Erector spinae plane block did not improve postoperative pain-related outcomes and recovery after video-assisted thoracoscopic surgery : a randomised controlled double-blinded multi-center trial.

INTRODUCTION: There is a sizable niche for a minimally invasive analgesic technique that could facilitate ambulatory video-assisted thoracoscopic surgery (VATS). Our study aimed to determine the analgesic potential of a single-shot erector spinae plane (ESP) block for VATS. The primary objective was the total hydromorphone consumption with patient-controlled analgesia (PCA) 24 h after surgery. METHODS: We conducted a randomized, controlled, double-blind study with patients scheduled for VATS in two major university-affiliated hospital centres. We randomized 52 patients into two groups: a single-shot ESP block using bupivacaine or an ESP block with normal saline (control). We administered a preoperative and postoperative (24 h) quality of recovery (QoR-15) questionnaire and assessed postoperative pain using a verbal numerical rating scale (VNRS) score. We evaluated the total standardized intraoperative fentanyl administration, total postoperative hydromorphone consumption (PCA; primary endpoint), and the incidence of adverse effects. RESULTS: There was no difference in the primary objective, hydromorphone consumption at 24 h (7.6 (4.4) mg for the Bupivacaine group versus 8.1 (4.2) mg for the Control group). Secondary objectives and incidence of adverse events were not different between the two groups at any time during the first 24 h following surgery. CONCLUSION: Our multi-centre randomized, controlled, double-blinded study found no advantage of an ESP block over placebo for VATS for opioid consumption, pain, or QoR-15 scores. Further studies are ongoing to establish the benefits of using a denser block (single-shot paravertebral with a continuous ESP block), which may provide a better quality of analgesia.

Multi-focal Stimulation of the Cortico-cerebellar Loop During the Acquisition of a Novel Hand Motor Skill in Chronic Stroke Survivors.

Impairment of hand motor function is a frequent consequence after a stroke and strongly determines the ability to regain a self-determined life. An influential research strategy for improving motor deficits is the combined application of behavioral training and non-invasive brain stimulation of the motor cortex (M1). However, a convincing clinical translation of the present stimulation strategies has not been achieved yet. One alternative and innovative approach is to target the functionally relevant brain network-based architecture, e.g., the dynamic interactions within the cortico-cerebellar system during learning. Here, we tested a sequential multifocal stimulation strategy targeting the cortico-cerebellar loop. Anodal transcranial direct current stimulation (tDCS) was applied simultaneously to a hand-based motor training in N = 11 chronic stroke survivors during four training sessions on two consecutive days. The tested conditions were: sequential multifocal (M1-cerebellum (CB)-M1-CB) vs. monofocal control stimulation (M1-sham-M1-sham). Additionally, skill retention was assessed 1 and 10 days after the training phase. Paired-pulse transcranial magnetic stimulation data were recorded to characterize stimulation response determining features. The application of CB-tDCS boosted motor behavior in the early training phase in comparison to the control condition. No faciliatory effects on the late training phase or skill retention were detected. Stimulation response variability was related to the magnitude of baseline motor ability and short intracortical inhibition (SICI). The present findings suggest a learning phase-specific role of the cerebellar cortex during the acquisition of a motor skill in stroke and that personalized stimulation strategies encompassing several nodes of the underlying brain network should be considered.

Comparative roadmaps of reprogramming and oncogenic transformation identify Bcl11b and Atoh8 as broad regulators of cellular plasticity.

Coordinated changes of cellular plasticity and identity are critical for pluripotent reprogramming and oncogenic transformation. However, the sequences of events that orchestrate these intermingled modifications have never been comparatively dissected. Here, we deconvolute the cellular trajectories of reprogramming (via Oct4/Sox2/Klf4/c-Myc) and transformation (via Ras/c-Myc) at the single-cell resolution and reveal how the two processes intersect before they bifurcate. This approach led us to identify the transcription factor Bcl11b as a broad-range regulator of cell fate changes, as well as a pertinent marker to capture early cellular intermediates that emerge simultaneously during reprogramming and transformation. Multiomics characterization of these intermediates unveiled a c-Myc/Atoh8/Sfrp1 regulatory axis that constrains reprogramming, transformation and transdifferentiation. Mechanistically, we found that Atoh8 restrains cellular plasticity, independent of cellular identity, by binding a specific enhancer network. This study provides insights into the partitioned control of cellular plasticity and identity for both regenerative and cancer biology.

