Morbidity associated with the immediate vertical rectus abdominus myocutaneous flap reconstruction after radical pelvic surgery.

AIM: Patients who undergo radical pelvic surgery often have problems with perineal wound healing and pelvic collections. While there is recognition of the perineal morbidity, there also remains uncertainty around the benefit of vertical rectus abdominus myocutaneous (VRAM) flaps due to the balance between primary healing and the complications associated with this form of reconstruction. This study aimed to evaluate factors associated with significant flap and donor site related complications following VRAM flap reconstruction for radical pelvic surgery. METHOD: A retrospective analysis of VRAM flap related complications was undertaken from prospectively maintained databases for all patients undergoing radical pelvic surgery (2001- 2017) in two cancer centres. RESULTS: In all, 154 patients were identified [median age 62 years (range 26-89 years), 80 (52%) men]. Thirty-three (21%) patients experienced significant donor or flap related complications. Major complications (Clavien-Dindo ≥ 3) related to the abdominal donor site occurred in nine (6%) patients, while those related to the flap or perineal site occurred in 28 (18%) patients. Only smoking (P = 0.003) and neoadjuvant radiotherapy (P = 0.047) were associated with the development of significant flap related complications on univariate analysis. Flap related complications resulted in a significantly longer hospital stay (P < 0.001). CONCLUSION: Careful patient selection is required to balance the risks vs the benefits of VRAM flap reconstruction. Immediate VRAM reconstruction in patients undergoing radical pelvic surgery can achieve early healing and stable perineal closure; it has a low but significant morbidity. Major flap related complications are significantly associated with smoking status and neoadjuvant radiotherapy and result in a prolonged length of hospital stay.

Colonic microbiota can promote rapid local improvement of murine colitis by thioguanine independently of T lymphocytes and host metabolism.

OBJECTIVE: Mercaptopurine (MP) and pro-drug azathioprine are 'first-line' oral therapies for maintaining remission in IBD. It is believed that their pharmacodynamic action is due to a slow cumulative decrease in activated lymphocytes homing to inflamed gut. We examined the role of host metabolism, lymphocytes and microbiome for the amelioration of colitis by the related thioguanine (TG). DESIGN: C57Bl/6 mice with or without specific genes altered to elucidate mechanisms responsible for TG's actions were treated daily with oral or intrarectal TG, MP or water. Disease activity was scored daily. At sacrifice, colonic histology, cytokine message, caecal luminal and mucosal microbiomes were analysed. RESULTS: Oral and intrarectal TG but not MP rapidly ameliorated spontaneous chronic colitis in Winnie mice (point mutation in Muc2 secretory mucin). TG ameliorated dextran sodium sulfate-induced chronic colitis in wild-type (WT) mice and in mice lacking T and B lymphocytes. Remarkably, colitis improved without immunosuppressive effects in the absence of host hypoxanthine (guanine) phosphoribosyltransferase (Hprt)-mediated conversion of TG to active drug, the thioguanine nucleotides (TGN). Colonic bacteria converted TG and less so MP to TGN, consistent with intestinal bacterial conversion of TG to so reduce inflammation in the mice lacking host Hprt. TG rapidly induced autophagic flux in epithelial, macrophage and WT but not Hprt-/- fibroblast cell lines and augmented epithelial intracellular bacterial killing. CONCLUSIONS: Treatment by TG is not necessarily dependent on the adaptive immune system. TG is a more efficacious treatment than MP in Winnie spontaneous colitis. Rapid local bacterial conversion of TG correlated with decreased intestinal inflammation and immune activation.

Voltage transfer function as an optical method to characterize electrical properties of liquid crystal devices.

The voltage transfer function is a rapid and visually effective method to determine the electrical response of liquid crystal (LC) systems using optical measurements. This method relies on crosspolarized intensity measurements as a function of the frequency and amplitude of the voltage applied to the device. Coupled with a mathematical model of the device it can be used to determine the device time constants and electrical properties. We validate the method using photorefractive LC cells and determine the main time constants and the voltage dropped across the layers using a simple nonlinear filter model.

A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer.

