Bulking agents: an analysis of 500 cases and review of the literature

Stress urinary incontinence (SUI) is common, impacts women's quality of life, and generates high costs. Physiotherapy is the first-line therapy, and if it fails, suburethral slings are the gold standard in SUI surgery. Bulking agents injected periurethrally might be a beneficial alternative, but there is a paucity of data on bulking therapy. The aim of this study was to prospectively analyze the efficacy and safety of bulking agents in the setting of a tertiary referral center.

Cascading climate effects and related ecological consequences during past centuries

The interface between climate and ecosystem structure and function is incompletely understood, partly because few ecological records start before the recent warming phase. Here, we analyse an exceptional 100-yr long record of the great tit (Parus major) population in Switzerland in relation to climate and habitat phenology. Using structural equation analysis, we demonstrate an uninterrupted cascade of significant influences of the large-scale atmospheric circulation (North-Atlantic Oscillation, NAO, and North-sea – Caspian Pattern, NCP) on habitat and breeding phenology, and further on fitness-relevant life history traits within great tit populations. We then apply the relationships of this analysis to reconstruct the circulation-driven component of fluctuations in great tit breeding phenology and productivity on the basis of new seasonal NAO and NCP indices back to 1500 AD. According to the structural equation model, the multi-decadal oscillation of the atmospheric circulation likely led to substantial variation in habitat phenology, productivity and consequently, tit population fluctuations with minima during the "Maunder Minimum" (∼ 1650–1720) and the Little Ice Age Type Event I (1810–1850). The warming since 1975 was not only related with a quick shift towards earlier breeding, but also with the highest productivity since 1500, and thus, the impact of the NAO and NCP has contributed to an unprecedented increase of the population. A verification of the structural equation model against two independent data series (1970–2000 and 1750–1900) corroborates that the retrospective model reliably depicts the major long-term NAO/NCP impact on ecosystem parameters. The results suggest a complex cascade of climate effects beginning at a global scale and ending at the level of individual life histories. This sheds light on how large-scale climate conditions substantially affect major life history parameters within a population, and thus influence key ecosystem parameters at the scale of centuries.

Financial analysis of various strategies for the control of Neospora caninum in dairy cattle in Switzerland

The present study was conducted to estimate the direct losses due to Neospora caninum in Swiss dairy cattle and to assess the costs and benefits of different potential control strategies. A Monte Carlo simulation spreadsheet module was developed to estimate the direct costs caused by N. caninum, with and without control strategies, and to estimate the costs of these control strategies in a financial analysis. The control strategies considered were "testing and culling of seropositive female cattle", "discontinued breeding with offspring from seropositive cows", "chemotherapeutical treatment of female offspring" and "vaccination of all female cattle". Each parameter in the module that was considered to be uncertain, was described using probability distributions. The simulations were run with 20,000 iterations over a time period of 25 years. The median annual losses due to N. caninum in the Swiss dairy cow population were estimated to be euro 9.7 million euros. All control strategies that required yearly serological testing of all cattle in the population produced high costs and thus were not financially profitable. Among the other control strategies, two showed benefit-cost ratios (BCR) >1 and positive net present values (NPV): "Discontinued breeding with offspring from seropositive cows" (BCR=1.29, NPV=25 million euros ) and "chemotherapeutical treatment of all female offspring" (BCR=2.95, NPV=59 million euros). In economic terms, the best control strategy currently available would therefore be "discontinued breeding with offspring from seropositive cows".

Impact of del32-71-GH (exon 3 skipped GH) on intracellular GH distribution, secretion and cell viability: a quantitative confocal microscopy analysis

