Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

BACKGROUND: Monitoring of in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) is necessary to detect as well as reduce the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the optimal ovarian response needed for assisted reproduction treatment. Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation IVF and ICSI treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered.  OBJECTIVES: To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. SEARCH METHODS: In this update conducted in March 2020, two review authors searched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the National Research Register, and web-based trial registers. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. SELECTION CRITERIA: Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. DATA COLLECTION AND ANALYSIS: Two review authors (IK, AW) independently selected the studies, extracted data and assessed risk of bias. We resolved disagreements by discussion. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. MAIN RESULTS: We did not identify any new eligible studies in this update in 2020. The evidence based on the six trials identified in 2014 remained unchanged. They included 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment. None of the six studies reported our primary outcome of live birth rate. Two studies presented pregnancy rate per initiated cycle and per embryo transfer, respectively. Four studies reported pregnancy rate per woman with pooled data; we are uncertain of the effect of monitoring with TVUS only versus combined monitoring on clinical pregnancy rate per woman (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests in women with a 36% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate using TVUS only would be between 31% and 46%. We are uncertain of any effect in the mean number of oocytes retrieved per woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence).  We are uncertain whether monitoring with TVUS only versus combined monitoring affected the incidence of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that in women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate monitored by TVUS only would be between 2% and 8%. The cycle cancellation rate was similar in both arms of two studies (0/34 versus 1/31, 1/25 versus 1/25; OR 0.57; 95% CI 0.07 to 4.39; N = 115; I² = 0%; low quality evidence).  The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. AUTHORS' CONCLUSIONS: This review update found no new randomised trials. Evidence from the six studies previously identified did not suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. The choice of one or the other method may depend upon the convenience of its use, and the associated costs. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Cost-effectiveness of Microsoft Academic Graph with machine learning for automated study identification in a living map of coronavirus disease 2019 (COVID-19) research.

Background: Identifying new, eligible studies for integration into living systematic reviews and maps usually relies on conventional Boolean updating searches of multiple databases and manual processing of the updated results. Automated searches of one, comprehensive, continuously updated source, with adjunctive machine learning, could enable more efficient searching, selection and prioritisation workflows for updating (living) reviews and maps, though research is needed to establish this. Microsoft Academic Graph (MAG) is a potentially comprehensive single source which also contains metadata that can be used in machine learning to help efficiently identify eligible studies. This study sought to establish whether: (a) MAG was a sufficiently sensitive single source to maintain our living map of COVID-19 research; and (b) eligible records could be identified with an acceptably high level of specificity. Methods: We conducted an eight-arm cost-effectiveness analysis to assess the costs, recall and precision of semi-automated workflows, incorporating MAG with adjunctive machine learning, for continually updating our living map. Resource use data (time use) were collected from information specialists and other researchers involved in map production. Our systematic review software, EPPI-Reviewer, was adapted to incorporate MAG and associated machine learning workflows, and also used to collect data on recall, precision, and manual screening workload. Results: The semi-automated MAG-enabled workflow dominated conventional workflows in both the base case and sensitivity analyses. At one month our MAG-enabled workflow with machine learning, active learning and fixed screening targets identified 469 additional, eligible articles for inclusion in our living map, and cost £3,179 GBP per week less, compared with conventional methods relying on Boolean searches of Medline and Embase. Conclusions: We were able to increase recall and coverage of a large living map, whilst reducing its production costs. This finding is likely to be transferrable to OpenAlex, MAG's successor database platform.

Cyberbullying and Children and Young People's Mental Health: A Systematic Map of Systematic Reviews.

Cyberbullying is associated with considerable negative mental and psychosocial consequences in children and young people, making it a serious public health concern. To review the highest level of available evidence, a systematic mapping review was conducted to identify systematic reviews that investigated the relationship between cyberbullying and mental and psychological outcomes in young people. Topic-relevant bibliographic databases and online resources were searched to identify reviews published since 2007. Data were extracted using a coding tool developed for this study. Methodological quality of included reviews was assessed using AMSTAR criteria. Nineteen systematic reviews satisfied the inclusion criteria and they reported a strong negative association between cyberbullying and mental health outcomes in young people. Meta-analysis was performed in 11 reviews and narrative synthesis in 8 reviews. Data were derived from predominantly cross-sectional studies and a clear causal relationship between cyberbullying and mental outcomes cannot be established. Two-third of the included reviews were classified to be of low or unclear quality, due to the lack of quality assessment of the primary studies included in individual reviews. This systematic map consolidates available evidence at review level and confirms the existing gaps in longitudinal and qualitative evidence synthesis. Closer examination of the moderating factors influencing cyberbullying behaviors in future research can advance our understanding and inform the development of tailored programs of intervention to mitigate the negative impact of this phenomenon.

