A prospective cohort study characterising patients declined emergency laparotomy: survival in the 'NoLap' population.

Patients eligible for emergency laparotomy who do not proceed to surgery are not as well characterised as patients who do proceed to surgery. We studied patients eligible for laparotomy, as defined by National Emergency Laparotomy Audit criteria, from August 2015 to October 2016. We analysed the association of individual variables with survival and two composite scores: P-POSSUM and a general survival model. Out of 314 patients, 214 (68%) underwent laparotomy and 100 (32%) did not. Median (IQR [range]) follow-up was 1.3 (0.1-1.8 [0.0-2.5]) years for the cohort, 1.5 (1.1-2.0 [0.0-2.6]) years after laparotomy and 0.0 (0.0-1.1 [0.0-2.2]) years without laparotomy. There were 126/314 (40%) deaths in the follow-up period, 52/214 (24%) deaths after laparotomy and 74/100 (74%) deaths without surgery. Ninety out of 126 deaths (71%) were within one month of hospital admission. Patient variables were different for the two groups, which when combined in the general survival model generated background median (IQR [range]) life expectancies of 12 (6-21 [0-49]) and 4 (2-6 [0-36]) years, respectively, p < 0.0001. 'Poor fitness' precluded laparotomy in 74/100 (74%) patients. The decision to not operate involved a consultant less often than the decision to operate: 66/100 (66%) vs. 178/214 (83%), p = 0.001. Our study supports the contention that survival beyond 30 postoperative days could be predicted reasonably accurately. Survival in patients who did not have laparotomy was shorter than expected. Emergency laparotomy might have prolonged survival in some patients.

Prolapse and sexual function in women with benign joint hypermobility syndrome.

OBJECTIVE: To determine whether pelvic organ prolapse (POP) and sexual dysfunction are more severe in women with benign joint hypermobility syndrome (BJHS) than in the normal population. DESIGN: Case-control study. SETTING: King's College Hospital NHS Foundation Trust, London, UK and University College Hospital, London, UK. POPULATION: Women diagnosed with BJHS (n = 60) at University College Hospital. Control participants (n = 60) recruited from King's College Hospital NHS Foundation Trust. METHODS: Objective assessment of POP was undertaken using the Pelvic Organ Prolapse Quantification System (POP-Q). Both groups were asked to complete the Prolapse quality of life (P-QOL) and pelvic organ prolapse/urinary incontinence sexual (PISQ-12) questionnaires. MAIN OUTCOME MEASURES: Comparison of vaginal anatomy using POP-Q between the two groups. Comparison of P-QOL and PISQ-12 quality of life scores between the two groups. RESULTS: In all, 120 women (60 in Study group, 60 in Control group) were recruited. All women in the study group were matched with healthy control women according to age, parity and ethnicity. There was a statistically significant difference between points Aa, Ba, Ap, Bp and C in study and control groups showing that prolapse is objectively more severe in those with BJHS. Significantly more women with BJHS felt that POP interfered with sex and defecation compared with the control group. The impact of prolapse symptoms on quality of life was statistically different in almost all nine P-QOL domains. CONCLUSIONS: A large number of women with BJHS have prolapse symptoms, which significantly affect their quality of life. POP is more severe in women with BJHS.

Does self-motivation improve success rates of pelvic floor muscle training in women with urinary incontinence in a secondary care setting?

