Search

Introduction: The coronavirus disease 2019 (COVID-19) is one of the greatest clinical challenges of the last decades. Clinical factors associated with severity of the disease remain unclear. The aim of the study was to characterize Polish patients hospitalized due to COVID-19 and to evaluate potential prognostic factors of severe course of the disease. Material and methods: An observational study was conducted from March to July 2020 in the Pulmonology and Allergology Department of the University Hospital in Kraków, Poland. Consecutive patients with confirmed SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection were enrolled, and data about past medical history, signs and symptoms, laboratory results, imaging studies results, in-hospital management and outcomes was prospectively gathered. Results: The study sample comprised 100 patients at the mean age of 59.2 (SD 16.1) years among whom 63 (63.0%) were male. Among them 10 (10.0%) died, 47 (47%) presented respiratory failure, 15 (15.0%) were transferred to the intensive care unit, 17 (17.0%) developed acute kidney injury, 7 (7.0%) had sepsis and 10 (10.0%) were diagnosed with pulmonary embolism. Multivariable analysis revealed age (OR 1.1; 95% CI 1.01–1.15), body mass index (BMI; OR 1.24; 95% CI 1.01–1.53), modified early warning score (MEWS; OR 3.95; 95% CI 1.48–12), the highest d-dimer value (OR 1.73; 95% CI 1.03–2.9) and lactate dehydrogenase (LDH; OR 1.16; 95% CI 1.03–1.3) to be associated with severe course of COVID-19. Conclusion: This observational study showed that almost half of hospitalized patients with COVID-19 developed respiratory failure in the course of the disease. Increasing age, BMI, MEWS, d-dimer value and LDH concentration were associated with the severity of COVID-19.

Background Breast cancer (BC) risk assessment models are statistical estimates based on patient characteristics. We developed a gene expression assay to assess BC risk using benign breast biopsy tissue. Methods A NanoString-based malignancy risk (MR) gene signature was validated for formalin-fixed paraffin-embedded (FFPE) tissue. It was applied to FFPE benign and BC specimens obtained from women who underwent breast biopsy, some of whom developed BC during follow-up to evaluate diagnostic capability of the MR signature. BC risk was calculated with MR score, Gail risk score, and both tests combined. Logistic regression and receiver operating characteristic curves were used to evaluate these 3 models. Results NanoString MR demonstrated concordance between fresh frozen and FFPE malignant samples (r = 0.99). Within the validation set, 563 women with benign breast biopsies from 2007 to 2011 were identified and followed for at least 5 y; 50 women developed BC (affected) within 5 y from biopsy. Three groups were compared: benign tissue from unaffected and affected patients and malignant tissue from affected patients. Kruskal–Wallis test suggested difference between the groups (P = 0.09) with trend in higher predicted MR score for benign tissue from affected patients before development of BC. Neither the MR signature nor Gail risk score were statistically different between affected and unaffected patients; combining both tests demonstrated best predictive value (AUC = 0.71). Conclusions FFPE gene expression assays can be used to develop a predictive test for BC. Further investigation of the combined MR signature and Gail Model is required. Our assay was limited by scant cellularity of archived breast tissue.

OBJECTIVE To assess the incidence of maternal group B Streptococcus (GBS) infection in England. DESIGN Population surveillance augmented through data linkage. SETTING England. POPULATION All pregnant women accessing the National Health Service (NHS) in England. METHODS Invasive GBS (iGBS) infections during pregnancy or within 6 weeks of childbirth were identified by linking Public Health England (PHE) national microbiology surveillance data for 2014 to NHS hospital admission records. Capsular serotypes of GBS were determined by reference laboratory typing of clinical isolates from women aged 15-44 years. Post-caesarean section surgical site infection (SSI) caused by GBS was identified in 21 hospitals participating in PHE SSI surveillance (2009-2015). MAIN OUTCOME MEASURES iGBS rate per 1000 maternities; risk of GBS SSI per 1000 caesarean sections. RESULTS Of 1601 patients diagnosed with iGBS infections in England in 2014, 185 (12%) were identified as maternal infections, a rate of 0.29 (95% CI 0.25-0.33) per 1000 maternities and representing 83% of all iGBS cases in women aged 18-44 years. Seven (3.8%) were associated with miscarriage. Fetal outcome identified excess rates of stillbirth (3.4 versus 0.5%) and extreme prematurity (

Background: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. Objectives: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. Methods: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (6 months). Results: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ± 4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ± 4.1 years (range 3 months–15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7–9 years beyond 6 months after implantation. Discussion: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. Conclusion: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

As our bodies age, the performance of all bodily organs and systems deteriorates, adversely affecting their functional capacity and increasing overall falls-risk, even in the most active individuals, including female students of the Third Age Universities (TAU). A well-developed and implemented physiotherapy programme makes it possible to appreciably reduce the falls-risk in TAU students, as well as any attendant negative consequences mitigated. The study aimed to assess the impact of a 6-month original physical therapy regimen on the attendant falls-risk, as established in the female TAU students. The study covered 131 female TAU students, aged 60 and over. The subjects were randomly split into two groups, i.e. Study Group (n = 66; mean age 67.2  5.4 years), and a Control Group (n = 65; mean age 66.2  3.5 years). All subjects were assessed twice, prior to, and up-on the conclusion of a 6-month physical therapy regimen. Falls-risk and individual sense of balance were assessed by a "Step Test" (ST), "One-Leg Standing Test" (OLST), and a "Func-tional Reach Test" (FRT). The study group ST and OLST test scores upon conclusion of the physical therapy regimen were significantly higher (i.e. longer time of a one-legged stand), as compared to the Control Group, for both right and left lower limbs (p > 0.05). FRT scores upon conclusion of the phys-ical therapy regimen were also significantly higher (p > 0.05), as a greater range of body ex-tension was observed. Falls-risk in the TAU students aged 60 and over was significantly decreased through the im-plementation of an original, 6-month physical therapy regimen, while an individual sense of balance in a standing position was also found to be appreciably enhanced. This article is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License. null

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%).

We present own results of the treatment of acute ischemic stroke by mechanical thrombectomy. Procedures were conducted in the Center for Acute Ischemic Stroke Treatment (CITO) at the University Hospital in Krakow that was established for this study. The Center works in the 24/7 system, and according to the protocol 6 professionals who participate in the procedure starts it within 45 minutes after the call of the Center coordinator. Since January the 1st 2013 till September the 30th 2016, 96 procedures were performed. Three months followup was performed in the consecutive 74 patients (39 men), mean age: 65,8±13,1 and here we present their data. Mean NIHSS score on admission was 15,4±4,2 points. In 46 patients (62.2%) mechanical thrombectomy was preceded by rt-PA-IV administration. Mean time from stroke onset to groin puncture was 265±88,5 minutes. After the procedure TICI=3 was obtained by 26 patients (35.1%), 2b – by 12 patients (16.2%), 2a – 19 patients (25.7%), 1 – 8 patients (10.8%) and 0 – by 9 patients (12.2%). Head CT scan done 24 hours after thrombectomy did not show hemorrhagic transformation in 37 patients. According to ECASS1 classification HI1 was found in 11 patients (14.9%), H12 – in 16 patients (21.6%), PH1 – in 4 patients (5.4%) and PH2 – in 6 patients (8.1%). Fourteen patients (18.9%) died within 90 days after stroke onset, and 38 – scored 80-100 points in Barthel Index (51.4%). Presented results indicate similar safety and efficacy profile of mechanical thrombectomy in the treatment of ischemic stroke performed in the system that was organized for this specific reason.