BACKGROUND: The neutrophil lymphocyte ratio (NLR) has prognostic value in patients with a variety of cancers. Many chemotherapeutic trial databases hold information on white cell and neutrophil counts only. The aim of the present study was to compare the prognostic value of the NLR with a derived score (dNLR), composed of white cell and neutrophil counts. METHODS: Patients (n=27,031) who were sampled incidentally between 2000 and 2007 for neutrophil, lymphocyte and white cell counts, and also had a diagnosis of cancer (Scottish Cancer Registry), were identified. Of this group, 12,118 patients who had been sampled within 2 years of their cancer diagnosis were studied. RESULTS: On follow-up, there were 7366 deaths, of which 6198 (84%) were cancer deaths. The median time from blood sampling to diagnosis was 2.1 months. The area under the receiver-operating characteristic (ROC) curve for cancer-specific survival was 0.650 for the NLR and 0.640 for the dNLR. The NLR and dNLR were independently associated with survival in all cancers studied (all P<0.001). The optimal thresholds, on the basis of hazard ratios and area under the curve, were 4 : 1 for the NLR and 2 : 1 for the dNLR. CONCLUSION: The results of the present study show that the dNLR has similar prognostic value to the NLR. Therefore, the universally available dNLR is to be commended for use in the risk stratification of patients undergoing chemotherapy.

An inflammation-based prognostic score (mGPS) predicts cancer survival independent of tumour site: a Glasgow Inflammation Outcome Study.

INTRODUCTION: A selective combination of C-reactive protein and albumin (termed the modified Glasgow Prognostic Score, mGPS) has been shown to have prognostic value, independent of tumour stage, in lung, gastrointestinal and renal cancers. It is also of interest that liver function tests such as bilirubin, alkaline phosphatase and γ-glutamyl transferase, as well as serum calcium, have also been reported to predict cancer survival. The aim of the present study was to examine the relationship between an inflammation-based prognostic score (mGPS), biochemical parameters, tumour site and survival in a large cohort of patients with cancer. METHODS: Patients (n=21,669) who had an incidental blood sample taken between 2000 and 2006 for C-reactive protein, albumin and calcium (and liver function tests where available) and a diagnosis of cancer were identified. Of this group 9608 patients who had an ongoing malignant process were studied (sampled within 2 years before diagnosis). Also a subgroup of 5397 sampled at the time of diagnosis (sampled within 2 months prior to diagnosis) were examined. Cancers were grouped by tumour site in accordance with International Classification of Diseases 10 (ICD 10). RESULTS: On follow up, there were 6005 (63%) deaths of which 5122 (53%) were cancer deaths. The median time from blood sampling to diagnosis was 1.4 months. Increasing age, male gender and increasing deprivation was associated with a reduced 5-year overall and cancer-specific survival (all P<0.001). An elevated mGPS, adjusted calcium, bilirubin, alkaline phosphatase, aspartate transaminase, alanine transaminase and γ-glutamyl transferase were associated with a reduced 5-year overall and cancer-specific survival (independent of age, sex and deprivation in all patients sampled), as well as within the time of diagnosis subgroup (all P<0.001). An increasing mGPS was predictive of a reduced cancer-specific survival in all cancers (all P<0.001). CONCLUSION: The results of the present study indicate that the mGPS is a powerful prognostic factor when compared with other biochemical parameters and independent of tumour site in patients with cancer.

The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow Inflammation Outcome Study.

BACKGROUND: Cancer incidence is increasing in the United Kingdom, as well as on a global basis. Biochemical parameters, such as C-reactive protein and albumin (combined to form the modified Glasgow Prognostic Score, mGPS), alkaline phosphatase (Alk phos), gamma-glutamyl transferase (GGT) and serum calcium have been reported to be associated with cancer and non-cancer mortality. Therefore, to definitively examine the interrelationships between the above biochemical parameters, the mGPS and the presence of cancer, the Glasgow Inflammation Outcome Study was undertaken. The aim of this initial study was to examine the effect of cancer on markers of systemic inflammation induced by the liver (mGPS) and on levels of routine biochemical parameters. METHODS: Patients (n=223 303) who had a single incidental sample taken for C-reactive protein, albumin, calcium and serum liver function tests where available, between 2000 and 2008 were studied. Those with a pathological diagnosis of cancer (n=22 715) were identified. The mGPS was constructed and liver function tests classified in accordance with the local reference ranges. RESULTS: Patients with cancer had higher C-reactive protein and lower albumin levels (and thus a higher mGPS), higher adjusted calcium, Alk phos and GGT levels, but lower aspartate transaminase (AST) and alanine transaminase (ALT) levels (all P<0.001). The strongest associations (Spearman's correlation > or =0.3) in both the non-cancer and cancer groups were found between albumin, C-reactive protein and Alk phos, AST and ALT, AST and GGT and ALT and GGT (all P<0.001). On multivariate analysis, the associations with the presence of cancer remained with age, deprivation, C-reactive protein, albumin, adjusted calcium, Alk phos and GGT (all P<0.01). Patients following a diagnosis of cancer had lower albumin levels and thus higher mGPS (all P<0.001). Also, post-diagnosis patients were more likely to have lower adjusted calcium, bilirubin, Alk Phos, AST, ALT and GGT levels (all P<0.05). When the cancer diagnoses were ranked from those with the lowest proportion of mGPS 1 or 2 to those with the highest, the percentage of cases with a mGPS of 1 or 2 ranged from 21% in breast cancer to 46% in prostate cancer and to 68% in pulmonary cancer. Compared with breast cancer the mGPS was significantly higher in those diagnosed with dermatological, bladder, endocrinological, gynaecological, prostate, musculoskeletal, gastroesophageal, haematological, renal, colorectal, head and neck, pancreaticobiliary and pulmonary cancers (all P<0.001). CONCLUSION: The results of the present study indicate that the systemic inflammatory response is common in a large patient cohort, increased by the presence of cancer and associated with the perturbation of a number of biochemical parameters previously reported to be associated with mortality. There is a striking parallel between the proportions of cases with a mGPS of 1 or 2 and reported survival rates in these tumours.