INTRODUCTION AND HYPOTHESIS: Pelvic floor muscle training (PFMT) is the recommended first-line treatment for women with urinary incontinence (UI). Success rates are variable and dependent on a number of factors. The development of an incontinence treatment motivation questionnaire (ITMQ) provides us with a tool to assess patient self-motivation with respect to PFMT and UI. The aim of this study was to determine the effect of women's self-motivation to perform PFMT on outcome. METHODS: Women with stress predominant UI completed an ITMQ and a 24-h pad test and then underwent a 12-week course of supervised PFMT. At the end of their treatment they completed a patient global impression of improvement questionnaire (PGI-I) and a second 24-h pad test. The PGI-I scores and the difference in pad test weight correlated with the ITMQ according to Spearman's correlation coefficient. RESULTS: Sixty-five women were recruited. Thirty-two (49%) patients perceived themselves as having improved, 28 women (43%) did not experience any change in symptoms and 5 women (8%) felt that their symptoms deteriorated following treatment. When correlating the PGI-I with the ITMQ, 3 of the 5 domains: MQS1 (positive attitude for treatment; p = 0.003), MQS3 (frustration of living with incontinence; p = 0.002) and MQS4 (desire for treatment; p = 0.002) correlated significantly with outcome. Desire for treatment was the only domain to correlate with change in pad weight (p = 0.001). CONCLUSION: Self-motivation is essential in order to determine improved success rates with PFMT.

Lower urinary tract symptoms in women with benign joint hypermobility syndrome: a case-control study.

INTRODUCTION AND HYPOTHESIS: Benign joint hypermobility syndrome (BJHS) is a connective tissue disorder associated with joint hypermobility. BJHS is under-recognised by medical professionals and is poorly managed. The aim of our study was to determine whether lower urinary tract symptoms (LUTS), including urinary incontinence (UI) and anterior compartment prolapse, are more common in women with BJHS than in the normal population. METHODS: This was a prospective case-control study. Women diagnosed with BJHS according to the Brighton criteria were recruited from a tertiary referral clinic. Controls were recruited from hospital personnel. Both groups completed the King's Health Questionnaire (KHQ) and the Prolapse Quality of Life Questionnaire (P-QoL). Objective assessment of pelvic organ prolapse (POP) was undertaken using the Pelvic Organ Prolapse Quantification (POP-Q) system. Analyses were performed using SPSS version 17.0. The statistical difference was analysed using McNemar's test. Comparison of QoL scores was performed with the Wilcoxon signed-rank test. RESULTS: Sixty individuals were recruited and matched with 60 healthy women. The prevalence of UI in those with BJHS was significantly higher than in controls(73.3 % vs. 48.3 %). The impact of UI on QoL was statistically significant in all domains of the KHQ. There was a significant difference between groups in most urinary-specific symptoms of the KHQ. A significant number of women with BJHS suffer from voiding difficulties. Prolapse of the anterior vaginal wall was objectively more severe in those with BJHS. CONCLUSIONS: Women with BJHS have LUTS and anterior compartment prolapse, which significantly impair their QoL. It is important to identify women who are symptomatic. The addition of a systematic active case-finding approach may be more effective in identifying these cases.

Studies of TBX4 and chromosome 17q23.1q23.2: an uncommon cause of nonsyndromic clubfoot.

Clubfoot is a common birth defect characterized by inward posturing and rigid downward displacement of one or both feet. The etiology of syndromic forms of clubfoot is varied and the causes of isolated clubfoot are not well understood. A microduplication of 2.2 Mb on chromosome 17q23.1q23.2 which includes T-box 4 (TBX4), a hindlimb-specific gene, and 16 other genes was recently identified in 3 of 66 families reported as nonsyndromic clubfoot, but additional non-foot malformations place them in the syndromic clubfoot category. Our study assesses whether variation in or around TBX4 contributes to nonsyndromic clubfoot. To determine whether this microduplication was a common cause of nonsyndromic clubfoot, 605 probands (from 148 multiplex and 457 simplex families) with nonsyndromic clubfoot were evaluated by copy number and oligonucleotide array CGH testing modalities. Only one multiplex family (0.68%) that had 16 with clubfoot and 9 with other foot anomalies, had a 350 kb microduplication, which included the complete duplication of TBX4 and NACA2 and partial duplication of BRIP1. The microduplication was transmitted in an autosomal dominant pattern and all with the microduplication had a range of phenotypes from short wide feet and toes to bilateral clubfoot. Minimal evidence was found for an association between TBX4 and clubfoot and no pathogenic sequence variants were identified in the two known TBX4 hindlimb enhancer elements. Altogether, these results demonstrate that variation in and around the TBX4 gene and the 17q23.1q23.2 microduplication are not a frequent cause of this common orthopedic birth defect and narrows the 17q23.1q23.2 nonsyndromic clubfoot-associated region.

