A new stoma for an older person-An association with quality of life and physical function: A systematic review.

BACKGROUND: Older people are more likely to have a stoma postabdominal surgery than younger people. Few studies have examined the effect of a stoma on older people. The aim of this review was to explore the effect of a stoma on functional independence of an older person. We explored secondary outcomes of poststoma formation length of hospital stay, quality of life and factors affecting stroma independence. METHODS: An exploratory systematic review was developed by our multidisciplinary group including an expert patient, colorectal surgeon, stoma nurse, physiotherapist, geriatrician, and methodologist. Four databases were searched including studies with participants 60 years old or older, who had undergone abdominal surgery for any pathology resulting in an abdominal stoma. RESULTS: We identified 857 studies, of which we included 25 in the final review incorporating 6972 participants (average age 67.4 years). There was a strong association between presence of stoma and (1) worse physical function (standardized MD = 0.7; 95% CI 0.21-1.19; I2  = 95) and (2) worse quality of life (standardized MD = 1.61; 95% CI 0.5-2.72, I2  = 98). The same effect was seen in fecal ostomy and urinary diversion. Few studies measured stoma independence and only one examined factors affecting this. No studies examined length of stay. CONCLUSIONS: Stoma have a negative association with the physical function and quality of life of older people. Future studies should focus on identifying modifiable factors that may affect physical function, quality of life, and stoma independence.

The emperor still looks naked.

Preimplantation genetic screening for aneuploidy continues to excite disagreement, discussion and confusion in the field of reproductive medicine. This commentary provides a contribution to the ongoing debate.

Assisted reproductive technologies to prevent human mitochondrial disease transmission.

Mitochondria are essential cytoplasmic organelles that generate energy (ATP) by oxidative phosphorylation and mediate key cellular processes such as apoptosis. They are maternally inherited and in humans contain a 16,569-base-pair circular genome (mtDNA) encoding 37 genes required for oxidative phosphorylation. Mutations in mtDNA cause a range of pathologies, commonly affecting energy-demanding tissues such as muscle and brain. Because mitochondrial diseases are incurable, attention has focused on limiting the inheritance of pathogenic mtDNA by mitochondrial replacement therapy (MRT). MRT aims to avoid pathogenic mtDNA transmission between generations by maternal spindle transfer, pronuclear transfer or polar body transfer: all involve the transfer of nuclear DNA from an egg or zygote containing defective mitochondria to a corresponding egg or zygote with normal mitochondria. Here we review recent developments in animal and human models of MRT and the underlying biology. These have led to potential clinical applications; we identify challenges to their technical refinement.

Implementation of a multicomponent intervention to optimise patient safety through improved oxygen prescription in a rural hospital.

OBJECTIVE: To rationalise oxygen procedures in adult medical and surgical inpatients with a view to improving patient safety. DESIGN: Prospective pre- and post-intervention audit. SETTING: Manning Hospital, a rural referral hospital in Taree NSW. PARTICIPANTS: Pre-intervention: 82 patients aged 72.7 ± 14.7 years. Post-intervention: 77 patients aged 73.6 ± 12.4 years. INTERVENTION: A multicomponent intervention composed of implementation of a local hospital oxygen policy, introduction of a specific oxygen prescription chart and targeted staff education. MAIN OUTCOME MEASURES: Satisfactory oxygen prescription, monitoring and titration. RESULTS: Only 2/82 (2.4%) patients had satisfactory oxygen prescription specifying target saturation, device and initial flow rate before the intervention compared with 26/77 (34%) patients post-intervention (χ(2) = 56.88, df = 5, P < 0.0001). Percentage of patients with conditions predisposing to hypercapnic respiratory failure who were overtreated with oxygen dropped from 9/19 (47%) to 4/22 (18%) following the study intervention (χ(2) = 4.011, df = 1, P = 0.04). Oxygen therapy monitoring was satisfactory during the audit period, but oxygen titration was unsatisfactory and did not significantly improve following the intervention. CONCLUSIONS: A multicomponent intervention can achieve a significantly increased rate of satisfactory oxygen prescriptions specifying target saturation, including in those who are at risk of hypercapnic respiratory failure.

