[Prophylaxis and therapy of postdural puncture headache--a critical evaluation of treatment options]

Since the first description of spinal and epidural anaesthesia, postdural puncture headache (PDPH) is a well known complication. Its prophylaxis and treatment has been studied and discussed for more than 100 years, but the evidence is still limited. Due to relatively low prevalence of PDPH, prospective RCTs are often missing, and the frequently self-limiting character of PDPH impedes an adequate interpretation of results from studies without a control group. Taking side effects and complications into account, a prophylactic treatment of PDPH cannot be recommended. In case of PDPH, non-opioid analgesics are the first choice treatment. The epidural blood patch remains the mainstay of severe PDPH therapy. Noninvasive therapies like theophylline, sumatriptan and ACTH can be an alternative. However, an evidence-based recommendation is lacking. The development of standard operating procedures for accidental dural punctures and PDPH is recommended.

A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer

The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable approach to risk estimation would be to use organ-specific non-linear risk models applied to the dose distributions of organs within or near the treatment fields (lungs and contralateral breast in the case of breast radiotherapy) as the majority of radiation-induced secondary cancers are found in the beam-bordering regions.

A critical evaluation of the clinical evidence for pomegranate preparations in the prevention and treatment of cardiovascular diseases

This study attempts a critical evaluation of the clinical evidence behind the use of dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases. A search of PubMed on August 10, 2014 identified 228 references, which yielded extractable data from 24 clinical studies of pomegranate preparations. Hand searching identified two further studies. The quality of the studies and evidence of effectiveness of pomegranate were assessed by an established set of conventional criteria. Overall, the study quality was poor. Even in the best studies, indications of benefit did not reach the conventional levels of statistical significance. The only study with a definitive design had a biochemical rather than a clinical endpoint: it showed the expected difference in blood concentrations of myeloperoxidase after a single dose of either pomegranate or placebo. Only 10 of the 26 studies provided HPLC data on the amounts of co-active ingredients in the preparations that were consumed by the subjects. If pomegranate has a role in the prevention and treatment of cardiovascular diseases, there is a pressing need for dose-finding and long-term confirmatory studies. The ultimate endpoint for definitive studies would be mortality, but reductions in blood pressure or demonstrable decreases in atherosclerotic plaques would be useful surrogates. Sample sizes for various assumptions are provided. Future studies need to prove the clinical benefit.

Recent developments for surgical aortic valve replacement: the concept of sutureless valve technology

Aortic stenosis has become the most frequent type of valvular heart disease in Europe and North America and presents in the large majority of patients as calcified aortic stenosis in adults of advanced age. Surgical aortic valve replacement has been recognized to be the definitive therapy which improves considerably survival for severe aortic stenosis since more than 40 years. In the most recent period, operative mortality of isolated aortic valve replacement for aortic stenosis varies between 1–3% in low-risk patients younger than 70 years and between 4 and 8% in selected older adults. Long-term survival following aortic valve replacement is close to that observed in a control population of similar age. Numerous observational studies have consistently demonstrated that corrective surgery in symptomatic patients is invariably followed by a subjective improvement in quality of life and a substantial increase in survival rates. More recently, transcatheter aortic valve implantation (TAVI) has been demonstrated to be feasible in patients with high surgical risk using either a retrograde transfemoral or transsubclavian approach or an antegrade, transapical access. Reported 30-day mortality ranges between 5 and 15%) and is acceptable when compared to the risk predicted by the logistic EuroSCORE (varying between 20 and 35%) and the STS Score, although the EuroScore has been shown to markedly overestimate the effective operative risk. One major concern remains the high rate of paravalvular regurgitation which is observed in up to 85% of the patients and which requires further follow-up and critical evaluation. In addition, long-term durability of these valves with a focus on the effects of crimping remains to be addressed, although 3-5 year results are promising. Sutureless biological valves were designed to simplify and significantly accelerate the surgical replacement of a diseased valve and allow complete excision of the calcified native valve. Until now, there are 3 different sutureless prostheses that have been approved. The 3f Enable valve from ATS-Medtronic received CE market approval in 2010, the Perceval S from Sorin during Q1 of 2011 and the intuity sutureless prosthesis from Edwards in 2012. All these devices aim to facilitate valve surgery and therefore have the potential to decrease the invasivness and to shorten the conventional procedure without compromise in term of excision of the diseased valve. This review summarizes the history and the current knowledge of sutureless valve technology.

