Explore the vast range of titles available.

Aspergillus spp. can lead to allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitisation and Aspergillus bronchitis in CF. The relative frequencies of these entities have recently been ascertained in a large UK adult CF cohort. We have used this data to estimate the burden of aspergillosis and ABPA cases in adult CF patients in 30 countries reporting CF. National and international CF registry data was accessed and assessed for completeness and age distribution. Published proportions of ABPA (17.7%), Aspergillus sensitisation (14.6%) and Aspergillus bronchitis (30%) in CF were applied to those >18 years and compared with notified ABPA cases. Of the 76,201 estimated CF patients worldwide (not including India), 37,714 were >18 years. The proportion of adults to children varied from 63% in Norway to 20% in Brazil. ABPA caseload in adults is anticipated to be 6,675 cases of which only 2,221 cases (33%) are currently recorded, indicating substantial underdiagnosis. The ABPA diagnosis rate compared with estimated rates varies by country from 101% (France) to 14.5% (Greece), although genetic variation could account for genuine differences compared with the UK. Aspergillus bronchitis is not currently recognised or recorded in CF registries but there are an anticipated 10,988 adult cases. Aspergillus sensitisation, associated with increased bronchiectasis and reduced FEV1, affects an anticipated 5,506 patients without ABPA or Aspergillus bronchitis. Together ABPA and Aspergillus bronchitis are estimated to affect 17,989 adults, 47.7% of the adult CF population. ABPA also occurs in children and teenagers and 984 cases were documented in registries. Diagnosed ABPA rates by age were available for the ECFS registry, USA, UK, Ireland, Belgium and Netherlands. The rate was <1% under 4 years, and increased throughout childhood and adolescence, with marked variation between countries. Newly published diagnostic criteria and methods should facilitate better recognition of aspergillosis in CF, allowing better CF disease control.

The BMJ’s statistical editors relish a quiet Christmas, so make their wish come true and pay attention to the list of common statistical faux pas presented here by Riley and colleagues

Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up-regulating angiogenesis as observed over multiple time points. This therapeutic approach may have potential application for clinical management of delayed and chronic wounds.

Systemic Lupus Erythematosus (SLE) typically affects females at far greater rates than males; however male SLE patients often have more severe disease than females. The gender disparities have been reported in clinical manifestations and in serological and hematological indices as well. In particular, SLE complicated with nephritis is more frequent in men than women, and several groups identified male gender as a risk factor for progression to renal failure. The specific differences in pathogenesis amongst genders have yet to be conclusively defined, though genetic, hormonal, and immune responses have been analyzed thus far. Further research is warranted to further elucidate these differences and permit the development of gender-tailored treatment regimens.

The influence of skin substitutes upon angiogenesis during wound healing is unclear. To compare the angiogenic response in acute cutaneous human wounds treated with autogenic, allogenic and xenogenic skin substitutes to those left to heal by secondary intention. On day 0, four 5mm full-thickness punch biopsies were harvested from fifty healthy volunteers (sites 1-4). In all cases, site 1 healed by secondary intention (control), site 2 was treated with collagen-GAG scaffold (CG), cadaveric decellularised dermis (DCD) was applied to site 3, whilst excised tissue was re-inserted into site 4 (autograft). Depending on study group allocation, healing tissue from sites 1-4 was excised on day 7, 14, 21 or 28. All specimens were bisected, with half used in histological and immunohistochemical evaluation whilst extracted RNA from the remainder enabled whole genome microarrays and qRT-PCR of highlighted angiogenesis-related genes. All wounds were serially imaged over 6 weeks using laser-doppler imaging and spectrophotometric intracutaneous analysis. Inherent structural differences between skin substitutes influenced the distribution and organisation of capillary networks within regenerating dermis. Haemoglobin flux (p = 0.0035), oxyhaemoglobin concentration (p = 0.0005), and vessel number derived from CD31-based immunohistochemistry (p = 0.046) were significantly greater in DCD wounds at later time points. This correlated with time-matched increases in mRNA expression of membrane-type 6 matrix metalloproteinase (MT6-MMP) (p = 0.021) and prokineticin 2 (PROK2) (p = 0.004). Corroborating evidence from invasive and non-invasive modalities demonstrated that treatment with DCD resulted in increased angiogenesis after wounding. Significantly elevated mRNA expression of pro-angiogenic PROK2 and extracellular matrix protease MT6-MMP seen only in the DCD group may contribute to observed responses.

Introduction COPD is an inflammatory disease with major co-morbidities. It has recently been suggested that depression may be the result of systemic inflammation. We aimed to explore the association between systemic inflammation and symptoms of depression and fatigue in patients with mainly moderate and clinically stable COPD using a range of inflammatory biomarkers, 2 depression and 2 fatigue scales. Method We assessed 120 patients with moderate COPD (FEV 1 % 52, men 62%, age 66). Depression was assessed using the BASDEC and CES-D scales. Fatigue was assessed using the Manchester COPD-fatigue scale (MCFS) and the Borg scale before and after 6MWT. We measured systemic TNF-α, CRP, TNF-α-R1, TNF-α-R2 and IL-6. Results A multivariate linear model of all biomarkers showed that TNF-α only had a positive correlation with BASDEC depression score (p = 0.007). TNF-α remained positively correlated with depression (p = 0.024) after further adjusting for TNF-α-R1, TNF-α-R2, 6MWD, FEV 1 %, and pack-years. Even after adding the MCFS score, body mass and body composition to the model TNF-α was still associated with the BASDEC score (p = 0.044). Furthermore, patients with higher TNF-α level (> 3 pg/ml, n = 7) had higher mean CES-D depression score than the rest of the sample (p = 0.03). Borg fatigue score at baseline were weakly correlated with TNF-α and CRP, and with TNF-α only after 6MWT. Patients with higher TNF-α had more fatigue after 6MWD (p = 0.054). Conclusion This study indicates a possible association between TNF-α and two frequent and major co-morbidities in COPD; i.e., depression and fatigue.

