Use of the 1.1 mm cryoprobe through the radial EBUS GS (without the need for a bronchial blocker) to obtain samples safely in diagnosing PPL.

Cryobiopsy for peripheral pulmonary lesions suspected of lung cancer is gaining popularity due to the larger non-crushed samples capable of an array of molecular testing. However, the method of performing this procedure so far had been resource-intensive and time-consuming limiting the procedure to tertiary centres. Having to remove the cryobiopsy en masse with the bronchoscope was the main issue that hindered the safety of the procedure. We report two cases where the 1.1 mm cryoprobe was used and the cryobiopsy was extracted through the Radial EBUS GS whilst the bronchoscope remained in the bronchial tree, with excellent control of bleeding, due to the tamponading of the GS as well as the ability to attend to bleeding as soon as it occurred, due to the bronchoscope being inside the airway. This method of obtaining the cryobiopsy through the GS and keeping the bronchoscope in the airway improved the safety of cryobiopsy for PPL. Further studies are required to assess the consistency of yield and safety of this method.

Using cryobiopsy with Radial EBUS in high-bleeding-risk, peripheral pulmonary lesions (PPL): description of cases and technique.

Cryobiopsy is an emerging tool in the diagnosis of peripheral pulmonary lesions (PPL) and becoming an important tool in the toolbox. Anecdotally the data on cryobiopsy use in the lung was extrapolated from the use of transbronchial cryobiopsy (TBCB) in Interstitial Lung disease (ILD). Similar to ILD data, cryobiopsy in PPL also provided larger tissue compared to forceps biopsies. Yet, unlike TBCB in ILD, the safety profile for cryobiopsy in PPL seems much more favourable, yet the number of publications on cryobiopsy in PPL remains sparse. Some PPL, both malignant and non-malignant are considered to be of a high bleeding risk due to vascularity of the tumour and/or inflammation of the blood vessels and surrounding tissue. The use of cryobiopsy and the risk of bleeding in this type of PPL have not been described. This paper describes four patients with PPL, undergoing cryobiopsy with radial EBUS for suspected lung cancer, and later diagnosed to have a PPL, deemed to be of a high bleeding risk. The use of cryobiopsy with radial ultrasonic examination for the vasculature of the PPL, bronchial blocker use, and airway protection as well as an expert team preserved the safety of the procedure.

Cryobiopsy with radial-endobronchial ultrasound (Cryo-Radial) has comparable diagnostic yield with higher safety in comparison to computed tomography-guided transthoracic biopsy for peripheral pulmonary lesions: An exploratory randomised study.

BACKGROUND: Computed tomography-guided transthoracic biopsy (CT-TTB) is the 'gold standard' biopsy for lung nodules. Radial-endobronchial ultrasound (R-EBUS) bronchoscopy is another recommended biopsy but carries a lower diagnostic yield. Addition of cryobiopsy with R-EBUS (Cryo-Radial) has shown promising results. There are no studies comparing CT-TTB with Cryo-Radial biopsy. AIM: The co-primary aims were the diagnostic yeild and safety. The secondary aim: ability to test epidermal growth factor receptor (EGFR). METHODS: A randomised controlled, multicentre exploratory study was conducted at three tertiary hospitals. Patients with nodules >1 cm on CT of the chest were randomised to CT-TTB or Cryo-Radial. With Cryo-Radial, patients had 1-3 cryo-biopsies in addition to at least one R-EBUS biopsy through the 2.6 mm guide sheath. RESULTS: Forty-eight patients were randomised: 22 to CT-TTB and 26 to Cryo-Radial. Sixteen in the CT-TTB and 20 in the Cryo-Radial received the allocated biopsy. The diagnostic yield was CT-TTB 93.8% (15/16) versus Cryo-Radial 85% (17/20) P = 0.61 and the odds ratio was 0.37. For 5/13 (38%), a diagnosis was solely made on cryobiopsy. Eleven (78%) of 14 in CT-TTB versus 7/10 (70%) Cryo-Radial were suitable for EGFR testing P = 0.66, with odds ratio 0.63. Pneumothorax occurrence was 44% (7/16) in CT-TTB versus 4.2% (1/24) in Cryo-Radial. Two (12.5%) of 16 CT-TTB required chest drain insertion. CONCLUSION: Cryo-Radial is comparable in diagnostic yield and ability to perform EGFR testing with a significantly lower risk of pneumothorax, compared with CT-TTB. Cryo-Radial has the additional advantage of mediastinal staging during the same procedure with Linear-EBUS and is a promising first-line tool in the diagnostic method of lung cancer.