The convective instability of a Maxwell-Cattaneo fluid in the presence of a vertical magnetic field.

We study the instability of a Bénard layer subject to a vertical uniform magnetic field, in which the fluid obeys the Maxwell-Cattaneo (MC) heat flux-temperature relation. We extend the work of Bissell (Proc. R. Soc. A 472, 20160649 (doi:10.1098/rspa.2016.0649)) to non-zero values of the magnetic Prandtl number p m . With non-zero p m , the order of the dispersion relation is increased, leading to considerably richer behaviour. An asymptotic analysis at large values of the Chandrasekhar number Q confirms that the MC effect becomes important when C Q 1/2 is O(1), where C is the MC number. In this regime, we derive a scaled system that is independent of Q. When CQ 1/2 is large, the results are consistent with those derived from the governing equations in the limit of Prandtl number p → ∞ with p m finite; here we identify a new mode of instability, which is due neither to inertial nor induction effects. In the large p m regime, we show how a transition can occur between oscillatory modes of different horizontal scale. For Q ≫ 1 and small values of p, we show that the critical Rayleigh number is non-monotonic in p provided that C > 1/6. While the analysis of this paper is performed for stress-free boundaries, it can be shown that other types of mechanical boundary conditions give the same leading-order results.

Sentinel lymph node biopsy for melanoma of the head and neck: a multicentre study to examine safety, efficacy, and prognostic value.

Sentinel lymph node biopsy (SLNB) is an accurate staging procedure for malignant melanoma but its use in patients with melanoma of the head and neck has been questioned in the past because of a perceived record of poor safety and accuracy. Technical improvements have sought to redress this. Vital structures and variable lymphatic pathways can make its use in the head and neck challenging. In our study we have examined the data and the experiences of clinicians from University Hospital Southampton and the Royal Surrey County Hospital. We retrospectively analysed the data and case notes of 143 patients who had SLNB to establish its safety, efficacy, and prognostic value. The detection rate of at least one sentinel lymph node was 100%. Nodes positive for metastatic melanoma were found in 20% of patients. Of them, 76% went on to have completion lymphadenectomy. Multivariate Cox regression analysis suggested that positive SLNB was a strong predictor of reduced overall survival for all Breslow-thickness melanomas (HR=3.9, p=0.019) and intermediate melanomas (HR=6.3, p=0.007). It predicted reduced recurrence-free survival for all melanomas (HR=7.4, p<0.001) and was a strong predictor for those of intermediate thickness (HR=8.3, p<0.001). The false negative rate was 9.4% and false omission rate 2.6%. Temporary and permanent morbidity rates were 2.1% and 0%, respectively. SLNB for melanoma in the head and neck is a safe, accurate staging procedure that offers prognostically useful information. The upstaging of disease allows access to trial-based targeted treatments.

Genetic variation in the dopamine D4 receptor (DRD4) gene and smoking cessation: follow-up of a randomised clinical trial of transdermal nicotine patch.

Smokers of European ancestry (n=720) who participated in a double-blind, randomised, placebo-controlled trial of transdermal nicotine replacement therapy, were genotyped for two functional polymorphisms (variable number of tandem repeats (VNTR) and a C to T transition at position -521 (C-521T)) in the dopamine D4 receptor gene (DRD4) gene. Logistic regression models of abstinence at 12- and 26-week follow-ups were carried out separately for each polymorphism. For the DRD4 VNTR models, the main effect of treatment was significant at both 12-week (P=0.001) and 26-week (P=0.006) follow-ups, indicating an increased likelihood of successful cessation on active nicotine replacement therapy transdermal patch relative to placebo. The main effect of DRD4 VNTR genotype was associated with abstinence at 12-week follow-up (P=0.034), with possession of one or more copies of the long allele associated with reduced likelihood of cessation (17 vs 23%), but this effect was not observed at 26-week follow-up. For the DRD4 C-521T models, no main effect or interaction terms involving genotype were retained in the models at either 12- or 26-week follow-up. These data are consistent with observations from studies of the DRD2 gene that genetic variants related to relatively decreased dopaminergic tone in the mesocorticolimbic system are associated with increased risk for relapse to smoking following a cessation attempt.

