Development and initial validation of the bronchiectasis exacerbation and symptom tool (BEST)

BACKGROUND: Recurrent bronchiectasis exacerbations are related to deterioration of lung function, progression of the disease, impairment of quality of life, and to an increased mortality. Improved detection of exacerbations has been accomplished in chronic obstructive pulmonary disease through the use of patient completed diaries. These tools may enhance exacerbation reporting and identification. The aim of this study was to develop a novel symptom diary for bronchiectasis symptom burden and detection of exacerbations, named the BEST diary. METHODS: Prospective observational study of patients with bronchiectasis conducted at Ninewells Hospital, Dundee. We included patients with confirmed bronchiectasis by computed tomography, who were symptomatic and had at least 1 documented exacerbation of bronchiectasis in the previous 12\u2009months to participate. Symptoms were recorded daily in a diary incorporating cough, sputum volume, sputum colour, dyspnoea, fatigue and systemic disturbance scored from 0 to 26. RESULTS: Twenty-one patients were included in the study. We identified 29 reported (treated exacerbations) and 23 unreported (untreated) exacerbations over 6-month follow-up. The BEST diary score showed a good correlation with the established and validated questionnaires and measures of health status (COPD Assessment Test, r =\u20090.61, p =\u20090.0037, Leicester Cough Questionnaire, r =\u2009-\u20090.52,p =\u20090.0015, St Georges Respiratory Questionnaire, r =\u20090.61,p <\u20090.0001 and 6\u2009min walk test, r =\u2009-\u20090.46,p =\u20090.037). The mean BEST score at baseline was 7.1 points (SD 2.2). The peak symptom score during exacerbation was a mean of 16.4 (3.1), and the change from baseline to exacerbation was a mean of 9.1 points (SD 2.5). Mean duration of exacerbations based on time for a return to baseline symptoms was 15.3\u2009days (SD 5.7). A minimum clinically important difference of 4 points is proposed. CONCLUSIONS: The BEST symptom diary has shown concurrent validity with current health questionnaires and is responsive at onset and recovery from exacerbation. The BEST diary may be useful to detect and characterise exacerbations in bronchiectasis clinical trials

The role of hospital midwives in the Netherlands

<p>Abstract</p> <p>Background</p> <p>Most midwives in the Netherlands work in primary care where they are the lead professionals providing care to women with 'normal' or uncomplicated pregnancies, while some midwives work in hospitals ("clinical midwives"). The actual involvement of midwives in maternity care in hospitals is unknown, because in all statistics births in secondary care are registered as births assisted by gynaecologists. The aim of this study is to gain insight in the involvement of midwives with births in secondary care, under supervision of a gynaecologist. This is done using data from the PRN (The Netherlands Perinatal Registry), a voluntary registration of births in the Netherlands. The PRN covers 97% to 99% of all births taking place under responsibility of a gynaecologist.</p> <p>Methods</p> <p>All births registered in secondary care in the period 1998-2007 (1,102,676, on average 61% of all births) were selected. We analyzed trends in socio-demographic, obstetric and organisational characteristics, associated with the involvement of midwives, using frequency tables and uni- and multivariate logistic regression analyses. As main outcome measure the percentage of births in secondary care with a midwife 'catching' the baby was used.</p> <p>Results</p> <p>The proportion of births attended by a midwife in secondary care increased from 8.3% in 1998 to 26.06% in 2007, the largest increase involving spontaneous births of a second or later child, on weekdays during day shifts (8.00-20.00 hr) from younger mothers with a gestational age (almost) at term. After 2002, parallel to the growing numbers of midwives working in hospitals, the percentage of instrumental births decreased.</p> <p>Conclusions</p> <p>In 2007 more midwives are assisting with more births in secondary care than in 1998. Hospital-based midwives are primarily involved with uncomplicated births of women with relatively low risk demographical and obstetrical characteristics. However, they are still only involved with half of the less complicated births, indicating that there may be room for more midwives in hospitals to care for women with relatively uncomplicated births. Whether an association exists between the growing involvement of midwives and the decreasing percentage of instrumental births needs further investigation.</p

A Fibreoptic Endoscopic Study of Upper Gastrointestinal Bleeding at Bugando Medical Centre in Northwestern Tanzania: a Retrospective Review of 240 Cases.

Upper gastrointestinal (GI) bleeding is recognized as a common and potentially life-threatening abdominal emergency that needs a prompt assessment and aggressive emergency treatment. A retrospective study was undertaken at Bugando Medical Centre in northwestern Tanzania between March 2010 and September 2011 to describe our own experiences with fibreoptic upper GI endoscopy in the management of patients with upper gastrointestinal bleeding in our setting and compare our results with those from other centers in the world. A total of 240 patients representing 18.7% of all patients (i.e. 1292) who had fibreoptic upper GI endoscopy during the study period were studied. Males outnumbered female by a ratio of 2.1:1. Their median age was 37 years and most of patients (60.0%) were aged 40 years and below. The vast majority of the patients (80.4%) presented with haematemesis alone followed by malaena alone in 9.2% of cases. The use of non-steroidal anti-inflammatory drugs, alcohol and smoking prior to the onset of bleeding was recorded in 7.9%, 51.7% and 38.3% of cases respectively. Previous history of peptic ulcer disease was reported in 22(9.2%) patients. Nine (3.8%) patients were HIV positive. The source of bleeding was accurately identified in 97.7% of patients. Diagnostic accuracy was greater within the first 24 h of the bleeding onset, and in the presence of haematemesis. Oesophageal varices were the most frequent cause of upper GI bleeding (51.3%) followed by peptic ulcers in 25.0% of cases. The majority of patients (60.8%) were treated conservatively. Endoscopic and surgical treatments were performed in 30.8% and 5.8% of cases respectively. 140 (58.3%) patients received blood transfusion. The median length of hospitalization was 8 days and it was significantly longer in patients who underwent surgical treatment and those with higher Rockall scores (P < 0.001). Rebleeding was reported in 3.3% of the patients. The overall mortality rate of 11.7% was significantly higher in patients with variceal bleeding, shock, hepatic decompensation, HIV infection, comorbidities, malignancy, age > 60 years and in patients with higher Rockall scores and those who underwent surgery (P < 0.001). Oesophageal varices are the commonest cause of upper gastrointestinal bleeding in our environment and it is associated with high morbidity and mortality. The diagnostic accuracy of fibreoptic endoscopy was related to the time interval between the onset of bleeding and endoscopy. Therefore, it is recommended that early endoscopy should be performed within 24 h of the onset of bleeding