Prognostic research and its potential role in modern gynaecology: a call for more prognostic research in urogynaecology.

Over the last 30 years, many researchers have focussed on therapeutic and aetiological studies. Randomised controlled trials (RCT) are considered the 'gold standard' in research circles ( Ward et al. 2004 ). Prognostic research has been neglected probably due to a combination of a lack of perception of its importance and also a failure to produce good quality trials. The word 'prognosis' means the ability to foresee or predict an outcome or an event. Prognostic research in medicine is the ability to predict the likelihood of outcomes from a number of clinical variables. There are two main forms of prognostic research. One form identifies the prognostic value of a single risk factor (e.g. a tumour marker). The second one focuses on the development of a model based on multiple variables and is called multivariable prognostic modelling. The planning and powering of prognostic studies is managed differently from traditional randomised controlled trials.

PAX2 gene mutations in pediatric and young adult transplant recipients: kidney and urinary tract malformations without ocular anomalies.

Heterozygous humans for PAX2 mutations show autosomal dominant papillorenal syndrome (PRS), consisting of ocular colobomas, renal hypo/dysplasia and progressive renal failure in childhood. PAX2 mutations have also been identified in patients with isolated renal hypo/dysplasia. Twenty unrelated children and young adults with kidney and urinary tract malformations and no ocular abnormalities were retrospectively recruited for PAX2 mutational analysis. All patients had undergone renal transplantation after end-stage renal disease. We identified two new sequence variations: (i) a deletion causing a frameshift (c.69delC) and (ii) a nucleotide substitution determining a splice site mutation (c.410+5 G/A) by predictive analysis. Therefore, we suggest PAX2 molecular analysis to be extended to all patients with congenital malformations of kidney and urinary tract (CAKUT).

Trauma video review utilization: A survey of practice in the United States.

INTRODUCTION: Trauma video review (TVR) for quality improvement and education in the United States has been described for nearly three decades. The most recent information on this practice indicated a declining prevalence. We hypothesized that TVR utilization has increased since most recent estimates. METHODS: We conducted a survey of TVR practices at level I and level II US trauma centers. We distributed an electronic survey covering past, current, and future TVR utilization to the Eastern Association for the Surgery of Trauma membership. RESULTS: 45.0% of US level I and level II trauma centers completed surveys. 71/249 centers (28.5%) had active TVR programs. The use of TVR did not differ between level I and level II centers (28.8% vs. 27.8%, p = 0.87). Respondents using TVR were overwhelmingly positive about its perception (median score 8, [IQR 6-9]; 10 = 'best') at their institutions. CONCLUSIONS: TVR use at Level I centers has increased over the past decade. Increased TVR utilization may form the basis for multicenter studies comparing processes of care during trauma resuscitation.

