Rapid policy change to single-embryo transfer while maintaining pregnancy rates per initiated cycle.

Public financing of IVF aims at increasing access to treatment while decreasing the expenses associated with multiple pregnancies. Critics argue that it is associated with lower pregnancy rates. This study compared cycles performed during 2009 (before implementation of Quebec's public IVF programme; period I) to those performed in the year following implementation (period II) in a single IVF centre. First fresh cycles in period I (499 women) and first fresh cycles (815 women) along with their corresponding first vitrified-warmed transfer (271 women) in period II were evaluated. From period I to period II, single-embryo transfer increased from 17.3% to 85.0% (P<0.001), multiple ongoing pregnancy rate decreased from 25.8% to 1.6% (P<0.001) and ongoing pregnancy rate decreased from 31.9% to 23.3% (P=0.001). During period II, the ongoing pregnancy rate per vitrified-warmed embryo transfer was 19.2%, leading to a cumulative ongoing pregnancy rate per initiated cycle of 29.7%, which was not different to the pregnancy rate per fresh cycle during period I (31.9%). To conclude, Quebec's public IVF programme decreased multiple pregnancy rates while maintaining an acceptable cumulative ongoing pregnancy rate, a more precise outcome to evaluate the impact of public IVF programmes.

Characterization of the distal esophagus high-pressure zone with manometry, ultrasound and micro-computed tomography.

BACKGROUND: We sought to determine how the individual components of the distal esophagus and proximal stomach form the gastroesophageal junction high-pressure zone (GEJHPZ) antireflux barrier. METHODS: An endoscopic ultrasound/manometry catheter was pulled through the proximal stomach and distal esophagus in 20 normal subjects. The axial length and width of individual structures on endoscopic ultrasound were measured. The anatomic orientation of gastroesophageal junction (GEJ) components was examined in two organ donor specimens using micro-computed tomography (micro-CT). KEY RESULTS: The three distinct structures identified within the GEJHPZ, from distal to proximal, were as follows: the gastric clasp and sling muscle fiber complex, crural diaphragm, and lower esophageal circular smooth muscle fibers (LEC). The LEC was statistically significantly thicker than adjacent esophageal muscles. These structures were associated with three pressure peaks. The pressure peak produced by the clasp/sling fiber complex often overlapped with the pressure peak from the crural diaphragm. The most proximal peak, associated with the LEC, was significantly greater and bimodal in nine of 20 subjects. This bimodal LEC pressure peak correlated with two areas of thickened muscle observed with ultrasound. Micro-CT of GEJ from organ donors confirmed the two areas of thickened muscle. CONCLUSIONS & INFERENCES: Three distinct anatomic structures, the clasp and sling muscle fibers, crural diaphragm, and LEC combine to form the antireflux barrier of the proximal stomach and distal esophagus. The clasp and sling muscle fibers combine with the crural diaphragm to form a distal pressure profile. The more proximal LEC has a bimodal pressure profile in some patients.

Working to eliminate multiple pregnancies: a success story in Québec.

In August 2010, the provincial government of Québec, Canada introduced funding of assisted reproduction treatment through the provincial health programme. Alongside this benefit, legislation was introduced to control assisted reproduction treatment activities in the province, including restrictions on the number of embryos that could be transferred in any one cycle. The aim of the programme was to transfer a single embryo in every cycle; multiple embryos could be transferred under suboptimal conditions but required physician justification. In the first 3 months of this programme, 1353 cycles of IVF were performed in five Québec assisted reproduction centres, with an overall clinical pregnancy rate of 32% per embryo transfer and 50% of transfers used elective single-embryo transfer (eSET). The multiple-pregnancy rate was only 3.7% per clinical pregnancy. In 2009, prior to the introduction of the programme, eSET was used in only 1.6% of embryo transfers, resulting in a multiple-pregnancy rate of 25.6%. These data demonstrate that providing provincially funded assisted reproduction treatment created an environment in which the aggressive use of eSET was not only possible, but also rapidly implemented. The result was a dramatic drop in multiple-pregnancy rates, approaching those for natural pregnancies.

Five-year survival of nonagenerian patients undergoing total hip replacement in the United Kingdom.