Techniques for surgical retrieval of sperm prior to intra-cytoplasmic sperm injection (ICSI) for azoospermia.

BACKGROUND: Azoospermia, the absence of sperm in ejaculated semen, is the most severe form of male-factor infertility and is present in approximately 5% of all investigated infertile couples. The advent of intra-cytoplasmic sperm injection (ICSI) has transformed treatment of this type of severe male-factor infertility. Sperm can be retrieved for ICSI from either the epididymis or the testis, depending on the type of azoospermia. OBJECTIVES: To evaluate the efficacy of the various surgical retrieval techniques for men with obstructive or non-obstructive azoospermia prior to ICSI. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (November 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4), MEDLINE (1966 to November 2007), EMBASE (1980 to November 2007), Biological Abstracts (1980 to November 2007), and reference lists of identified articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effectiveness of different sperm-retrieval techniques in men with azoospermia prior to ICSI. Due to the lack of RCTs, non-randomised trials that used the participants as their own control were also considered in the review but their results were not included in the meta-analysis. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: The search was revised and re-run in November 2007. No new trials were located therefore the results of the updated review remain unchanged from those published in 2006. Two trials involving 98 men were included. The first small RCT had 59 participants and compared two epididymal techniques. The trial gave limited evidence that microsurgical epididymal sperm aspiration (MESA) achieved a significantly lower pregnancy rate (one pregnancy in 29 procedures compared with seven pregnancies in 30 procedures; OR 0.19, 95% CI 0.04 to 0.83) and fertilisation rate (OR 0.16, 95% CI 0.05 to 0.48) than the micropuncture with perivascular nerve stimulation technique. The other RCT comparing two testicular aspiration techniques (TSA) in 39 participants gave no statistically significant evidence for the superiority of the ultrasound-guided technique compared to the aspiration technique without ultrasound. TSA with ultrasound resulted in pregnancy in three out of 16 participants compared with four out of 23 participants (OR 1.10, 95% CI 0.21 to 5.74). AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend any specific sperm retrieval technique for azoospermic men undergoing ICSI. In the absence of evidence to support more invasive or more technically difficult methods, the review authors recommend the least invasive and simplest technique available. Further randomised trials are warranted, preferably multi-centred trials. The classification of azoospermia as obstructive and non-obstructive appears to be relevant to a successful clinical outcome and a distinction according to the cause of azoospermia is important for future clinical trials.

Chinese herbal medicine for primary dysmenorrhoea.

BACKGROUND: Conventional treatment for primary dysmenorrhoea has a failure rate of 20% to 25% and may be contraindicated or not tolerated by some women. Chinese herbal medicine may be a suitable alternative. OBJECTIVES: To determine the efficacy and safety of Chinese herbal medicine for primary dysmenorrhoea when compared with placebo, no treatment, and other treatment. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group Trials Register (to 2006), MEDLINE (1950 to January 2007), EMBASE (1980 to January 2007), CINAHL (1982 to January 2007), AMED (1985 to January 2007), CENTRAL (The Cochrane Library issue 4, 2006), China National Knowledge Infrastructure (CNKI, 1990 to January 2007), Traditional Chinese Medicine Database System (TCMDS, 1990 to December 2006), and the Chinese BioMedicine Database (CBM, 1990 to December 2006) were searched. Citation lists of included trials were also reviewed. SELECTION CRITERIA: Any randomised controlled trials involving Chinese herbal medicine versus placebo, no treatment, conventional therapy, heat compression, another type of Chinese herbal medicine, acupuncture or massage. Exclusion criteria were identifiable pelvic pathology and dysmenorrhoea resulting from the use of an intra-uterine contraceptive device. DATA COLLECTION AND ANALYSIS: Quality assessment, data extraction and data translation were performed independently by two review authors. Attempts were made to contact study authors for additional information and data. Data were combined for meta-analysis using either Peto odds ratios or relative risk (RR) for dichotomous data or weighted mean difference for continuous data. A fixed-effect statistical model was used, where suitable. If data were not suitable for meta-analysis, any available data from the trial were extracted and presented as descriptive data. MAIN RESULTS: Thirty-nine randomised controlled trials involving a total of 3475 women were included in the review. A number of the trials were of small sample size and poor methodological quality. Results for Chinese herbal medicine compared to placebo were unclear as data could not be combined (3 RCTs). Chinese herbal medicine resulted in significant improvements in pain relief (14 RCTs; RR 1.99, 95% CI 1.52 to 2.60), overall symptoms (6 RCTs; RR 2.17, 95% CI 1.73 to 2.73) and use of additional medication (2 RCTs; RR 1.58, 95% CI 1.30 to 1.93) when compared to use of pharmaceutical drugs. Self-designed Chinese herbal formulae resulted in significant improvements in pain relief (18 RCTs; RR 2.06, 95% CI 1.80 to 2.36), overall symptoms (14 RCTs; RR 1.99, 95% CI 1.65 to 2.40) and use of additional medication (5 RCTs; RR 1.58, 95% CI 1.34 to 1.87) after up to three months of follow-up when compared to commonly used Chinese herbal health products. Chinese herbal medicine also resulted in better pain relief than acupuncture (2 RCTs; RR 1.75, 95% CI 1.09 to 2.82) and heat compression (1 RCT; RR 2.08, 95% CI 2.06 to 499.18). AUTHORS' CONCLUSIONS: The review found promising evidence supporting the use of Chinese herbal medicine for primary dysmenorrhoea; however, results are limited by the poor methodological quality of the included trials.