Introduction In-hospital incomplete and terminated at discharge myocardial revascularization has significant impact on mortality after acute myocardial infarction (AMI), also in patients (pts) with reduced left ventricle ejection fraction (LVEF) ≤35%. However, subjects with LVEF >35%, who are not candidates for implantable cardioverter defibrillators, are still at risk. Authors hypothesized, that in those pts, the prognosis could be related to completeness of revascularization. Purpose To evaluate the risk of death and major adverse cardiovascular events (MACE) among pts with AMI and LVEF>35% in relation to myocardial revascularization status. Methods Single center prospective study encompassed 445-pts with AMI and LVEF>35%, who were treated with percutaneous coronary intervention and who survived in-hospital period. Study population was divided into two groups: group 1. – 73-pts with in-hospital incomplete and terminated revascularization at discharge; group 2. – 372-pts with complete or incomplete revascularization, in whom scheduled procedures were planned and performed (either percutaneous or surgical). The incidence of death and MACE was compared between groups during mean follow-up of 47.5 months after AMI. MACE was defined as a composite of death, recurrent AMI, non-scheduled revascularization, acute heart failure, stroke. Independent predictors for death were identified with multivariate Cox-regression models and expressed as hazard ratio (HR) with 95% confidence interval (CI). Results Patients in group 1. had higher mortality rate than in group 2. (26.4% vs. 9.1%; p Conclusions After invasive treatment of AMI, the prognosis in patients with LVEF>35% is related to revascularization status. In-hospital incomplete and terminated revascularization at discharge is an independent risk factor for death in this population.

Pulmonary rehabilitation (PR) has been recommended as an integral part of treatment for patients with chronic obstructive pulmonary disease (COPD). Climate therapy in salt mine chambers has been found of benefit in chronic respiratory diseases. The study compares long-term effects of underground PR in the Wieliczka Salt Mine with that conducted on the surface. There were 42 COPD patients enrolled in the study, with FEV1/FVC

Objective To estimate the economic burden to the health service of surgical site infection following caesarean section and to identify potential savings achievable through implementation of a surveillance programme.\ud Design Economic model to evaluate the costs and benefits of surveillance from community and hospital healthcare providers’ perspective.\ud Setting England.\ud Participants Women undergoing caesarean section in National Health Service\ud hospitals.\ud Main outcome measure Costs attributable to treatment and management of surgical site infection following caesarean section.\ud Results The costs (2010) for a hospital carrying out 800 caesarean sections a year based on infection risk of 9.6% were estimated at £18,914 (95% CI 11,521 to 29,499) with 28% accounted for by community care (£5,370). With inflation to 2019 prices, this equates to an estimated cost of £5.0m for all caesarean sections performed annually in England 2018-19, approximately £1,866 and £93 per infection managed in hospital and community respectively. The cost of surveillance for a hospital for one calendar quarter was estimated as £3,747 (2010 costs).\ud Modelling a decrease in risk of infection of 30, 20 or 10% between successive surveillance periods indicated that a variable intermittent surveillance strategy achieved higher or similar net savings than continuous surveillance. Breakeven was reached sooner with the variable surveillance strategy than continuous surveillance\ud when the baseline risk of infection was 10 or 15% and smaller loses with a baseline risk of 5%.\ud Conclusion Surveillance of surgical site infections after caesarean section with feedback of data to surgical teams offers a potentially effective means to reduce infection risk, improve patient experience and save money for the health service.\ud Strengths and limitations\ud • The model estimated both community (28%) and hospital costs (72%), providing a more representative estimate of overall economic burden to the health service.\ud • Time-matching of patients with and without infection according to length of post-operative stay provided a more accurate assessment of excess bed-days attributable to surgical site infection (2.6 days) than average excess length of stay (median difference 5 days) comparison by disentangling the impact of prolonged length of stay on increased chance of detecting an infection.\ud • Through capture and assessment of the costs and impact of surveillance, our model demonstrated the potential for savings through reductions in incidence of surgical site infections.\ud • Costs were obtained from NHS National Schedule Reference Costs and other sources rather than observed expenditure and assumptions made about the number of extra midwife and general practitioner appointments resulting from infection.\ud • The study was based on healthcare utilisation and did not assess direct and indirect costs borne by the patients or their carers.

Little is known about the prognostic role of fasting glucose after mechanical thrombectomy (MT).We investigated whether fasting glucose on the next day after MT was associated with long-term outcome in acute ischemic stroke patients according to diabetes.We retrospectively analyzed 181 consecutive patients with acute anterior circulation ischemic stroke who underwent MT in 2 comprehensive stroke centers in Poland. Glucose levels were evaluated on admission and on the next day after MT. Fasting hyperglycemia (FHG) was defined as the glucose level above 5.5 mmol/L. Unfavorable outcome was defined as modified Rankin scale (mRS) of 3-6 at day 90 from stroke onset.Patients with FHG had higher mRS at 3-month follow-up compared with those without FHG (3.71 ± 2.56 versus 1.87 ± 2.22, P.001). In the subgroup analyses, FHG was associated with poor neurological outcome in the group without diabetes (3.74 ± 2.52 versus 1.81 ± 3.74, P.001) but not with diabetes (3.64 ± 2.67 versus 2.30 ± 3.74, P= .11). Patients without diabetes who had FHG were older, had higher glucose on admission, higher prevalence of atrial fibrillation, cardioembolic stroke etiology and bleeding brain complications compared with the group with normal fasting glucose. After adjustment for potential confounders, fasting glucose (odds ratio [OR] 1.46; 95% CI 1.19-1.79, P.001), age (OR 1.06; 95% CI 1.02-1.10, P = .001), successful reperfusion (OR 0.09; 95% CI 0.04-0.22, P.001) and baseline NIHSS score (OR 1.18; 95% CI 1.08-1.29, P.001) were predictors of mRS 3-6 at 3-month follow-up in the whole group. In the subgroup without diabetes, fasting glucose (OR 1.57; 95% CI 1.17-2.11, P = .002), age (OR 1.05; 95% CI 1.01-1.08, P = .008), successful reperfusion (OR 0.11; 95% CI 0.04-0.30, P.001) and baseline NIHSS score (OR 1.14; 95% CI 1.04-1.26, P = .011) were independent predictors of unfavorable 3-month outcome.Fasting glucose on the next day after MT in patients with acute ischemic stroke is an independent risk factor for worse 3-month outcome.