Pain relief for women undergoing oocyte retrieval for assisted reproduction.

BACKGROUND: Various methods of conscious sedation and analgesia (CSA) have been used during oocyte retrieval for assisted reproduction. The choice of agent has been influenced by the quality of sedation and analgesia and by concerns about possible detrimental effects on reproductive outcomes. OBJECTIVES: To assess the effectiveness and safety of different methods of conscious sedation and analgesia for pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval. SEARCH METHODS: We searched; the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL, and trials registers in November 2017. We also checked references, and contacted study authors for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different methods and administrative protocols for conscious sedation and analgesia during oocyte retrieval. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our primary outcomes were intraoperative and postoperative pain. Secondary outcomes included clinical pregnancy, patient satisfaction, analgesic side effects, and postoperative complications. MAIN RESULTS: We included 24 RCTs (3160 women) in five comparisons. We report the main comparisons below. Evidence quality was generally low or very low, mainly owing to poor reporting and imprecision.1. CSA versus other active interventions.All evidence for this comparison was of very low quality.CSA versus CSA plus acupuncture or electroacupunctureData show more effective intraoperative pain relief on a 0 to 10 visual analogue scale (VAS) with CSA plus acupuncture (mean difference (MD) 1.00, 95% confidence interval (CI) 0.18 to 1.82, 62 women) or electroacupuncture (MD 3.00, 95% CI 2.23 to 3.77, 62 women).Data also show more effective postoperative pain relief (0 to 10 VAS) with CSA plus acupuncture (MD 0.60, 95% CI -0.10 to 1.30, 61 women) or electroacupuncture (MD 2.10, 95% CI 1.40 to 2.80, 61 women).Evidence was insufficient to show whether clinical pregnancy rates were different between CSA and CSA plus acupuncture (odds ratio (OR) 0.61, 95% CI 0.20 to 1.86, 61 women). CSA alone may be associated with fewer pregnancies than CSA plus electroacupuncture (OR 0.22, 95% CI 0.07 to 0.66, 61 women).Evidence was insufficient to show whether rates of vomiting were different between CSA and CSA plus acupuncture (OR 1.64, 95% CI 0.46 to 5.88, 62 women) or electroacupuncture (OR 1.09, 95% CI 0.33 to 3.58, 62 women).Trialists provided no usable data for other outcomes of interest.CSA versus general anaesthesia Postoperative pain relief was greater in the CSA group (0 to 3 Likert: mean difference (MD) 1.9, 95% CI 2.24 to 1.56, one RCT, 50 women).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 1.00, 95% CI 0.43 to 2.35, two RCTs, 108 women, I2 = 0%).Evidence was insufficient to show whether groups differed in rates of vomiting (OR 0.46, 95% CI 0.08 to 2.75, one RCT, 50 women) or airway obstruction (OR 0.14, 95% CI 0.02 to 1.22, one RCT, 58 women). Fewer women needed mask ventilation in the CSA group (OR 0.05, 95% CI 0.01 to 0.20, one RCT, 58 women).Evidence was also insufficient to show whether groups differed in satisfaction rates (OR 0.66, 95% CI 0.11 to 4.04, two RCTs, 108 women, I2 = 34%; very low-quality evidence).Trialists provided no usable data for outcomes of interest.2. CSA + paracervical block (PCB) versus other interventions.CSA + PCB versus electroacupuncture + PCB Intraoperative pain scores were lower in the CSA + PCB group (0 to 10 VAS: MD -0.66, 95% CI -0.93 to -0.39, 781 women, I2 = 76%; low-quality evidence).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.96, 95% CI 0.72 to 1.29, 783 women, I2 = 9%; low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus general anaesthesiaEvidence was insufficient to show whether groups differed in postoperative pain scores (0 to 10 VAS: MD 0.49, 95% CI -0.13 to 1.11, 50 women; very low-quality evidence).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.70, 95% CI 0.22 to 2.26, 51 women; very low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus spinal anaesthesiaPostoperative pain scores were higher in the CSA + PCB group (0 to 10 VAS: MD 1.02, 95% CI 0.48 to 1.56, 36 women; very low-quality evidence).Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.93, 95% CI 0.24 to 3.65, 38 women; very low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus PCBEvidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.93, 95% CI 0.44 to 1.96, 150 women; low-quality evidence) or satisfaction (OR 1.63, 95% CI 0.68 to 3.89, 150 women, low-quality evidence).Trialists provided no usable data for other outcomes of interest.CSA + PCB versus CSA only Evidence was insufficient to show whether groups differed in clinical pregnancy rates (OR 0.62, 95% CI 0.28 to 1.36, one RCT, 100 women; very low-quality evidence). Rates of postoperative nausea and vomiting were lower in the CS + PCB group (OR 0.42, 95% CI 0.18 to 0.97, two RCTs, 140 women, I2 = 40%; very low-quality evidence).Trialists provided no usable data for other outcomes of interest. AUTHORS' CONCLUSIONS: The evidence does not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte retrieval. Simultaneous use of sedation combined with analgesia such as the opiates, further enhanced by paracervical block or acupuncture techniques, resulted in better pain relief than occurred with one modality alone. Evidence was insufficient to show conclusively whether any of the interventions influenced pregnancy rates. All techniques reviewed were associated with a high degree of patient satisfaction. Women's preferences and resource availability for choice of pain relief merit consideration in practice.

