diseases including abdominal colic. This study was conducted to determine the spasmolytic effect of DCD-684 (100% v/v) and its individual plant components on isolated rabbit jejunum (in vitro) and their possible mechanism of action. The effects were evaluated on spontaneous and pre-contracted tissues using KCl (80mM) and other contractile agonists including acetylcholine (0.3µM), carbamylcholine (0.3µM), serotonin (10 µM) and histamine (100µM) in the presence and absence of DCD-684. The various concentrations of DCD-684 (0.1-3% v/v) demonstrated spasmolytic effects on both spontaneous (IC50=0.75%) and KCl-induced contractions (IC50=1.6%), respectively. It also inhibited the contractions induced by acetylcholine (IC50=0.45%), carbamylcholine (IC50=0.95%), serotonin (IC50=0.95%) and histamine (IC50=0.87%). The DCD-684 exhibited synergistic effect due to its five plant components suggesting that spasmolytic cascade is probably governed by muscarinic and/or nicotinic receptors, serotonergic histaminergic, as well as calcium channel blocking mechanisms. Thereby, providing the pharmacological basis of its therapeutic use in the gastrointestinal motility disorders and related inflammatory ailments.

Analgesic refractory colic pain: Is prolonged conservative management appropriate?

OBJECTIVES: To propose a clear definition and management pathway of patients with analgesic refractory colic pain (ARCP). PATIENTS AND METHODS: Prospective cohort study from February 2018 to February 2019 including patients with ARCP defined as ongoing renal colic pain after one dose of IV NSAID, IV paracetamol, and a parenteral opioid, given sequentially in that order. Patients were observed in-hospital under full parenteral analgesic management for 8-12 h, whenever patients had minimal or absent pain after conservative management (CM) they were discharged, and followed-up with new imaging within four weeks. If the pain was not controlled after CM, surgical management (double-J stent or ureteroscopy) was performed. We excluded patients with any other indication for urgent intervention or in cases where CM was deemed inappropriate (sepsis, acute renal failure, stones >10 mm in size, suspected concomitant urinary tract infection, bilateral ureteral stones, pregnancy, patients with a single kidney, kidney transplant recipients, difficult access to medical care or refusal to undergo CM). RESULTS: Data from 60 patients was collected. The only variable associated with an increased risk of failed CM was a history of previous renal colic (OR 3.98 [95% CI 1.14-13.84], p = 0.02). Neither gender, age, stone size, location, or hydronephrosis grade were able to predict CM failure. 41.6% of patients were successfully managed conservatively and only 8% of them required scheduled surgical management at follow-up. CONCLUSION: Our results show that a high proportion of patients with ARCP may be successfully managed conservatively with an extended observation period without complications at follow-up. These results should be replicated in a randomized controlled trial to confirm them.

Medical treatment for acute renal colic. / Tratamiento médico del cólico renoureteral en su fase aguda.

INTRODUCTION: Renoureteral colic (CRU) is the most common urological emergency, with a wide spectrum of severity that generates high morbidity and high health costs. However, there is no homogeneous scheme of pharmacological treatment in its acutephase. AIMS: The main objective of our work is to evaluate the effectiveness and safety profile of the different drugs used in the treatment of CCR and to propose a practical treatment scheme. The secondary objectives are to evaluate the role of fluid therapy in CRU and the treatment of CRU in pregnant women. MATERIAL AND METHODS: We have carried out a literature search on PubMed using the MeSH terms "renalcolic", "treatment", "anti-inflammatory drugs", "antiemeticdrugs", "fluid therapy" and "pregnant". The most relevant clinical trials, meta-analyses and systematic reviews published from 1 January 2005 to 15 September 2020 in Spanish, English and French were reviewed. RESULTS: In the different studies reviewed, non-steroidalanti-inflammatory drugs (NSAIDs) show better pain control, with lower rescue doses and fewer side effects than treatment with opioids. However, fluid therapy has failed to demonstrate an impact on the treatment of CRU. CONCLUSIONS: The initial treatment for CRU is NSAIDs, reserving opioids for successive treatment lines. The control of vegetative cortex can be accomplished with Ondansetron as first choice.