Airway mechanoreceptor deactivation.

Airway sensors play an important role in control of breathing. Recently, it was found that pulmonary slowly adapting stretch receptors (SARs) cease after a brief excitation following sodium pump blockade by ouabain. This deactivation can be explained by overexcitation. If this is true, mechanical stimulation of the SARs should also lead to a deactivation. In this study, we recorded unit activity of the SARs in anesthetized, open-chest, and mechanically ventilated rabbits and examined their responses to lung inflation at different constant pressures. Forty-seven of 137 units had a clear deactivation during the lung inflation. The deactivation threshold varied from unit to unit. For a given unit, the higher the inflation pressure, the sooner the deactivation occurs. For example, the SARs deactivated at 3.0 +/- 0.3 and 4.8 +/- 0.4 s when the lungs were inflated to constant pressures of 30 and 20 cmH(2)O, respectively (n = 25, P < 0.0001). The units usually ceased after a brief intense discharge. In some units, their activity shifted to a lower level, indicating a pacemaker switching. Our results support the notion that SARs deactivate due to overexcitation.

Cleavage stage versus blastocyst stage embryo transfer in assisted conception.

BACKGROUND: Recent advances in cell culture media have led to a shift in IVF practice from early cleavage embryo transfer to blastocyst stage transfer. The rationale for blastocyst culture is to improve both uterine and embryonic synchronicity and self selection of viable embryos thus resulting in higher implantation rates. OBJECTIVES: To determine if blastocyst stage embryo transfers (ETs) affect live birth rate and associated outcomes compared with cleavage stage ETs and to investigate what factors may influence this. SEARCH STRATEGY: Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. The last search date was January 2007. SELECTION CRITERIA: Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. DATA COLLECTION AND ANALYSIS: Of the 50 trials that were identified, 18 randomised controlled trials (RCTs) met the inclusion criteria and were reviewed. The primary outcome was rate of live birth. Secondary outcomes were rates per couple of clinical pregnancy, multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos and cryopreservation. Quality assessment, data extraction and meta-analysis were performed following Cochrane guidelines. MAIN RESULTS: Evidence of a significant difference in live-birth rate per couple between the two treatment groups was detected in favour of blastocyst culture (9 RCTs; OR 1.35, 95% CI 1.05 to 1.74 (Day 2/3: 29.4% versus Day 5/6: 36.0%)). This was particularly for trials with good prognosis patients, equal number of embryos transferred (including single embryo transfer) and those in which the randomisation took place on Day 3. Rates of embryo freezing per couple was significantly higher in Day 2 to 3 transfers (9 RCTs; OR 0.45, 95% CI 0.36 to 0.56). Failure to transfer any embryos per couple was significantly higher in the Day 5 to 6 group (16 RCTs; OR 2.85, 95% CI 1.97 to 4.11 (Day 2/3: 2.8% versus Day 5/6: 8.9%)) but was not significantly different for good prognosis patients (9 RCTs; OR 1.50, 95% CI 0.79 to 2.84). AUTHORS' CONCLUSIONS: This review provides evidence that there is a significant difference in pregnancy and live birth rates in favour of blastocyst transfer with good prognosis patients with high numbers of eight-cell embryos on Day three being the most favoured in subgroup for whom there is no difference in cycle cancellation. There is emerging evidence to suggest that in selected patients, blastocyst culture maybe applicable for single embryo transfer.

Gonadotrophins for idiopathic male factor subfertility.