Between January 2000 and December 2007, 31 patients 90 years of age or older underwent total hip replacement at our hospital. Their data were collected prospectively. The rate of major medical complications was 9%. The surgical re-operation rate was 3%. The requirement for blood transfusion was 71% which was much higher than for younger patients. The 30-day, one-year and current mortality figures were 6.4% (2 of 31), 9.6% (3 of 31) and 55% (17 of 31), respectively, with a mean follow-up for the 14 surviving patients of six years. Cox's regression analysis revealed no significant independent predictors of mortality. Only 52% of patients returned immediately to their normal abode, with 45% requiring a prolonged period of rehabilitation. This is the first series to assess survival five years after total hip replacement for patients in their 90th year and beyond. Hip replacement in the extreme elderly should not be discounted on the grounds of age alone, although the complication rate exceeds that for younger patients. It can be anticipated that almost half of the patients will survive five years after surgery.

Aligning conservation priorities across taxa in Madagascar with high-resolution planning tools.

Globally, priority areas for biodiversity are relatively well known, yet few detailed plans exist to direct conservation action within them, despite urgent need. Madagascar, like other globally recognized biodiversity hot spots, has complex spatial patterns of endemism that differ among taxonomic groups, creating challenges for the selection of within-country priorities. We show, in an analysis of wide taxonomic and geographic breadth and high spatial resolution, that multitaxonomic rather than single-taxon approaches are critical for identifying areas likely to promote the persistence of most species. Our conservation prioritization, facilitated by newly available techniques, identifies optimal expansion sites for the Madagascar government's current goal of tripling the land area under protection. Our findings further suggest that high-resolution multitaxonomic approaches to prioritization may be necessary to ensure protection for biodiversity in other global hot spots.

A case-control study of tissue plasminogen activator for acute ischemic stroke.

BACKGROUND: Randomized trials demonstrate that intravenous tissue plasminogen activator (tPA) improves outcome in acute ischemic stroke (AIS). To assess translation of this efficacy into effectiveness in routine clinical practice we performed a case-control study of tPA treatment for AIS in a single hospital. METHODS: 151 tPA-treated AIS patients (1996-2005) were matched 1:1 with blinding to outcome to controls from a prospective registry based on age, gender, pre-stroke Oxford handicap scale (OHS), stroke severity, and subtype. The outcomes were in-hospital death, symptomatic intracranial hemorrhage (SICH), length-of-stay (LOS), discharge OHS and long-term survival. RESULTS: In-hospital mortality (23% vs. 24%) or long-term survival (median follow-up of 2 years) was not different between cases and controls (p = 0.83). SICH occurred in 7.8% (95% CI 4.2-13.5%) of tPA-treated patients. Median LOS was non-significantly shorter for cases (13 [7-29] vs. 16 [8-32] days, p = 0.14) but significantly shorter in tPA-treated vs. non-treated women (14 [7-28] vs. 20 [11-34] days, p = 0.04). At discharge 6.6% (95% CI 1.1-12.0%) more tPA-treated patients than controls had no disability (OHS < or = 1, p = 0.02). However, there was no difference in discharge independence rates or proportion discharged home. CONCLUSION: We demonstrate minor improvements in early recovery after stroke with tPA but the impact is less dramatic than that reported in randomized trials. This may relate to timing of treatment and the type of patients treated.

External validation of a six simple variable model of stroke outcome and verification in hyper-acute stroke.

We aimed to validate a previously described six simple variable (SSV) model that was developed from acute and sub-acute stroke patients in our population that included hyper-acute stroke patients. A Stroke Outcome Study enrolled patients from 2001 to 2002. Functional status was assessed at 6 months using the modified Rankin Scale (mRS). SSV model performance was tested in our cohort. 538 acute ischaemic (87%) and haemorrhagic stroke patients were enrolled, 51% of whom presented to hospital within 6 h of symptom recognition. At 6 months post-stroke, 42% of patients had a good outcome (mRS < or = 2). Stroke patients presenting within 6 h of symptom recognition were significantly older with higher stroke severity. In our Stroke Outcome Study dataset, the SSV model had an area under the curve of 0.792 for 6 month outcomes and performed well for hyper-acute or post-acute stroke, age < or > or = 75 years, haemorrhagic or ischaemic stroke, men or women, moderate and severe stroke, but poorly for mild stroke. This study confirms the external validity of the SSV model in our hospital stroke population. This model can therefore be utilised for stratification in acute and hyper-acute stroke trials.