INTRODUCCIÓN: El cólico renoureteral (CRU) es la urgencia urológica más frecuente, con un amplio espectro de gravedad que genera una alta morbilidad y elevados costes sanitarios. Sin embargo, no existe un esquema homogéneo de tratamiento farmacológico en su fase aguda. OBJETIVOS: El objetivo principal de nuestro trabajo es evaluar la efectividad y perfil de seguridad de los distintos fármacos empleados en el tratamiento del CRU y proponer un esquema práctico de tratamiento. Los objetivos secundarios son evaluar el papel de la fluidoterapia en el CRU y el tratamiento del CRU en embarazadas.MATERIAL Y MÉTODOS: Hemos realizado una búsqueda bibliográfica en PubMed utilizando los términos MeSH "renal colic", "treatment", "anti-inflammatory- drugs", "antiemetic drugs", "fluid therapy" y "pregnant". Se revisaron ensayos clínicos, metaanálisis y revisiones sistemáticas de mayor relevancia, publicados desde el 1 de enero de 2005 hasta el 15 de septiembre de 2020, escritos en lengua española, inglesa y francesa. RESULTADOS: En los diferentes estudios revisados los antiinflamatorios no esteroideos (AINES) muestran un mejor control del dolor, con menores dosis de rescate y menos efectos secundarios que el tratamiento con opioides. Sin embargo, la fluidoterapia no ha logrado demostrar una repercusión en el tratamiento del CRU. CONCLUSIONES: El tratamiento de primera elección para el CRU son los AINES, reservando los opioides para sucesivas líneas de tratamiento. El control del cortejo vegetativo se puede realizar con ondansetrón comoprimera elección.

The efficacy of intravenous lidocaine and its side effects in comparison with intravenous morphine sulfate in patients admitted to the ED with right upper abdominal pain suspected of biliary colic.

BACKGROUND: Intravenous (IV) Lidocaine can be used as analgesic in acute pain management in the emergency department (ED). OBJECTIVE: Efficacy of IV Lidocaine in comparison with IV morphine in acute pain management in the ED. METHOD: This is a double-blind randomized clinical trial on adult (18-64 year) patients with right upper abdominal pain suspected of biliary colic who needed pain management. Participants randomly received IV lidocaine (5 cc = 100 mg) or morphine sulfate (5 cc = 5 mg). In both groups, patients' pain scores were recorded and assessed by Numeric Rating Scale (NRS) at baseline, 10, 20, 30, 45, 60 and 120 min after drug administration. Adverse side effects of lidocaine and morphine sulfate and changes in vital signs were also recorded and compared. RESULTS: A total number of 104 patients were enrolled in the study, including 49 men and 55 women. IV lidocaine reduced pain in less time in comparison with morphine sulfate. Mean (±SD) basic pain score was 8.23 (±1.76) in the lidocaine group and 8.73 (±0.96) in the morphine group. Patients' mean (±SD) pain score in both groups had no significant difference during the study except that of NRS2 (10 min after drug administration), which was 5.05 (±2.69) in lidocaine group compared with 6.39 (±2.06) in the morphine group and NRS4 (30 min after drug administration), which was significantly lower (P-value = 0.01) in the morphine group [3.84(±1.73) vs 4.41(±2.82)]. Only 9 patients had adverse effects in either group. CONCLUSION: The findings of this study suggest that IV lidocaine can be a good choice in pain management in biliary colic and can reduce pain in less time than morphine sulfate (in 10 min) without adding significant side effects; however, our primary outcome was the comparison of these two drugs after 60 min of drug administration in pain reduction which showed no significant difference between two groups.

Effectiveness of a homeopathic complex medicine in infantile colic: A randomized multicenter study.

