Bruce Shadbolt

Inhaled mannitol improves lung function in cystic fibrosis

BACKGROUND The airways in patients with cystic fibrosis (CF) are characterized by the accumulation of tenacious, dehydrated mucus that is a precursor for chronic infection, inflammation, and tissue destruction. The clearance of mucus is an integral component of daily therapy. Inhaled mannitol is an osmotic agent that increases the water content of the airway surface liquid, and improves the clearance of mucus with the potential to improve lung function and respiratory health. To this end, this study examined the efficacy and safety of therapy with inhaled mannitol over a 2-week period. METHODS This was a randomized, double-blind, placebo-controlled, crossover study. Thirty-nine subjects with mild-to-moderate CF lung disease inhaled 420 mg of mannitol or placebo twice daily for 2 weeks. Following a 2-week washout period, subjects were entered in the reciprocal treatment arm. Lung function, respiratory symptoms, quality of life, and safety were assessed. RESULTS Mannitol treatment increased FEV(1) from baseline by a mean of 7.0% (95% confidence interval [CI], 3.3 to 10.7) compared to placebo 0.3% (95% CI, - 3.4 to 4.0; p < 0.001). The absolute improvement with mannitol therapy was 121 mL (95% CI, 56.3 to 185.7), which was significantly more than that with placebo (0 mL; 95% CI, - 64.7 to 64.7). The forced expiratory flow in the middle half of the FVC increased by 15.5% (95% CI, - 6.5 to 24.6) compared to that with placebo (increase, 0.7%; 95% CI, - 8.3 to 9.7; p < 0.02). The safety profile of mannitol was adequate, and no serious adverse events related to treatment were observed. CONCLUSIONS Inhaled mannitol treatment over a period of 2 weeks significantly improved lung function in patients with CF. Mannitol therapy was safe and well tolerated. TRIAL REGISTRATION (ClinicalTrials.gov) Identifier: NCT00455130.

Intralesional corticosteroid injection versus extracorporeal shock wave therapy for plantar fasciopathy.

Objective:To compare the efficacy of low-energy extracorporeal shock wave therapy (ESWT) and intralesional corticosteroid injection (CSI) for the treatment of plantar fasciopathy present for at least 6 weeks. Design:A prospective, randomized, controlled, observer-blinded study over a period of 12 months. Setting:Primary care and hospital setting. Patients:A total of 132 patients were enrolled in the study, and 125 completed the study. Nineteen nonrandomized patients acted as a surrogate control group. Interventions:All patients performed a standardized Achilles tendon and plantar fascia stretching program. The patients were randomly allocated to either treatment group A or B. Group A received a single CSI, while group B were referred for a course of low-dose ESWT comprising 3 treatments over a period of 3 weeks. Group C consisted of 19 nonrandomized patients who performed the standardized stretching program only. Main Outcome Measurements:The worst daily pain recorded on a visual analogue scale (VAS), and the tenderness at the plantar fascia insertion as determined by an algometer. These measures were recorded immediately prior to the commencement of treatment and 3 months and 12 months posttreatment. Results:With regard to VAS pain scores, values for the CSI (1.48; 0-7) were significantly lower than both ESWT (3.69; 0-8), and controls (3.58; 2-5) at 3 months. At 12 months, VAS scores for CSI (0.84; 0-7) and ESWT (0.84; 0-4) were both significantly lower than controls (2.42; 1-4). The tenderness values at 3 months were significantly higher for CSI (9.42; 7-11) than both ESWT (6.72; 4-11) and controls (7.63; 6-9). P < 0.05 was used throughout. Conclusions:Corticosteroid injection is more efficacious and multiple times more cost-effective than ESWT in the treatment of plantar fasciopathy that has been symptomatic for more than 6 weeks.

Effect of proton pump inhibitors on markers of risk for high‐grade dysplasia and oesophageal cancer in Barrett’s oesophagus

Background It has been shown that the presence on diagnosis of endoscopic macroscopic markers indicates a high‐risk group for Barrett’s oesophagus.

Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial

Background Controversy exists whether different continuous positive airway pressure (CPAP) weaning methods influence time to wean off CPAP, CPAP duration, oxygen duration, Bronchopulmonary Dysplasia (BPD) or length of admission. Aims In a multicentre randomised controlled trial, the authors have primarily compared CPAP weaning methods impact on time to wean off CPAP and CPAP duration and secondarily their effect on oxygen duration, BPD and time of admission. Methods Between April 2006 and October 2009, 177 infants <30 weeks gestational age (GA) who fulfilled stability criteria on CPAP were randomised to one of the three CPAP weaning methods (M). M1: Taken ‘OFF’ CPAP with the view to stay ‘OFF’. m2: Cycled on and off CPAP with incremental time ‘OFF’. M3: As with m2, cycled on and off CPAP but during ‘OFF’ periods were supported by 2 mm nasal cannula at a flow of 0.5 l/min. Results Based on intention to treat analysis, there was no significant difference in mean GA or birthweight between the groups (27.1±1.4, 26.9±1.6 and 27.3±1.5 (weeks±1SD) and 988±247, 987±249 and 1015±257 (grams±1SD), respectively). Primary outcomes showed M1 produced a significantly shorter time to wean from CPAP (11.3±0.8, 16.8±1.0, 19.4±1.3 (days±1SE) p<0.0001, respectively) and CPAP duration (24.4±0.1, 38.6±0.1, 30.5±0.1 (days±1SE) p<0.0001, respectively). All the secondary outcomes were significantly shorter with M1, (oxygen duration: 24.1±1.5, 45.8±2.2, 34.1±2.0 (days±1SE) p<0.0001, BPD: 7/56 (12.5%), 29/69 (42%), 10/52 (19%) p=0.011 and length of admission: 58.5±0.1, 73.8±0.1 69.5±0.1 (days±1SE) p<0.0001, respectively). Conclusion Method 1 significantly shortens CPAP weaning time, CPAP duration, oxygen duration, BPD and admission time.