Recipients with blood group A associated with longer survival rates in cardiac valvular bioprostheses.

BACKGROUND: Pigs/bovines share with humans some of the antigens present on cardiac valves. Two such antigens are: the major xenogenic Ag, "Gal" present in all pig/bovine very close to human B-antigen of ABO-blood-group system; the minor Ag, pig histo-blood-group AH-antigen identical to human AH-antigen and present by some animals. We hypothesize that these antigens may modify the immunogenicity of the bioprosthesis and also its longevity. ABO distribution may vary between patients with low (<6 years) and high (≥15 years) bioprostheses longevity. METHODS: Single-centre registry study (Paris, France) including all degenerative porcine bioprostheses (mostly Carpentier-Edwards 2nd/3rd generation heart valves) explanted between 1985 and 1998 and some bovine bioprostheses. For period 1998-2014, all porcine bioprostheses with longevity ≥13 years (follow-up ≥29 years). Important predictive factors for bioprosthesis longevity: number, site of implantation, age were collected. Blood group and other variables were entered into an ordinal logistic regression analysis model predicting valve longevity, categorized as low (<6 years), medium (6-14.9 years), and high (≥15 years). FINDINGS: Longevity and ABO-blood group were obtained for 483 explanted porcine bioprostheses. Mean longevity was 10.2 ±â€¯3.9 years [0-28] and significantly higher for A-patients than others (P = 0.009). Using multivariate analysis, group A was a strong predictive factor of longevity (OR 2.09; P < 0.001). For the 64 explanted bovine bioprosthesis with low/medium longevity, the association, with A-group was even more significant. INTERPRETATION: Patients of A-group but not B have a higher longevity of their bioprostheses. Future graft-host phenotyping and matching may give rise to a new generation of long-lasting bioprosthesis for implantation in humans, especially for the younger population. FUND: None.

Left ventricular assist device in the management of refractory electrical storm.

Electrical storm refers to a state of cardiac electrical instability characterized by multiple episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) within a relatively short period of time and is associated with increased mortality and morbidity. The management of electrical storm involves a variety of strategies, including sedation, anti-arrhythmic and electrolyte replacement as well as revascularization and electrical ablation. However, the management strategy in patients with refractory storm is less clear and may require more invasive approaches. We present a case of severe ventricular tachycardia storm refractory to conservative management that was managed with a HeartMate II left ventricular assist device.

Predictors and impact of myocardial injury after transcatheter aortic valve replacement: a multicenter registry

BACKGROUND:Cardiac biomarker release signifying myocardial injury post-transcatheter aortic valve replacement (TAVR) is common, yet its clinical impact within a large TAVR cohort receiving differing types of valve and procedural approaches is unknown.OBJECTIVES:This study sought to determine the incidence, clinical impact, and factors associated with cardiac biomarker elevation post TAVR.METHODS:This multicenter study included 1,131 consecutive patients undergoing TAVR with balloon-expandable (58%) or self-expandable (42%) valves. Transfemoral and transapical (TA) approaches were selected in 73.1% and 20.3% of patients, respectively. Creatine kinase-myocardial band (CK-MB) measurements were obtained at baseline and at several time points within the initial 72 h post TAVR. Echocardiography was performed at baseline and at 6- to 12-month follow-up.RESULTS:Overall, 66% of the TAVR population demonstrated some degree of myocardial injury as determined by a rise in CK-MB levels (peak value: 1.6-fold [interquartile range (IQR): 0.9 to 2.8-fold]). A TA approach and major procedural complications were independently associated with higher peak of CK-MB levels (p < 0.01 for all), which translated into impaired systolic left ventricular function at 6 to 12 months post TAVR (p < 0.01). A greater rise in CK-MB levels independently associated with an increased 30-day, late (median of 21 [IQR: 8 to 36] months) overall and cardiovascular mortality (p < 0.001 for all)...