BACKGROUND: Familial isolated growth hormone deficiency (IGHD) is a disorder with about 5-30% of patients having affected relatives. Among those familial types, IGHD type II is an autosomal dominant form of short stature, associated in some families with mutations that result in missplicing to produce del32-71-GH, a GH peptide which cannot fold properly. The mechanism by which this mutant GH may alter the controlled secretory pathway and therefore suppress the secretion of the normal 22-kDa GH product of the normal allele is not known in detail. Previous studies have shown variance depending on cell type, transfection technique used, as well as on the method of analysis performed. AIM: The aim of our study was to analyse and compare the subcellular distribution/localization of del32-71-GH or wild-type (wt)-GH (22-kDa GH), each stably transfected into AtT-20, a mouse pituitary cell line endogenously producing ACTH, employed as the internal control for secretion assessment. METHODS: Colocalization of wt- and del32-71 mutant GH form was studied by quantitative confocal microscopy analysis. Using the immunofluorescent technique, cells were double stained for GH plus one of the following organelles: endoplasmic reticulum (ER anti-Grp94), Golgi (anti-betaCOP) or secretory granules (anti-Rab3a). In addition, GH secretion and cell viability were analysed in detail. RESULTS/CONCLUSIONS: Our results show that in AtT-20 neuroendocrine cells, in comparison to the wt-GH, the del32-71-GH has a major impact on the secretory pathway not only affecting GH but also other peptides such as ACTH. The del32-71-GH is still present at the secretory vesicles' level, albeit in reduced quantity when compared to wt-GH but, importantly, was secretion-deficient. Furthermore, while focusing on cell viability an additional finding presented that the various splice site mutations, even though leading eventually to the same end product, namely del32-71-GH, have different and specific consequences on cell viability and proliferation rate.

[Urine analyses for workup of kidney stone disease--interpretation and therapeutic consequences]

Nephrolithiasis is a disease with a high and even rising incidence. It has a high morbidity, generates high costs and has a high recurrence rate. Urinalysis is of importance especially in recurrent stone formers. It allows the identification and quantification of risk factors and the establishment of individual risk profiles. Based on these individual risk profiles, rational therapy for metaphylaxis of kidney stones lowers stone recurrence rates significantly. This review article aims to give a focussed overview of the most important risk factors for kidney stones and reasonable urine tests for evaluation of recurrent kidney stone formers.

Partner notification of chlamydia infection in primary care: randomised controlled trial and analysis of resource use

OBJECTIVE: To evaluate the effectiveness of a practice nurse led strategy to improve the notification and treatment of partners of people with chlamydia infection. DESIGN: Randomised controlled trial. SETTING: 27 general practices in the Bristol and Birmingham areas. PARTICIPANTS: 140 men and women with chlamydia (index cases) diagnosed by screening of a home collected urine sample or vulval swab specimen. INTERVENTIONS: Partner notification at the general practice immediately after diagnosis by trained practice nurses, with telephone follow up by a health adviser; or referral to a specialist health adviser at a genitourinary medicine clinic. MAIN OUTCOME MEASURES: Primary outcome was the proportion of index cases with at least one treated sexual partner. Specified secondary outcomes included the number of sexual contacts elicited during a sexual history, positive test result for chlamydia six weeks after treatment, and the cost of each strategy in 2003 sterling prices. RESULTS: 65.3% (47/72) of participants receiving practice nurse led partner notification had at least one partner treated compared with 52.9% (39/68) of those referred to a genitourinary medicine clinic (risk difference 12.4%, 95% confidence interval -1.8% to 26.5%). Of 68 participants referred to the clinic, 21 (31%) did not attend. The costs per index case were 32.55 pounds sterling for the practice nurse led strategy and 32.62 pounds sterling for the specialist referral strategy. CONCLUSION: Practice based partner notification by trained nurses with telephone follow up by health advisers is at least as effective as referral to a specialist health adviser at a genitourinary medicine clinic, and costs the same. Trial registration Clinical trials: NCT00112255.