OBJECTIVES: Infantile colic is a common benign disease occurring in early infancy that may have a great impact on family life. In the present study, the effectiveness and safety of the complex homeopathic medicine Enterokind was compared with Simethicone for treating infantile colic. DESIGN AND SETTING: Current data were drawn from a prospective, multicenter, randomized, open-label, controlled clinical trial that was conducted in 2009 in 3 Russian outpatient clinics. Children received either Enterokind (Chamomilla D6, Cina D6, Colocynthis D6, Lac defloratum D6 and Magnesium chloratum D6) or Simethicone. Data from infants ≤ 6 months with infantile colic are presented here. MAIN OUTCOME MEASURES: The main outcomes assessments were the change of total complaints score (maximum 17 points) and total objective symptoms score (maximum 22 points) after 10 days of treatment. RESULTS: Data from 125 infants ≤ 6 months with infantile colic were analyzed. The differences in total complaints and objective symptoms scores between baseline and day 10, estimated from the ANCOVA model, were found to be highly significant (p < 0.0001; ITT) in favor of Enterokind, both for complaints (Δ=-2.38; 95% confidence interval (CI): [-2.87; -1.89]) and for objective symptoms (Δ=-2.07; 95% CI: [-2.65; -1.49]). 1 adverse event (AE), vomiting, occurred under Enterokind and was rated to be unlikely related to it; 4 AEs occurred under Simethicone. All AEs were non-serious. CONCLUSIONS: The current study indicates that Enterokind is an effective and safe homeopathic treatment for functional intestinal colic in infants ≤ 6 months.

Is There Still a Place for Lidocaine in the (Postoperative) Management of Colics?

Intravenous lidocaine is widely used to prevent or treat postoperative ileus in horses. Clinical studies that support this approach are flawed and contradicted by others. Also, physical obstruction could be more important in causing postoperative reflux than postoperative ileus in the horse. The antiinflammatory properties of lidocaine and the role of inflammation from intestinal handling in the genesis of postoperative reflux are questionable. Because of cost and questionable efficacy of lidocaine, a well-designed clinical trial is required to support its continued use. However, lidocaine could be given to provide or enhance analgesia in selected cases with postoperative colic.

Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases.

The human intestinal microbiota, establishing a symbiotic relationship with the host, plays a significant role for human health. It is also well known that a disease status is frequently characterized by a dysbiotic condition of the gut microbiota. A probiotic treatment can represent an alternative therapy for enteric disorders and human pathologies not apparently linked to the gastrointestinal tract. Among bifidobacteria, strains of the species Bifidobacterium breve are widely used in paediatrics. B. breve is the dominant species in the gut of breast-fed infants and it has also been isolated from human milk. It has antimicrobial activity against human pathogens, it does not possess transmissible antibiotic resistance traits, it is not cytotoxic and it has immuno-stimulating abilities. This review describes the applications of B. breve strains mainly for the prevention/treatment of paediatric pathologies. The target pathologies range from widespread gut diseases, including diarrhoea and infant colics, to celiac disease, obesity, allergic and neurological disorders. Moreover, B. breve strains are used for the prevention of side infections in preterm newborns and during antibiotic treatments or chemotherapy. With this documentation, we hope to increase knowledge on this species to boost the interest in the emerging discipline known as "therapeutic microbiology".

Effectiveness and Safety of a Probiotic-Mixture for the Treatment of Infantile Colic: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial with Fecal Real-Time PCR and NMR-Based Metabolomics Analysis.

INTRODUCTION: To investigate the effectiveness and the safety of a probiotic-mixture (Vivomixx®, Visbiome®, DeSimone Formulation®; Danisco-DuPont, Madison, WI, USA) for the treatment of infantile colic in breastfed infants, compared with a placebo. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in exclusively breastfed infants with colic, randomly assigned to receive a probiotic-mixture or a placebo for 21 days. A structured diary of gastrointestinal events of the infants was given to the parents to complete. Samples of feces were also collected to evaluate microbial content and metabolome using fecal real-time polymerase chain reaction (qPCR) and Nuclear magnetic resonance (NMR)-based analysis. Study registered at ClinicalTrials.gov (NCT01869426). RESULTS: Fifty-three exclusively-breastfed infants completed three weeks of treatment with a probiotic-mixture (n = 27) or a placebo (n = 26). Infants receiving the probiotic-mixture had less minutes of crying per day throughout the study by the end of treatment period (68.4 min/day vs. 98.7 min/day; p = 0.001). A higher rate of infants from the probiotic-mixture group responded to treatment (defined by reduction of crying times of ≥50% from baseline), on day 14, 12 vs. 5 (p = 0.04) and on day 21, 26 vs. 17 (p = 0.001). A higher quality of life, assessed by a 10-cm visual analogue scale, was reported by parents of the probiotic-mixture group on day 14, 7.1 ± 1.2 vs. 7.7 ± 0.9 (p = 0.02); and on day 21, 6.7 ± 1.6 vs. 5.9 ± 1.0 (p = 0.001). No differences between groups were found regarding anthropometric data, bowel movements, stool consistency or microbiota composition. Probiotics were found to affect the fecal molecular profile. No adverse events were reported. CONCLUSIONS: Administration of a probiotic-mixture appears safe and reduces inconsolable crying in exclusively breastfed infants.