BACKGROUND: Male factor infertility accounts for 50% of all infertility. The treatment of idiopathic male infertility is empirical. Urinary, purified, and recombinant gonadotrophins have been used to improve sperm parameters in idiopathic male infertility with the goal of increasing pregnancy rates. Research addressing pregnancy rates in partners of men treated with gonadotrophins has had conflicting results and needs to be analysed. OBJECTIVES: To determine the effectiveness of gonadotrophin administration in men with idiopathic subfertility in improving spontaneous pregnancy rate and in assisted reproductive technique cycles. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (31 May 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 2, 2007), MEDLINE (1966 to May 2007), EMBASE and Biological Abstracts (1980 to Week 21 2007). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Truly randomised controlled trials where gonadotrophins were administered for the treatment of idiopathic male subfertility with reporting of pregnancy rates were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We analysed data regarding pregnancy occurring within three months after gonadotrophin therapy. MAIN RESULTS: Four RCTs with 278 participants were included in the analysis. None of the studies had an adequate sample size and they had variable follow-up periods. None of the studies reported live birth or miscarriage rates. Compared to placebo or no treatment, gonadotrophins showed a significantly higher pregnancy rate per couple randomized within three months of completing therapy ( OR 4.17, 95% CI 1.30 to 7.09). AUTHORS' CONCLUSIONS: The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.

Chinese herbal medicine for primary dysmenorrhoea.

BACKGROUND: Conventional treatment for primary dysmenorrhoea (PD) has a failure rate of 20% to 25% and may be contraindicated or not tolerated by some women. Chinese herbal medicine (CHM) may be a suitable alternative. OBJECTIVES: To determine the efficacy and safety of CHM for PD when compared with placebo, no treatment, and other treatment. SEARCH STRATEGY: The Cochrane Menstrual Disorders and Subfertility Group Trials Register (to 2006), MEDLINE (1950 to January 2007), EMBASE (1980 to January 2007), CINAHL (1982 to January 2007), AMED (1985 to January 2007), CENTRAL (The Cochrane Library issue 4, 2006), China National Knowledge Infrastructure (CNKI, 1990 to January 2007), Traditional Chinese Medicine Database System (TCMDS, 1990 to Dec 2006), and the Chinese BioMedicine Database (CBM, 1990 to Dec 2006) were searched. Citation lists of included trials were also reviewed. SELECTION CRITERIA: Any randomised controlled trials (RCTs) involving CHM versus placebo, no treatment, conventional therapy, heat compression, another type of CHM, acupuncture or massage. Exclusion criteria were identifiable pelvic pathology and dysmenorrhoea resulting from the use of an intra-uterine contraceptive device (IUD). DATA COLLECTION AND ANALYSIS: Quality assessment, data extraction and data translation were performed independently by two review authors. Attempts were made to contact study authors for additional information and data. Data were combined for meta-analysis using either Peto odds ratios or relative risk (RR) for dichotomous data or weighted mean difference for continuous data. A fixed-effect statistical model was used, where suitable. If data were not suitable for meta-analysis, any available data from the trial were extracted and presented as descriptive data. MAIN RESULTS: Thirty-nine RCTs involving a total of 3475 women were included in the review. A number of the trials were of small sample size and poor methodological quality. Results for CHM compared to placebo were unclear as data could not be combined (3 RCTs). CHM resulted in significant improvements in pain relief (14 RCTs; RR 1.99, 95% CI 1.52 to 2.60), overall symptoms (6 RCTs; RR 2.17, 95% CI 1.73 to 2.73) and use of additional medication (2 RCTs; RR 1.58, 95% CI 1.30 to 1.93) when compared to use of pharmaceutical drugs. Self-designed CHM resulted in significant improvements in pain relief (18 RCTs; RR 2.06, 95% CI 1.80 to 2.36), overall symptoms (14 RCTs; RR 1.99, 95% CI 1.65 to 2.40) and use of additional medication (5 RCTs; RR 1.58, 95% CI 1.34 to 1.87) after up to three months follow up when compared to commonly used Chinese herbal health products. CHM also resulted in better pain relief than acupuncture (2 RCTs; RR 1.75, 95% CI 1.09 to 2.82) and heat compression (1 RCT; RR 2.08, 95% CI 2.06 to 499.18). AUTHORS' CONCLUSIONS: The review found promising evidence supporting the use of CHM for primary dysmenorrhoea; however, results are limited by the poor methodological quality of the included trials.

Selective serotonin reuptake inhibitors (SSRIs) for depressive disorders in children and adolescents.