Increasing incidence of glioblastoma multiforme and meningioma, and decreasing incidence of Schwannoma (2000–2008): Findings of a multicenter Australian study

Background: The incidence of primary brain tumors by subtype is currently unknown in Australia. We report an analysis of incidence by tumor subtype in a retrospective multicenter study in the state of New South Wales (NSW) and the Australian Capital Territory (ACT), with a combined population of >7 million with >97% retention rate for medical care. Methods: Data from histologically confirmed primary brain tumors diagnosed from January 2000 through December 2008 were weighted for patient outflow and data completeness, and age standardized and analyzed using joinpoint analysis. Results: A significant increasing incidence in glioblastoma multiforme (GBM) was observed in the study period (annual percentage change [APC], 2.5; 95% confidence interval [CI], 0.4–4.6, n = 2275), particularly after 2006. In GBM patients in the ≥65-year group, a significantly increasing incidence for men and women combined (APC, 3.0; 95% CI, 0.5–5.6) and men only (APC, 2.9; 95% CI, 0.1–5.8) was seen. Rising trends in incidence were also seen for meningioma in the total male population (APC, 5.3; 95% CI, 2.6–8.1, n = 515) and males aged 20–64 years (APC, 6.3; 95% CI, 3.8–8.8). Significantly decreasing incidence trends were observed for Schwannoma for the total study population (APC, –3.5; 95% CI, –7.2 to –0.2, n = 492), significant in women (APC, –5.3; 95% CI, –9.9 to –0.5) but not men. Conclusion: This collection is the most contemporary data on primary brain tumor incidence in Australia. Our registries may observe an increase in malignant tumors in the next few years that they are not detecting now due to late ascertainment. We recommend a direct, uniform, and centralized approach to monitoring primary brain tumor incidence by subtype, including the introduction of nonmalignant data collection.

Vitamin D status and its predictive factors in pregnancy in 2 Australian populations

Background:  High prevalence rates of suboptimal vitamin D levels have been observed in women who are not considered ‘at risk’. The effect of behavioural factors such as sun exposure, attire, sunscreen use and vitamin D supplementation on vitamin D levels in pregnancy is unknown.

Infliximab reverses inflammatory muscle wasting (sarcopenia) in Crohn's disease

Muscle wasting or sarcopenia arising from chronic inflammation is found in 60% of patients with Crohns disease. Transcriptional protein NF‐κB reduces muscle formation through MyoD transcription and increases muscle breakdown by proteolysis.

Lymphocytopenia as a prognostic marker for diffuse large B cell lymphomas

Lymphocytopenia has been reported to confer adverse outcomes in a number of hematological malignancies. Recently, it has been reported to be associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to determine the incidence of lymphocytopenia at diagnosis in patients with DLBCL, and to confirm its significance as a prognostic factor, particularly in relation to the international prognostic index (IPI). Medical and laboratory records of 165 patients diagnosed with DLBCL were retrieved and analysed. Lymphocyte counts were correlated with overall survival and role as a prognostic marker independent of IPI was determined. Lymphocytopenia (lymphocyte count ≤1×109/L) was noted in 35.8%; it correlated adversely with overall survival (3.4 years vs. 10.3 years, p=0.002). A Cox regression model established that the prognostic significance was independent of the IPI.

A comparative study of the quality of DNA obtained from fresh frozen and formalin-fixed decalcified paraffin-embedded bone marrow trephine biopsy specimens using two different methods

Background: Given its prognostic value, there is renewed interest in molecular staging in non-Hodgkin’s lymphoma (NHL) using immunoglobulin heavy and light chain (IgH, IgL) gene rearrangements. Aims: To compare the efficiency of DNA amplification from fresh frozen and formalin-fixed decalcified paraffin-embedded (FFDPE) bone marrow trephines for use in molecular staging using two methods. Methods: After manually extracting DNA from 13 FFDPE and 14 fresh frozen trephine biopsy specimens, two methods were used to test for amplifiability: use of the amplification control master mix supplied in the In Vivo Scribe immunoglobulin heavy chain (IgH) clonality kit, which creates 5 amplicons between 96–600 base pairs (bp); and real-time amplification of the β-globin gene. Results: Using the first method, the mean maximum length of amplicons generated from FFDPE trephines was statistically lower at 300 bp compared to fresh frozen samples, all of which generated amplicons up to 600 bp in size (p<0.001). Real-time amplification of the β-globin gene showed that the mean crossing threshold of fresh frozen samples was statistically lower than that of FFDPE samples (23.48 (95% CI 22.47 to 24.48) vs 33.64 (95% CI 32.15 to 35.12); p<0.001). Conclusions: Although amplifiable DNA can be extracted from both fresh-frozen and FFDPE trephine samples for IgH/IgL analysis, freshly frozen specimens are superior as a source of template DNA, especially for higher base pair PCR products.

Kjelland's forceps in the new millennium. Maternal and neonatal outcomes of attempted rotational forceps delivery

Background:  The use of Kjellands forceps is now uncommon, and published maternal and neonatal outcome data are from deliveries conducted more than a decade ago. The role of Kjellands rotational delivery in the ‘modern era’ of high caesarean section rates is unclear.