Effects of deworming on child and maternal health: a literature review and meta-analysis

Background

Soil-transmitted helminth infections are widespread. Many studies have been published on the topic of deworming. The Lives Saved Tool (LiST) is a software package that uses a deterministic mathematical model to estimate the effect of scaling up interventions on maternal and child health outcomes. This review investigates the scope of available evidence for benefits of deworming treatments in order to inform a decision about possible inclusion of deworming as an intervention in LiST.

Methods

We searched PubMed, the Cochrane Library, and Google Scholar. We included studies that reported pre/post data in children younger than 5 years or pregnant women for outcomes related to mortality and growth. We excluded studies that compared different anthelminthic treatments but did not include a placebo or non-treatment group, and those that did not report post-intervention outcomes. We categorized articles by treated population (children younger than 5 years and pregnant women), experimental versus observational, mass drug administration (MDA) versus treatment, and reported outcome.

Results

We identified 58 relevant trials; 27 investigated children younger than 5 years and 11 investigated pregnant women; one reported on both children younger than 5 years and pregnant women. We conducted meta-analyses of relevant outcomes in children younger than 5 years.

Conclusions

Deworming did not show consistent benefits for indicators of mortality, anemia, or growth in children younger than five or women of reproductive age. We do not recommend including the effect of deworming in the LiST model.

     

Integration of ruxolitinib into dose‐intensified therapy targeted against a novel JAK2 F694L mutation in B‐precursor acute lymphoblastic leukemia

A 17‐year‐old girl with B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL) with persistent minimal residual disease (MRD) who underwent standard chemotherapy was found to have a BCR‐ABL1‐like gene expression pattern. Genome sequencing revealed a JAK2 mutation not previously described in BCP‐ALL and a potential therapeutic target. Due to concern for an on‐therapy relapse, the JAK2 inhibitor ruxolitinib was incorporated into a modified chemotherapy backbone to achieve complete remission prior to stem cell transplant. Treatment was well tolerated and she had undetectable MRD prior to a matched allogeneic stem cell transplant and remained in remission at day +100.     

Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial

Jaffer A. Ajani, MD; Kathryn A. Winter, MS; Leonard L. Gunderson, MD; John Pedersen, MD; Al B. Benson III, MD; Charles R. Thomas Jr, MD; Robert J. Mayer, MD; Michael G. Haddock, MD; Tyvin A. Rich, MD; Christopher Willett, MD

JAMA. 2008;299(16):1914-1921.

Context  Chemoradiation as definitive therapy is the preferred primary therapy for patients with anal canal carcinoma; however, the 5-year disease-free survival rate from concurrent fluorouracil/mitomycin and radiation is only approximately 65%.

Objective  To compare the efficacy of cisplatin-based (experimental) therapy vs mitomycin-based (standard) therapy in treatment of anal canal carcinoma.

Design, Setting, and Participants  US Gastrointestinal Intergroup trial RTOG 98-11, a multicenter, phase 3, randomized controlled trial comparing treatment with fluorouracil plus mitomycin and radiotherapy vs treatment with fluorouracil plus cisplatin and radiotherapy in 682 patients with anal canal carcinoma enrolled between October 31, 1998, and June 27, 2005. Stratifications included sex, clinical nodal status, and tumor diameter.

Intervention  Participants were randomly assigned to 1 of 2 intervention groups: (1) the mitomycin-based group (n = 341), who received fluorouracil (1000 mg/m² on days 1-4 and 29-32) plus mitomycin (10 mg/m² on days 1 and 29) and radiotherapy (45-59 Gy) or (2) the cisplatin-based group (n = 341), who received fluorouracil (1000 mg/m² on days 1-4, 29-32, 57-60, and 85-88) plus cisplatin (75 mg/m² on days 1, 29, 57, and 85) and radiotherapy (45-59 Gy; start day = day 57).

Main Outcome Measures  The primary end point was 5-year disease-free survival; secondary end points were overall survival and time to relapse.

Results  A total of 644 patients were assessable. The median follow-up for all patients was 2.51 years. Median age was 55 years, 69% were women, 27% had a tumor diameter greater than 5 cm, and 26% had clinically positive nodes. The 5-year disease-free survival rate was 60% (95% confidence interval [CI], 53%-67%) in the mitomycin-based group and 54% (95% CI, 46%-60%) in the cisplatin-based group (P = .17). The 5-year overall survival rate was 75% (95% CI, 67%-81%) in the mitomycin-based group and 70% (95% CI, 63%-76%) in the cisplatin-based group (P = .10). The 5-year local-regional recurrence and distant metastasis rates were 25% (95% CI, 20%-30%) and 15% (95% CI, 10%-20%), respectively, for mitomycin-based treatment and 33% (95% CI, 27%-40%) and 19% (95% CI, 14%-24%), respectively, for cisplatin-based treatment. The cumulative rate of colostomy was significantly better for mitomycin-based than cisplatin-based treatment (10% vs 19%; P = .02). Severe hematologic toxicity was worse with mitomycin-based treatment (P < .001).