Long gonadotropin-releasing hormone agonist versus short agonist versus antagonist regimens in poor responders undergoing in vitro fertilization: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of the long GnRH agonist vs. the short GnRH agonist vs. the GnRH antagonist regimens in poor responders undergoing IVF. DESIGN: Randomized controlled trial. SETTING: Tertiary referral fertility units. PATIENT(S): Women with previous poor ovarian response undergoing IVF. INTERVENTION(S): One hundred eleven women were randomized to the long GnRH agonist, short agonist, and antagonist regimens. MAIN OUTCOME MEASURE(S): The primary outcome was the number of oocytes retrieved. Secondary outcome measures were gonadotropin consumption, duration of stimulation, cycle cancellation rate, mature oocytes retrieved, fertilization rate, cycles reaching ET, and clinical and ongoing pregnancy rates. RESULT(S): Number of oocytes retrieved was significantly higher with long GnRH agonist compared with the short agonist regimen (4.42 ± 3.06 vs. 2.71 ± 1.60), while there was no significant difference between long agonist and antagonist regimens (4.42 ± 3.06 vs. 3.30 ± 2.91). Duration of stimulation and total gonadotropin dose were significantly higher with long agonist compared with short agonist and antagonist regimens. The ongoing pregnancy rate was 8.1% with long and short agonist regimens and 16.2% with the antagonist regimen. CONCLUSION(S): Long GnRH agonist and antagonist regimens offer a suitable choice for poor responders, whereas the short agonist regimen may be less effective because of fewer eggs retrieved.

Selecting the 'best' embryos: prospects for improvement.

This review considers why and how embryos are selected for transfer and with what consequences. It concludes that: (i) current selection methods are inadequate or at least inadequately subjected to evidential scrutiny; (ii) decisions about number of embryos should be based not solely on input (numbers transferred) but on the likelihood of the transfer resulting in multiple pregnancies - out turn; and (iii) what is needed are better methods not just for selecting better embryos, but also for selecting responsible clinicians who collude less with their patients' demands but advise them more responsibly.

Evidence-based medicine and the role of the private sector in assisted reproduction: a response to Dr Fishel's commentary 'Evidenced-based medicine and the role of the National Health Service in assisted reproduction'.

We respond to Dr Fishel's commentary on evidenced-based medicine in assisted reproduction and the role of the UK's National Health Service. We agree that proper randomised clinical trials are not easy to set up or execute. Recruitment is also challenging but requires that all personnel involved in the study, clinicians, embryologists and nurses, agree with its aims and buy in to the need for an answer. Those who believe fervently in the method under scrutiny prior to the availability of robust evidence are likely to undermine the success of any trial. New technologies are not necessarily better technologies. Neither is the supposed 'logic' of a treatment nor anecdotal clinical experience a substitute for evidence properly gained and fairly demonstrated. Dr Fishel would agree that the first obligation of healthcare professionals, whether they are in the public or private sector, is not to do harm to their patients. Adopting new interventions without rigorous assessment of the potential for harm flies in the face of this basic principle.

Derivation and propagation of human embryonic stem cell lines from frozen embryos in an animal product-free environment.

The protocols described here are comprehensive instructions for deriving human embryonic stem (hES) cell lines in xeno-free conditions from cryopreserved embryos. Details are included for propagation, cryopreservation and characterization. Initial derivation is on feeder cells and is followed by adaptation to a feeder-free environment; competent technicians can perform these simplified methods easily. From derivation to cryopreservation of fully characterized initial stocks takes 3-4 months. These protocols served as the basis for standard operating procedures (SOPs), with both operational and technical components, that we set to meet good manufacturing practice (GMP) and UK regulatory body requirements for derivation of clinical-grade cells. As such, these SOPs are currently used in our current GMP compliant facility to derive hES cell lines ab initio, in an animal product-free environment; these lines are suitable for research and potentially for clinical use in cell therapy. So far, we have derived eight clinical-grade lines, which will be freely available to the scientific community after submission/accession to the UK Stem Cell Bank.

The procurement of cells for the derivation of human embryonic stem cell lines for therapeutic use: recommendations for good practice.

The donation of human embryos for the derivation of embryonic stem cell lines that may be used in the development of therapeutic products raises more complex ethical, practical and regulatory problems than the donation of embryos for non-clinical research. This review considers these issues and offers recommendations for good practice.

Derivation and feeder-free propagation of human embryonic stem cells under xeno-free conditions.