Analysis of stapling versus endoloops in appendiceal stump closure

BACKGROUND: The effectiveness of various appendiceal stump closure methods has not been evaluated systematically. The aim of this study was to compare the morbidity of stump closure by stapling or use of endoloops. METHODS: A non-concurrent cohort study of prospectively acquired data was performed. The primary outcome variable was the rate of intra-abdominal surgical-site infection. Secondary outcome measures were complications, duration of intervention, hospital stay, rate of readmission to hospital and the difference in direct costs of the operation. RESULTS: Staples were used in 60.5 per cent and endoloops in 39.5 per cent of 6486 patients operated on for suspected appendicitis between January 1995 and December 2003. Among 4489 patients with acute appendicitis the rate of intra-abdominal surgical-site infection was 0.7 per cent in the stapler group and 1.7 per cent in the endoloop group (P = 0.004). The rate of readmission to hospital was 0.9 and 2.1 per cent respectively (P = 0.001). CONCLUSION: Application of a stapler for transection and closure of the appendiceal stump in patients with acute appendicitis lowered the risk of postoperative intra-abdominal surgical-site infection and the need for readmission to hospital.

Simulation-based cost-utility analysis of population screening-based alendronate use in Switzerland

A simulation model adopting a health system perspective showed population-based screening with DXA, followed by alendronate treatment of persons with osteoporosis, or with anamnestic fracture and osteopenia, to be cost-effective in Swiss postmenopausal women from age 70, but not in men. INTRODUCTION: We assessed the cost-effectiveness of a population-based screen-and-treat strategy for osteoporosis (DXA followed by alendronate treatment if osteoporotic, or osteopenic in the presence of fracture), compared to no intervention, from the perspective of the Swiss health care system. METHODS: A published Markov model assessed by first-order Monte Carlo simulation was refined to reflect the diagnostic process and treatment effects. Women and men entered the model at age 50. Main screening ages were 65, 75, and 85 years. Age at bone densitometry was flexible for persons fracturing before the main screening age. Realistic assumptions were made with respect to persistence with intended 5 years of alendronate treatment. The main outcome was cost per quality-adjusted life year (QALY) gained. RESULTS: In women, costs per QALY were Swiss francs (CHF) 71,000, CHF 35,000, and CHF 28,000 for the main screening ages of 65, 75, and 85 years. The threshold of CHF 50,000 per QALY was reached between main screening ages 65 and 75 years. Population-based screening was not cost-effective in men. CONCLUSION: Population-based DXA screening, followed by alendronate treatment in the presence of osteoporosis, or of fracture and osteopenia, is a cost-effective option in Swiss postmenopausal women after age 70.

Healthcare and patient costs of a proactive chlamydia screening programme: the Chlamydia Screening Studies project

BACKGROUND AND OBJECTIVE: Most economic evaluations of chlamydia screening do not include costs incurred by patients. The objective of this study was to estimate both the health service and private costs of patients who participated in proactive chlamydia screening, using mailed home-collected specimens as part of the Chlamydia Screening Studies project. METHODS: Data were collected on the administrative costs of the screening study, laboratory time and motion studies and patient-cost questionnaire surveys were conducted. The cost for each screening invitation and for each accepted offer was estimated. One-way sensitivity analysis was conducted to explore the effects of variations in patient costs and the number of patients accepting the screening offer. RESULTS: The time and costs of processing urine specimens and vulvo-vaginal swabs from women using two nucleic acid amplification tests were similar. The total cost per screening invitation was 20.37 pounds (95% CI 18.94 pounds to 24.83). This included the National Health Service cost per individual screening invitation 13.55 pounds (95% CI 13.15 pounds to 14.33) and average patient costs of 6.82 pounds (95% CI 5.48 pounds to 10.22). Administrative costs accounted for 50% of the overall cost. CONCLUSIONS: The cost of proactive chlamydia screening is comparable to those of opportunistic screening. Results from this study, which is the first to collect private patient costs associated with a chlamydia screening programme, could be used to inform future policy recommendations and provide unique primary cost data for economic evaluations.

rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants

BACKGROUND: The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. METHODS: Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C). RESULTS: All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. CONCLUSION: IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.