Comparison of MRI, MRA, and DSA for Detection of Cerebral Arteriovenous Malformations in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND PURPOSE: Patients with hereditary hemorrhagic telangiectasia (HHT) have a high prevalence of brain vascular malformations, putting them at risk for brain hemorrhage and other complications. Our aim was to evaluate the relative utility of MR imaging and MRA compared with DSA in detecting cerebral AVMs in the HHT population. MATERIALS AND METHODS: Of 343 consecutive patients evaluated at the University of California, San Francisco HTT Center of Excellence, 63 met the study inclusion criteria: definite or probable hereditary hemorrhagic telangiectasia defined by meeting at least 2 Curacao criteria or positive genetic testing, as well as having at least 1 brain MR imaging and 1 DSA. MRIs were retrospectively reviewed, and the number of AVMs identified was compared with the number of AVMs identified on DSA. RESULTS: Of 63 patients, 45 (71%) had AVMs on DSA with a total of 92 AVMs identified. Of those, 24 (26%) were seen only on DSA; 68 (74%), on both DSA and MR imaging; and 5 additional lesions were seen only on MR imaging. Of the 92 lesions confirmed on DSA, 49 (53.3%) were seen on the 3D-T1 postgadolinium sequence, 52 (56.5%) were seen on the 2D-T1 postgadolinium sequence, 35 (38.0%) were seen on the SWI sequence, 24 (26.1%) were seen on T2 sequence, and 25 (27.2%) were seen on MRA. The sensitivity and specificity of MR imaging as a whole in detecting AVMs then confirmed on DSA were 80.0% and 94.4%, respectively, and the positive and negative predictive values were 97.3% and 65.4%, respectively. CONCLUSIONS: This study reinforces the use of MR imaging as a primary screening tool for cerebral AVMs in patients with hereditary hemorrhagic telangiectasia and suggests that 3D-T1 postgadolinium and 2D-T1 postgadolinium performed at 3T are the highest yield sequences.

Prevalence of incontinence and incontinence-specific quality of life impairment in women with cystic fibrosis.

AIMS: Cystic fibrosis (CF) is the commonest autosomal recessive disorder in Caucasians. With advancing medical technology, the life expectancy has more than double in the last twenty years. This has led to new unforeseen health problems like urinary incontinence. The aim was to establish the prevalence, symptomatic typology, and quality of life impact of incontinence in a population of women with CF. METHODS: Women were recruited from two London tertiary referral centres for CF. They were asked to fill in a self- completed anonymous King's Health Questionnaire (KHQ) for assessment of symptoms and quality of life Impairment. Their age was also noted. Descriptive statistics are reported. Correlation was assessed using Pearson's Product Moment Correlation Coefficient (r). RESULTS: One hundred and forty six women were approached for enrolment. 98(67%) consented to take part in study. Their mean age was 28. Seventy three (74%) reported symptoms of urinary incontinence, which in all cases was perceived as stress urinary incontinence. Of these 44(60%) reported mild stress incontinence, 16(22%) moderate stress incontinence and 13(18%) severe stress incontinence. Continent and incontinent women perceived their general health to be similarly poor (mean score 40 vs 44 points). Strong positive correiations were found between age and stress urinary incontinence severity (r=0.742; P <0.001) and between age and total King's Health Questionnaire score (r=0.828; P <0.001). CONCLUSIONS: Women with CF have a higher prevalence of stress urinary incontinence than the general population, with both the prevalence and associated quality of life impairment increasing with age.

Deoxyribonucleic acid polymorphism in the apolipoprotein A-1-C-III gene cluster. Association with hypertriglyceridemia.

A DNA sequence polymorphism, revealed by digestion of human DNA with the restriction endonuclease Sst-1 and hybridization with an apolipoprotein A-I complementary DNA clone, has been shown to be located in or close to the 3' noncoding region of the apolipoprotein C-III gene. This polymorphism is found in significantly increased prevalence (P less than 0.001) in Caucasian hypertriglyceridemic subjects compared with race-matched controls, and its distribution in normal individuals of differing racial origins is reported. Furthermore, no alteration of high density lipoprotein or apolipoprotein A-I and apolipoprotein C-III phenotypes was observed in individuals with or without the polymorphism.

Tolerability and efficacy of duloxetine in a nontrial situation.