Efficacy of a standardized extract of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) in infantile colic: An open randomized controlled trial.

BACKGROUND: Infant colic (IC) is a prevalent physiological event of infants, which can disrupt the child's home environment. We aimed to investigate the effectiveness of a mixture of Matricariae chamomilla L., Melissa officinalis L. and tyndallized Lactobacillus acidophilus (HA122) compared with Lactobacillus reuteri DSM 17938 and with simethicone for the treatment of IC. METHODS: A multicenter randomized comparative study was conducted in infants with colic, according to Rome III criteria, who were randomly assigned to receive M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) (Colimil® Plus® ; Milte Italia Spa, Milan, Italy) (Group A), L. reuteri DSM 17938 (Group B) and simethicone (Group C). Treatment was given to subjects for 28 days. KEY RESULTS: One-hundred and seventy-six patients completed the study. Mean daily crying time at day 28 was significantly lower in group A (-44, 95% CI: -58 to -30, P<.001) and group B (-35, 95% CI: -49 to -20, P<.001) when compared to group C. No significant difference was observed between Group A and Group B (mean difference: -9 minutes, 95% CI -23 to +5, P=.205). At day 28, 39 of 57 (68.4%) of infants in Group C responded to the treatment compared with 57 out of 60 patients (95%) of Group A and 51 out of 59 (86.4%) of Group B (P<.001). CONCLUSIONS: This study suggests that administration of M. chamomilla L., M. officinalis L. and tyndallized L. acidophilus (HA122) and L. reuteri DSM 17938 are significantly more effective than simethicone in IC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02708238.

Comparison of efficacy and safety of hyoscine butylbromide versus anisodamine for acute gastric or intestinal spasm-like pain: A randomized, double-blinded, multicenter Phase III trial.

OBJECTIVE: Acute gastric or intestinal spasm-like pain is common in clinical setting. Hyoscine butylbromide (HBB), an anti-cholinergic agent, relieves pain in stomach and bowel cramps by inhibiting smooth muscle contractility. In this study, we aimed to compare the efficacy and safety of parenteral HBB and anisodamine for treating acute gastric or intestinal pain. METHODS: In this randomized, controlled, double-blind, parallel-group, multicenter non-inferiority trial, 299 Chinese patients were randomly assigned to HBB or anisodamine in a ratio of 1:1. They were administrated a single dose of either HBB 20 mg or anisodamine 10 mg, and a second dose was given when needed. The primary end-point was the difference in pain intensity (PID) from the pre-dose baseline at 20 min after the first injection. RESULTS: Altogether 295 patients completed the protocol (153 in the HBB and 142 in the anisodamine group). For the primary end-point, the PID was -4.09 (95% confidence interval [CI]: -4.41, -3.76) for the HBB group and -3.66 (95% CI: -4.02, -3.31) for the anisodamine group (P < 0.0001 for non-inferiority). The percentage of patients with at least one adverse event was lower in the HBB group than in the anisodamine group (13.1% vs 17.6%), but there was no statistical significance (P = 0.279). The most frequent adverse events were thirst (7.8%) and dry mouth (2.6%) in the HBB group, and thirst (7.0%), dry mouth (3.5%) and nodal arrhythmia (2.1%) in the anisodamine group. CONCLUSIONS: HBB 20 mg was not inferior to anisodamine 10 mg in pain relief of patients with acute gastric or intestinal spasm-like pain. Both drugs were safe and well tolerated.