The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis

STUDY QUESTION Is there an association between high levels of sperm DNA damage and miscarriage?SUMMARY ANSWERMiscarriage rates are positively correlated with sperm DNA damage levels.WHAT IS KNOWN ALREADYMost ejaculates contain a subpopulation of sperm with DNA damage, also referred to as DNA fragmentation, in the form of double or single-strand breaks which have been induced in the DNA prior to or following ejaculation. This DNA damage may be particularly elevated in some subfertile men, hence several studies have examined the link between sperm DNA damage levels and conception and miscarriage rates.STUDY DESIGN, SIZE, DURATIONA systematic review and meta-analysis of studies which examined the effect of sperm DNA damage on miscarriage rates was performed. Searches were conducted on MEDLINE, EMBASE and the Cochrane Library without any language restrictions from database inception to January 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSWe used the terms 'DNA damage' or 'DNA fragmentation' combined with 'miscarriage', 'abortion' or 'pregnancy' to generate a set of relevant citations. Data extraction was performed by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale. Meta-analysis of relative risks of miscarriage was performed with a random effects model. Subgroup analyses were performed by the type of DNA damage test, whether the sperm examined were prepared or from raw semen and for pregnancies resulting from IVF or ICSI treatment.MAIN RESULTS AND THE ROLE OF CHANCEWe identified 16 cohort studies (2969 couples), 14 of which were prospective. Eight studies used acridine orange-based assays, six the TUNEL assay and two the COMET assay. Meta-analysis showed a significant increase in miscarriage in patients with high DNA damage compared with those with low DNA damage [risk ratio (RR) = 2.16 (1.54, 3.03), P <0.00001)]. A subgroup analysis showed that the miscarriage association is strongest for the TUNEL assay (RR = 3.94 (2.45, 6.32), P <0.00001).LIMITATIONS, REASONS FOR CAUTIONThere is some variation in study characteristics, including the use of different assays and different thresholds for DNA damage and the definition of pregnancy loss.WIDER IMPLICATIONS OF THE FINDINGSThe use of methods which select sperm without DNA damage for use in assisted conception treatment may reduce the risk of miscarriage. This finding indicates that assays detecting DNA damage could be considered in those suffering from recurrent pregnancy loss. Further research is necessary to study the mechanisms of DNA damage and the potential therapeutic effects of antioxidant therapy.STUDY FUNDING/COMPETING INTEREST(S)None.

A systematic review of quantitative studies reporting selected patient experienced outcomes, with a specific focus on gender differences in people with colorectal cancer

Men with colorectal cancer have a higher mortality rate than their female counterparts. Despite this, there is a limited understanding of the impact gender has on the experience of colorectal cancer.

Human papillomavirus related head and neck cancer survival: A systematic review and meta-analysis

Human Papillomavirus (HPV) related oropharyngeal squamous cell carcinomas (OPSCCs) are reported to have improved prognosis and survival in comparison to other head and neck squamous cell cancers (HNSCCs). This systematic review and meta-analysis examines survival differences in HPV-positive HNSCC and OPSCC subtypes including tonsillar carcinoma in studies not previously investigated. Four electronic databases were searched from their inception till April 2011. A random effects meta-analysis was used to pool study estimates evaluating disease-specific (death from HNSCC), overall (all-cause mortality), progression-free and disease-free (recurrence free) survival outcomes in HPV-positive vs. HPV-negative HNSCCs. All statistical tests were two-sided. Forty-two studies were included. Patients with HPV-positive HNSCC had a 54% better overall survival compared to HPV-negative patients HR 0.46 (95% CI 0.37-0.57); the pooled HR for tonsillar cancer and OPSCC was 0.50 (95% CI 0.33-0.77) and HR 0.47 (95% CI 0.35-0.62) respectively. The pooled HR for disease specific survival was 0.28 (95% CI 0.19-0.40); similar effect sizes were found irrespective of the adjustment for confounders, HPV detection methods or study location. Both progression-free survival and disease-free survival were significantly improved in HPV-positive HNSCCs. HPV-positive HNSCCs and OPSCCs patients have a significantly lower disease specific mortality and are less likely to experience progression or recurrence of their cancer than HPV-negative patients; findings which have connotations for treatment selection in these patients.

Public health interventions in midwifery: a systematic review of systematic reviews

Background: Maternity care providers, particularly midwives, have a window of opportunity to influence pregnant women about positive health choices. This aim of this paper is to identify evidence of effective public health interventions from good quality systematic reviews that could be conducted by midwives.