Background Antiphospholipid syndrome (APS) is an autoimmune disease characterised by the presence of antiphospholipid (aPL) antibodies that have prothrombotic activity. Antiphospholipid antibodies are associated with an increased risk of pregnancy complications (recurrent miscarriage, premature birth, intrauterine growth retardation) and thrombotic events (both arterial and venous). The most common thrombotic events include brain ischaemia (stroke or transient ischaemic attack) and deep vein thrombosis. To diagnose APS, the presence of aPL antibodies in two measurements and at least one thrombotic event or pregnancy complication are required. It is unclear if people with positive aPL antibodies but without any previous thrombotic events should receive primary antithrombotic prophylaxis. Objectives To assess the effects of antiplatelet or anticoagulant agents versus placebo or no intervention or other intervention on the development of thrombosis in people with aPL antibodies who have not had a thrombotic event. We did not address obstetric outcomes in this review as these have been thoroughly addressed by other Cochrane Reviews. Search methods We searched the Cochrane Vascular Specialised Register (4 December 2017), the Cochrane Central Register of Controlled Trials (CENTRAL) (last search 29 November 2017), MEDLINE Ovid, Embase Ovid, CINAHL, and AMED (searched 4 December 2017), and trials registries (searched 29 November 2017). We also checked reference lists of included studies, systematic reviews, and practice guidelines, and contacted experts in the field. Selection criteria We included randomised controlled trials (RCTs) that compared any antiplatelet or anticoagulant agents, or their combinations, at any dose and mode of delivery with placebo, no intervention, or other intervention. We also included RCTs that compared antiplatelet or anticoagulant agents with each other or that compared two different doses of the same drug. We included studies performed in people of any age and with no history of thrombosis (as defined by APS Sapporo classification criteria or updated Sydney classification criteria), but with aPL antibodies confirmed on at last two separate measurements. The studies included both pregnant women who tested positive for aPL antibodies and had a history of recurrent obstetric complications, as well as non-pregnancy related cases with positive screening for antibodies, in accordance with the criteria mentioned above. Data collection and analysis Pairs of authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies and quality of evidence using GRADE. Any discrepancies were resolved through discussion or by consulting a third review author when necessary. In addition, one review author checked all the extracted numerical data. Main results We included nine studies involving 1044 randomised participants. The studies took place in several countries and had different funding sources. No study was at low risk of bias in all domains. We classified all included studies as at unclear or high risk of bias in two or more domains. Seven included studies focused mainly on obstetric outcomes. One study included non-pregnancy-related cases, and one study included both pregnancy-related cases and other patients with positive results for aPL antibodies. The remaining studies concerned women with aPL antibodies and a history of pregnancy failure. Four studies compared anticoagulant with or without acetylsalicylic acid (ASA) versus ASA only and observed no clear difference in thrombosis risk (risk ratio (RR) 0.98, 95% confidence interval (CI) 0.25 to 3.77; 4 studies; 493 participants; low-quality evidence). No major bleeding was reported, but minor bleeding risk (nasal bleeding, menorrhagia) was higher in the anticoagulant with ASA group as compared with ASA alone in one study (RR 22.45, 95% CI 1.34 to 374.81; 1 study; 164 participants; low-quality evidence). In one study ASA was compared with placebo, and there were no clear differences in thrombosis (RR 5.21, 95% CI 0.63 to 42.97; 1 study; 98 participants; low-quality evidence) or minor bleeding risk between the groups (RR 3.13, 95% CI 0.34 to 29.01; 1 study; 98 participants; low-quality evidence), and no major bleeding was observed. Two studies compared ASA with low molecular weight heparin (LMWH) versus placebo or intravenous immunoglobulin (IVIG), and no thrombotic events were observed in any of the groups. Moreover, there were no clear differences in the risk of bleeding requiring transfusion (RR 9.0, 95% CI 0.49 to 164.76; 1 study; 180 participants; moderate-quality evidence) or postpartum bleeding (RR 1.30, 95% CI 0.60 to 2.81; 1 study; 180 participants; moderate-quality evidence) between the groups. Two studies compared ASA with high-dose LMWH versus ASA with low-dose LMWF or unfractionated heparin (UFH); no thrombotic events or major bleeding was reported. Mortality and quality of life data were not reported for any of the comparisons. Authors' conclusions There is insufficient evidence to demonstrate benefit or harm of using anticoagulants with or without ASA versus ASA alone in people with aPL antibodies and a history of recurrent pregnancy loss and with no such history; ASA versus placebo in people with aPL antibodies; and ASA with LMWH versus placebo or IVIG, and ASA with high-dose LMWH versus ASA with low-dose LMWH or UFH, in women with aPL antibodies and a history of recurrent pregnancy loss, for the primary prevention of thrombotic events. In a mixed population of people with a history of previous pregnancy loss and without such a history treated with anticoagulant combined with ASA, the incidence of minor bleeding (nasal bleeding, menorrhagia) was increased when compared with ASA alone. Studies that are adequately powered and that focus mainly on thrombotic events are needed to draw any firm conclusions on the primary prevention of thrombotic events in people with antiphospholipid antibodies.

Wstęp: Trening mięśni oddechowych (IMT) należy do niefarmakologicznych, nieinwazyjnych metod terapeutycznych, które mogą prowadzić do poprawy jakości życia pacjentów z chorobami układu oddechowego. Skuteczność IMT może zależeć od rodzaju urządzenia użytego do treningu oraz sposobu prowadzenia programu treningowego. Cele: Celem przeglądu było przedstawienie różnych technik i protokołów IMT stosowanych u pacjentów z obturacyjnymi chorobami płuc. Metody: W celu zidentyfikowania publikacji z ostatnich 5 lat potencjalnie kwalifikujących się do analizy przeszukano elektroniczne bazy MEDLINE i EMBASE. Szczegółowo przeanalizowano i opisano protokoły IMT stosowane w różnych pracach badawczych. Wyniki: W efekcie wyszukiwania w bazie danych zidentyfikowano 333 rekordy, z których 22 zostały włączone do ostatecznej analizy. Wszystkie finalnie włączone do przeglądu badania zrealizowano u pacjentów z przewlekłą obturacyjną chorobą płuc (POChP). Protokoły IMT stosowane w badaniach różniły się rodzajem stosowanego urządzenia, czasem trwania programu treningowego, liczbą i czasem trwania sesji treningowych, początkowym obciążeniem oraz szybkością zmiany obciążenia podczas treningu. Wnioski: IMT jest stosowany głównie w badaniach nad pacjentami z POChP, a nie z astmą. Nie istnieje jeden zatwierdzony program treningowy dla IMT. Najczęściej stosowanym rodzajem IMT jest trening z obciążeniem progowym. Najbardziej rozpowszechnionymi urządzeniami do IMT są POWERbreath i Threshold IMT. Protokoły IMT wykorzystywane w badaniach naukowych są bardzo zróżnicowane. Background: Inspiratory muscle training (IMT) is a non-pharmacological, non-invasive therapeutic method that can improve the quality of life in patients with obstructive lung diseases. The effectiveness of IMT may depends on the type of the device used in the training and the parameters of the training programme. Objectives: The aim of the review was to present different techniques and protocols of IMT used in patients with obstructive lung diseases. Methods: The MEDLINE and EMBASE were searched to identify the potentially eligible publications from the previous 5 years. The various protocols of IMT used in different studies were analyzed and described in detail. Results: A database search identified 333 records, of which 22 were included into the final analysis. All of the finally analyzed studies were conducted in patients with chronic obstructive pulmonary disease (COPD). The protocols of IMT used in the studies differed in the type of the device used, the duration of the training program, the number and the duration of training sessions, the initial load, and the rate at which the load was changed during the training. Conclusions: IMT is used mainly in studies on patients with COPD and not with asthma. There is no one approved training programme for IMT. The most predominant type of IMT is a training with threshold loading. The most frequently used devices for IMT are POWERbreath and Threshold IMT. The protocols of IMT used in the studies are very diverse.