Early autonomic dysfunction in patients with diabetes mellitus assessed by spectral analysis of heart rate and blood pressure variability

Patients with diabetes mellitus (DM) often have alterations of the autonomic nervous system (ANS), even early in their disease course. Previous research has not evaluated whether these changes may have consequences on adaptation mechanisms in DM, e.g. to mental stress. We therefore evaluated whether patients with DM who already had early alterations of the ANS reacted with an abnormal regulatory pattern to mental stress. We used the spectral analysis technique, known to be valuable and reliable in the investigation of disturbances of the ANS. We investigated 34 patients with DM without clinical evidence of ANS dysfunction (e.g. orthostatic hypotension) and 44 normal control subjects (NC group). No patients on medication known to alter ANS responses were accepted. The investigation consisted of a resting state evaluation and a mental stress task (BonnDet). In basal values, only the 21 patients with type 2 DM were different in respect to body mass index and systolic blood pressure. In the study parameters we found significantly lower values in resting and mental stress spectral power of mid-frequency band (known to represent predominantly sympathetic influences) and of high-frequency and respiration bands (known to represent parasympathetic influences) in patients with DM (types 1 and 2) compared with NC group (5.3 +/- 1.2 ms2 vs. 6.1 +/- 1.3 ms2, and 5.5 +/- 1.6 ms2 vs. 6.2 +/- 1.5 ms2, and 4.6 +/- 1.7 ms2 vs. 6.2 +/- 1.5 ms2, for resting values respectively; 4.7 +/- 1.4 ms2 vs. 5.9 +/- 1.2 ms2, and 4.6 +/- 1.9 ms2 vs. 5.6 +/- 1.7 ms2, and 3.7 +/- 2.1 ms2 vs. 5.6 +/- 1.7 ms2, for stress values respectively; M/F ratio 6/26 vs. 30/14). These differences remained significant even when controlled for age, sex, and body weight. However, patients with DM type 2 (and significantly higher body weight) showed only significant values in mental stress modulus values. There were no specific group effects in the patients with DM in adaptation mechanisms to mental stress compared with the NC group. These findings demonstrate that power spectral examinations at rest are sufficiently reliable to diagnose early alterations in ANS in patients with DM. The spectral analysis technique is sensitive and reliable in investigation of ANS in patients with DM without clinically symptomatic autonomic dysfunction.

Risk analysis of light-frame wood construction due to multiple hazards

Light-frame wood buildings are widely built in the United States (U.S.). Natural hazards cause huge losses to light-frame wood construction. This study proposes methodologies and a framework to evaluate the performance and risk of light-frame wood construction. Performance-based engineering (PBE) aims to ensure that a building achieves the desired performance objectives when subjected to hazard loads. In this study, the collapse risk of a typical one-story light-frame wood building is determined using the Incremental Dynamic Analysis method. The collapse risks of buildings at four sites in the Eastern, Western, and Central regions of U.S. are evaluated. Various sources of uncertainties are considered in the collapse risk assessment so that the influence of uncertainties on the collapse risk of lightframe wood construction is evaluated. The collapse risks of the same building subjected to maximum considered earthquakes at different seismic zones are found to be non-uniform. In certain areas in the U.S., the snow accumulation is significant and causes huge economic losses and threatens life safety. Limited study has been performed to investigate the snow hazard when combined with a seismic hazard. A Filtered Poisson Process (FPP) model is developed in this study, overcoming the shortcomings of the typically used Bernoulli model. The FPP model is validated by comparing the simulation results to weather records obtained from the National Climatic Data Center. The FPP model is applied in the proposed framework to assess the risk of a light-frame wood building subjected to combined snow and earthquake loads. The snow accumulation has a significant influence on the seismic losses of the building. The Bernoulli snow model underestimates the seismic loss of buildings in areas with snow accumulation. An object-oriented framework is proposed in this study to performrisk assessment for lightframe wood construction. For home owners and stake holders, risks in terms of economic losses is much easier to understand than engineering parameters (e.g., inter story drift). The proposed framework is used in two applications. One is to assess the loss of the building subjected to mainshock-aftershock sequences. Aftershock and downtime costs are found to be important factors in the assessment of seismic losses. The framework is also applied to a wood building in the state of Washington to assess the loss of the building subjected to combined earthquake and snow loads. The proposed framework is proven to be an appropriate tool for risk assessment of buildings subjected to multiple hazards. Limitations and future works are also identified.

