Lack of Association of Initial Vasopressor Dosing with Survival and Cardiac Re-Arrest Likelihood After Return of Spontaneous Circulation.

BACKGROUND: Cardiac arrest occurs in approximately 350,000 patients outside the hospital and approximately 30,000 patients in the emergency department (ED) annually in the United States. When return of spontaneous circulation (ROSC) is achieved, hypotension is a common complication. However, optimal dosing of vasopressors is not clear. OBJECTIVE: The objective of this study was to determine if initial vasopressor dosing was associated with cardiac re-arrest in patients after ROSC. METHODS: This was a retrospective, single-center analysis of adult patients experiencing cardiac arrest prior to arrival or within the ED. Patients were assigned to one of four groups based on starting dose of vasopressor: low dose (LD; < 0.25 µg/kg/min), medium dose (MD; 0.25-0.49 µg/kg/min), high dose (HD; 0.5-0.99 µg/kg/min), and very high dose (VHD; ≥ 1 µg/kg/min). Data collection was performed primarily via manual chart review of medical records. The primary outcome was incidence of cardiac re-arrest within 1 h of vasopressor initiation. Multivariate logistic regression analysis was conducted to identify any covariates strongly associated with the primary outcome. RESULTS: No difference in cardiac re-arrest incidence was noted between groups. The VHD group was significantly more likely to require a second vasopressor (p = 0.003). The HD group had lower survival rates to hospital discharge compared with the LD and MD groups (p = 0.0033 and p = 0.0147). In the multivariate regression, longer duration of pre-vasopressor re-arrests and hyperkalemic cardiac arrest etiology were significant predictors of cardiac re-arrest after vasopressor initiation. CONCLUSIONS: Initial vasopressor dosing was not found to be associated with risk of cardiac re-arrest or, conversely, risk of adverse events.

Is there a role for phosphodiesterase inhibitors in the treatment of male subfertility?

Intracytoplasmic sperm injection (ICSI) is frequently used to overcome severe deficits in semen quality. Concerns, however, are arising over its increasing use for non-male factor infertility. Moreover, increased risk of cardiovascular disease, congenital abnormalities, aneuploidies and childhood cancers have all been reported in the literature in relation to ICSI and it is possible that the quality of sperm chosen for injection may be an important factor in these unwanted outcomes. Given the wider adoption of ICSI to treat beyond the requirements of male infertility alone, research focussed on alternative methods to diagnose and treat the infertile couple is gaining increasing attention. This review focuses on the information available to date on the use of non-selective phosphodiesterase inhibitors (PDEI), specifically pentoxifylline (PF), caffeine (CF) and theophylline (TP) to stimulate sperm motility, thereby potentially reducing the need for ICSI in certain patient groups who may benefit from either expectant management or from a less stressful, minimally invasive and inexpensive treatment such as intrauterine insemination (IUI). The review focuses firstly on the mechanism of action of PDEI followed by treatment effects on sperm parameters such as motility and hyperactivated motility and sperm DNA integrity. Specific clinical implications are discussed that outline the potential role of PDEI in clinical practice and highlights areas in need of further research.

Management of recurrent implantation failure: British Fertility Society policy and practice guideline.

Recurrent implantation failure (RIF) is defined as the absence of a positive pregnancy test after three consecutive transfers of good quality embryos. There remains significant variation in clinical practice in the management of RIF. This British Fertility Society (BFS) Policy and Practice guideline analyses the evidence for investigations and therapies that are employed in RIF and provides recommendations for clinical practice and for further research. Evidence for investigations of sperm and egg quality, uterine and adnexal factors, immunological factors and thrombophilia, endocrine conditions and genetic factors and for associated therapies have been evaluated. This guideline has been devised to assist reproductive medicine specialists and patients in making shared decisions concerning management of RIF. Finally, suggestions for research towards improving understanding and management of RIF have also been provided.

Ethnic variation in the live birth rate and perinatal outcomes following frozen embryo transfer: an analysis of the HFEA database from 2000 to 2016.

The literature suggests that ethnicity affects live birth rate (LBR) and preterm birth (PTB) rate after fresh but not frozen embryo transfer (FET). We analysed 64,530 FET cycles from 2000 to 2016 using the Human Fertilisation and Embryology Authority (HFEA) database. Ethnicity was recorded for 43,735 as White British, 3,034 as Indian, 1,946 as Pakistani, 1,400 as Black African, 1,090 as White Irish, 520 as Chinese, 319 as Bangladeshi and 277 as Black Caribbean women. The LBR per FET when compared with White British women (26.1%) was significantly reduced in women of White Irish (23.4%; adjusted Odds Ratio (aOR) 0.85, 95% CI 0.73 to 1.00), Indian (25.2%; aOR 0.95, 95% CI 0.91 to 0.99), Bangladeshi (21.1%; aOR 0.87, 95% CI 0.79 to 0.95) and Pakistani (25.7%; aOR 0.97, 95% CI 0.94 to 0.99) ethnicities. The PTB rate, when compared with White British women (8.4%) was significantly higher for women of Indian (11.1%; aOR 1.38, 95% CI 1.06 to 1.79), Pakistani (11.8%; aOR 1.49, 95% CI 1.09 to 2.03) and White Irish (12.3%; aOR 1.55, 95% CI 1.01 to 2.38) ethnicities. This study suggests that FET outcomes are influenced by ethnicity.