On the Helical Structure of Guanosine 5'-Monophosphate Formed at pH 5: Is It Left- or Right-Handed?

Early X-ray fiber diffraction studies have established that the spontaneous gel formation of guanosine 5'-monophosphate (5'-GMP) under slightly acidic conditions (e.g., pH 5) results from self-assembly of 5'-GMP into a helical structure in which hydrogen-bonded guanine bases form a continuous helix with 15 nucleotides per 4 turns. For more than five decades, the sense of this helix is believed to be left-handed. Using multinuclear solid-state NMR and IR spectroscopic methods, we have finally determined the long-missing structural details of this helix. First, we found that this 5'-GMP helix is right-handed containing exclusive C3'-endo sugar puckers. Second, we showed that the central channel of this helix is free of Na+ ions, which is in sharp contrast to the helix formed by 5'-GMP at pH 8 where the central channel is filled with Na+ ions.

Premenstrual syndrome.

INTRODUCTION: A woman has premenstrual syndrome (PMS) if she complains of recurrent psychological and/or physical symptoms occurring during the luteal phase of the menstrual cycle, and often resolving by the end of menstruation. Symptom severity can vary between women. Premenstrual symptoms occur in 95% of women of reproductive age. Severe, debilitating symptoms occur in about 5% of those women. There is no consensus on how symptom severity should be assessed for PMS, which has led to the use of a wide variety of symptom scores and scales, thus making it difficult to synthesise data on treatment efficacy. The cyclical nature of the condition also makes it difficult to conduct RCTs. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of continuous hormonal treatments in women with premenstrual syndrome? We searched: Medline, Embase, The Cochrane Library, and other important databases up to April 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 132 studies. After deduplication and removal of conference abstracts, 132 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 102 studies and the further review of 30 full publications. Of the 30 full articles evaluated, one systematic review and three RCTs were added to this overview. We performed a GRADE evaluation for three PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for three interventions based on information relating to the effectiveness and safety of continuous combined oral contraceptives, continuous transdermal estradiol, and continuous subcutaneous estradiol implants.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

BACKGROUND: Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the good ovarian response needed for assisted reproduction treatment. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. OBJECTIVES: To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the National Research Register, and web-based trial registers such as Current Controlled Trials. The last search was conducted in May 2014. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. SELECTION CRITERIA: Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. DATA COLLECTION AND ANALYSIS: Three review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the authors. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. MAIN RESULTS: With this update, four new studies were identified resulting in a total of six trials including 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment.None of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate per woman between monitoring with TVUS only and combined monitoring (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%.There was no evidence of a difference between the groups in the reported cases of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUSS only was between 2% and 8%.There was no evidence of a difference between the groups in the mean number of oocytes retrieved pre woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence).The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. AUTHORS' CONCLUSIONS: This review update found no evidence from randomised trials to suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. A combined monitoring protocol including both TVUS and serum estradiol may need to be retained as precautionary good clinical practice and as a confirmatory test in a subset of women to identify those at high risk of OHSS. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Psychosocial predictors, assessment, and outcomes of cosmetic procedures: a systematic rapid evidence assessment.