In silico target fishing for rationalized ligand discovery exemplified on constituents of Ruta graveolens

The identification of targets whose interaction is likely to result in the successful treatment of a disease is of growing interest for natural product scientists. In the current study we performed an exemplary application of a virtual parallel screening approach to identify potential targets for 16 secondary metabolites isolated and identified from the aerial parts of the medicinal plant RUTA GRAVEOLENS L. Low energy conformers of the isolated constituents were simultaneously screened against a set of 2208 pharmacophore models generated in-house for the IN SILICO prediction of putative biological targets, i. e., target fishing. Based on the predicted ligand-target interactions, we focused on three biological targets, namely acetylcholinesterase (AChE), the human rhinovirus (HRV) coat protein and the cannabinoid receptor type-2 (CB (2)). For a critical evaluation of the applied parallel screening approach, virtual hits and non-hits were assayed on the respective targets. For AChE the highest scoring virtual hit, arborinine, showed the best inhibitory IN VITRO activity on AChE (IC (50) 34.7 muM). Determination of the anti-HRV-2 effect revealed 6,7,8-trimethoxycoumarin and arborinine to be the most active antiviral constituents with IC (50) values of 11.98 muM and 3.19 muM, respectively. Of these, arborinine was predicted virtually. Of all the molecules subjected to parallel screening, one virtual CB (2) ligand was obtained, i. e., rutamarin. Interestingly, in experimental studies only this compound showed a selective activity to the CB (2) receptor ( Ki of 7.4 muM) by using a radioligand displacement assay. The applied parallel screening paradigm with constituents of R. GRAVEOLENS on three different proteins has shown promise as an IN SILICO tool for rational target fishing and pharmacological profiling of extracts and single chemical entities in natural product research.

“But look: we have sat here too long”: Hilary Mantel’s tightrope walk of present-tense usage

Even after Hilary Mantel has won the Man Booker prize two times in a row with Wolf Hall and Bring up the Bodies, her novelistic account of the life of Thomas Cromwell, her intriguing decision to write these historical novels in the present tense gave cause to surprisingly little extended comment beyond a perfunctory nod to its evocation of immediacy. This presents not only a lacunae in the discussion about Mantel’s novels, but is also symptomatic for a change in the contemporary critical evaluation of present-tense narration in general. If present-tense narration once used to be a marker for experimental daring and might even have implied a certain hostility towards fictionality, Mantel’s novels give ample evidence that literary sensibilities have changed. In order to understand the scope and nature of this change, my paper puts Mantel’s use of the present tense in the context of both the historical development of present-tense usage and the ample contemporary landscape of present-tense narration. This allows me to show that the complexities of present-tense usage belie a reduction of its effect to an evocation of immediacy. Rather, I argue, Mantel uses it for a delicate tightrope walk between proximity and distance, history and fiction, authenticity and imagination.

Evaluation of an inventory for the assessment of critical incidents involving football fans