Hemolysis after subcutaneous deoxycholic acid overdose.

This report describes a case of hemolysis in a patient injecting deoxycholic acid and benzyl alcohol for aesthetic benefit without medical supervision. The concentration and dose injected by the patient resulted in a 10-fold overdose of deoxycholic acid in comparison to the FDA-recommended dosing for the approved indication. Providers should be aware of medically unsupervised use of DCA and other injectables and the potential risks associated with this practice.

Immunogenicity of High Dose Influenza Vaccine for Patients with Inflammatory Bowel Disease on Anti-TNF Monotherapy: A Randomized Clinical Trial.

BACKGROUND: Patients with inflammatory bowel disease (IBD) on anti-tumor necrosis factor alpha (TNF) agents may have lower immune response to the influenza vaccine. We aimed to evaluate the immunogenicity of the high dose (HD) vs standard dose (SD) influenza vaccine in patients with IBD on anti-TNF monotherapy. METHODS: We performed a randomized clinical trial at a single academic center evaluating the immunogenicity of the HD vs SD influenza vaccine in patients with IBD on anti-TNF monotherapy. Influenza antibody concentration was measured at immunization, at 2 to 4 weeks postimmunization, and at 6 months. RESULTS: Sixty-nine patients with IBD were recruited into the study, 40 on anti-TNF monotherapy, and 19 on vedolizumab, along with 20 healthy controls (HC). Patients with IBD receiving the HD influenza vaccine had significantly higher H3N2 postimmunization antibodies compared with those who received the SD influenza vaccine (160 [interquartile range 80 to 320] vs 80 [interquartile range 40 to 160]; P = 0.003). The H1N1 postimmunization levels were not significantly higher in the HD influenza vaccine (320 [interquartile range 150 to 320] vs 160 [interquartile range 80 to 320]; P = 0.18). Patients with IBD receiving the HD influenza vaccine and those on vedolizumab who received SD had equivalent antibody concentrations to HC (H1N1 P = 0.85; H3N2 P = 0.23; B/Victoria P = 0.20 and H1N1 P = 0.46; H3N2 P = 0.21; B/Victoria P = 1.00, respectively). CONCLUSIONS: Patients with IBD on anti-TNF monotherapy receiving the HD influenza vaccine had significantly higher postimmunization antibody levels compared with SD vaccine. Clinicaltrials.gov (#NCT02461758).