BACKGROUND: Recent breast implant complications led to a UK government policy review of the evidence concerning cosmetic interventions. We synthesised cosmetic intervention research evidence covering psychosocial factors associated with requesting procedures and psychological outcomes, effects of procedures on psychological outcomes, preintervention assessments for identifying those at risk, alternative therapy effectiveness, and issues in achieving informed consent. METHODS: Undertaking a systematic rapid evidence assessment, six databases and three journals were searched. Included studies were systematic reviews or primary studies of participants requesting cosmetic procedures; published 2002-2012; containing either psychological or psychosocial measures, a psychological outcome, or evaluation of informed consent. Reviewers independently assessed study eligibility, extracted data, and assessed quality, undertaking narrative synthesis. RESULTS: Methodological quality of the included 13 systematic reviews and 179 primary studies was low, with wide variation in psychosocial measures. Findings suggest several psychosocial factors (e.g., intimate partner violence) may be associated with requesting cosmetic surgery. Multiple factors (e.g., unrealistic expectations) may predict poor psychological outcomes. Current psychological screening tools focus predominantly on body dysmorphic disorder (BDD) symptoms. Psychological and pharmacological interventions are effective alternative BDD treatments. Patients and doctors bring different needs to informed consent discussions, inconsistently matched to those required by professional ethics, litigation risk, and facilitating profit. CONCLUSIONS: Systematically reviewing this literature for UK policy has highlighted that some groups may be at risk of poor post-cosmetic procedure outcomes. Practitioners and patients must explore reasons for seeking cosmetic procedures and discuss all potential results and alternative solutions. Future research should employ more robust methodologies to identify effects in those at risk, led by consensus on a core set of psychological outcomes.

Timing and volume of fluid administration for patients with bleeding.

BACKGROUND: Treatment of haemorrhagic shock involves maintaining blood pressure and tissue perfusion until bleeding is controlled. Different resuscitation strategies have been used to maintain the blood pressure in trauma patients until bleeding is controlled. However, while maintaining blood pressure may prevent shock, it may worsen bleeding. OBJECTIVES: To examine the effect on mortality and coagulation times of two intravenous fluid administration strategies in the management of haemorrhagic hypovolaemia, early compared to delayed administration and larger compared to smaller volume of fluid administered. SEARCH METHODS: We searched the Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic + Embase (OvidSP), ISI Web of Science (SCI-Expanded and CPCI-S) and clinical trials registries. We checked reference lists of identified articles and contacted authors and experts in the field. The most recent search was run on 5 February 2014. SELECTION CRITERIA: Randomised trials of the timing and volume of intravenous fluid administration in trauma patients with bleeding. Trials in which different types of intravenous fluid were compared were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. MAIN RESULTS: Six trials involving a total of 2128 people were included in this review. We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration Three trials reported mortality and two reported coagulation data.In the first trial (n = 598) the relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval (CI) 1.00 to 1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9 to 4.5) and 4.3 (95% CI 1.74 to 6.9) seconds, respectively.In the second trial (n = 50) the RR for death with early blood transfusion was 5.4 (95% CI 0.3 to 107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0 to 8.0) seconds. In the third trial (n = 1309) the RR for death with early fluid administration was 1.06 (95% CI 0.77 to 1.47). Larger versus smaller volume of fluid administration Three trials reported mortality and one reported coagulation data.In the first trial (n = 36) the RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28 to 22.29). Prothrombin time and partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid, as compared to 13.9 and 35.1 seconds in the comparison group.In the second trial (n = 110) the RR for death with a high systolic blood pressure resuscitation target (100 mm Hg) maintained with a larger volume of fluid as compared to a low systolic blood pressure resuscitation target (70 mm Hg) maintained with a smaller volume of fluid was 1.00 (95% CI 0.26 to 3.81). In the third trial (n = 25) there were no deaths. AUTHORS' CONCLUSIONS: We found no evidence from randomised controlled trials for or against early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy.

Is consumer response to plain/standardised tobacco packaging consistent with framework convention on tobacco control guidelines? A systematic review of quantitative studies.