Does salvage and tranexamic acid reduce the need for blood transfusion in revision hip surgery?

We carried out a retrospective case-control study in 80 patients who underwent a revision total hip replacement. Group A (40 patients) received tranexamic acid and intra-operative cell salvage. Group B (40 patients) was a matched control group and did not receive this management. Each group was divided into four subgroups: revision of both components, revision of both components with bone grafting, revision of the acetabular component with or without bone graft, and revision of the femoral component with or without bone graft. In group A the total number of units transfused was 52, compared with 139 in group B, representing a reduction in blood usage of 62.5%. The mean amount of blood transfused from cell salvage in each group was 858 ml (113 to 2100), 477 ml (0 to 2680), 228 ml (75 to 315) and 464 ml (120 to 1125), respectively. There was a significant difference in the amount of blood returned between the groups (p < 0.0001). In group A, 22 patients needed transfusion and in group B, 37 (p < 0.0001). A cost analysis calculation showed a total revenue saving of pounds sterling 70 000 and a potential saving throughout our facility of pounds sterling 318 288 per year. Our results show that a significant reduction in blood transfusion can be made using combined cell salvage and tranexamic acid in revision surgery of the hip.

Thrombogenic influence of biomaterials in patients with the Omni series heart valve: pyrolytic carbon versus titanium.

An opportunity to assess the thromboembolic rates caused by the construction materials on valve replacements is possible with the Omni series of mechanical heart valves. The Omnicarbon and Omniscience valves are identical in form but differ in that the Omnicarbon valve is constructed entirely of pyrolytic carbon, whereas the Omniscience valve uses titanium for its housing, the rest of its structure being pyrolytic carbon. The literature was reviewed and a comparison in similar groups of patients was made between these two model valves for their thromboembolic rates in the mitral and aortic positions. A total of 569 aortic Omnicarbon valves (4,146 patient years [pt yrs.1) had a thromboembolic events (T/E rate) of 0.5% compared with 1.7% for 468 aortic Omniscience (1,552 pt yrs); p < 0.0001. A total of 298 mitral Omnicarbon valves (3,333 pt yrs) had a T/E rate of 1.6% compared with 2.6% for 716 mitral Omniscience valves (2,134 pt yrs), p < 0.001. There was no difference in the anticoagulation management between the two model valves although the Omniscience valve required higher prothrombin or International Normalized Rate maintenance levels, which resulted in higher bleeding rates among patients with Omniscience valves.

Glycine antagonist in neuroprotection for patients with acute stroke: GAIN Americas: a randomized controlled trial.

CONTEXT: Elucidation of the ischemic cascade has helped stimulate development of neuroprotective drugs aimed at limiting brain injury in the hours following an ischemic stroke. To date, none of these drugs has shown clinical efficacy. OBJECTIVE: To examine the efficacy of gavestinel (GV150526), an antagonist of the glycine site of the N-methyl-D-aspartate receptor, as a neuroprotective therapy for acute ischemic stroke when administered within 6 hours of symptom onset. DESIGN: The Glycine Antagonist in Neuroprotection (GAIN) Americas trial, a randomized, double-blind placebo-controlled trial with enrollment from April 1998 to October 1999. SETTING: One hundred thirty-two hospital centers across the United States and Canada. PATIENTS: The primary efficacy population consisted of 1367 ischemic stroke patients with a predefined level of limb weakness and functional independence prior to stroke, stratified at randomization by age (75 years) and initial stroke severity (National Institutes of Health [NIH] Stroke Scale scores of 2-5, 6-13, or >/=14). INTERVENTION: Patients were randomly assigned to receive an intravenous loading dose (800 mg) plus 5 maintenance doses (200 mg every 12 hours) of gavestinel (n = 701) or placebo (n = 666) for 3 days. MAIN OUTCOME MEASURE: Functional capability at 3 months, measured by the Barthel Index (BI), with scores trichotomized as dead/0-55, 60-90, and 95-100, compared between the gavestinel and placebo groups. RESULTS: Treatment groups were well matched for baseline characteristics. For each group, median NIH Stroke Scale was 12, median age was 72 years, and median time to treatment was 5.2 hours. No statistically significant improvement on the 3-month BI trichotomy was demonstrated for gavestinel (P =.79). The proportion who were functionally independent (BI score = 95-100) was 39% in the gavestinel group and 37% in the placebo group. No statistically significant difference in 3-month survival was observed using Kaplan-Meier curves (P =.11). No other secondary end point suggested an advantage for gavestinel. Among the 333 patients (24%) who received recombinant tissue-type plasminogen activator, there was also no benefit for gavestinel (P =.53). There were no serious safety issues. CONCLUSION: In this study, gavestinel administered up to 6 hours after an acute ischemic stroke did not improve functional outcome at 3 months.