Metformin for ovulation induction (excluding gonadotrophins) in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is characterised by infrequent or absent ovulation, and high levels of androgens and insulin (hyperinsulinaemia). Hyperinsulinaemia occurs secondary to insulin resistance and is associated with an increased biochemical risk profile for cardiovascular disease and an increased prevalence of diabetes mellitus. Insulin-sensitising agents such as metformin may be effective in treating PCOS-related anovulation. This is an update of Morley 2017 and only includes studies on metformin. OBJECTIVES: To evaluate the effectiveness and safety of metformin in combination with or in comparison to clomiphene citrate (CC), letrozole and laparoscopic ovarian drilling (LOD) in improving reproductive outcomes and associated gastrointestinal side effects for women with PCOS undergoing ovulation induction. SEARCH METHODS: We searched the following databases from inception to December 2018: Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL. We searched registers of ongoing trials and reference lists from relevant studies. SELECTION CRITERIA: We included randomised controlled trials of metformin compared with placebo, no treatment, or in combination with or compared with CC, letrozole and LOD for women with PCOS subfertility. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility and bias. Primary outcomes were live birth rate and gastrointestinal adverse effects. Secondary outcomes included other pregnancy outcomes and ovulation. We combined data to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs). We assessed statistical heterogeneity using the I2 statistic and reported quality of the evidence for primary outcomes and reproductive outcomes using GRADE methodology. MAIN RESULTS: We included 41 studies (4552 women). Evidence quality ranged from very low to moderate based on GRADE assessment. Limitations were risk of bias (poor reporting of methodology and incomplete outcome data), imprecision and inconsistency. Metformin versus placebo or no treatment The evidence suggests that metformin may improve live birth rates compared with placebo (OR 1.59, 95% CI 1.00 to 2.51; I2 = 0%; 4 studies, 435 women; low-quality evidence). For a live birth rate of 19% following placebo, the live birth rate following metformin would be between 19% and 37%. The metformin group probably experiences more gastrointestinal side effects (OR 4.00, 95% CI 2.63 to 6.09; I2 = 39%; 7 studies, 713 women; moderate-quality evidence). With placebo, the risk of gastrointestinal side effects is 10% whereas with metformin this risk is between 22% and 40%. There are probably higher rates of clinical pregnancy (OR 1.98, 95% CI 1.47 to 2.65; I2 = 30%; 11 studies, 1213 women; moderate-quality evidence). There may be higher rates of ovulation with metformin (OR 2.64, 95% CI 1.85 to 3.75; I2 = 61%; 13 studies, 684 women; low-quality evidence). We are uncertain about the effect on miscarriage rates (OR 1.08, 95% CI 0.50 to 2.35; I2 = 0%; 4 studies, 748 women; low-quality evidence). Metformin plus CC versus CC alone We are uncertain if metformin plus CC improves live birth rates compared to CC alone (OR 1.27, 95% CI 0.98 to 1.65; I2 = 28%; 10 studies, 1219 women; low-quality evidence), but gastrointestinal side effects are probably more common with combined therapy (OR 4.26, 95% CI 2.83 to 6.40; I2 = 8%; 6 studies, 852 women; moderate quality evidence). The live birth rate with CC alone is 24%, which may change to between 23% to 34% with combined therapy. With CC alone, the risk of gastrointestinal side effects is 9%, which increases to between 21% to 37% with combined therapy. The combined therapy group probably has higher rates of clinical pregnancy (OR 1.62, 95% CI 1.32 to 1.99; I2 = 31%; 19 studies, 1790 women; moderate-quality evidence). The combined group may have higher rates of ovulation (OR 1.65, 95% CI 1.35 to 2.03; I2 = 63%;21 studies, 1568 women; low-quality evidence). There was no clear evidence of an effect on miscarriage (OR 1.35, 95% CI 0.91 to 2.00; I2 = 0%; 10 studies, 1206 women; low-quality evidence). Metformin versus CC When all studies were combined, findings for live birth were inconclusive and inconsistent (OR 0.71, 95% CI 0.49 to 1.01; I2 = 86%; 5 studies, 741 women; very low-quality evidence). In subgroup analysis by obesity status, obese women had a lower birth rate in the metformin group (OR 0.30, 95% CI 0.17 to 0.52; 2 studies, 500 women), while the non-obese group showed a possible benefit from metformin, with high heterogeneity (OR 1.71, 95% CI 1.00 to 2.94; I2 = 78%, 3 studies, 241 women; very low-quality evidence). However, due to the very low quality of the evidence we cannot draw any conclusions. Among obese women taking metformin there may be lower rates of clinical pregnancy (OR 0.34, 95% CI 0.21 to 0.55; I2 = 0%; 2 studies, 500 women; low-quality evidence) and ovulation (OR 0.29, 95% CI 0.20 to 0.43; I2 = 0%; 2 studies, 500 women; low-quality evidence) while among non-obese women, the metformin group may have more pregnancies (OR 1.56, 95% CI 1.06 to 2.29; I2 = 26%; 6 studies, 530 women; low-quality evidence) and no clear difference in ovulation rates (OR 0.80, 95% CI 0.52 to 1.25; I2 = 0%; 5 studies, 352 women; low-quality evidence). We are uncertain whether there is a difference in miscarriage rates between the groups (overall: OR 0.92, 95% CI 0.51 to 1.66; I2 = 36%; 6 studies, 781 women; low-quality evidence) and no studies reported gastrointestinal side effects. AUTHORS' CONCLUSIONS: Our updated review suggests that metformin may be beneficial over placebo for live birth however, more women probably experience gastrointestinal side effects. We are uncertain if metformin plus CC improves live birth rates compared to CC alone, but gastrointestinal side effects are probably increased with combined therapy. When metformin was compared with CC, data for live birth were inconclusive, and the findings were limited by lack of evidence. Results differed by body mass index (BMI), emphasising the importance of stratifying results by BMI. No studies reported gastrointestinal side effects in this comparison. Due to the low quality of the evidence, we are uncertain of the effect of metformin on miscarriage in all three comparisons.

Reproductive outcome following pre-implantation genetic diagnosis (PGD) in the UK.