Injected matrix stimulates myogenesis and regeneration of mouse skeletal muscle after ischaemic injury.

Biomaterial-guided regeneration represents a novel approach for the treatment of myopathies. Revascularisation and the intramuscular extracellular matrix are important factors in stimulating myogenesis and regenerating muscle damaged by ischaemia. In this study, we used an injectable collagen matrix, enhanced with sialyl LewisX (sLeX), to guide skeletal muscle differentiation and regeneration. The elastic properties of collagen and sLeX-collagen matrices were similar to those of skeletal muscle, and culture of pluripotent mESCs on the matrices promoted their differentiation into myocyte-like cells expressing Pax3, MHC3, myogenin and Myf5. The regenerative properties of matrices were evaluated in ischaemic mouse hind-limbs. Treatment with the sLeX-matrix augmented the production of myogenic-mediated factors insulin-like growth factor (IGF)-1, and IGF binding protein-2 and -5 after 3 days. This was followed by muscle regeneration, including a greater number of regenerating myofibres and increased transcription of Six1, M-cadherin, myogenin and Myf5 after 10 days. Simultaneously, the sLeX-matrix promoted increased mobilisation and engraftment of bone marrow-derived progenitor cells, the development of larger arterioles and the restoration of tissue perfusion. Both matrix treatments tended to reduce maximal forces of ischaemic solei muscles, but sLeX-matrix lessened this loss of force and also prevented muscle fatigue. Only sLeX-matrix treatment improved mobility of mice on a treadmill. Together, these results suggest a novel approach for regenerative myogenesis, whereby treatment only with a matrix, which possesses an inherent ability to guide myogenic differentiation of pluripotent stem cells, can enhance the endogenous vascular and myogenic regeneration of skeletal muscle, thus holding promise for future clinical use.

Antimicrobial isothiocyanates from the seeds of Moringa oleifera Lam.

4-(alpha-L-Rhamnosyloxy)benzyl isothiocyanate (1) and 4-(4'-O-acetyl-alpha-L-rhamnosyloxy)-benzyl isothiocyanate (2) isolated from Moringa oleifera seeds were screened for their antibacterial activities against Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and for their antifungal activities against Candida albicans, Trichophyton rubrum, and Epidermophyton floccosum using the disk diffusion method. Isothiocyanates 1 and 2 were found active at the lowest inhibitory concentration of 1 mg/ml against all Gram-positive bacteria tested (S. aureus, S. epidermidis, B. subtilis) and against the dermatophytic fungi E. floccosum and T. rubrum. Statistically significant differences were found between the mean inhibition zones (IZ) of 1 and 2 and the standard drugs, ofloxacin and clotrimazole. The minimum inhibitory concentration (MIC) values confirmed the good antimicrobial activity of 1 and 2 against S. aureus, good to moderate activity against S. epidermidis, moderate activity against B. subtilis, and weak activity against E. floccosum and T. rubrum. The in vitro bactericidal effect of 1 and 2 against the Gram-positive bacterial strains tested is suggested by MBC:MIC ratios of 2:1.

A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell response and blood vessel growth in ischaemic skeletal muscle.

Although many regenerative cell therapies are being developed to replace or regenerate ischaemic muscle, the lack of vasculature and poor persistence of the therapeutic cells represent major limiting factors to successful tissue restoration. In response to ischaemia, stromal cell-derived factor-1 (SDF-1) is up-regulated by the affected tissue to stimulate stem cell-mediated regenerative responses. Therefore, we encapsulated SDF-1 into alginate microspheres and further incorporated these into an injectable collagen-based matrix in order to improve local delivery. Microsphere-matrix impregnation reduced the time for matrix thermogelation, and also increased the viscosity reached. This double-incorporation prolonged the release of SDF-1, which maintained adhesive and migratory bioactivity, attributed to chemotaxis in response to SDF-1. In vivo, treatment of ischaemic hindlimb muscle with microsphere-matrix led to increased mobilisation of bone marrow-derived progenitor cells, and also improved recruitment of angiogenic cells expressing the SDF-1 receptor (CXCR4) from bone marrow and local tissues. Both matrix and SDF-1-releasing matrix were successful at restoring perfusion, but SDF-1 treatment appeared to play an earlier role, as evidenced by arterioles that are phenotypically older and by increased angiogenic cytokine production, stimulating the generation of a qualitative microenvironment for a rapid and therefore more efficient regeneration. These results support the release of implanted SDF-1 as a promising method for enhancing progenitor cell responses and restoring perfusion to ischaemic tissues via neovascularisation.