Background: Good asthma control is considered as the main goal of asthma treatment. ACT is one of the simpliest and most widespread tools developed to assess asthma control. Aim: To analyze clinical factors influencing asthma control assessed by ACT. Methods: Asthma control was assessed using ACT among 104 stable asthmatics. Detailed clinical data was obtained by designed questionnaire. Spirometry was also evaluated. Results: Patients with uncontrolled asthma (ACT score Conclusions: Uncontrolled asthma according to ACT, is associated with more severe disease and increased incidence of asthma exacerbations during the last 12 months. Despite ACT assesses control of asthma in the last 4 weeks, it seems to be a useful screening tool in detection of patients who are prone to more frequent asthma exacerbations. Asthmatics with higher BMI, GERD or depression require profound evaluation as they are at risk of uncontrolled asthma.

Amputacja prowadząca do utraty części ciała wiąże się nie tylko ze znacznymi kosztami ekonomicznymi, ale i poważnymi konsekwencjami natury medycznej i społeczno-psychologicznej. Jest ostatecznym środkiem mającym na celu ochronę życia lub poprawę jego jakości. Do najtrudniejszych wyzwań, z jakimi przychodzi mierzyć się osobom po amputacji należy zaliczyć zaakceptowanie zmian we własnej fizjonomii oraz wynikające z nich, ograniczenia życiowe. Pacjent po amputacji ma przed sobą niezwykle trudny okres adaptacyjny, w trakcie którego powinien dążyć do maksymalnego stopnia samodzielności. Niestety duża ich grupa zmaga się także z różnego rodzaju doznaniami i dolegliwościami bólowymi umiejscowionymi w obrębie utraconej kończyny - tak zwanymi wrażeniami fantomowymi. Jest to szczególna grupa odczuć o zróżnicowanym charakterze "umiejscowionych" w obrębie utraconej kończyny. Występowanie zespołu kończyny fantomowej u pacjentów po amputacjach jest niezwykle częste. Problem ten dotyka od 45% do nawet 98% z nich po amputacji jednej lub obu kończyn górnych i dolnych. Głównym celem artykułu było opisanie wrażeń fantomowych, obserwowanych u chorych po amputacji kończyn w świetle aktualnej literatury. Przedstawiono definicję wrażeń fantomowych i ich rodzaje, rys historyczny, hipotetyczne patomechanizmy, czynniki wpływające na częstość i intensywność wrażeń fantomowych oraz dostępne sposoby leczenia. Praca powstała w oparciu o liczne źródła tekstowe i doświadczenia własne. Amputation leading to the loss of a body part is associated not only with significant economic costs, but also serious consequences of medical and socio-psychological nature. It is the ultimate means to save a life or improve its quality. The most difficult challenges faced by amputees include accepting changes regarding their own physiognomy and the resulting life restrictions. The patient subjected to amputation is faced with an extremely difficult adaptation process, during which s/he should strive for a maximum degree of independence. Unfortunately, a large group of patients also struggles with various types of sensations and pain located within the lost limb - i.e., so-called phantom phenomena. This is a special group of phenomena of diverse nature, "located" within the lost limb. The occurrence of phantom limb syndrome in amputee patients is extremely common. This problem affects from 45% to even 98% of patients after amputation of one or both upper and lower limbs. The main purpose of this article is to describe phantom phenomena observed in patients after limb amputation in light of current literature. The definition, historical outline, types of phantom phenomena are presented, as well as hypothetical pathomechanisms, factors influencing the frequency and intensity of phantom phenomena and available treatment methods. The work was based on numerous text sources and the author’s own experience.

Introduction: Deep brain stimulation of the globus pallidus internus (GPi-DBS) can be effective in patients with dyskinetic cerebral palsy (CP), but outcome in terms of dystonia severity is often less pronounced and more variable compared to patients with inherited monogenic dystonia. A few published case series encompassing retrospective data have shown that GPi-DBS is associated with favorable quality of life outcomes, even in patients without changes in the BFMDRS, suggesting that the sole use of clinical rating scales may not reflect the full effects of DBS, especially not in patients with acquired forms of dystonia such as dyskinetic CP. However, there is no prospective data on DBS effects in children. We hypothesize an improvement in quality of life by GPi-DBS. Therefore, the mean change in the CPCHILD questionnaire from baseline to 12 months is chosen as the primary outcome parameter. Secondary outcome parameters encompass dystonia severity, motor function, speech, mood, cognition, pain, and quality of life of the carers before and up to 36 months after implantation. Methods: This is a prospective single-arm study to investigate the effects of GPi-DBS in young patients with dyskinetic CP. 20 patients aged 7-18 years will be recruited in a multicenter setting. 12 months after lead implantation patients are randomized by a double-blind cross-over into two groups: One group starts with ongoing stimulation, in the other group stimulation is turned off. After 24 h they switch stimulation settings. Dystonia severity will be assessed at the end of each phase. We hypothesize an improvement in quality of life by GPi-DBS. Therefore, the mean change in the CPCHILD questionnaire from baseline to 12 months is chosen as the primary outcome parameter. Secondary outcome parameters encompass dystonia severity, motor function, speech, mood, cognition, pain, and quality of life of the carers before and up to 36 months after implantation. Discussion: This is the first prospective trial investigating the effects of GPi-DBS on motor and non-motor outcome in a cohort of exclusively pediatric patients in a multicenter setting. Furthermore, long-term data on effects and side effects of GPi-DBS in young patients with dyskinetic cerebral palsy will be generated.