Introduction: Fan violence is a frequent occurrence in Swiss football (Bundesamt für Polizei, 2015) leading to high costs for prevention and control (Mensch & Maurer, 2014). Various theories put forward an explanation of fan violence, such as the Elaborated Social Identity Model (Drury & Reicher, 2000)and the Aggravation Mitigation Model (Hylander & Guvå, 2010). Important observations from these theories are the multi-dimensional understanding of fan violence and the Dynamics occurring in the fan group. Nevertheless, none of them deal with critical incidents (CIs) which involve a tense atmosphere combined with a higher risk of fan violence. Schumacher Dimech, Brechbühl and Seiler (2015) tackled this gap in research and explored CIs where 43 defining criteria were identified and compiled in an integrated model of CIs. The defining criteria were categorised in four higher-order themes “antecedents” (e.g. a documented history of fan rivalry), “triggers” (e.g. the arrest of a fan), “reactions” (e.g. fans masking themselves) and “consequences” (e.g. fans avoiding communication with fan social workers). Methods: An inventory based on this model is being developed including these 43 criteria. In an exploratory phase, this inventory was presented as an online questionnaire and was completed by 143 individuals. Three main questions are examined: Firstly, the individual items are tested using descriptive analyses. An item analysis is conducted to test reliability, item difficulty and discriminatory power. Secondly, the model’s four higher-order themes are tested using exploratory factor analysis (EFA). Thirdly, differences between sub -groups are explored, such as gender and age-related differences. Results: Respondents rated the items’ importance as high and the quota of incomplete responses was not systematic. Two items were removed from the inventory because of low mean or a high rate of “don’t know”-responses. EFA produced a six-factor solution grouping items into match-related factors, repressive measures, fans’ delinquent behaviour, intra-group behaviour, communication and control and inter-group factors. The item “fans consume alcohol” could not be ordered into any category but was retained since literature accentuates this factor’s influence on fan violence. Analyses examining possible differences between groups are underway. Discussion: Results exploring the adequacy of this inventory assessing defining criteria of CIs in football are promising and thus further evaluative investigation is recommended. This inventory can be used in two ways: as a standardised instrument of assessment for experts evaluating specific CIs and as an instrument for exploring differences in perception and assessment of a CI e.g. gender and age differences, differences between interest groups and stakeholders.

Evaluation of an inventory for the assessment of critical incidents involving football fans

Introduction: Fan violence is a frequent occurrence in Swiss football (Bundesamt für Polizei, 2015) leading to high costs for prevention and control (Mensch & Maurer, 2014). Various theories put forward an explanation of fan violence, such as the Elaborated Social Identity Model (Drury & Reicher, 2000) and the Aggravation Mitigation Model (Hylander & Guvå, 2010). Important observations from these theories are the multi-dimensional understanding of fan violence and the dynamics occurring in the fan group. Nevertheless, none of them deal with critical incidents (CIs) which involve a tense atmosphere combined with a higher risk of fan violence. Schumacher Dimech, Brechbühl and Seiler (2015) tackled this gap in research and explored CIs where 43 defining criteria were identified and compiled in an integrated model of CIs. The defining criteria were categorised in four higher-order themes “antecedents” (e.g. a documented history of fan rivalry), “triggers” (e.g. the arrest of a fan), “reactions” (e.g. fans masking themselves) and “consequences” (e.g. fans avoiding communication with fan social workers). Methods: An inventory based on this model is being developed including these 43 criteria. In an exploratory phase, this inventory was presented as an online questionnaire and was completed by 143 individuals. Three main questions are examined: Firstly, the individual items are tested using descriptive analyses. An item analysis is conducted to test reliability, item difficulty and discriminatory power. Secondly, the model’s four higher-order themes are tested using exploratory factor analysis (EFA). Thirdly, differences between sub-groups are explored, such as gender and agerelated differences. Results: Respondents rated the items’ importance as high and the quota of incomplete responses was not systematic. Two items were removed from the inventory because of low mean or a high rate of “don’t know”-responses. EFA produced a six-factor solution grouping items into match-related factors, repressive measures, fans’ delinquent behaviour, intra-group behaviour, communication and control and inter-group factors. The item “fans consume alcohol” could not be ordered into any category but was retained since literature accentuates this factor’s influence on fan violence. Analyses examining possible differences between groups are underway. Discussion: Results exploring the adequacy of this inventory assessing defining criteria of CIs in football are promising and thus further evaluative investigation is recommended. This inventory can be used in two ways: as a standardised instrument of assessment for experts evaluating specific CIs and as an instrument for exploring differences in perception and assessment of a CI e.g. gender and age differences, differences between interest groups and stakeholders. References: Bundesamt für Polizei. (2015). Jahresbericht 2014. Kriminalitätsbekämpfung Bund. Lage, Massnahmen und Mittel [Electronic Version]. Drury, J., & Reicher, S. (2000). Collective action and psychological change. The emergence of new social identities. British Journal of Social Psychology, 39, 579-604. Hylander, I., & Guvå, G. (2010). Misunderstanding of out-group behaviour: Different interpretations of the same crowd events among police officers and demonstrators. Nordic Psychology, 62, 25-47. Schumacher-Dimech, A., Brechbühl, A. &, Seiler, R. (2016). Dynamics of critical incidents with potentially violent outcomes involving ultra fans: an explorative study. Sport in Society. Advance online publication. doi: 10.1080/17430437.2015.1133597