BACKGROUND: Depressive disorders are common in young people and are associated with significant negative impacts. Selective serotonin reuptake inhibitors (SSRIs) are often used, however, evidence of their effectiveness in children and adolescents is not clear. Furthermore, there have been warnings against their use in this population due to concerns about increased risk of suicidal ideation and behaviour. OBJECTIVES: To determine the efficacy and adverse outcomes, including definitive suicidal behaviour and suicidal ideation, of SSRIs compared to placebo in the treatment of depressive disorders in children and adolescents. SEARCH STRATEGY: We searched the CCDAN Trials Register, MEDLINE, PSYCHINFO and CENTRAL. Reference lists were checked, letters were sent to key researchers and internet databases searched. SELECTION CRITERIA: We included published and unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Two or three review authors selected the trials, assessed the quality and extracted trial and outcome data. We used a fixed-effect meta-analysis. The relative risk was used to summarise dichotomous outcomes and the mean difference to summarise continuous measures. MAIN RESULTS: Twelve trials were eligible for inclusion, with ten providing usable data. At 8-12 weeks, there was evidence that children and adolescents 'responded' to treatment with SSRIs (RR 1.28, 95% CI 1.17 to 1.41). There was also evidence of an increased risk of suicidal ideation and behaviour for those prescribed SSRIs (RR 1.80, 95% CI 1.19 to 2.72). Fluoxetine was the only SSRI where there was consistent evidence from three trials that it was effective in reducing depression symptoms in both children and adolescents (CDRS-R treatment effect -5.63, 95% CI -7.38 to -3.88), and 'response' to treatment (RR 1.86, 95% CI 1.49 to 2.32). Where rates of adverse events were reported, this was higher for those prescribed SSRIs. AUTHORS' CONCLUSIONS: Caution is required to interpret the results. First, there were methodological issues, including high attrition, issues regarding measurement instruments and clinical usefulness of outcomes, often variously defined across trials. Second, patients seen in clinical practice are likely to be more unwell, and at greater risk of suicide, compared to those in the trials, and it is unclear how this group would respond to SSRIs. This needs to be considered, along with the evidence of an increased risk of suicide related outcomes in those treated with SSRIs. It is unclear what the effect of SSRIs is on suicide completion. While untreated depression is associated with the risk of completed suicide and impacts on functioning, it is unclear whether SSRIs would modify this risk in a clinically meaningful way.

Behavioural interventions for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition with considerable morbidity. The behavioural approach assumes that psychological and environmental factors interact with, and influence, physiological processes. Behavioural interventions for dysmenorrhoea may include both physical and cognitive procedures and focus on both physical and psychological coping strategies for dysmenorrhoeic symptoms rather than modification of any underlying organic pathology. OBJECTIVES: To determine the effectiveness of any behavioural interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or conventional medical treatments for example non-steroidal anti-inflammatory drugs (NSAIDs). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2005), Cochrane Central Register of Controlled Trials (CENTRAL on The Cochrane Library, Issue 2, 2005), MEDLINE (1966 to April 2005), EMBASE (1980 to April 2005), Social Sciences Index (1980 to April 2005), PsycINFO (1972 to April 2005) and CINAHL (1982 to April 2005) and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials comparing behavioural interventions with placebo or other interventions in women with dysmenorrhoea. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Five trials involving 213 women were included. Behavioural intervention vs control: One trial of pain management training reported reduction in pain and symptoms compared to a control. Three trials of relaxation compared to control reported varied results, two trials showed no difference in symptom severity scores however one trial reported relaxation was effective for reducing symptoms in menstrual sufferers with spasmodic symptoms. Two trials reported less restriction in daily activities following treatment with either relaxation of pain management training compared to a control. One trial also reported less time absent from school following treatment wit pain management training compared to a control. Behavioural intervention vs other behavioural interventions: Three trials showed no difference between behavioural interventions for the outcome of improvement in symptoms. One trial showed that relaxation resulted in a decrease in the need for resting time compared to the relaxation and imagery. AUTHORS' CONCLUSIONS: There is some evidence from five RCTs that behavioural interventions may be effective for dysmenorrhoea however results should be viewed with caution as they varied greatly between trials due to inconsistency in the reporting of data, small trial size, poor methodological quality and age of the trials.

Lifting degeneracy in nematic liquid crystal viscosities with a single optical measurement.

The viscosity of complex, anisotropic fluids, such as liquid crystals or their colloidal suspensions, is characterized by a number of coefficients. Methods to measure them are, typically, sensitive only to their particular combinations, hence unable to determine them individually. Using an Ericksen-Leslie model and propagation of light through aligned layers of such materials, we show theoretically and verify experimentally how this degeneracy can be lifted by exploiting both the amplitude and frequency of the voltage applied to the cell as control parameters.

Gonadotrophins for idiopathic male factor subfertility.