BACKGROUND AIMS: Human embryonic stem (hES) cells hold great potential for cell therapy and regenerative medicine because of their pluripotency and capacity for self-renewal. The conditions used to derive and culture hES cells vary between and within laboratories depending on the desired use of the cells. Until recently, stem cell culture has been carried out using feeder cells, and culture media, that contain animal products. Recent advances in technology have opened up the possibility of both xeno-free and feeder-free culture of stem cells, essential conditions for the use of stem cells for clinical purposes. To date, however, there has been limited success in achieving this aim. METHODS, RESULTS AND CONCLUSIONS: Protocols were developed for the successful derivation of two normal and three specific mutation-carrying (SMC) (Huntington's disease and myotonic dystrophy 1) genomically stable hES cell lines, and their adaptation to feeder-free culture, all under xeno-free conditions.

Viral screening before each cycle of assisted conception treatment is expensive and unnecessary: a survey of results from a UK inner city clinic.

The European Union Tissues and Cells Directive requires screening of tissue and cell donors for infective organisms to prevent inter-patient transmission. The Directive includes the unique term partner donation, which refers to "donation of reproductive cells between a man and a woman who declare that they have an intimate physical relationship". In line with the Directive, partners undergoing Assisted Reproductive Technology (ART) now require screening before each treatment, regardless of the time interval between consecutive cycles. Evidence to support this recommendation is lacking. Therefore, we conducted a retrospective study of all virology screening tests undertaken over a three year period for individuals attending an assisted conception unit serving a high risk inner city population. We ascertained prevalence and seroconversion rates for HIV, hepatitis B and C and estimated the additional cost of implementing the Directive fully in our unit. With more than 3910 ART individuals screened between January 2007 and December 2009, the prevalence of HIV, hepatitis B and C was 0.6, 1.7 and 0.4%, respectively. A total of 422 individuals had a second screening test during the three year period and none seroconverted. This study suggests that increasing the frequency of screening individuals undergoing ART to less than 12 months would not confer added benefit and has significant cost implications.

Influence of BMI on risk of miscarriage after single blastocyst transfer.

BACKGROUND: Debate exists regarding the effect of raised BMI on the outcome of pregnancies after assisted reproduction technology. We assessed the effect of BMI on the risk of miscarriage in women conceiving following single blastocyst transfer (SBT) after controlling for confounding factors. METHODS: Fresh and cryo-thawed cycles of SBT that resulted in a pregnancy between January 2006 and March 2010 were included. Patients with BMI < 18.5 kg/m(2) or older than 40 years were excluded. Patients were grouped according to their BMI at the start of treatment cycle. The main outcome measure was the miscarriage rate before 23 weeks gestation. Confounding variables examined included female age, duration and cause of infertility, previous miscarriage, smoking status and quality of blastocyst replaced. RESULTS: A total of 413 women conceived following SBT in fresh (n = 325) or cryo-thawed (n = 88) IVF cycles, of whom 244 had a normal BMI (18.5-24.9) and 169 had a raised BMI of ≥ 25. Overall, 27% (113/413) of women miscarried before 23 weeks gestation. Women with a BMI of ≥ 25 had more than double the risk of miscarriage compared with women who had normal BMI [38 versus 20%, odds ratio (OR): 2.4, 95% confidence interval (CI) 1.6-3.8, P < 0.001, respectively]. After adjusting for confounding variables, having a BMI of ≥ 25 significantly increased the risk of clinical miscarriage before 23 weeks gestation in both fresh (adjusted OR = 2.7, 95% CI 1.5-4.9, P = 0.001) and cryo-thawed IVF cycles (OR = 6.8, 95% CI 1.5-31.1, P = 0.012). CONCLUSIONS: Raised BMI is independently associated with higher miscarriage rate after IVF treatment.

Reducing multiple pregnancies after assisted reproduction treatment: Québec says 'Yes, we can!'.

Multiple pregnancy (MP) is widely recognized as the single biggest risk to children born as a result of assisted reproduction treatment. There is an emerging trend in Europe and Canada to promote single-embryo transfer (SET). In this issue, Gleicher argues that twin pregnancies should not be seen as an unfavourable outcome of assisted reproduction treatment. He argues that SET policies 'make no sense' since they will aggravate already unsatisfactory population growth in some countries. He also argues that governmental intervention to impose SET policies, despite proving successful in reducing MP, are inappropriate. The overwhelming evidence in the literature indicates that his opinion is not supported by credible data. Views should be based on solid data rather than personal judgement. Governmental interventions to reduce twin pregnancies, as demonstrated previously in Belgium and now in Québec, have been successful. The risks of twin pregnancies are real and borne by women and children, not their doctors. Doctors managing infertile couples are no longer entitled to take risks with the health of the next generation.