Economic viability of shale gas production in the Marcellus Shale; indicated by production rates, costs and current natural gas prices

The U.S. natural gas industry has changed because of the recent ability to produce natural gas from unconventional shale deposits. One of the largest and most important deposits is the Marcellus Shale. Hydraulic fracturing and horizontal drilling have allowed for the technical feasibility of production, but concerns exist regarding the economics of shale gas production. These concerns are related to limited production and economic data for shale gas wells, declines in the rates of production, falling natural gas prices, oversupply issues coupled with slow growth in U.S. natural gas demand, and rising production costs. An attempt to determine profitability was done through the economic analysis of an average shale gas well using data that is representative of natural gas production from 2009 to 2011 in the Marcellus Shale. Despite the adverse conditions facing the shale gas industry it is concluded from the results of this analysis that a shale gas well in the Marcellus Shale is profitable based on NPV, IRR and breakeven price calculations.

Alveolar echinococcosis: from a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years

BACKGROUND/AIMS: Alveolar echinococcosis (AE) is a serious liver disease. The aim of this study was to explore the long-term prognosis of AE patients, the burden of this disease in Switzerland and the cost-effectiveness of treatment. METHODS: Relative survival analysis was undertaken using a national database with 329 patient records. 155 representative cases had sufficient details regarding treatment costs and patient outcome to estimate the financial implications and treatment costs of AE. RESULTS: For an average 54-year-old patient diagnosed with AE in 1970 the life expectancy was estimated to be reduced by 18.2 and 21.3 years for men and women, respectively. By 2005 this was reduced to approximately 3.5 and 2.6 years, respectively. Patients undergoing radical surgery had a better outcome, whereas the older patients had a poorer prognosis than the younger patients. Costs amount to approximately Euro108,762 per patient. Assuming the improved life expectancy of AE patients is due to modern treatment the cost per disability-adjusted life years (DALY) saved is approximately Euro6,032. CONCLUSIONS: Current treatments have substantially improved the prognosis of AE patients compared to the 1970s. The cost per DALY saved is low compared to the average national annual income. Hence, AE treatment is highly cost-effective in Switzerland.

Citrate- vs. acetate-based dialysate in bicarbonate haemodialysis: consequences on haemodynamics, coagulation, acid-base status, and electrolytes

BACKGROUND: A concentrate for bicarbonate haemodialysis acidified with citrate instead of acetate has been marketed in recent years. The small amount of citrate used (one-fifth of the concentration adopted in regional anticoagulation) protects against intradialyser clotting while minimally affecting the calcium concentration. The aim of this study was to compare the impact of citrate- and acetate-based dialysates on systemic haemodynamics, coagulation, acid-base status, calcium balance and dialysis efficiency. METHODS: In 25 patients who underwent a total of 375 dialysis sessions, an acetate dialysate (A) was compared with a citrate dialysate with (C+) or without (C) calcium supplementation (0.25 mmol/L) in a randomised single-blind cross-over study. Systemic haemodynamics were evaluated using pulse-wave analysis. Coagulation, acid-base status, calcium balance and dialysis efficiency were assessed using standard biochemical markers. RESULTS: Patients receiving the citrate dialysate had significantly lower systolic blood pressure (BP) (-4.3 mmHg, p < 0.01) and peripheral resistances (PR) (-51 dyne.sec.cm-5, p < 0.001) while stroke volume was not increased. In hypertensive patients there was a substantial reduction in BP (-7.8 mmHg, p < 0.01). With the C+ dialysate the BP gap was less pronounced but the reduction in PR was even greater (-226 dyne.sec.cm-5, p < 0.001). Analyses of the fluctuations in PR and of subjective tolerance suggested improved haemodynamic stability with the citrate dialysate. Furthermore, an increase in pre-dialysis bicarbonate and a decrease in pre-dialysis BUN, post-dialysis phosphate and ionised calcium were noted. Systemic coagulation activation was not influenced by citrate. CONCLUSION: The positive impact on dialysis efficiency, acid-base status and haemodynamics, as well as the subjective tolerance, together indicate that citrate dialysate can significantly contribute to improving haemodialysis in selected patients.