Background: Deep brain stimulation (DBS) is an established therapy for movement disorders. It is currently under investigation in neuropsychiatric disorders. Neurophobia is a common phenomenon that might have a negative impact in medical education. Little is known about medical students' knowledge about DBS when they enter university and what they learn about it during their medical formation. Methods: A 10-item questionnaire was designed. Questions addressed indications for DBS, costs of DBS, complications, the percentage of Parkinson disease (PD) patients who might profit from DBS, etc. Students at Hannover Medical School were asked to complete the questionnaire in the preclinical study period and in the last year of the study. Results: Comparing the “early group” (204 students) and the “advanced group” (162 students), there was a significant gain of knowledge. More common disorders such as PD and tremor were known to be indications for DBS. Knowledge about the impact of DBS on specific symptoms in PD and about DBS targets was limited in both groups. Conclusions: DBS is partly known among medical students in the preclinical phase with a gain of knowledge during further study. Future studies on this topic addressing general practitioners as neurologists are needed to better understand why knowledge on DBS is still limited.

BackgroundA deep infection of the surgical site is reported in 0.7% of all cases of total hip arthroplasty (THA). This often leads to revision surgery that is invasive, painful and costly. A range of strategies is employed in NHS hospitals to reduce risk, yet no economic analysis has been undertaken to compare the value for money of competing prevention strategies.ObjectivesTo compare the costs and health benefits of strategies that reduce the risk of deep infection following THA in NHS hospitals. To make recommendations to decision-makers about the cost-effectiveness of the alternatives.DesignThe study comprised a systematic review and cost-effectiveness decision analysis.Setting77,321 patients who had a primary hip arthroplasty in NHS hospitals in 2012.InterventionsNine different treatment strategies including antibiotic prophylaxis, antibiotic-impregnated cement and ventilation systems used in the operating theatre.Main outcome measuresChange in the number of deep infections, change in the total costs and change in the total health benefits in quality-adjusted life-years (QALYs).Data sourcesLiterature searches using MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature and the Cochrane Central Register of Controlled Trials were undertaken to cover the period 1966–2012 to identify infection prevention strategies. Relevant journals, conference proceedings and bibliographies of retrieved papers were hand-searched. Orthopaedic surgeons and infection prevention experts were also consulted.Review methodsEnglish-language papers only. The selection of evidence was by two independent reviewers. Studies were included if they were interventions that reported THA-related deep surgical site infection (SSI) as an outcome. Mixed-treatment comparisons were made to produce estimates of the relative effects of competing infection control strategies.ResultsTwelve studies, six randomised controlled trials and six observational studies, involving 123,788 total hip replacements (THRs) and nine infection control strategies, were identified. The quality of the evidence was judged against four categories developed by the National Institute for Health and Care ExcellenceMethods for Development of NICE Public Health Guidance(http://publications.nice.org.uk/methods-for-the-development-of-nice-public-health-guidance-third-edition-pmg4), accessed March 2012. All evidence was found to fit the two highest categories of 1 and 2. Nine competing infection control interventions [treatments (Ts) 1–9] were used in a cohort simulation model of 77,321 patients who had a primary THR in 2012. Predictions were made for cases of deep infection and total costs, and QALY outcomes. Compared with a baseline of T1 (no systemic antibiotics, plain cement and conventional ventilation) all other treatment strategies reduced risk. T6 was the most effective (systemic antibiotics, antibiotic-impregnated cement and conventional ventilation) and prevented a further 1481 cases of deep infection, and led to the largest annual cost savings and the greatest gains to QALYs. The additional uses of laminar airflow and body exhaust suits indicate higher costs and worse health outcomes.ConclusionsT6 is an optimal strategy for reducing the risk of SSI following THA. The other strategies that are commonly used among NHS hospitals lead to higher cost and worse QALY outcomes. Policy-makers, therefore, have an opportunity to save resources and improve health outcomes. The effects of laminar air flow and body exhaust suits might be further studied if policy-makers are to consider disinvesting in these technologies.LimitationsA wide range of evidence sources was synthesised and there is large uncertainty in the conclusions.FundingThe National Institute for Health Research Health Technology Assessment programme and the Queensland Health Quality Improvement and Enhancement Programme (grant number 2008001769).

Please cite this paper as: Wloch C, Wilson J, Lamagni T, Harrington P, Charlett A, Sheridan E. Risk factors for surgical site infection following caesarean section in England: results from a multicentre cohort study. BJOG 2012;119:1324–1333. Objective To assess the frequency and risk factors for surgical site infection following caesarean section. Design Prospective multicentre cohort study. Setting Fourteen NHS hospitals in England, April to September 2009. Population Women who underwent caesarean section at participating hospitals during designated study periods. Methods Infections that met standard case definitions were identified through active follow up by healthcare staff during the hospital stay, on return to hospital, during midwife home visits and through self-completed patient questionnaires. Main outcome measure Surgical site infection within 30 days of operation. Results Altogether, 9.6% (394/4107) of women in the study developed a postsurgical infection following caesarean section with 0.6% (23/4107) readmitted for treatment of the infection. Being overweight (body mass index [BMI] 25–30 kg/m2 odds ratio [OR] 1.6, 95% confidence interval [95% CI] 1.2–2.2) or obese (BMI 30–35 kg/m2 OR 2.4, 95% CI 1.7–3.4; BMI > 35 kg/m2 OR 3.7, 95% CI 2.6–5.2) were major independent risk factors for infection (compared with BMI 18.5–25 kg/m2). There was a suggestion that younger women, and operations performed by associate specialist and staff grade surgeons had a greater odds of developing surgical site infection with OR 1.9, 95% CI 1.1–3.4 (

Purpose To assess the adequacy of dose delivery to the clinical target volume (CTV) using external beam (EB) accelerated partial breast irradiation (APBI). Methods and Materials Sixteen patients treated with EB APBI underwent cone beam CT (CBCT) before each fraction and daily helical CT (HCT) scans to determine setup errors and calculate the dose per fraction. For 12 patients, an in-house image-intensity-based deformable registration program was used to register the HCTs to the planning CT and generate the cumulative dose. Treatment was 38.5 Gy in 10 fractions. EB APBI constraints from the National Surgical Adjuvant Breast and Bowel Project B39/Radiation Therapy Oncology Group 0413 Phase III protocol were used. Results The mean setup error per CBCT registration was 9 ± 5 mm. Dose–volume histogram analysis showed only one patient (8%) with a decrease in the CTV V90 (8% underdosage). All other patients demonstrated adequate target coverage. PTV_EVAL V90 was on average 3% (range, 0%–16%) less than planned. For the ipsilateral breast, four patients had an increase in V50 (≤1% increase) and three patients had an increase in V100 (≤9% increase). Only one patient showed an increase >5%. Four patients had an increase in ipsilateral lung V30 (maximum 3%), and one had an increase in heart V5 (1%). Four patients had an increase in MaxDose (maximum 89 cGy). Conclusions The current CTV-to-PTV margin of 10 mm appears sufficient for ∼92% of patients treated with EB APBI. Although expansion of the population PTV margin to 14 mm would provide ∼97% confidence level for CTV coverage, online image guidance should be considered.