Multiple obesity QTLs identified in an intercross between the NZO (New Zealand obese) and the SM (small) mouse strains.

The inheritance of adiposity levels has been investigated in an intercross of the obese, diabetes-prone NZO and the small, lean SM mouse strains. Adiposity index (AI) was defined as the sum of four fat pad weights divided by body weight. DNA pools from fat and lean mice were analyzed with microsatellite variants to screen the genome for quantitative trait loci (QTLs) affecting AI. Ten significant QTLs affecting AI were identified on Chromosome (Chr) 1 (three loci), Chr 2, Chr 5 (two loci), Chr 6 (two loci), Chr 7, and Chr 17. Most of the QTLs appear to be novel. Several QTLs differentially affect specific fat depots. Thus, Chr 2 and Chr 7 QTLs affect gonadal more than inguinal fat, while the converse is true for the Chr 17 QTL. Gender influences the expression of several of the QTLs. For example, effects of the proximal Chr 1 QTL (Obq7) on AI appears to be primarily in males. The proximal AI QTL on Chr 6 (Obq13) maps near the neuropeptide Y (Npy) locus. Sequence analysis of the Npy gene revealed a 1-nucleotide deletion within a highly conserved portion of the 3' untranslated region in strain NZO. However, the deletion is polymorphic among mouse strains. Furthermore, lack of association between this same variant and AI in previously analyzed crosses raises doubt that it is the basis of Obq13. The present cross is the fourth in a series of intercrosses among 10 inbred strains arranged such that each strain is crossed with each adjacent strain within a circle. This design affords multiple opportunities to analyze each segregating QTL.

Poor postnatal weight gain: a risk factor for severe retinopathy of prematurity.

PURPOSE: This study aimed to investigate the relationship between rate of postnatal weight gain and severity of retinopathy of prematurity (ROP). METHODS: All infants (n = 111) screened for ROP at a single tertiary intensive care nursery over a 2-year period with an estimated gestational age of 30 weeks or less and follow-up to at least 42 weeks' postconception were included. The authors performed a retrospective review of records and statistical analysis of risk factors for ROP using multivariate analysis. RESULTS: Infants with severe (stage 3 or greater) ROP gained an average 10.9 g/kg per day in the first 6 weeks of life, compared to a mean of 9.6 g/kg per day for those with mild or no ROP (P =.04). By multiple regression, which included birth weight, gestational age, and 9 other reported risk factors, there was an association between rate of postnatal weight gain and severity of ROP (P =.02). By stepwise regression, 4 variables were associated with ROP severity: estimated gestational age at birth (P =.002), rate of postnatal weight gain (P = .0002), volume of transfused erythrocytes (P =.0001), and culture-proven sepsis (P = .02). CONCLUSION: Poor postnatal weight gain is a risk factor for the development of severe (stage 3 or greater) ROP. Ophthalmologists should take note of those infants who gain less than 50% of their birth weight in the first 6 weeks of life.

Physiology of wound healing and surgical wound care.

Wound healing is a systemic process, which occurs stepwise and involves the stages of hemostasis, inflammation, and repair. Hemostasis with fibrin formation creates a protective wound scab. The scab provides a surface beneath which cell migration and movement of the wound edges can occur. Inflammation brings nutrients to the area of the wound, removes debris and bacteria, and provides chemical stimuli for wound repair. Repair begins immediately after wounding and proceeds rapidly through the processes of epithelialization, fibroplasia, and capillary proliferation into the healing area. Different tissues have their own normal rates of growth during the process of healing. The optimal rate of healing is approached when factors advantageous to healing are present and factors having the ability to disturb or retard the healing processes are controlled or absent. These factors are discussed.