Methods: Relevant databases including MEDLINE, Pubmed, EBSCO, CRD, MIDIRS, Web of Science, The Cochrane Library and Econlit were searched to identify systematic reviews in October 2010. Quality assessment of all reviews was conducted.

Results: Thirty-six good quality systematic reviews were identified which reported on effective interventions. The reviews were conducted on a diverse range of interventions across the reproductive continuum and were categorised under: screening; supplementation; support; education; mental health; birthing environment; clinical care in labour and breast feeding. The scope and strength of the review findings are discussed in relation to current practice. A logic model was developed to provide an overarching framework of midwifery public health roles to inform research policy and practice.

Conclusions: This review provides a broad scope of high quality systematic review evidence and definitively highlights the challenge of knowledge transfer from research into practice. The review also identified gaps in knowledge around the impact of core midwifery practice on public health outcomes and the value of this contribution. This review provides evidence for researchers and funders as to the gaps in current knowledge and should be used to inform the strategic direction of the role of midwifery in public health in policy and practice.

Hypermobility and musculoskeletal pain in children:a systematic review

Objective: To examine the evidence of an association between hypermobility and musculoskeletal pain in children. Methods: A systematic review of the literature was performed using the databases PubMed, EMBASE, NHS Evidence, and Medline. Inclusion criteria were observational studies investigating hypermobility and musculoskeletal pain in children. Exclusion criteria were studies conducted on specialist groups (i.e. dancers) or hospital referrals. Pooled odds ratios (ORs) were calculated using random effects models and heterogeneity was tested using ?(2)-tests. Study quality was assessed using the Newcastle-Ottawa Scale for case-control studies. Results: Of the 80 studies identified, 15 met the inclusion criteria and were included in the review. Of these, 13 were included in the statistical analyses. Analysing the data showed that the heterogeneity was too high to allow for interpretation of the meta-analysis (I(2) = 72%). Heterogeneity was much lower when the studies were divided into European (I(2) = 8%) and Afro-Asian subgroups (I(2) = 65%). Sensitivity analysis based on data from studies reporting from European and Afro-Asian regions showed no association in the European studies [OR 1.00, 95% confidence interval (CI) 0.79-1.26] but a marked relationship between hypermobility and joint pain in the Afro-Asian group (OR 2.01, 95% CI 1.45-2.77). Meta-regression showed a highly significant difference between subgroups in both meta-analyses (p <0.001). Conclusion: There seems to be no association between hypermobility and joint pain in Europeans. There does seem to be an association in Afro-Asians; however, there was a high heterogeneity. It is unclear whether this is due to differences in ethnicity, nourishment, climate or study design.

The effect of increasing fruit and vegetable consumption on overall diet: a systematic review and meta-analysis

Increasing fruit and vegetable (FV) consumption is associated with reduced risk of major diseases. However, it is unclear if health benefits are related to increased micronutrient intake or to improvements in overall diet profile. This review aimed to assess if increasing FV consumption had an impact on diet profile. In the systematic review, twelve studies revealed increases in micronutrient intakes, whilst the meta-analysis confirmed macronutrient findings from the systematic review showing no significant difference between the intervention and control groups in energy (kcals) in seven studies (mean difference = 1 kcals [95% CI = -115, 117]; P = 0.98), significant decreases in total fat (% energy) in 5 studies (Mean difference = -4% [95% CI = -5, -3]; P = <0.00001) and significant increases in fibre in 6 studies (Mean difference = 5.36 grams [95% CI = 4, 7]; P = <0.00001) and total carbohydrate (% energy) in 4 studies (Mean = 4% [95% CI = 2, 5]; P = <0.00001). In conclusion, results indicate that increased FV consumption increases micronutrient, carbohydrate and fibre intakes and possibly reduces fat intake, with no overall effect on energy intake. Therefore health benefits may act through an improvement in overall diet profile alongside increased micronutrient intakes.

A systematic review of systematic reviews to improve maternal mental health and well-being

Objective: to identify non-invasive interventions in the perinatal period that could enable midwives to offer effective support to women within the area of maternal mental health and well-being.

Methods: a total of 9 databases were searched: MEDLINE, PubMed, EBSCO (CINAHL/British Nursing Index), MIDIRS Online Database, Web of Science, The Cochrane library, CRD (NHS EED/DARE/HTA), Joanne Briggs Institute and EconLit. A systematic search strategy was formulated using key MeSH terms and related text words for midwifery, study aim, study design and mental health. Inclusion criteria were articles published from 1999 onwards, English language publications and articles originating from economically developed countries, indicated by membership of the Organisation for Economic Co-operation and Development (OECD). Data were independently extracted using a data collection form, which recorded data on the number of papers reviewed, time frame of the review, objectives, key findings and recommendations. Summary data tables were set up outlining key data for each study and findings were organised into related groups. The methodological quality of the reviews was assessed based on predefined quality assessment criteria for reviews.