Retrospective evaluation of postoperative nasotracheal tubes for oxygen supplementation in dogs following surgery for brachycephalic syndrome: 36 cases (2003-2007)

OBJECTIVE: To assess the utility of nasotracheal tubes in postoperative oxygen supplementation in dogs following corrective surgery for brachycephalic syndrome. DESIGN: Retrospective study 2003-2007. SETTING: University teaching hospital. ANIMALS: Thirty-six client-owned dogs that underwent corrective surgery for brachycephalic syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for animals that underwent surgical interventions for brachycephalic syndrome including palatoplasty, ventriculectomy, and rhinoplasty. Data collected included signalment, presenting complaints, analgesic and surgical interventions, type of supplemental oxygen therapy, complications and mortality occurring during hospitalization. A nasotracheal tube (NTT) was placed in 20 dogs at the end of surgery; 16 dogs received other forms of oxygen supplementation (8) or no oxygen supplementation (8) during recovery. The total number of postoperative complications was similar in both groups (8/20 dogs with NTTs and 7/16 in those without NTTs). However, respiratory distress was observed in 5 dogs without NTTs but was not observed in any dog while an NTT was in place. One dog in each group died postoperatively. CONCLUSION: Placement of an NTT was found to be easy and may offer benefit in dogs with brachycephalic syndrome as a noninvasive means of delivering oxygen. The use of NTT may minimize severe postoperative morbidity, in particular by reducing postoperative respiratory distress.

Evaluation of respiratory parameters at presentation as clinical indicators of the respiratory localization in dogs and cats with respiratory distress

OBJECTIVE: To describe clinical respiratory parameters in cats and dogs with respiratory distress and identify associations between respiratory signs at presentation and localization of the disease with particular evaluation between the synchrony of abdominal and chest wall movements as a clinical indicators for pleural space disease. Design - Prospective observational clinical study. SETTING: Emergency service in a university veterinary teaching hospital. ANIMALS: Cats and dogs with respiratory distress presented to the emergency service between April 2008 and July 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The following parameters were systematically determined at time of admission: respiratory rate, heart rate, temperature, type of breathing, movement of the thoracic and abdominal wall during inspiration, presence of stridor, presence and type of dyspnea, and results of thoracic auscultation. Abdominal and chest wall movement was categorized as synchronous, asynchronous, or inverse. Diagnostic test results, diagnosis, and outcome were subsequently recorded. Based on the final diagnoses, animals were assigned to 1 or more of the following groups regarding the anatomical localization of the respiratory distress: upper airways, lower airways, lung parenchyma, pleural space, thoracic wall, nonrespiratory causes, and normal animals. One hundred and seventy-six animals (103 cats and 73 dogs) were evaluated. Inspiratory dyspnea was associated with upper airway disease in dogs and expiratory dyspnea with lower airway disease in cats. Respiratory noises were significantly associated and highly sensitive and specific for upper airway disease. An asynchronous or inverse breathing pattern and decreased lung auscultation results were significantly associated with pleural space disease in both dogs and cats (P<0.001). The combination is highly sensitive (99%) but not very specific (45%). Fast and shallow breathing was not associated with pleural space disease. Increased or moist pulmonary auscultation findings were associated with parenchymal lung disease. CONCLUSIONS: Cats and dogs with pleural space disease can be identified by an asynchronous or inverse breathing pattern in combination with decreased lung sounds on auscultation.