Mice with cisplatin and oxaliplatin-induced painful neuropathy develop distinct early responses to thermal stimuli

<p>Abstract</p> <p>Background</p> <p>Cisplatin has been in use for 40 years for treatment of germ line and other forms of cancer. Oxaliplatin is approved for treatment of metastatic colorectal cancer. Thirty to forty percent of cancer patients receiving these agents develop pain and sensory loss. Oxaliplatin induces distinctive cold-associated dysesthesias in up to 80% of patients.</p> <p>Results</p> <p>We have established mouse models of cisplatin and oxaliplatin-induced neuropathy using doses similar to those used in patients. Adult male C57BL6J mice were treated with daily intraperitoneal injection for 5 days, followed by 5 days of rest, for two cycles. Total cumulative doses of 23 mg/kg cisplatin and 30 mg/kg oxaliplatin were used. Behavioral evaluations included cold plate, von Frey, radiant heat, tail immersion, grip strength and exploratory behavior at baseline and at weekly intervals for 8 weeks. Following two treatment cycles, mice in the cisplatin and oxaliplatin treatment groups demonstrated significant mechanical allodynia compared to control mice. In addition, the cisplatin group exhibited significant thermal hyperalgesia in hind paws and tail, and the oxaliplatin group developed significant cold hyperalgesia in hind paws.</p> <p>Conclusion</p> <p>We have therefore established a model of platinum drug-induced painful peripheral neuropathy that reflects the differences in early thermal pain responses that are observed in patients treated with either cisplatin or oxaliplatin. This model should be useful in studying the molecular basis for these different pain responses and in designing protective therapeutic strategies.</p

Repeated Bout Effect of Two Resistance Training Bouts on Bowling-Specific Performance in Male Cricketers

To examine the repeated bout effect (RBE) following two identical resistance bouts and its effect on bowling-specific performance in male cricketers. Male cricket pace bowlers (N = 10), who had not undertaken resistance exercises in the past six months, were invited to complete a familiarisation and resistance maximum testing, before participating in the study protocol. The study protocol involved the collection of muscle damage markers, a battery of anaerobic (jump and sprint), and a bowling-specific performance test at baseline, followed by a resistance training bout, and a retest of physical and bowling-specific performance at 24 h (T24) and 48 h (T48) post-training. The study protocol was repeated 7–10 days thereafter. Indirect markers of muscle damage were lower (creatine kinase: 318.7 ± 164.3 U·L−1; muscle soreness: 3 ± 1), whilst drop jump was improved (~47.5 ± 8.1 cm) following the second resistance training bout when compared to the first resistance training bout (creatine kinase: 550.9 ± 242.3 U·L−1; muscle soreness: 4 ± 2; drop jump: ~43.0 ± 9.7 cm). However, sport-specific performance via bowling speed declined (Bout 1: −2.55 ± 3.43%; Bout 2: 2.67 ± 2.41%) whilst run-up time increased (2.34 ± 3.61%; Bout 2: 3.84 ± 4.06%) after each bout of resistance training. Findings suggest that while an initial resistance training bout reduced muscle damage indicators and improved drop jump performance following a second resistance training bout, this RBE trend was not observed for bowling-specific performance. It was suggested that pace bowlers with limited exposure to resistance training should minimise bowling-specific practice for 1–2 days following the initial bouts of their resistance training program

Identifying the optimal donor for natural killer cell adoptive therapy to treat paediatric B- and T-cell acute lymphoblastic leukaemia.

Objectives: Natural killer (NK) cells are an attractive source of cells for an 'off the shelf' cellular therapy because of their innate capacity to target malignant cells, and ability to be transferred between donors and patients. However, since not all NK cells are equally effective at targeting cancer, selecting the right donor for cellular therapy is critical for the success of the treatment. Recently, cellular therapies utilising NK cells from cytomegalovirus (CMV)-seropositive donors have been explored. However, whether these NK cells are the best source to treat paediatric acute lymphoblastic leukaemia (ALL) remains unclear. Methods: Using a panel of patient-derived paediatric B- and T-ALL, we assessed the ability of NK cells from 49 healthy donors to mount an effective functional response against these two major subtypes of ALL. Results: From this cohort, we have identified a pool of donors with superior activity against multiple ALL cells. While these donors were more likely to be CMV+, we identified multiple CMVneg donors within this group. Furthermore, NK cells from these donors recognised B- and T-ALL through different activating receptors. Dividing functional NK cells into 29 unique subsets, we observed that within each individual the same NK cell subsets dominated across all ALL cells. Intriguingly, this occurred despite the ALL cells in our panel expressing different combinations of NK cell ligands. Finally, we can demonstrate that cellular therapy products derived from these superior donors significantly delayed leukaemia progression in preclinical models of ALL. Conclusions: We have identified a pool of superior donors that are effective against a range of ALL cells, representing a potential pool of donors that can be used as an adoptive NK cell therapy to treat paediatric ALL