A randomized double-blind placebo-controlled trial showing rifaximin to improve constipation by reducing methane production and accelerating colon transit: A pilot study

Objective

Gut microbe-derived methane may slow colon transit causing chronic constipation (CC). Effect of rifaximin on breath methane and slow-transit CC was evaluated.

Method

Bristol stool form, frequency, colon transit time (CTT), and breath methane were evaluated in 23 patients with CC (10 patients with constipation-predominant irritable bowel syndrome [IBS-C], 13 functional constipation, Rome III) and m-ethane production compared with 68 non-constipating IBS. Methane-producing CC (basal ≥?10 PPM and/or post-lactulose rise by >?10 PPM) was randomized (double-blind) to rifaximin (400-mg thrice/day, 2-weeks) or placebo. Stool forms, frequency, breath methane, and CTT were recorded afterward.

Results

CC patients tended to be methane producer more often (13/23 [56.5%] vs. 25/68 [36.5%], p?=?0.07) and had greater area under curve (AUC) for methane (2415 [435–23,580] vs. 1335 [0–6562.5], p?=?0.02) than non-constipating IBS. Methane producers (8/13 [61.5%]) and 5/10 (50%) non-producers had abnormal CTT (marker retention: 36-h, 53 [0–60] vs. 19 [8–56], p?=?0.06; 60-h, 16 [0–57] vs. 13 [3–56], p?=?0.877). Six and 7/13 methane producers were randomized to rifaximin and placebo, respectively. Rifaximin reduced AUC for methane more (6697.5 [1777.5–23,580] vs. 2617.5 [562.5–19,867.5], p?=?0.005) than placebo (3945 [2415–12,952.5] vs. 3720 [502.5–9210], p?=?0.118) at 1 month. CTT normalized in 4/6 (66.7%) on rifaximin (36-h retention, 54 [44–57] vs. 36 [23–60], p?=?0.05; 60-h, 45 [3–57] vs. 14 [11–51], p?=?0.09) but none on placebo (p?=?0.02) (36-h, 31 [0–60] vs. 25 [0–45], p?=?0.078; 60-h, 6 [0–54] vs. 12 [0–28], p?=?0.2). Weekly stool frequency (3 [1–9] and 7 [1–14], p?=?0.05) and forms improved with rifaximin than placebo.

Conclusion

Rifaximin improves CC by altering methane production and colon transit.

Trial registration

Clinical Trial Registry, India: REF/2012/01/003216

Open image in new window

? ?

     

Pharmacy based surveillance for identifying missing tuberculosis cases: A mixed methods study from South India

BackgroundNo Indian studies have assessed the implementation of recent policy on pharmacy based surveillance and its contribution in TB notification. So, this study was conducted with objectives to describe: a) pharmacy based TB surveillance and TB notification, and b) experiences of pharmacy based surveillance implementation from the programme managers and pharmacists perspective.MethodsA mixed methods study—quantitative (cross-sectional) and qualitative (in-depth interviews) in two selected districts Dharmapuri and Salem districts of Tamil Nadu State, India.ResultsIn 2018, 45 (11%) of 397 pharmacies in Dharmapuri and 90 (6%) of 1457 pharmacies in Salem districts reported sale of anti-TB drugs to 1307 and 1673 persons respectively. Upon validation through direct patient contact 942 (72%) persons in Dharmapuri and 863 (52%) persons were identified as previously ‘un-notified’ TB patients. These patients constituted 20% and 29% of the total TB cases notified in Dharmapuri and Salem respectively. The enablers for implementing this activity were: understanding the importance of notification, availability of resources (manpower, computers) to record, report and validate the patient data, repeated trainings and partnerships. The barriers were: patients' hesitancy to share their details to pharmacists (confidentiality), cumbersome recording and reporting process, difficulties in recording patient details during high workload busy business hours.ConclusionThis process contributed about one-fourth of the TB patients notified in these districts. Its implementation needs to be strengthened and should be scaled up in other parts of the country.     

Role of p34cdc2-mediated phosphorylations in two-step activation of pp60c-src during mitosis.

Phosphorylation of pp60c-src by p34cdc2 at three amino-proximal serine/threonine residues is temporally correlated with, but insufficient for, mitotic activation of c-Src kinase. The direct cause of activation during mitosis appears to be temporally correlated partial dephosphorylation of Tyr-527, a residue whose phosphorylation strongly suppresses pp60c-src activity. Site-directed mutagenesis of the serine/threonine phosphorylation sites blocks half the mitosis-specific decrease in Tyr-527 phosphorylation and half the increase in pp60c-src kinase activity. We conclude that p34cdc2 partially activates pp60c-src by a two-step process in which its serine/threonine phosphorylations either sensitize pp60c-src to a Tyr-527 phosphatase or desensitize it to a Tyr-527 kinase. Furthermore, additional events, independent of these p34cdc2-mediated phosphorylations, participate in mitotic activation of pp60c-src.