BACKGROUND AND OBJECTIVES: Standardised or 'plain' tobacco packaging was introduced in Australia in December 2012 and is currently being considered in other countries. The primary objective of this systematic review was to locate, assess and synthesise published and grey literature relating to the potential impacts of standardised tobacco packaging as proposed by the guidelines for the international Framework Convention on Tobacco Control: reduced appeal, increased salience and effectiveness of health warnings, and more accurate perceptions of product strength and harm. METHODS: Electronic databases were searched and researchers in the field were contacted to identify studies. Eligible studies were published or unpublished primary research of any design, issued since 1980 and concerning tobacco packaging. Twenty-five quantitative studies reported relevant outcomes and met the inclusion criteria. A narrative synthesis was conducted. RESULTS: Studies that explored the impact of package design on appeal consistently found that standardised packaging reduced the appeal of cigarettes and smoking, and was associated with perceived lower quality, poorer taste and less desirable smoker identities. Although findings were mixed, standardised packs tended to increase the salience and effectiveness of health warnings in terms of recall, attention, believability and seriousness, with effects being mediated by the warning size, type and position on pack. Pack colour was found to influence perceptions of product harm and strength, with darker coloured standardised packs generally perceived as containing stronger tasting and more harmful cigarettes than fully branded packs; lighter coloured standardised packs suggested weaker and less harmful cigarettes. Findings were largely consistent, irrespective of location and sample. CONCLUSIONS: The evidence strongly suggests that standardised packaging will reduce the appeal of packaging and of smoking in general; that it will go some way to reduce consumer misperceptions regarding product harm based upon package design; and will help make the legally required on-pack health warnings more salient.

Pain relief for women undergoing oocyte retrieval for assisted reproduction.

BACKGROUND: Various methods of conscious sedation and analgesia have been used for pain relief during oocyte recovery in in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) procedures. The choice of agent has also been influenced by the quality of sedation and analgesia as well as by concerns about possible detrimental effects on reproductive outcomes. OBJECTIVES: To assess the effectiveness and safety of different methods of conscious sedation and analgesia on pain relief and pregnancy outcomes in women undergoing transvaginal oocyte retrieval. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL (from their inception to present); the National Research Register and Current Controlled Trials. We searched reference lists of included studies for relevant studies and contacted authors for information on unpublished and ongoing trials. There was no language restriction. The search was updated in July 2012. SELECTION CRITERIA: Only randomised controlled trials comparing different methods of conscious sedation and analgesia for pain relief during oocyte recovery were included. DATA COLLECTION AND ANALYSIS: Quality assessment and data extraction were performed independently by two review authors. Interventions were classified and analysed under broad categories or strategies of sedation and pain relief to compare different methods and administrative protocols of conscious sedation and analgesia. Outcomes were extracted and the data were pooled when appropriate. MAIN RESULTS: With this update, nine new studies were identified resulting in a total of 21 trials including 2974 women undergoing oocyte retrieval. These trials compared five different categories of conscious sedation and analgesia: 1) conscious sedation and analgesia versus placebo; 2) conscious sedation and analgesia versus other active interventions such as general and acupuncture anaesthesia; 3) conscious sedation and analgesia plus paracervical block versus other active interventions such as general, spinal and acupuncture anaesthesia; 4) patient-controlled conscious sedation and analgesia versus physician-administered conscious sedation and analgesia; and 5) conscious sedation and analgesia with different agents or dosage. Evidence was generally of low quality, mainly due to poor reporting of methods, small sample sizes and inconsistency between the trials.Conflicting results were shown for women's experience of pain. Compared to conscious sedation alone, more effective pain relief was reported when conscious sedation was combined with electro-acupuncture: intra-operative pain mean difference (MD) on 1 to 10 visual analogue scale (VAS) of 3.00 (95% CI 2.23 to 3.77); post-operative pain MD in VAS units of 2.10 (95% CI 1.40 to 2.80; N = 61, one trial, low quality evidence); or paracervical block (MD not calculable).The pooled data of four trials showed a significantly lower intra-operative pain score with conscious sedation plus paracervical block than with electro-acupuncture plus paracervical block (MD on 10-point VAS of -0.66; 95% CI -0.93 to -0.39; N = 781, 4 trials, low quality evidence) with significant statistical heterogeneity (I(2) = 76%). Patient-controlled sedation and analgesia was associated with more intra-operative pain than physician-administered sedation and analgesia (MD on 10-point VAS of 0.60; 95% CI 0.16 to 1.03; N = 379, 4 trials, low quality evidence) with high statistical heterogeneity (I(2) = 83%). Post-operative pain was reported in only nine studies. As different types and dosages of sedative and analgesic agents, as well as administrative protocols and assessment tools, were used in these trials the data should be interpreted with caution.There was no evidence of a significant difference in pregnancy rate in the 12 studies which assessed this outcome, and pooled data of four trials comparing electro-acupuncture combined with paracervical block with conscious sedation and analgesia plus paracervical block showed an odds ratio (OR) of 0.96 (95% CI 0.72 to 1.29; N = 783, 4 trials) for pregnancy. High levels of women's satisfaction were reported for all modalities of conscious sedation and analgesia as assessed in 12 studies. Meta-analysis of all the studies was not attempted due to considerable heterogeneity.For the rest of the trials a descriptive summary of the outcomes was presented. AUTHORS' CONCLUSIONS: The evidence from this review of 21 randomised controlled trials did not support one particular method or technique over another in providing effective conscious sedation and analgesia for pain relief during and after oocyte recovery. The simultaneous use of more than one method of sedation and pain relief resulted in better pain relief than one modality alone. The various approaches and techniques reviewed appeared to be acceptable and were associated with a high degree of satisfaction in women. As women vary in their experience of pain and in coping strategies, the optimal method may be individualised depending on the preferences of both the women and the clinicians and resource availability.