OBJECTIVE: To assess the tolerability and efficacy of duloxetine in a nontrial situation. DESIGN: Prospective observational study. SETTING: Urogynaecology Unit, District General Hospital, UK. POPULATION: Two hundred and twenty-two women with a diagnosis of urodynamic stress incontinence (USI) or mixed USI and detrusor overactivity (DOA) took duloxetine for 4 weeks. METHODS: The results of therapy were assessed with a Patient Global Impression of Improvement (PGI-I) questionnaire. One hundred and forty-eight (67%) women were initially treated with 40 mg twice a day, 67 (30%) women were treated with an escalating dose initially at 20 mg twice a day increasing to 40 mg twice a day after 2 weeks and seven (3%) women were started on a dose of 20 mg twice a day which they continued. MAIN OUTCOME MEASURES: Discontinuation rates and PGI-I scores. RESULTS: Overall 146/222 (66%) women discontinued therapy due to adverse effects or lack of efficacy. Significantly more women starting on the 40 mg twice a day dose stopped due to adverse effects when compared with the escalating dose (P < 0.025). Of the women who tolerated therapy, 80 out of 120 (67%) had a PGI-I score indicating an improvement. However, the overall rate of improvement was 37%. PGI-I scores and discontinuation rates were not significantly different between the group with USI and the group with mixed USI and DOA (P > 0.05). CONCLUSION: In a nontrial situation duloxetine is poorly tolerated. Introducing an escalating dose may improve tolerability. A similar number of women with USI and mixed incontinence had a PGI-I score indicating improvement.

Surgery for ulcerative colitis.

Ulcerative colitis is an inflammatory condition of unknown aetiology affecting all or part of the rectum and colon. The mainstay of treatment is medical but there are specific indications for surgical intervention. This article reviews the evolution of surgical management and in particular compares outcome from proctocolectomy and pouch surgery. A number of factors determining choice of procedure are examined, including elective or emergency presentation, patient selection, technical issues, morbidity and quality of life. Emphasis is made regarding a full explanation of these factors so that the patient is fully involved in the final decision regarding choice of procedure.

New developments in the treatment of urinary incontinence.

Urinary incontinence is a common and distressing condition. The two main types of incontinence in the developed world are urodynamic stress incontinence and detrusor overactivity. Recent advances have focussed on the development of a drug for stress incontinence and on the production of newer more M3 specific anticholinergics. Duloxetine, a relatively balanced and potent serotonin noradrenaline reuptake inhibitor, is the first drug to be licensed for stress incontinence. Until recently, the pharmacological treatment options for stress urinary incontinence (SUI) have been limited to the off-the label use of several medications including oestrogens, alfa adrenergic receptor agonists, beta adrenergic receptor antagonists, tricyclic antidepressants and anticholinergics. However, these medications have questionable efficacy which may be associated with adverse effects. Randomised trials have shown duloxetine to be effective at reducing incontinence episode frequency and improving quality of life scores. Hence medical management has now become a more realistic option for treatment of patients with sui. Recently newer more M3 receptor selective anticholinergics have come on to the market. Their increased bladder receptor selectivity implies that they have improved efficacy with a lower side effect profile. Both solifenacin and more recently darifenacin have been marketed and have the above described properties. The oxybutynin patch is now also available adding a new route of delivery. Because it is absorbed transdermally, its manufacturers claim it also has a better efficacy/tolerability ratio then conventional oxybutynin. This review article gives a detailed description of these new pharmacologic developments.

Four cases of Raoultella planticola conjunctivitis.

AIMS: This brief report of four cases of conjunctivitis caused by Raoultella planticola provides a description of possibly the first documented cases of this eye infection. METHODS: The laboratory database and medical records were used to trace all the R. planticola-positive conjunctival swabs obtained in our institution. Four cases were identified and available relevant information was obtained. RESULTS: This organism causes a non-specific purulent conjunctivitis that seems to have a benign course and tends to be responsive to a topical fluoroquinolone. CONCLUSIONS: The possibility of atypical organisms must be considered when managing infective conjunctivitis. Conjunctival swabs should be obtained and topical treatment switched when initial empirical therapy fails.

New developments in the management of urinary incontinence.