Gender differences in the long-term outcomes after valve replacement surgery.

OBJECTIVE: To compare the long-term outcomes in women and men after valve replacement surgery. DESIGN: Observational study. SETTING: Postoperative aortic valve replacement (AVR) or mitral valve replacement (MVR). PATIENTS: 3118 patients (1261 women, 1857 men) who underwent AVR or MVR between 1976 and 2006 (2255 AVR, 863 MVR), with mean follow-up of 5.6 (4.5) years. MAIN OUTCOME MEASURES: The independent effect of gender on the risk of long-term complications (reoperation, stroke and death) after valve replacement surgery using multivariate actuarial methods. RESULTS: After implantation of an aortic valve bioprosthesis, women had a significantly lower rate of reoperation compared to men (comorbidity-adjusted hazard ratio (HR) 0.4; 95% confidence intervals (CI) 0.2 to 0.9). In contrast, if an aortic mechanical prosthesis had been implanted, women were more at risk for late stroke compared to men (HR 1.7; CI 1.1 to 2.7). After adjustment for age and co-morbidities, women had significantly better long-term survival compared to men after bioprosthetic AVR (HR 0.5; CI 0.3 to 0.6), but there was no survival difference between genders after mechanical AVR. Trends existed towards better survival for women after bioprosthetic MVR (HR 0.6; CI 0.4 to 1.0) and mechanical MVR (HR 0.8; CI 0.5 to 1.1). CONCLUSION: The long-term outcomes after valve replacement surgery differ between women and men. Although women have more late strokes after valve replacement, they undergo fewer reoperations and have better overall long-term survival compared to men.

The overlap of overweight and anaemia among women in three countries undergoing the nutrition transition.

OBJECTIVE: To compare the odds of anaemia in overweight and obese (OVWT) (body mass index (BMI) > or =25) versus non-overweight (non-OVWT) (BMI<25) women in three countries at different stages of the nutrition transition. DESIGN: Analysis of cross-sectional data. SETTING: Nationally representative data from Mexico (1998 National Nutrition Survey), Peru and Egypt (2000 Demographic and Health Surveys) were analyzed. SUBJECTS: Data from non-pregnant women ages 18-49 years were used. ANALYSIS: Logistic regression was used to test whether the odds of anaemia differed by BMI category, controlling for sociodemographic factors. RESULTS: More than half of the women were OVWT in all three countries and the prevalence of OVWT reached 77% in Egypt. Anaemia prevalence was similar across countries (28, 31 and 23% in Egypt, Peru and Mexico respectively). In Egypt, OVWT women had significantly lower odds of anaemia than non-OVWT women (OR=0.78, 95% CI: 0.68, 0.90). Similar results were found in Peru, but the difference was smaller in magnitude (OR=0.83, 95% CI: 0.71, 0.96). In Mexico, there were no differences in the odds of anaemia by BMI group. CONCLUSIONS: These findings show that the iron needs of OVWT women in developing countries are not necessarily being met. The intakes of other micronutrients might also be insufficient. Diet quality remains an important issue even among women with sufficient energy intakes.

Invited review: Role of livestock in human nutrition and health for poverty reduction in developing countries.

Livestock keeping is critical for many of the poor in the developing world, often contributing to multiple livelihood objectives and offering pathways out of poverty. Livestock keeping also affects an indispensable asset of the poor, their human capital, through its impact on their own nutrition and health. This paper outlines the linkages between livestock keeping and the physical well-being of the poor, and examines a number of commonly held beliefs that misrepresent livestock development issues related to these linkages. These beliefs limit the scope of intervention programs to promote livestock and limit their potential contribution to poverty reduction. Recognition of the complexity of the role livestock play in household decision-making and of the opportunities foregone due to these misconceptions can enhance the ability of livestock to contribute to human well-being in the developing world.