Postabortion family planning counseling and services for women in low-income countries: a systematic review.

BACKGROUND: Unsafe abortion imposes heavy burdens on both individuals and society, particularly in low-income countries, many of which have restrictive abortion laws. Providing family planning counseling and services to women following an abortion has emerged as a key strategy to address this issue. STUDY DESIGN: This systematic review gathered, appraised and synthesized recent research evidence on the effects of postabortion family planning counseling and services on women in low-income countries. RESULTS: Of the 2965 potentially relevant records that were identified and screened, 15 studies satisfied the inclusion criteria. None provided evidence on the effectiveness of postabortion family planning counseling and services on maternal morbidity and mortality. One controlled study found that, compared to the group of nonbeneficiaries, women who received postabortion family planning counseling and services had significantly fewer unplanned pregnancies and fewer repeat abortions during the 12-month follow-up period. All 15 studies examined contraception-related outcomes. In the seven studies which used a comparative design, there was greater acceptance and/or use of modern contraceptives in women who had received postabortion family planning counseling and services relative to the no-program group. CONCLUSIONS: The current evidence on the use of postabortion family planning counseling and services in low-income countries to address the problem of unsafe abortion is inconclusive. Nevertheless, the increase in acceptance and/or use of contraceptives is encouraging and has the potential to be further explored. Adequate funding to support robust research in this area of reproductive health is urgently needed.

High-resolution 39K NMR spectroscopy of bio-organic solids.

We report the first implementation of the multiple-quantum magic-angle-spinning method to obtain high-resolution (39)K NMR spectra for bio-organic solids. The observed spectral resolution in the isotropic dimension is nearly at the sub-ppm level, which approaches the intrinsic resolution limit determined primarily by quadrupole relaxation. We show that high-resolution solid-state (39)K NMR spectroscopy can be used as a new means of probing K(+) ions in biomolecular systems.

Single atom modification leads to enhanced nucleotide self-assembly: the role of cation bridging.

We report that the ability of disodium 5'-deoxy-5'-thioguanosine-5'-monophosphate, Na(2)(5'-GSMP), to self-associate into a helical G-quadruplex structure in aqueous solution at pH 8 is significantly higher than that of disodium guanosine-5'-monophosphate, Na(2)(5'-GMP), which supports our earlier hypothesis regarding the importance of cation bridging.

Recombinant versus urinary gonadotrophin for ovarian stimulation in assisted reproductive technology cycles.