Multiplicity and variety of chest physical therapy (CPT) methods for increasing bronchial clearance in patients with chronic obstructive pulmonary disease (COPD) require an assessment of validity and reliability of the available clinical evidence. The aim of the review was to evaluate publications on CPT in COPD patients and to establish the basis (objective criteria) on which given methods and techniques are recommended or refuted. Systematic reviews, narrative reviews, and clinical practice guidelines, published in English between January 1, 2000 and July 1, 2010, were identified from the PubMed/MEDLINE and Cochrane (DARE, CRD, The Cochrane Airways Review Group Register) databases. The PEDro and SIGN scales were used to assess the quality and grade of recommendations for selected papers. Generally, the papers that we identified were based on small studies, limited to short-term outcomes, mostly using crossover designs, and rarely including sham therapy. Recommendations from clinical guidelines were mainly grade C or D. Health-related quality-of-life analyses, including working and exercise capacity, are lacking. The evidence from the studies in patients with cystic fibrosis cannot be directly extrapolated to COPD subjects. Despite the lack of convincing evidence, clinical practice supports the value of CPT in COPD. However, when making a clinical decision, potential side effects should be considered.

Background: Oxidative stress plays an important role in vascular pathology and contributes to the pathophysiology of primary intracerebral hemorrhage (PICH). Glutathione peroxidase 1 (GPX1) is a key enzyme of the antioxidant system. Here, we investigated whether a functional C593T polymorphism of GPX1 gene is associated with PICH in a Polish population. Methods: Genotyping was performed in 192 PICH patients and 197 unrelated controls matched for age and sex. All were of Caucasian origin. The C593T GPX1 polymorphism was investigated using the polymerase chain reaction/restriction fragment length polymorphism method. Results: Multivariable logistic regression analysis revealed a significant association between genotypes containing the T allele and the entire PICH group (OR = 1.53; 95% CI = 1.02–2.29) and lobar PICH (OR = 2.36; 95% CI = 1.31–4.26) but not nonlobar PICH (OR = 1.19; 95% CI = 0.75–1.89). Conclusions: We found a positive association between the studied GPX1 polymorphism and lobar PICH in a Polish population.

The angiotensin-converting enzyme (ACE) catalyzes the formation of angiotensin II and the breakdown of bradykinin into inactive products. The insertion/deletion (I/D) polymorphism affects the activity of the enzyme, with the DD genotype being responsible for the highest activity of the enzyme. Meta-analysis of 11 studies including white persons showed that the DD genotype was a risk factor for ischemic stroke. No such correlation was found in an Asian population. Studies on different etiologies or intermediate phenotypes of ischemic stroke did not bring univocal results. There are still no convincing data on whether the I/D polymorphism of the ACE gene is a risk factor for spontaneous intracerebral hemorrhage and intracranial aneurysms, ruptured or unruptured. Several pharmacogenetic studies analyzed the influence of the ACE I/D polymorphism on the response to acute stroke therapy (thrombolysis) or prevention strategies (lifestyle modification and treatment of vascular risk factors). Presently, however, there is no consensus on whether the efficacy of these therapies is affected by the ACE gene I/D polymorphism.

Yoga, pilates and fitness activities involve poses or exercises that require a specific response from the body (Wang et al. 2013). In order to make the exercise easier or more pleasant, the mat has...

Introduction: The technique of laparoscopic or retroperitoneoscopic donor nephrectomy has been increasingly propagated in recent years. The central advantage is supposed to be a reduction of perioperative discomfort. However, there have not been many reports describing the subjective feeling associated with an open donor nephrectomy, particularly with respect to the pain level in the perioperative and long-term course. This retrospective study examines the perioperative pain and morbidity and long-term outcome of living kidney donors from 35 yr of experience at the University Hospital Benjamin Franklin of the Free University of Berlin. Methods: A total of 102 living kidney donors were asked to fill out a questionnaire. Five epidemiological questions were posed and the rest dealt mainly with lasting subjective and objective surgical impairments. There were also questions relating to the perioperative pain level (VAS/NAS-Score). In addition, basic information was obtained regarding the donor's current health status (physical examination, serum creatinine; sometimes also ultrasound, protein IU, blood pressure), and/or examinations were performed. Results: The mean age at the time of donation was 45.5 and 55% were women. Donor nephrectomies were left-sided in 78 cases and right-sided in 24. There was a total complication rate of 53%, but serious complications only occurred in two cases (1.9%). A total of 53 donors could be reached. Although 41.5% felt they had a lasting impairment, somatic sequelae like respiratory, abdominal or scar problems were rare, affecting a maximum of only four patients in each case. Fifteen patients reported neurological problems such as sensory disturbances. The mean serum creatinine was 89.9 μmol/L in female and 114.2 μmol/L in male donors. Microalbuminuria was found in 22.6% of the donors, hypertension in 35.8%. Persistent pain was reported by 20.7%, its occurrence being permanent in two of the donors and very frequent in one. All the others rarely have pain. The median perioperative VAS/NAS score was 8 on the first day after surgery, 5 after 1 wk and 1 after 1 month. The analgesia was rated as good or very good by 71%. Everyday life was managed as well as before surgery after 2–4 wk by the highest percentage (42%) of patients, but working capacity was only regained after 1–3 months by a comparable percentage (44%). Forty-six percent had a very good and 33% a good feeling after the kidney donation. The relationship to the recipient had intensified in most cases. Ninety-one percent would again decide in favor of a donation. Conclusion: Donor nephrectomy in an open technique is a safe and reliable procedure with low morbidity. After a median post-operative period of 7 yr, however, 42% of the donors still report general impairment due to the intervention, although concrete somatic problems were only detected in a few cases. Nearly all these patients underwent surgery in a full flank position. Wound-healing impairments were also significantly more frequent with this surgical technique. This positioning should thus be avoided. The post-operative pain level was relatively high, but a marked improvement was achieved in the course of the observation period by optimizing analgesic management.

Background. Recommendations for identifying age-related muscle dysfunction have recently been published. We aimed to compare definitions for clinically relevant weakness and low lean mass proposed by the Foundation for the National Institutes of Health (FNIH) Sarcopenia project with the definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP). Methods. A total of 1566 men and women from a British birth cohort had measures of appendicular lean mass, grip strength and timed up, and go speed at ages 60–64. Prevalence of low lean mass, weakness and slowness, identified using the FNIH and EWGSOP recommendations were estimated and compared: using kappa statistics and; by testing cross-sectional associations of both definitions of low lean mass and weakness with slowness and self-reported difficulties walking. Results. The combined prevalence of low lean mass and weakness ranged from 1.1% in men using FNIH criteria to 6.4% in women using EWGSOP criteria. There was limited overlap between the groups identified using the different criteria, driven by limited agreement between the two definitions of low lean mass. Using FNIH criteria, both low lean mass and weakness were associated with higher odds of slowness and difficulties walking; whereas low lean mass classified using EWGSOP criteria was not associated with these markers of mobility impairment. Conclusions. At relatively young ages, signs of skeletal muscle function deficit with potential clinical relevance are already identifiable in the general population. This suggests that implementation of strategies to prevent mobility limitations, related to age-related muscle dysfunction, may need to start at least as early as midlife.