Membrane microdialysis: Evaluation of a new method to assess splanchnic tissue metabolism

OBJECTIVE: Measuring peritoneal lactate concentrations could be useful for detecting splanchnic hypoperfusion. The aims of this study were to evaluate the properties of a new membrane-based microdialyzer in vitro and to assess the ability of the dialyzer to detect a clinically relevant decrease in splanchnic blood flow in vivo. DESIGN: A membrane-based microdialyzer was first validated in vitro. The same device was tested afterward in a randomized, controlled animal experiment. SETTING: University experimental research laboratory. SUBJECTS: Twenty-four Landrace pigs of both genders. INTERVENTIONS: In vitro: Membrane microdialyzers were kept in warmed sodium lactate baths with lactate concentrations between 2 and 8 mmol/L for 10-120 mins, and microdialysis lactate concentrations were measured repeatedly (210 measurements). In vivo: An extracorporeal shunt with blood reservoir and roller pump was inserted between the proximal and distal abdominal aorta, and a microdialyzer was inserted intraperitoneally. In 12 animals, total splanchnic blood flow (measured by transit time ultrasound) was reduced by a median 43% (range, 13% to 72%) by activating the shunt; 12 animals served as controls. MEASUREMENTS AND MAIN RESULTS: In vitro: The fractional lactate recovery was 0.59 (0.32-0.83) after 60 mins and 0.82 (0.71-0.87) after 90 mins, with no further increase thereafter. At 60 and 90 mins, the fractional recovery was independent of the lactate concentration. In vivo: Abdominal blood flow reduction resulted in an increase in peritoneal microdialysis lactate concentration from 1.7 (0.3-3.8) mmol/L to 2.8 (1.3-6.2) mmol/L (p = .006). At the same time, mesenteric venous-arterial lactate gradient increased from 0.1 (-0.2-0.8) mmol/L to 0.3 (-0.3 -1.8) mmol/L (p = .032), and mesenteric venous-arterial Pco2 gradients increased from 12 (8-19) torr to 21 (11-54) torr (p = .005). CONCLUSIONS: Peritoneal membrane microdialysis provides a method for the assessment of splanchnic ischemia, with potential for clinical application.

Cementless hemiarthroplasty in femoral neck fractures: evaluation of clinical results and measurement of migration by EBRA-FCA

Aim of the present study was to evaluate migration rates of cementless primary hemiarthroplasty in acute femoral neck fractures. In a longitudinal, prospective study 46 patients were treated by cementless hemiarthroplasty. Clinical follow up was correlated with the EBRA-FCA method. In 30% of all patients stem migration amounted to more than 2 mm; further, these patients were seen to have a high level of activity. A high degree of migration in more than 30% of all patients requires critical scepticism toward further use of the investigated cementless stem as hemiarthroplasty. According to literature, migration of more than 2 mm suggests a high probability of early aseptic loosening. In patients with a low degree of activity good results could be observed; nevertheless, in patients with a high level of activity the combination of the investigated cementless stem with a solid fracture head cannot be recommended.

Therapeutic angiogenesis with intramuscular NV1FGF improves amputation-free survival in patients with critical limb ischemia

This study evaluated the efficacy and safety of intramuscular administration of NV1FGF, a plasmid-based angiogenic gene delivery system for local expression of fibroblast growth factor 1 (FGF-1), versus placebo, in patients with critical limb ischemia (CLI). In a double-blind, randomized, placebo-controlled, European, multinational study, 125 patients in whom revascularization was not considered to be a suitable option, presenting with nonhealing ulcer(s), were randomized to receive eight intramuscular injections of placebo or 2.5 ml of NV1FGF at 0.2 mg/ml on days 1, 15, 30, and 45 (total 16 mg: 4 x 4 mg). The primary end point was occurrence of complete healing of at least one ulcer in the treated limb at week 25. Secondary end points included ankle brachial index (ABI), amputation, and death. There were 107 patients eligible for evaluation. Improvements in ulcer healing were similar for use of NV1FGF (19.6%) and placebo (14.3%; P = 0.514). However, the use of NV1FGF significantly reduced (by twofold) the risk of all amputations [hazard ratio (HR) 0.498; P = 0.015] and major amputations (HR 0.371; P = 0.015). Furthermore, there was a trend for reduced risk of death with the use of NV1FGF (HR 0.460; P = 0.105). The adverse event incidence was high, and similar between the groups. In patients with CLI, plasmid-based NV1FGF gene transfer was well tolerated, and resulted in a significantly reduced risk of major amputation when compared with placebo.