BACKGROUND: Several systematic reviews compared recombinant gonadotrophin with urinary gonadotrophins (HMG, purified FSH, highly purified FSH) for ovarian hyperstimulation in IVF and ICSI cycles and these reported conflicting results. Each of these reviews used different inclusion and exclusion criteria for trials. Our aim in producing this review is to bring together all randomised studies in this field under common inclusion criteria with consistent and valid statistical methods. OBJECTIVES: To compare the effectiveness of recombinant gonadotrophin (rFSH) with the three main types of urinary gonadotrophins (i.e. HMG, FSH-P and FSH-HP) for ovarian stimulation in women undergoing IVF or ICSI treatment cycles. SEARCH STRATEGY: An extended search was done according to Cochrane guidelines including the Menstrual Disorders & Subfertility Group's Specialised Register of controlled trials, The Cochrane Central Register of Controlled Trials, MEDLINE (1966 to May 2010), EMBASE (1980 to May 2010), CINAHL (1982 to May 2010), National Research Register, and Current Controlled Trials. SELECTION CRITERIA: All randomised controlled trials reporting data comparing clinical outcomes for women undergoing IVF/ICSI cycles and using recombinant FSH in comparison with HMG or highly purified HMG, purified urinary FSH (FSH-P), and highly purified urinary FSH (FSH-HP) for ovarian hyperstimulation in IVF or ICSI cycles were included. DATA COLLECTION AND ANALYSIS: Primary outcome measure was live birth rate and OHSS per randomised woman.Binary outcomes were analysed using odds ratios and also reported in absolute terms. Grouped analyses were carried out for all outcomes to explore whether relative effects differed due to key features of the trials. MAIN RESULTS: We included 42 trials with a total of 9606 couples. Comparing rFSH to any of the other gonadotrophins irrespective of the down-regulation protocol used, did not result in any evidence of a statistically significant difference in live birth rate (28 trials, 7339 couples, odds ratio 0.97, 95% CI 0.87 to 1.08). This suggests that for a group with a 25% live birth rate using urinary gonadotrophins the rate would be between 22.5% and 26.5% using rFSH. There was also no evidence of a difference in the OHSS rate (32 trials, 7740 couples, OR 1.18, 95% CI 0.86 to 1.61). This means that for a group with 2% risk of OHSS using urinary gonadotrophins, the risk would be between 1.7% and 3.2% using rFSH. AUTHORS' CONCLUSIONS: Clinical choice of gonadotrophin should depend on availability, convenience and costs. Further research on these comparisons is unlikely to identify substantive differences in effectiveness or safety.

Quadrupole-central-transition 17O NMR spectroscopy of protein-ligand complexes in solution.

We report the first (17)O quadrupole-central-transition (QCT) NMR spectroscopic study of protein-ligand complexes in solution. This work shows that it is possible to obtain high resolution (17)O NMR spectra for (17)O-labeled ligands bound to proteins. At high magnetic fields such as 21.14 T, this (17)O QCT NMR approach should be applicable to studies of all oxygen-containing functional groups in large proteins (>30 kDa).

Methods to increase response to postal and electronic questionnaires.