Urinary incontinence is a common and distressing condition known to adversely affect quality of life. In this article the authors aim to highlight developments in the methods of classification, investigation and the treatment of incontinence. It gives a detailed description of the newer drugs and their mode of action, that have recently come on to the market. These include duloxetine for the treatment of stress incontinence and the newer M3 selective antagonists. It also describes the latest surgical procedures, for example the newer slings and injectables used to treat stress incontinence. They are compared with the standard forms of treatment used and the evidence in favour and against these have been given.

Changes of plasma endothelin and growth factor levels, and of left ventricular mass, after chronic AT1-receptor blockade in human hypertension.

The stimulation of autocrine and paracrine factors such as basic fibroblast- (bFGF) and platelet-derived (PDGF) growth factors mediates many of the growth-promoting actions of angiotensin II. The aim of this study was to evaluate the effect of chronic AT1-receptor blockade on plasma endothelin-1 (ET-1) and growth factors levels, and on left ventricular mass, in essential hypertension (EH). The study population consisted of 16 patients with mild-moderate EH, and 25 normotensive controls. In the EH patients under basal conditions, and after 3 and 6 months of chronic therapy with Losartan 50 mg/day, we measured serum levels of ET-1, bFGF and PDGF, and tumor necrosis factor (TNF). At the same time, all patients underwent 24-h ambulatory blood pressure monitoring and an echocardiographic evaluation to measure the thickness of the posterior wall (PWT) of the left ventricle and of the interventricular septum (IVS). The healthy controls underwent the same analyses, under basal conditions, at baseline and after 3 and 6 months of observation. In the EH patients, after 3 months of AT1-receptor blockade bFGF was reduced from 13.6 +/- 0.7 to 10.9 +/- 0.7 pg/mL (P < .004), and both TNF and PDGF were significantly decreased (P < .006 and P < .007, respectively). After 6 months of therapy, ET-1 was significantly diminished in comparison with baseline (6.9 +/- 0.8 v 5.5 +/- 0.1 fmol/mL; P < .05), and the reduction in the levels of growth factors were even more significant than at 3 months of treatment. Both PWT and IVS were significantly changed after 6 months of therapy with losartan after basal evaluation (P < .05, respectively). Systolic and diastolic 24-h blood pressures declined significantly after 3 and 6 months of therapy with losartan (P < .01, respectively). It seems likely that the inhibition of the action of angiotensin II by the specific AT1-receptor blockade, by reducing circulating levels of ET-1 and those of some growth factors, may offer an advantage regarding the effect on hypertensive cardiovascular changes in human hypertension.

Endothelium-derived factors in microalbuminuric and nonmicroalbuminuric essential hypertensives.

Previous evidence has demonstrated a relationship between growth factors and cardiovascular diseases. This study was aimed at evaluating levels of some endothelium-derived growth factors, and their relationship with microalbuminuria (MAU), in essential hypertension. Ninety-nine mild-moderate essential hypertensives (EH) and 25 healthy controls were studied. All patients underwent 24-h blood pressure monitoring, serum endothelin-1 (ET-1), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF), and 24-h MAU assays. Later, EH were divided into two subsets consisting of microalbuminurics (MAU >11 microg/min) and nonmicroalbuminurics (MAU <11 microg/min). In microalbuminuric EH, circulating ET-1, bFGF, and PDGF were significantly higher than in nonmicroalbuminurics (P < .0001, P < .0001, P < .005, respectively) or in controls. In the group of 99 EH, significant positive correlations of MAU with both ET-1 and bFGF (r = 0.35, P < .001, and r = 0.34, P < .001, respectively) were found. ET-1 and bFGF correlated significantly (r = 0.31, P < .002). Circulating bFGF also correlated significantly with MAU in the microalbuminuric EH subset (r = 0.49, P < .01). Our results show that in microalbuminuric EH circulating levels of certain growth factors are increased. In human essential hypertension these factors are linked with MAU, an early cardiovascular and renal damage marker.