Conclusions  In this population of patients with anal canal carcinoma, cisplatin-based therapy failed to improve disease-free-survival compared with mitomycin-based therapy, but cisplatin-based therapy resulted in a significantly worse colostomy rate. These findings do not support the use of cisplatin in place of mitomycin in combination with fluorouracil and radiotherapy in the treatment of anal canal carcinoma.

Trial Registration  clinicaltrials.gov Identifier: NCT00003596

     

Fear of cancer recurrence in survivor and caregiver dyads: differences by sexual orientation and how dyad members influence each other

Purpose

The purpose of this study was to identify explanatory factors of fear of recurrence (FOR) in breast cancer survivors of different sexual orientations and their caregivers and to assess the directionality in the survivor and caregiver dyads’ FOR.

Methods

We recruited survivors of non-metastatic breast cancer of different sexual orientations and invited their caregivers into this study. Using a telephone survey, we collected data from 167 survivor and caregiver dyads. Using simultaneous equation models and a stepwise selection process, we identified the significant determinants of survivors’ and caregivers’ FOR and determined the directionality of survivors’ and caregivers’ FOR. Weighting the model by the inverse propensity score ensured that differences by sexual orientation in age and proportion of life in the caregiver-survivor relationship were accounted for.

Results

Caregivers’ FOR predicted survivors’ FOR, and sexual orientation had a significant effect on survivors’ FOR, in that sexual minority women reported less FOR than heterosexual women. Other determinants of survivors’ FOR included their medical characteristics, coresidence with caregivers, and caregivers’ social support and use of counseling. Caregivers’ FOR was related to their social support and survivors’ medical characteristics.

Conclusions

This study suggests a need for caregiver interventions. Because survivors’ FOR is affected by caregivers’ FOR, caregiver interventions will likely benefit survivors’ FOR.

Implications for cancer survivors

Both sexual minority and heterosexual breast cancer survivors’ FOR are affected by their caregivers’ FOR, which suggests that the caregivers of breast cancer survivors are central for the survivors’ well-being and shall therefore be integrated into the care process.

     

Bipolar radio-frequency-induced thermofusion of intestinal tissue – In vivo evaluation of a new fusion technique in an experimental study

Purpose: Bipolar radio-frequency-induced thermofusion (BiRTh) of intestinal tissue might replace conventional stapling devices which are associated with technical and functional complications. Previous results of our study group confirmed the feasibility to fuse intestinal tissue using BiRTh-induced thermofusion ex vivo. The aim of this study was now to evaluate the efficacy of fusing intestinal tissue in vivo by BiRTh-induced thermofusion.

Materials and methods: In male Wistar rats a blind bowel originating from the caecum was closed either by BiRTh (n = 24) or conventional suture (n = 16). At 6?h, 48?h, 4 days, and 2 weeks after the procedure caecum bursting pressure was measured to compare both groups.

Results: In total 18 of 21 (85.7%) thermofused and 15 of 16 (93.7%) sutured cecal stumps were primarily tight and leakage-proof (p > 0.05). The operative time was comparable in both groups without significant differences. Both groups showed increases in bursting pressure over the post-operative period. The mean bursting pressure for thermofusion was 47.8, 48.3, 55.2, and 68.0?mmHg, compared to 69.8, 51.5, 70.0 and 71.0?mmHg in the hand-sutured group (p?>?0.05) after 6?h, 48?h, 4 days, and 2 weeks, respectively.

Conclusion: These results suggest that BiRTh-induced thermofusion is a safe and feasible method for fusing intestinal tissue in this experimental in vivo model and could be an innovative approach for achieving gastrointestinal anastomoses.     

Differential role of tachykinin NK3 receptors on cholinergic excitatory neurotransmission in the mouse stomach and small intestine

Background and purpose:

Tachykinin NK₃ receptors are widely expressed in the mouse gastrointestinal tract but their functional role in enteric neuromuscular transmission remains unstudied in this species. We investigated the involvement of NK₃ receptors in cholinergic neurotransmission in the mouse stomach and small intestine.

Experimental approach:

Muscle strips of the mouse gastric fundus and ileum were mounted in organ baths for tension recordings. Effects of NK₃ agonists and antagonists were studied on contractions to EFS of enteric nerves and to carbachol.

Key results:

EFS induced frequency-dependent tetrodotoxin-sensitive contractions, which were abolished by atropine. The cholinergic contractions to EFS in the stomach were enhanced by the NK₃ antagonist SR142801, but not affected by the NK₃ agonist senktide or neurokinin B. The cholinergic contractions to EFS in the small intestine were not affected by SR142801, but dose-dependently inhibited by senktide and neurokinin B. This inhibitory effect was prevented by SR142801 but not by hexamethonium. SR142801, senktide or neurokinin B did not induce any response per se in the stomach and small intestine and did not affect contractions to carbachol.

Conclusions and implications:

NK₃ receptors modulate cholinergic neurotransmission differently in the mouse stomach and small intestine. Blockade of NK₃ receptors enhanced cholinergic transmission in the stomach but not in the intestine. Activation of NK₃ receptors inhibited cholinergic transmission in the small intestine but not in the stomach. This indicates a physiological role for NK₃ receptors in mouse stomach contractility and a pathophysiological role in mouse intestinal contractility.