Findings: 32 reviews were identified as examining interventions that could be used or co-ordinated by midwives in relation to some aspect of maternal mental health and well-being from the antenatal to the postnatal period and met the inclusion criteria. The review highlighted that based on current systematic review evidence it would be premature to consider introducing any of the identified interventions into midwifery training or practice. However there were a number of examples of possible interventions worthy of further research including midwifery led models of care in the prevention of postpartum depression, psychological and psychosocial interventions for treating postpartum depression and facilitation/co-ordination of parent-training programmes. No reviews were identified that supported a specific midwifery role in maternal mental health and well-being in pregnancy, and yet, this is the point of most intensive contact.

Key conclusions and implications for practice: This systematic review of systematic reviews provides a valuable overview of the current strengths and gaps in relation to maternal mental health interventions in the perinatal period. While there was little evidence identified to inform the current role of midwives in maternal mental health, the review provides the opportunity to reflect on what is achievable by midwives now and in the future and the need for high quality randomised controlled trials to inform a strategic approach to promoting maternal mental health in midwifery.

Dietary fat and breast cancer survival: a systematic review and meta-analysis

As the number of breast cancer survivors increases worldwide(1), there is growing interest in the potential effect of dietary and lifestyle behaviours on overall prognosis. This is especially important as a cancer diagnosis is often referred to as a ‘teachable moment’(2) as patients seek information about lifestyle behaviours and so provision of evidence-based guidelines is essential. A positive association between dietary fat and breast cancer risk has been previously reported(3) but its influence upon breast cancer survival is unclear. The aim of this review and meta-analysis is to critically appraise the literature published to date and to conduct meta-analyses to pool the results of studies to clarify the association between dietary fat and breast cancer survival.
Relevant articles published up to March 2011 that examined dietary fat and breast cancer recurrence and survival were identified from searches in MEDLINE and EMBASE. Meta-analyses were conducted in which we evaluated the risk of all-cause or breast cancer death in women in the highest compared with the lowest categories of total fat intake (g/d) and per 20 g increase in intake of dietary fat. Multivariable adjusted relative risks (RR) and 95% CI from individual studies were weighted and combined using a random-effects model to produce a pooled estimate.
Twelve prospective cohort studies that investigated total fat intake (g) and breast cancer survival, and/or provided information on fat intake from which a linear trend could be estimated, were included in the analyses. There was no evidence of a difference in risk of breast cancer death (RR=1.14; 95% CI 0.86, 1.52; P=0.34) or all cause death (RR=1.73; 95% CI 0.82, 3.6; P=0.15) between the highest and lowest categories of total fat intake. Similarly, no significant difference in risk of breast cancer death (RR=1.03; 95% CI 0.97, 1.10; P=0.261) or all-cause death (RR=1.06; 95% CI 0.88, 1.28; P=0.52) was found per linear (20 g) increase in total fat intake.
The results of this systematic review and meta-analysis do not support an association between total dietary fat and breast cancer survival. Further investigation into the effect of specific types of dietary fat and breast cancer survival is of interest.

Systematic methodology for the design of high performance recursive digital filters

A systematic design methodology is described for the rapid derivation of VLSI architectures for implementing high performance recursive digital filters, particularly ones based on most significant digit (msd) first arithmetic. The method has been derived by undertaking theoretical investigations of msd first multiply-accumulate algorithms and by deriving important relationships governing the dependencies between circuit latency, levels of pipe-lining and the range and number representations of filter operands. The techniques described are general and can be applied to both bit parallel and bit serial circuits, including those based on on-line arithmetic. The method is illustrated by applying it to the design of a number of highly pipelined bit parallel IIR and wave digital filter circuits. It is shown that established architectures, which were previously designed using heuristic techniques, can be derived directly from the equations described.

Computation of stress intensity factors in functionally graded materials using partition-of-unity meshfee method

This paper describes the computation of stress intensity factors (SIFs) for cracks in functionally graded materials (FGMs) using an extended element-free Galerkin (XEFG) method. The SIFs are extracted through the crack closure integral (CCI) with a local smoothing technique, non-equilibrium and incompatibility formulations of the interaction integral and the displacement method. The results for mode I and mixed mode case studies are presented and compared with those available in the literature. They are found to be in good agreement where the average absolute error for the CCI with local smoothing, despite its simplicity, yielded a high level of accuracy.