BACKGROUND: Male factor infertility accounts for 50% of infertility. The treatment of idiopathic male infertility is empirical. Urinary, purified, and recombinant gonadotrophins have been used to improve sperm parameters in idiopathic male infertility with the goal of increasing pregnancy rates. Research addressing pregnancy rates in partners of men treated with gonadotrophins has had conflicting results and needs to be analysed. OBJECTIVES: To determine the effectiveness of gonadotrophin administration to men with idiopathic subfertility on spontaneous pregnancy rate and in assisted reproductive techniques (ARTs). SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group trials register (19 November 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library, issue 4, 2004), MEDLINE (1966 to April 2005), EMBASE and Biological Abstracts (1980 to November 2004). Searches were not limited by language. The bibliographies of included, excluded trials and abstracts of major meetings were searched for additional trials. Authors and pharmaceutical companies were contacted for missing and unpublished data. SELECTION CRITERIA: Truly randomised controlled trials where gonadotrophins were administered for the treatment of idiopathic male subfertility with reporting of pregnancy rates were included in the review. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. We analysed data regarding pregnancy occurring within 3 months after gonadotrophin therapy. MAIN RESULTS: Four RCTs with 278 participant were included in the analysis. None of the studies had an adequate sample size and they had variable follow-up periods. None of the studies reported live birth or miscarriage rates. Compared to placebo or no treatment, gonadotrophins showed a significantly higher pregnancy rate per couple randomized within 3 months of completing therapy (OR 3.03, 95% CI 1.30 to 7.09). Pregnancy rate was 13.4% (19/142) in the gonadotrophin group and 4.4% (6/136) in the control group. AUTHORS' CONCLUSIONS: The number of trials and participants is insufficient to draw final conclusions. A large multicenter study with adequate power is needed.

Spinal manipulation for primary and secondary dysmenorrhoea.

BACKGROUND: Dysmenorrhoea refers to the occurrence of painful menstrual cramps of uterine origin and is a common gynaecological condition. One possible treatment is spinal manipulation therapy. One hypothesis is that mechanical dysfunction in certain vertebrae causes decreases spinal mobility. This could affect the sympathetic nerve supply to the blood vessels supplying the pelvic viscera, leading to dysmenorrhoea as a result of vasoconstriction. Manipulation of these vertebrae increases spinal mobility and may improve pelvic blood supply. Another hypothesis is that dysmenorrhoea is referred pain arising from musculoskeletal structures that share the same pelvic nerve pathways. The character of pain from musculoskeletal dysfunction can be very similar to gynaecological pain as it can present as cyclic pain altered by hormonal influences associated with menstruation. OBJECTIVES: To determine the safety and efficacy of spinal manipulative interventions for the treatment of primary or secondary dysmenorrhoea when compared to each other, placebo, no treatment, or other medical treatment. SEARCH STRATEGY: We searched the Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched April 2006), CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE (1966 to March 2006), EMBASE (1980 to April 2006), CINAHL (1982 to March 2006), AMED (1985 to April 2006), Biological Abstracts (1969 to March 2006), PsycINFO (1806 to April 2006), and SPORTDiscus (1830 to April 2006). Attempts were also made to identify trials from the metaRegister of Controlled Trials and the citation lists of review articles and included trials. In most cases the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: Any randomised controlled trials (RCTs) including spinal manipulative interventions (for example chiropractic, osteopathy, or manipulative physiotherapy) versus each other, placebo, no treatment, or other medical treatment were considered. Exclusion criteria were: mild or infrequent dysmenorrhoea or dysmenorrhoea from an intrauterine device (IUD). DATA COLLECTION AND ANALYSIS: Four trials of high velocity, low amplitude manipulation (HVLA), and one of the Toftness manipulation technique were included. Quality assessment and data extraction were performed independently by two review authors. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis were reported as descriptive data and were also included for discussion. The outcome measures were pain relief or pain intensity (dichotomous, visual analogue scales, descriptive) and adverse effects. MAIN RESULTS: Results from the four trials of high velocity, low amplitude manipulation suggest that the technique was no more effective than sham manipulation for the treatment of dysmenorrhoea, although it was possibly more effective than no treatment. Three of the smaller trials indicated a difference in favour of HVLA, however the one trial with an adequate sample size found no difference between HVLA and sham treatment. There was no difference in adverse effects experienced by participants in the HVLA or sham treatment. The Toftness technique was shown to be more effective than sham treatment by one small trial, but no strong conclusions could be made due to the small size of the trial and other methodological considerations. AUTHORS' CONCLUSIONS: Overall there is no evidence to suggest that spinal manipulation is effective in the treatment of primary and secondary dysmenorrhoea. There is no greater risk of adverse effects with spinal manipulation than there is with sham manipulation.