Safety paradigm: genetic evaluation of therapeutic grade human embryonic stem cells.

The use of stem cells for regenerative medicine has captured the imagination of the public, with media attention contributing to rising expectations of clinical benefits. Human embryonic stem cells (hESCs) are the best model for capital investment in stem cell therapy and there is a clear need for their robust genetic characterization before scaling-up cell expansion for that purpose. We have to be certain that the genome of the starting material is stable and normal, but the limited resolution of conventional karyotyping is unable to give us such assurance. Advanced molecular cytogenetic technologies such as array comparative genomic hybridization for identifying chromosomal imbalances, and single nucleotide polymorphism analysis for identifying ethnic background and loss of heterozygosity should be introduced as obligatory diagnostic tests for each newly derived hESC line before it is deposited in national stem cell banks. If this new quality standard becomes a requirement, as we are proposing here, it would facilitate and accelerate the banking process, since end-users would be able to select the most appropriate line for their particular application, thus improving efficiency and streamlining the route to manufacturing therapeutics. The pharmaceutical industry, which may use hESC-derived cells for drug screening, should not ignore their genomic profile as this may risk misinterpretation of results and significant waste of resources.

The influence of delayed blastocyst formation on the outcome of frozen-thawed blastocyst transfer: a systematic review and meta-analysis.

BACKGROUND: There are conflicting results on whether the rate of blastocyst development before freezing influences the outcome of frozen-thawed blastocyst transfers. METHODS: We conducted a systematic review and meta-analysis of controlled studies to compare pregnancy outcomes following transfer of thawed blastocysts that were frozen either on Day 5 or Day 6 following fertilization in vitro. Searches were conducted on MEDLINE, EMBASE, Cochrane Library and Web of Science. Study selection and data extraction were conducted independently by two reviewers. The Newcastle-Ottawa Quality Assessment Scale was used for quality assessment. RESULTS: We identified 15 controlled studies comprising 2502 frozen-thawed transfers involving blastocysts that were either frozen on Day 5 or Day 6. Meta-analysis of these studies showed significantly higher clinical pregnancy rate [relative risk (RR) = 1.14, 95% confidence interval (CI): 1.03-1.26, P = 0.01] and ongoing pregnancy/live birth rate (RR = 1.15, 95% CI: 1.01-1.30, P = 0.03) with Day 5 compared with Day 6 frozen-thawed blastocyst transfers. Sensitivity analysis of those studies where blastocysts frozen on Day 5 or Day 6 were at the same stage of development showed no significant difference in the clinical pregnancy rate (RR = 1.07, 95% CI: 0.87-1.33, P = 0.51) and ongoing pregnancy/live birth rate (RR = 1.08, 95% CI: 0.92-1.27, P = 0.36). CONCLUSION: Slower developing blastocysts cryopreserved on Day 6 but at the same stage of development as those developing to the blastocyst stage on Day 5 have similar clinical pregnancy and ongoing pregnancy/live birth rates following frozen-thawed blastocyst transfers.

Preimplantation genetic diagnosis for a carrier of a Y;autosome translocation resulting in a healthy male offspring.

OBJECTIVE: To demonstrate the feasibility of establishing a successful pregnancy for a carrier of a balanced Y;autosome translocation. DESIGN: Four locus-specific fluorescence in situ hybridization (FISH) probes, informative for the translocation, were identified and tested on peripheral lymphocyte metaphase chromosomes and interphase preparations from the translocation carrier and his partner. SETTING: National health service genetics center, cytogenetics laboratory, and assisted conception unit. PATIENT(S): An infertile man, presenting with a balanced Y;13 translocation, and his reproductive partner. INTERVENTION(S): After ovarian stimulation, 15 eggs were collected, nine were injected, and three were suitable for blastomere biopsy on day 3; a single blastomere was taken from each embryo and tested with four locus-specific FISH probes. MAIN OUTCOME MEASURE(S): Birth of a healthy child. RESULT(S): One embryo showed a triploid signal pattern and one had fragmented nuclei; neither was suitable for transfer. One embryo showed a balanced male signal pattern and was transferred. A singleton pregnancy was established, resulting in the birth of a healthy male child. CONCLUSION(S): This first report of successful preimplantation genetic diagnosis treatment for infertile males with y:autosome translocations demonstrates that this treatment option can result in successful pregnancies and healthy offspring.