Previous cross-sectional surveys in different European countries within the EUROASPIRE programme demonstrated a high prevalence of modifiable risk factors, unhealthy lifestyles and inadequate drug treatment in coronary heart disease patients. Comparable data for ischaemic stroke patients is lacking.A stroke-specific study module was added to the EUROASPIRE III core survey. This cross-sectional multicentre survey included consecutive patients with first-ever ischaemic stroke from four European countries. Data were obtained from medical records, patient interviews and patient examinations within 6-36 months after the stroke event. Control of modifiable risk factors after stroke was evaluated against contemporary European guidelines.A total of 881 patients was recruited. Median age was 66 years, 37.5% were female; average time from the stroke event to interview was 550 days. At the time of the interview, 17.6% of stroke patients smoked cigarettes, 35.5% had a body mass index ≥30 kg/m(2), 62.4% showed elevated blood pressure and 75.7% exhibited elevated LDL cholesterol levels. Antiplatelet drugs or oral anticoagulants were used by 87.2%, antihypertensive medication by 84.4% and statins by 56.8% of stroke patients. Among patients using antihypertensive drugs and lipid-lowering medication at the time of the interview, 34.3% and 34.4%, respectively, achieved target blood pressure and total cholesterol values according to current European guidelines.The EUROASPIRE III stroke-specific module shows that secondary prevention and risk factor control in patients after ischaemic stroke need to be improved in four European centres at the time of the study since about half of patients are not achieving risk factor targets defined in European guidelines.

Summary Objective To determine the effectiveness of music therapy in asthma. Methods Searches for experimental and observational studies published between 01.01.92 and 31.12.13 were conducted through electronic databases: Medline/PubMed, Embase, SportDiscus, Cochrane Library, Teacher Reference Centre, Web of Science, Academic Search Complete, PsycINFO, PsycARTICLES, PEDro and Scopus. The selection criteria included any method of music therapy applied to patients with asthma, with respect to asthma symptoms and lung function. Two reviewers screened the records independently. The risk of bias was assessed using the Cochrane Collaboration's tool. Strength of recommendation was graded according to GRADE recommendation. Results The literature search identified 867 citations, from which 8 (three RCTs and five nRCTs) low and high risk of bias studies were included in the review. All RCTs used music listening as a form of complementary treatment. One RCT of the low risk of bias indicated positive effects on lung function in mild asthma. In two others, despite the decrease in asthma symptoms, music was not more effective than the control condition. In two nRCTs a decrease in asthma symptoms was reported as an effect of playing a brass or wind instrument; in two nRCTs the same effect was observed after music assisted vocal breathing exercises and singing. Mood improvement, decrease of depression and anxiety were also observed. Conclusion The paucity, heterogeneity, and significant methodological limitations of available studies allow for only a weak recommendation for music therapy in asthma. This study highlights the need for further research of mixed methodology.

Phantom phenomena are subject of various, often inconsistent, descriptions, and new concepts and treatment approaches emerge. The aim of the study is to describe contemporary terminology and developments in the field, and to share personal experience. A review of English and French language literature, published prior to 27th February, 2012, extracted from PubMed/MEDLINE, Google.fr, GoogleScholar databases, and by hand searching of selected full text papers and textbooks with correspondence to personal clinical experience was performed. The terminology and classification of phantom phenomena sensations, relations between intensity and character of phantom pain to the etiology and level of amputations, as well as the influence of presence and intensity of pre-operative limb pain and post-operative stump pain on phantom phenomena are described. The benefits of mirror therapy and early introduction of prosthesis and applying functional prosthesis are also presented, with a glance at other conservative and surgical treatment approaches.

Summary Background The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes. Methods To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16 851 cases with state-of-the-art phenotyping data and 32 473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20 941 cases and 364 736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis. Findings We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13–1·30, p=4·50 × 10 −8 ; joint OR 1·19, 1·12–1·26, p=1·30 × 10 −9 ). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29–1·49, p=3·26 × 10 −19 ; joint OR 1·37, 1·30–1·45, p=2·79 × 10 −32 ) and ZFHX3 (first stage OR 1·19, 1·11–1·27, p=2·93 × 10 −7 ; joint OR 1·17, 1·11–1·23, p=2·29 × 10 −10 ) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18–1·42, p=3·50 × 10 −8 ; joint OR 1·24, 1·15–1·33, p=4·52 × 10 −9 ) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2 , which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12–1·28, p=6·82 × 10 −8 ; joint OR 1·17, 1·11–1·23, p=2·92 × 10 −9 ). Other loci associated with stroke in previous studies, including NINJ2 , were not confirmed. Interpretation Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke. Funding US National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 × 10 -11; odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes. © 2012 Nature America, Inc. All rights reserved.

Background Interventions to increase hand washing in schools have been advocated as a means to reduce the transmission of pandemic influenza and other infections. However, the feasibility and acceptability of effective school-based hygiene interventions is not clear. Methods A pilot study in four primary schools in East London was conducted to establish the current need for enhanced hand hygiene interventions, identify barriers to their implementation and to test their acceptability and feasibility. The pilot study included key informant interviews with teachers and school nurses, interviews, group discussions and essay questions with the children, and testing of organised classroom hand hygiene activities. Results In all schools, basic issues of personal hygiene were taught especially in the younger age groups. However, we identified many barriers to implementing intensive hygiene interventions, in particular time constraints and competing health issues. Teachers' motivation to teach hygiene and enforce hygienic behaviour was primarily educational rather than immediate infection control. Children of all age groups had good knowledge of hygiene practices and germ transmission. Conclusion The pilot study showed that intensive hand hygiene interventions are feasible and acceptable but only temporarily during a period of a particular health threat such as an influenza pandemic, and only if rinse-free hand sanitisers are used. However, in many settings there may be logistical issues in providing all schools with an adequate supply. In the absence of evidence on effectiveness, the scope for enhanced hygiene interventions in schools in high income countries aiming at infection control appears to be limited in the absence of a severe public health threat.