In 2013, the National Health Service Commissioning board centralized the funding in England for up to three cycles of pre-implantation genetic diagnosis (PGD) for couples who have, or are carriers of, a specific genetic disorder. This study presents the historical data of PGD cycles and their clinical outcomes in UK as extrapolated from the national data registry. Retrospective analysis of outcome of cycles undergoing pre-implantation genetic diagnosis in the UK over the past 20 years was performed from the Human Fertilisation and Embryology Authority database (n = 2974). Binary logistic regression was used to determine trends over time and adjusted for maternal age. Briefly, the number of PGD cycles has risen 127-fold from 1991 to 2012 with 3.6-fold increase (360% rise) from 2004 to 2012. A total of one in four embryos following pre-implantation genetic diagnosis did not reach embryo transfer and 92% of these were due to a failure to survive. The live birth rate has risen over 20 years and there has been a steady decline in reported incidence of congenital abnormalities (p < 0.07). PGD has thus emerged as a safe and effective alternative to prenatal diagnosis but with ever evolving technological advances, a robust system of data collection that incorporates techniques used and reporting of mutation-specific clinical outcomes is suggested.

The Impact of Systematic Point-of-Care Ultrasound on Management of Patients in a Resource-Limited Setting.

Although target point-of-care (POC) ultrasonography has been shown to benefit patients in resource-limited settings, it is not clear whether a systematic POC ultrasound assessment in these settings can also lead to similar changes in patient management. A predefined systematic set of POC ultrasound scans were performed on inpatients at a tertiary referral hospital in Tanzania to see if this resulted in changes to patient management. Of the 55 patients scanned, an abnormality was detected in 75% (N = 41), and a change in patient management was recommended or implemented on the basis of POC ultrasound findings in 53% (N = 29). The main impact was earlier initiation of treatment due to more rapid and accurate diagnosis. Further research is warranted to determine whether systematic POC ultrasonography would result in improved patient outcomes in resource-limited settings.

Upper-limb muscle responses to epidural, subdural and intraspinal stimulation of the cervical spinal cord.

OBJECTIVE: Electrical stimulation of the spinal cord has potential applications following spinal cord injury for reanimating paralysed limbs and promoting neuroplastic changes that may facilitate motor rehabilitation. Here we systematically compare the efficacy, selectivity and frequency-dependence of different stimulation methods in the cervical enlargement of anaesthetized monkeys. APPROACH: Stimulating electrodes were positioned at multiple epidural and subdural sites on both dorsal and ventral surfaces, as well as at different depths within the spinal cord. Motor responses were recorded from arm, forearm and hand muscles. MAIN RESULTS: Stimulation efficacy increased from dorsal to ventral stimulation sites, with the exception of ventral epidural electrodes which had the highest recruitment thresholds. Compared to epidural and intraspinal methods, responses to subdural stimulation were more selective but also more similar between adjacent sites. Trains of stimuli delivered to ventral sites elicited consistent responses at all frequencies whereas from dorsal sites we observed a mixture of short-latency facilitation and long-latency suppression. Finally, paired stimuli delivered to dorsal surface and intraspinal sites exhibited symmetric facilitatory interactions at interstimulus intervals between 2­5 ms whereas on the ventral side interactions tended to be suppressive for near-simultaneous stimuli. SIGNIFICANCE: We interpret these results in the context of differential activation of afferent and efferent roots and intraspinal circuit elements. In particular, we propose that distinct direct and indirect actions of spinal cord stimulation on motoneurons may be advantageous for different applications, and this should be taken into consideration when designing neuroprostheses for upper-limb function.

Acute paediatric paraplegia: a case series review.

UNLABELLED: Paediatric paraplegia resulting from spinal cord pathology of any cause is rare; hence prognostic information for children less than 16 years is limited. This case series review aims to ascertain all cases of paediatric paraplegia from 1997 to 2012 in the former Northern Region of England. METHODS: Children presenting with sudden paraplegia before the age of 16 years were multiply ascertained from databases in the regional paediatric neurology, neuroradiology, neuro-oncology and adult spinal injuries units. Data were obtained from retrospective case note review. RESULTS: A total of 44 cases (24 female) were identified. The incidence is estimated at 0.49 per 100,000 children under 16/year (95% confidence interval 0.41-0.57). Mean age of onset was 8.8 years and the most common aetiology was inflammatory. Twelve months post presentation, mortality was zero and a good outcome (defined as Gross Motor Function Classification System grades I or II) was seen in 66.6%. Motor outcome at 12 months was associated with the presence of bladder/bowel signs at presentation, previous viral illness and initial severity of paraplegia. Bladder signs at presentation were the strongest predictor of prognosis (OR for poor motor outcome 10.3). We were unable to demonstrate a relationship between aetiology and late outcome. CONCLUSION: Paediatric paraplegia is rare. Mortality rates are low and 66.6% have a good outcome with fully or nearly independent walking. Bladder signs are the strongest predictor of prognosis.