Background It is important to monitor health related quality of life in order to determine the efficacy of interventions and physical functioning of patients with cystic fibrosis in their daily activities. There is no a single-item global quality of life scale for routine clinical practice for adult patients with cystic fibrosis. We assessed the reliability and validity of a single-item global quality of life scale and compared with the Cystic Fibrosis Quality of Life Questionnaire (CF-QOL) for adult patients with cystic fibrosis. Method 121 ( men = 66, women = 55) adult cystic fibrosis patients self-completed the CF-QOL, the Hospital Anxiety Depression Scale, and the single item global quality of life scale at the out patient clinic. 33 (17 women) completed the repeat questionnaires at home within two weeks. Socio-demographic characteristic and lung function data were extracted from the recent medical notes. Results Mean (SD) age was 29.6 (8.9) years and mean (SD) forced expiratory volume in 1 second was 2.20 (0.94) litres. The test-retest reproducibility using the intra-class correlation coefficient (ICC) for the CF-QOL was 0.83, 95% confidence interval 0.68 to 0.91. The single item global quality of life ICC score was 0.78, 95% confidence interval 0.59 to 0.88. Concurrent validity of the single-item global quality of life was examined in relation to all items of the CF-QOL, frequent episodes of readmission, anxiety and depression (all, p < 0.01) were moderately correlated. Conclusion The study provides preliminary evidence that the single-item quality of life scale is acceptable, valid and repeatable for adult patients with cystic fibrosis. It is a promising tool that can be easily incorporated into a routine clinical practice to assess patients' quality of life.

The use of statistical methods in medical research has long been a concern and careful review of these methods is required to ensure that published papers are of sufficient statistical quality. However, there is a shortage of statistical reviewers for medical journals and there is a dearth of training for those with little or no experience. An online workshop on statistical reviewing for medical journals was convened by the Improving Statistical Literacy and Early Career Development streams of the National Institute for Health and Care Research (NIHR) Statistics Group to address this gap. This article summarizes the key learnings from this workshop and provides some practical advice for those potentially interested in undertaking statistical reviews for a medical journal.

Around 25% of women undergoing Axillary Clearance (ANC) develop lymphedema (LE). Intervention with a compression garment is recommended to prevent LE but no randomised evidence exists to support this strategy. Methods A randomised trial tested standard management versus application of graduated compression garments (20‐24 mmHg) to affected arm, for 1 year. Women with node positive breast cancer (n = 1300) undergoing ANC consented to arm volume measurements and those developing a 4–9% relative arm volume increase (RAVI) (subclinical LE) within 9 months post‐surgery were randomised. Primary outcome was proportion of patients developing LE (RAVI > 10%) by 24‐months in each group. Secondary endpoints included Quality of life in each group. Results In total 143 patients were randomised (74 no sleeve: 69 compression sleeve) between October 2010 and November 2015. The lymphoedema rate at 24 months in the ‘no sleeve’ group was at 41%, similar to the ‘sleeve’ group (30%: p = 0.32). Thirtytwo patients randomised to the ‘no sleeve’ group had a sleeve applied within 24 months. Body Mass Index (BMI) at randomisation predicted LE at any time point HR 1.04 (CI 1.01–1.08; p = 0.01). Patients with obesity (BMI > 30) had higher rates of LE in both groups (46%) compared to those with BMI < 30 (24%). No difference between patients was found in either group in changes in QoL. Compression sleeves applied after development of LE improved QoL scores (FACT‐B p = 0.007:TOI p = 0.042). Conclusion Early intervention with External Compression garments does not prevent clinical LE, particularly in women with a high BMI > 30. The use of prophylactic garments in subclinical LE (RAVI < 9%) is unwarranted. A Randomised trial of external arm compression garments after axillary node clearance in women developing early arm swelling failed to find an effect of the intervention in preventing lymphoedema.

Patients with irritable bowel syndrome and constipation (IBS-C) show more abdominal distension than do those with diarrhea. Because constipation is often associated with delayed gastrointestinal transit, this study aimed at establishing whether patients with delayed transit show more distension and bloating than do those with normal transit. Abdominal girth was recorded for 24 h using abdominal inductance plethysmography (AIP) in 30 IBS-C (Rome II criteria) patients (aged 18-68 years; 27 women) and in 30 healthy volunteers (21-58 years of age; 26 women). Within 2 weeks of this recording, orocecal and colonic transits were assessed. Orocecal transit was determined from the increase in breath hydrogen after a standard meal, and colonic transit from the number of radio-opaque markers identified on a plain abdominal X-ray. Bloating severity was assessed hourly during AIP recording using a 0-5 scale. IBS-C patients showed more bloating and distension than did healthy volunteers (P<0.001). They also had prolonged colonic (P<0.001) and orocecal (P=0.05) transits than did healthy volunteers, such that 47 and 17%, respectively, had colonic and orocecal transit times greater than the normal reference range. Those with delayed colonic (P=0.025) and orocecal (P=0.13) transits had greater distension but not bloating (P=0.63 and P=0.48, respectively) compared with those with normal transit. Moreover, distension directly correlated with orocecal (r=0.40; P=0.03) and colonic (r=0.51; P=0.004) transit times and inversely with stool consistency (r=-0.43; P=0.07). IBS-C patients with delayed transit show greater abdominal distension than do those with normal transit. Therefore, drugs that accelerate transit may be expected to alleviate this troublesome problem.