Promotion of angiogenesis in tissue engineering: developing multicellular matrices with multiple capacities.

One of the aims of tissue engineering is to be able to develop multi-tissue organs in the future. This requires the optimization of conditions for the differentiation of multiple cell types and maintenance of the differentiated phenotype within complex engineered tissues. The goal of this study was to develop prototype tissue engineered matrices to support the simultaneous growth of different cell types with a particular focus on the angiogenic process. We examined two different matrix compositions for the promotion of blood vessel and tube formation. A fibrin-based matrix with the addition of a combination of growth factors supported vascular growth and the invasion of inflammatory cells. Using this fibrin matrix, in combination with a collagen-based hydrogel, a simple in vitro model of the cornea with adjacent sclera was developed that was complete with innervation and vascular structures. In addition, we showed that collagen-based matrices were effective in delivering mononuclear endothelial progenitor cells to ischemic tissue in vivo, and allowing these cells to incorporate into vascular structures. It is anticipated that with further development, these matrices have potential for use as delivery matrices for cell transplantation and for in vitro study purposes of multiple cell types.

Scalp nerve blocks decrease the severity of pain after craniotomy.

UNLABELLED: Up to 80% of patients report moderate to severe pain after craniotomy. In this study, we assessed the efficacy of scalp block for decreasing postoperative pain in brain surgery. Thirty patients scheduled for supratentorial craniotomy were enrolled. They were randomly divided into two groups: Ropivacaine (scalp block with 20 mL of ropivacaine 0.75%) and Saline (scalp block with 20 mL of saline 0.9%). Anesthesia was standardized. The scalp block was performed after skin closure and before awakening. Postoperative pain was assessed at 4, 8, 12, 16, 20, 24, and 48 h by using a 10-cm visual analog scale. Analgesia was provided with sub- cutaneous codeine as requested by the patient. Average visual analog scale scores were higher in the Saline group as compared with Ropivacaine (3.7 +/- 2.4 vs 2.0 +/- 1.6; P = 0.036). The total dose of codeine did not differ, nor did the duration of time before the first dose of codeine was required in the Ropivacaine (571 +/- 765 min) versus Saline (319 +/- 409 min; P = 0.17) group. In conclusion, we found that postoperative scalp block decreases the severity of pain after craniotomy and that this effect is long lasting, possibly through a preemptive mechanism. IMPLICATIONS: Up to 80% of patients report moderate to severe pain after craniotomy. This randomized double-blinded study demonstrated that ropivacaine scalp block decreases the severity of pain after supratentorial craniotomy.

Voluntary hyperventilation before a rapid-sequence induction of anesthesia does not decrease postintubation PaCO2.

UNLABELLED: To prevent hypercapnia, voluntary hyperventilation is recommended for patients with increased intracranial pressure before the induction of general anesthesia. We sought to determine whether this maneuver results in a lower PaCO2 than breathing 3 min of oxygen 100% by face mask (preoxygenation) after intubation. Thirty patients requiring general anesthesia were randomly assigned to breathe either 3 min of oxygen 100% by face mask (Group P) or 1 min of oxygen 100% followed by 2 min of voluntary hyperventilation with oxygen 100% (Group H). All patients received a standard rapid-sequence induction of anesthesia followed by a 90-s period of apnea. Patients were then tracheally intubated and mechanically ventilated. Five arterial blood gas samples were taken: with room air, after preoxygenation or hyperventilation, after 60 and 90 s of apnea, and after tracheal intubation. Voluntary hyperventilation decreased PaCO2 before rapid-sequence induction (hyperventilation, 30.0 +/- 3.5 mm Hg versus preoxygenation, 37.9 +/- 5.2 mm Hg; P < 0.0001), but after 60 s of apnea, both groups had similar PaCO2 (hyperventilation, 36.1 +/- 3.3 mm Hg versus preoxygenation, 35.6 +/- 3.4 mm Hg; P = 0.673), and no benefit was found after intubation (hyperventilation, 40.5 +/- 3.9 mm Hg versus preoxygenation, 41.4 +/- 2.7 mm Hg; P = 0.603). We conclude that voluntary hyperventilation before rapid-sequence induction does not provide protection against potential hypercapnia during intubation. IMPLICATIONS: Voluntary hyperventilation before anesthesia induction is recommended for patients with increased intracranial pressure to prevent hypercapnia. This randomized, prospective study demonstrated that this maneuver does not result in a lower postintubation PaCO2 than standard preoxygenation.