Background – Plasminogen activator inhibitor type 1 (PAI-1) is the major inhibitor of fibrinolysis. It was reported that PAI-1 gene polymorphisms affected PAI-1 level and might therefore influence the risk of vascular diseases, including stroke. We studied the association of three common polymorphisms in PAI-1 gene (−844 G/A, −675 4G/5G, and HindIII G/C) with the odds of different causes of ischemic stroke. Methods – We studied 390 patients with ischemic stroke due to large vessel disease (n = 117), small vessel disease (n = 121), and cardioembolism (n = 152) as well as 291 controls. The etiology of ischemic stroke was established using TOAST criteria. PAI-1 polymorphisms were genotyped with restriction fragment length polymorphism and single strand conformation polymorphism method. Results – A-G-4G haplotype of PAI-1 gene was found more frequently in stroke patients with small vessel disease than in control subjects (44.9% vs 35.7%; P = 0.02). No association was found between investigated genotype or allele frequencies and distinct causes of ischemic stroke. Conclusions – Our results demonstrate that A-G-4G PAI-1 gene haplotype is associated with increased risk of small vessel disease stroke, but this study does not support an association of −844 G/A, −675 4G/5G, and HindIII G/C PAI-1 gene polymorphisms with particular etiology of ischemic stroke.

Platelet glycoproteins are involved in pathophysiology of cerebrovascular diseases. The aim of this study was to investigate the association between the GpIIIa gene A1/A2 polymorphism and a risk of aneurysmal subarachnoid haemorrhage (SAH) in a Polish population. In a case-control study we genotyped 288 Caucasian patients with aneurysmal SAH and 457 age-, gender- and race-matched controls. The GpIIIa A1/A2 polymorphism was genotyped with RFLP technique. No difference was found in the distribution of the polymorphism between the cases and controls (cases: A1A1—201 (69.8%), A1A2—83 (28.8%) and A2A2—4 (1.4%) vs. controls: A1A1—323 (70.7%); A1A2—128 (28.0%); A2A2—6 (1.3%), P > 0.05. In a multivariate analysis female gender (OR = 1.950; 95%CI: 1.308–2.907), hypertension (OR = 4.774; 95%CI: 3.048–7.478) and smoking (OR = 2.034; 95%CI: 1.366–3.030), but not GpIIIa A1/A2 polymorphism, were independent risk factors for aneurysmal SAH. The GpIIIa A1/A2 polymorphism is not a risk factor of aneurysmal SAH in a Polish population.

We have recently demonstrated elevated plasma levels of an endogenous nitric oxide synthase inhibitor, asymmetric dimethyl-l-arginine (ADMA), and its association with carotid atherosclerosis in rheumatoid arthritis (RA). Both an elevated risk of myocardial infarction and increased levels of anticitrullinated protein antibodies (ACPAs), specific for RA, had been shown to precede the onset of clinical RA symptoms. Therefore, our aim was to verify the hypothesis that ADMA accumulation might accompany raised ACPAs titers in RA of short duration (≤3 years). Twenty patients (16 women, 4 men; mean age, 45 ± 12 years; mean disease duration, 2.3 ± 0.5 years) with active RA despite chronic disease-modifying antirheumatic medication, free of cardiovascular disease or atherosclerotic risk factors, were studied. Plasma levels of ADMA and its stereoisomer, symmetric dimethyl-l-arginine (SDMA), were assayed by liquid chromatography/tandem mass spectrometry. The ACPAs were measured by a second-generation enzyme-linked immunosorbent assay. In addition to routine biochemical assays, plasma concentrations of tumor necrosis factor α , monocyte chemoattractant protein–1, and vascular cell adhesion molecule–1 soluble form were analyzed with respective enzyme-linked immunosorbent assays. A significant positive correlation between levels of ACPAs and ADMA ( r = .60, P = .005), but not SDMA ( r = −.02, P = .9), was found. Neither ADMA nor SDMA was correlated to any of the clinical or biochemical parameters reflecting disease activity and inflammatory activation. Thus, excessive ADMA accumulation accompanies elevated ACPAs levels in patients with RA of short duration free of cardiovascular disease or risk factors.

Objective Similarities between rheumatoid arthritis (RA) and atherosclerosis include endothelial dysfunction (an antecedent of plaque formation) and depletion of circulating bone marrow–derived endothelial progenitor cells. This study was undertaken to test the hypothesis that endothelial progenitor cell depletion and subclinical atherosclerosis in RA may be related to accumulation of an endogenous inhibitor of nitric oxide (NO) synthesis, asymmetric dimethyl-L-arginine. Methods We studied 30 patients with active RA and 20 age- and sex-matched healthy controls. Exclusion criteria were clinically evident atherosclerosis, traditional risk factors, hyperhomocysteinemia, and renal dysfunction. The blood endothelial progenitor cell count was assayed by flow cytometry and expressed as a percentage of lymphocytes. Plasma L-arginine, asymmetric dimethyl-L-arginine, and symmetric dimethyl-L-arginine were measured with liquid chromatography–mass spectrometry. Mean carotid intima-media thickness (IMT) was assessed by B-mode ultrasound. Results In RA patients, we found elevated levels of asymmetric dimethyl-L-arginine (mean ± SD 0.49 ± 0.07 μmoles/liter versus 0.40 ± 0.07 μmoles/liter in controls; P < 0.001), a depressed endothelial progenitor cell count (0.039 ± 0.025% versus 0.063 ± 0.035%; P < 0.05), and increased IMT (0.65 ± 0.13 mm versus 0.55 ± 0.10 mm; P < 0.01), with no differences in levels of L-arginine or symmetric dimethyl-L-arginine. The endothelial progenitor cell count was inversely correlated with the level of asymmetric dimethyl-L-arginine. IMT was positively related to the ratio of asymmetric dimethyl-L-arginine to L-arginine and negatively related to the endothelial progenitor cell count, in univariate and multivariate analyses. Conclusion Plasma asymmetric dimethyl-L-arginine levels are elevated in RA patients free of cardiovascular disease or risk factors. Asymmetric dimethyl-L-arginine accumulation may contribute to endothelial progenitor cell depletion via depressed NO-dependent endothelial progenitor cell mobilization and/or survival, with consequent impairment of endothelial progenitor cell–mediated endothelial repair, which can promote atherogenesis in RA.

Objectives – Data concerning an association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and ischemic stroke (IS) remain inconsistent. Results of some studies suggest that DD genotype may be a risk factor for small vessel disease (SVD) stroke. Here, we investigated whether this polymorphism is associated with IS of different etiologies in a Polish population. Subjects and methods – Ischemic stroke etiology was established according to the TOAST criteria. We studied 92 stroke patients with large vessel disease and their 184 matched controls; 96 stroke patients with SVD and 192 controls; 180 patients with cardioembolic stroke (CE) and 180 controls. ACE I/D polymorphism was determined using the polymerase chain reaction method. Results – The distribution of ACE genotypes and alleles was essentially the same in all analyzed IS subtypes and their matched controls. Conclusions – We failed to find an association between ACE polymorphism and etiological subtypes of IS in a Polish population.

Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.

Updates to the British Thoracic Society (BTS) asthma guidelines have been recently highlighted by Turner and colleagues.1 2 To our concern, the content on physiotherapy interventions has not been revised or updated since the 2006 version. We reviewed the contents of the new BTS guidelines relevant for physiotherapists. The timescale for literature search indicates that the relevant section was last updated in February 2006, with coverage in Medline …