Impact of reducing the number of embryos transferred from three to two in women under the age of 35 who produced three or more high-quality embryos.

OBJECTIVE: To investigate the effect of a reduction in the number of good-quality embryos transferred in patients <35 years of age on pregnancy and multiple pregnancy rate. DESIGN: Prospective observational study with historical controls. SETTING: Academic tertiary referral unit. PATIENT(S): Three hundred eight patients <35 years of age undergoing IVF-ET. INTERVENTION(S): For patients who had three or more good quality embryos available for transfer, those in group 1 were given the option to have either two or three embryos replaced, whereas those in group 2 were allowed a maximum of two embryos transferred. In both groups, patients who had less than three good-quality embryos had the option to have three embryos transferred. MAIN OUTCOME MEASURE(S): Pregnancy and multiple pregnancy rates. RESULT(S): Patients in group 1, compared with those in group 2, had significantly more embryos (3 vs. 2) of significantly higher cumulative embryo score (31 vs. 24) transferred. This resulted in significantly higher multiple (57.8% vs. 30.8%) and triplet (15.6% vs. 1.4%) pregnancy rates in group 1. However, no difference in overall clinical pregnancy rate (37.2% vs. 41.2%) or live birth rate (28.1% vs. 29.4%) was observed between group 1 and 2. CONCLUSION(S): In women <35 years of age, who have three or more good-quality embryos available for transfer, a maximum of two embryos should generally be transferred.

The outcome of IVF-embryo transfer treatment in patients who develop three follicles or less.

Among 828 patients undergoing IVF-embryo transfer treatment, the implantation and pregnancy rates of patients who developed < or = 3 follicles were compared prospectively with those patients who had a normal response. Patients who developed 1 to 3 follicles during ovarian stimulation elected to proceed with oocyte collection, have intrauterine insemination if appropriate, or to have their cycle cancelled. In the group of patients who developed < or = 3 follicles and who were aged <40 years, despite a significantly lower number of oocytes collected [2 versus 7; median difference (MD) = 9; confidence interval (CI) = 7-11, and lower number of embryos developed and transferred (1 versus 3; MD = 2; CI = 1-2), no difference in either implantation rate [27.8 versus 20.4%; odds ratio (OR) = 1.58; CI = 0.46-4.54] or pregnancy rate (27.8 versus 36.7%; OR = 0.7; CI = 0.2-2.0) was noted when compared with similarly aged patients who developed >3 follicles. However, in patients aged >40 years who developed < or = 3 follicles, a moderate, albeit non-significant decrease in implantation rate (3.8 versus 7.8%; OR = 1.91; CI = 0.4-57.0) and pregnancy rate (4.2 versus 18.3%; OR = 1.92; CI = 0.38-57.0) was observed when compared with patients of a similar age who developed >3 follicles. Patients aged <40 years, unlike older patients, maintain good implantation and pregnancy rates despite a poor response to ovarian stimulation. This study indicates that for this group of women, continuation of IVF treatment is a better option than cancellation.

How Baby-Friendly are Manitoba hospitals? The Provincial Infant Feeding Study. Breastfeeding Promotion Steering Committee of Manitoba.

The Breastfeeding Promotion Steering Committee of Manitoba conducted the cross-sectional Provincial Infant Feeding Study in 1996 to examine: correlation between breastfeeding policies and actual practices in Manitoba hospitals; compliance with Baby-Friendly Hospital Initiative (BFHI) criteria; and associations between hospital practices and two-week breastfeeding duration. Three separate surveys obtained information from: administrators concerning hospital policy; nursing staff concerning hospital practices; and all women giving birth in a five-week period, concerning breastfeeding rates and maternal perceptions of hospital practices. The results highlighted the need for policy and practice changes to comply with BFHI criteria. 92% initiated breastfeeding, and 84% were breastfeeding at two weeks postpartum. Independent predictors of weaning included: in-hospital supplementation (adjusted RR = 2.1, 95% CI 1.02-4.36, p = 0.04); temporarily interrupting breastfeeding while in hospital (adjusted RR = 4.9, 95% CI 2.7-8.9, p = 0.0001); no previous breastfeeding experience (adjusted RR = 2.5, 95% CI 1.4-4.4, p = 0.002); and Grade 12 or less maternal education.