Is tranexamic acid safe in patients undergoing coronary endarterectomy?

BACKGROUND: Patients undergoing coronary endarterectomy during coronary artery bypass grafting (CABG) are at increased risk of perioperative myocardial infarction due to coronary intimal disruption. Data assessing the safety of the antifibrinolytic drug tranexamic acid (TA) in patients undergoing this procedure are lacking. METHODS: From September 1997 to December 1999, 221 patients underwent nonemergency primary CABG with endarterectomy of the right coronary artery alone in 149, the left anterior descending in 35, or both right and left anterior descending in 27. TA was administered intraoperatively to 87 patients (TA group: average total dose 62 +/- 4.4 mg/kg; range 20 to 109 mg/kg), and was not administered to 134 patients (No TA group). RESULTS: The patient characteristics of the 2 groups were similar. In-hospital mortality consisted of 2 patients in the TA group and 4 patients in the No TA group. Perioperative myocardial infarction rates were 2% and 5% in the TA and No TA groups, respectively (p = 0.49). The relative risk for any type of perioperative cardiac ischemic event in the TA group versus the No TA group was 0.77 (95% CI; 0.4, 1.2). Patients in the TA group had a significant reduction in postoperative chest tube drainage (685 versus 894 mL in the TA versus No TA groups, respectively) and in the use of fresh-frozen plasma (p = 0.03). CONCLUSIONS: These results suggest that the clinical effectiveness of tranexamic acid in reducing postoperative blood loss in patients undergoing coronary endarterectomy is not associated with a higher incidence of myocardial ischemia-related complications.

Non-pharmacological strategies for blood conservation in cardiac surgery.

PURPOSE: Of all surgical specialties, cardiac operations are most often associated with coagulopathy, blood loss, and the need for transfusions. This not only represents a major burden on blood procurement and banking organizations at all levels, but also constitutes a risk for each patient receiving allogeneic blood products. This paper reviews current non-pharmacological strategies aimed at decreasing blood use in patients undergoing cardiac surgery. SOURCE: The literature pertaining to each blood conservation strategy was searched, reviewed, and appraised. Meta- analyses were also consulted and their results complemented with subsequent reports when available. PRINCIPAL FINDINGS: Preoperative autologous donation programs are effective in decreasing allogeneic transfusions, but are costly and applicable to elective patients only. Off-pump revascularization strategies also appear to decrease transfusion requirements in suitable patients. The effectiveness of acute normovolemic hemodilution, retrograde autologous priming, small volume cardiopulmonary bypass circuits, platelet-rich plasmapheresis, alternative heparin strategies, and postoperative cell salvage are more difficult to appraise as a high proportion of available studies suffer from lack of transfusion guidelines or the absence of blinding. Biological glues, surgical adhesives, and postoperative increases in positive end-expiratory pressure (PEEP) have no demonstrated efficacy. CONCLUSION: The applicability or effectiveness of many of these modalities remains controversial and more studies are needed before they may be employed routinely in cardiac surgical patients. The judicious use of rational transfusion guidelines may still be the simplest and most cost-effective means of blood conservation today.

Resection of right atrial tumor thrombi without circulatory arrest.

Resectable retroperitoneal tumors with right atrial tumor thrombus extension have been excised previously using cardiopulmonary bypass and deep hypothermic circulatory arrest. We have used a technique involving clamping of the descending aorta with avoidance of deep hypothermic circulatory arrest in 6 patients. The approach provided a virtually bloodless field and allowed complete resection to be performed with low morbidity.

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.

BACKGROUND: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. OBJECTIVE: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. DESIGN: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. RESULTS: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. CONCLUSION: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.