BACKGROUND: Postal and electronic questionnaires are widely used for data collection in epidemiological studies but non-response reduces the effective sample size and can introduce bias. Finding ways to increase response to postal and electronic questionnaires would improve the quality of health research. OBJECTIVES: To identify effective strategies to increase response to postal and electronic questionnaires. SEARCH STRATEGY: We searched 14 electronic databases to February 2008 and manually searched the reference lists of relevant trials and reviews, and all issues of two journals. We contacted the authors of all trials or reviews to ask about unpublished trials. Where necessary, we also contacted authors to confirm methods of allocation used and to clarify results presented. We assessed the eligibility of each trial using pre-defined criteria. SELECTION CRITERIA: Randomised controlled trials of methods to increase response to postal or electronic questionnaires. DATA COLLECTION AND ANALYSIS: We extracted data on the trial participants, the intervention, the number randomised to intervention and comparison groups and allocation concealment. For each strategy, we estimated pooled odds ratios (OR) and 95% confidence intervals (CI) in a random-effects model. We assessed evidence for selection bias using Egger's weighted regression method and Begg's rank correlation test and funnel plot. We assessed heterogeneity among trial odds ratios using a Chi(2) test and the degree of inconsistency between trial results was quantified using the I(2) statistic. MAIN RESULTS: PostalWe found 481 eligible trials. The trials evaluated 110 different ways of increasing response to postal questionnaires. We found substantial heterogeneity among trial results in half of the strategies. The odds of response were at least doubled using monetary incentives (odds ratio 1.87; 95% CI 1.73 to 2.04; heterogeneity P < 0.00001, I(2) = 84%), recorded delivery (1.76; 95% CI 1.43 to 2.18; P = 0.0001, I(2) = 71%), a teaser on the envelope - e.g. a comment suggesting to participants that they may benefit if they open it (3.08; 95% CI 1.27 to 7.44) and a more interesting questionnaire topic (2.00; 95% CI 1.32 to 3.04; P = 0.06, I(2) = 80%). The odds of response were substantially higher with pre-notification (1.45; 95% CI 1.29 to 1.63; P < 0.00001, I(2) = 89%), follow-up contact (1.35; 95% CI 1.18 to 1.55; P < 0.00001, I(2) = 76%), unconditional incentives (1.61; 1.36 to 1.89; P < 0.00001, I(2) = 88%), shorter questionnaires (1.64; 95% CI 1.43 to 1.87; P < 0.00001, I(2) = 91%), providing a second copy of the questionnaire at follow up (1.46; 95% CI 1.13 to 1.90; P < 0.00001, I(2) = 82%), mentioning an obligation to respond (1.61; 95% CI 1.16 to 2.22; P = 0.98, I(2) = 0%) and university sponsorship (1.32; 95% CI 1.13 to 1.54; P < 0.00001, I(2) = 83%). The odds of response were also increased with non-monetary incentives (1.15; 95% CI 1.08 to 1.22; P < 0.00001, I(2) = 79%), personalised questionnaires (1.14; 95% CI 1.07 to 1.22; P < 0.00001, I(2) = 63%), use of hand-written addresses (1.25; 95% CI 1.08 to 1.45; P = 0.32, I(2) = 14%), use of stamped return envelopes as opposed to franked return envelopes (1.24; 95% CI 1.14 to 1.35; P < 0.00001, I(2) = 69%), an assurance of confidentiality (1.33; 95% CI 1.24 to 1.42) and first class outward mailing (1.11; 95% CI 1.02 to 1.21; P = 0.78, I(2) = 0%). The odds of response were reduced when the questionnaire included questions of a sensitive nature (0.94; 95% CI 0.88 to 1.00; P = 0.51, I(2) = 0%).ElectronicWe found 32 eligible trials. The trials evaluated 27 different ways of increasing response to electronic questionnaires. We found substantial heterogeneity among trial results in half of the strategies. The odds of response were increased by more than a half using non-monetary incentives (1.72; 95% CI 1.09 to 2.72; heterogeneity P < 0.00001, I(2) = 95%), shorter e-questionnaires (1.73; 1.40 to 2.13; P = 0.08, I(2) = 68%), including a statement that others had responded (1.52; 95% CI 1.36 to 1.70), and a more interesting topic (1.85; 95% CI 1.52 to 2.26). The odds of response increased by a third using a lottery with immediate notification of results (1.37; 95% CI 1.13 to 1.65), an offer of survey results (1.36; 95% CI 1.15 to 1.61), and using a white background (1.31; 95% CI 1.10 to 1.56). The odds of response were also increased with personalised e-questionnaires (1.24; 95% CI 1.17 to 1.32; P = 0.07, I(2) = 41%), using a simple header (1.23; 95% CI 1.03 to 1.48), using textual representation of response categories (1.19; 95% CI 1.05 to 1.36), and giving a deadline (1.18; 95% CI 1.03 to 1.34). The odds of response tripled when a picture was included in an e-mail (3.05; 95% CI 1.84 to 5.06; P = 0.27, I(2) = 19%). The odds of response were reduced when "Survey" was mentioned in the e-mail subject line (0.81; 95% CI 0.67 to 0.97; P = 0.33, I(2) = 0%), and when the e-mail included a male signature (0.55; 95% CI 0.38 to 0.80; P = 0.96, I(2) = 0%). AUTHORS' CONCLUSIONS: Health researchers using postal and electronic questionnaires can increase response using the strategies shown to be effective in this systematic review.

Probing the Na+ binding site in a calix[4]arene-guanosine conjugate dimer by solid-state 23Na NMR and quantum chemical calculation.

Using solid-state (23)Na NMR and quantum chemical calculations we have found that the Na(+) ion bound to a calix[4]arene-guanosine conjugate dimer resides slightly above the G-quartet plane and simultaneously coordinates to a water molecule in a square-pyramidal (penta-coordination) geometry.

Helical structure of disodium 5'-guanosine monophosphate self-assembly in neutral solution.

Nucleic acid molecules (DNA and RNA) are formed by linking many different basic units known as nucleotides together via covalent phosphodiester bonds. Nucleic acid molecules often form helical structures known as B-DNA (right-handed), A-DNA/RNA (right-handed), and Z-DNA (left-handed). We have found that spontaneous self-assembly of just one nucleotide, guanosine 5'-monophosphate (5'-GMP), leads to formation of a right-handed helix in neutral solution. The linkage between individual 5'-GMP molecules along the helix is provided by hydrogen bonds, as opposed to the covalent phosphodiester bonds found in regular polynucleotides. The most surprising finding is that this right-handed 5'-GMP helix has alternating C2'-endo and C3'-endo sugar puckers along the helical strand, a situation only seen to date in left-handed Z-DNA. The self-organized structure of 5'-GMP provides a perfect condition for phosphodiester bond formation which may provide a clue for formation of RNA oligomers under prebiotic conditions. We anticipate that similar helical structures could exist in other nucleic acid systems.