Using the GenCut core biopsy tool with the radial endobronchial ultrasound guide sheath enables a high-quality histology sample capable of programmed cell death ligand 1 (PD-L1) testing.

Radial EndoBronchial UltraSound (R-EBUS)-guided biopsies are a promising biopsy technique for pulmonary nodules suspected of lung cancer with great safety profile. Programmed cell death ligand 1 (PD-L1) testing is increasingly demanded from lung biopsies. GenCut is a novel blunt tool that can be used to obtain core biopsies. This case series explores prospective performance of the GenCut core biopsy with R-EBUS. Once Peripheral Pulmonary Lesion was located, GenCut biopsy was performed followed by conventional (forceps ± cytology brush) R-EBUS biopsies. The overall diagnostic yield for the 16 patients with a mean peripheral pulmonary lesion (PPL) size of 4.1 cm was 100% from multi-modal R-EBUS sampling. The diagnostic yield for GenCut tool alone was 13/16 (81.2%) and the ability to perform PD-L1 from GenCut was 10/16 (62.5%). There were no adverse events recorded. GenCut tool is a novel blunt instrument that can be used safely to obtain a core biopsy suitable for PD-L1 in combination with R-EBUS without compromising the high safety profile.

Cross-inhibition of Turing patterns explains the self-organized regulatory mechanism of planarian fission.

Planarian worms reproduce asexually by fission, resulting in two separated pieces each repatterning and regenerating a complete animal. The induction of this process is known to be dependent on the size of the worm as well as on environmental factors such as population density, temperature, and light intensity. However, despite much progress in understanding the signaling mechanisms of planarian regeneration and the biomechanics of fissioning, no induction mechanism has been proposed for the signaling of fission. Here, we propose and analyze a cross-inhibited Turing system in a growing domain for the signaling of fission in planaria and the regeneration of the anterior-posterior opposite head and tail gene expression gradient patterns. This self-regulated mechanism explains when and where growing planaria fission, and its dependence on the worm length. Furthermore, we show how a delayed control mechanism of the cross-inhibited Turing system explains the asymmetry of the resulting fragments, the induction of fission with an anterior amputation even in a short worm, the consecutive multiple fissions called fragmentation, and the effects of environmental factors in the signaling of fission. We discuss the possible molecular and biophysical implementations of the proposed model and suggest specific experiments to elucidate them. In summary, the proposed controlled cross-inhibited Turing system represents a completely self-regulated model of the fission and regeneration signaling in planaria.

Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

BACKGROUND: There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine whether or not regular (continuous, intermittent or pulsed) treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was performed on 27 July 2018. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. DATA COLLECTION AND ANALYSIS: We used the standard Cochrane methods. Two independent review authors selected studies for inclusion, extracted data, and assessed risk of bias. We resolved discrepancies by involving a third review author. MAIN RESULTS: We included 14 studies involving 3932 participants in this review. We identified two further studies meeting inclusion criteria but both were terminated early without providing results. All studies were published between 2001 and 2015. Nine studies were of continuous macrolide antibiotics, two studies were of intermittent antibiotic prophylaxis (three times per week) and two were of pulsed antibiotic regimens (e.g. five days every eight weeks). The final study included one continuous, one intermittent and one pulsed arm. The antibiotics investigated were azithromycin, erythromycin, clarithromycin, doxycyline, roxithromycin and moxifloxacin. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the pooled results were of moderate quality. The risk of bias of the included studies was generally low.The studies recruited participants with a mean age between 65 and 72 years and mostly at least moderate-severity COPD. Five studies only included participants with frequent exacerbations and two studies recruited participants requiring systemic steroids or antibiotics or both, or who were at the end stage of their disease and required oxygen. One study recruited participants with pulmonary hypertension secondary to COPD and a further study was specifically designed to asses whether eradication of Chlamydia pneumoniae reduced exacerbation rates.The co-primary outcomes for this review were the number of exacerbations and quality of life.With use of prophylactic antibiotics, the number of participants experiencing one or more exacerbations was reduced (odds ratio (OR) 0.57, 95% CI 0.42 to 0.78; participants = 2716; studies = 8; moderate-quality evidence). This represented a reduction from 61% of participants in the control group compared to 47% in the treatment group (95% CI 39% to 55%). The number needed to treat for an additional beneficial outcome with prophylactic antibiotics given for three to 12 months to prevent one person from experiencing an exacerbation (NNTB) was 8 (95% CI 5 to 17). The test for subgroup difference suggested that continuous and intermittent antibiotics may be more effective than pulsed antibiotics (P = 0.02, I² = 73.3%).The frequency of exacerbations per patient per year was also reduced with prophylactic antibiotic treatment (rate ratio 0.67; 95% CI 0.54 to 0.83; participants = 1384; studies = 5; moderate-quality evidence). Although we were unable to pool the result, six of the seven studies reporting time to first exacerbation identified an increase (i.e. benefit) with antibiotics, which was reported as statistically significant in four studies.There was a statistically significant improvement in quality of life as measured by the St George's Respiratory Questionnaire (SGRQ) with prophylactic antibiotic treatment, but this was smaller than the four unit improvement that is regarded as being clinically significant (mean difference (MD) -1.94, 95% CI -3.13 to -0.75; participants = 2237; studies = 7, high-quality evidence).Prophylactic antibiotics showed no significant effect on the secondary outcomes of frequency of hospital admissions, change in forced expiratory volume in one second (FEV1), serious adverse events or all-cause mortality (moderate-quality evidence). There was some evidence of benefit in exercise tolerance, but this was driven by a single study of lower methodological quality.The adverse events that were recorded varied among the studies depending on the antibiotics used. Azithromycin was associated with significant hearing loss in the treatment group, which was in many cases reversible or partially reversible. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice.The development of antibiotic resistance in the community is of major concern. Six studies reported on this, but we were unable to combine results. One study found newly colonised participants to have higher rates of antibiotic resistance. Participants colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. A further study with three active treatment arms found an increase in the degree of antibiotic resistance of isolates in all three arms after 13 weeks treatment. AUTHORS' CONCLUSIONS: Use of continuous and intermittent prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All studies of continuous and intermittent antibiotics used macrolides, hence the noted benefit applies only to the use of macrolide antibiotics prescribed at least three times per week. The impact of pulsed antibiotics remains uncertain and requires further research.The studies in this review included mostly participants who were frequent exacerbators with at least moderate-severity COPD. There were also older individuals with a mean age over 65 years. The results of these studies apply only to the group of participants who were studied in these studies and may not be generalisable to other groups.Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse. Monitoring of significant side effects including hearing loss, tinnitus, and long QTc in the community in this elderly patient group may require extra health resources.

Radial-probe endobronchial ultrasound outcomes in the investigation of peripheral pulmonary lesions: a New Zealand perspective.

BACKGROUND: Radial-probe endobronchial ultrasound (radial-EBUS) is becoming an important investigation for peripheral pulmonary lesions (PPL). A key advantage of radial-EBUS is the favourable risk profile compared with current gold-standard computerised tomography-guided biopsy. AIM: To investigate the diagnostic yield, predictors of positive yield and radial-EBUS safety in a New Zealand institution. We also determined whether molecular analysis was possible on the same tissue samples. METHODS: We performed a retrospective analysis of all patients (n = 68) from Middlemore Hospital, Auckland, undergoing radial-EBUS with guide-sheath for PPL from March 2015 to August 2016. Clinical, radiological and procedural data were collected. Radial-EBUS diagnostic yield was determined for malignant and benign diagnoses, and molecular analysis yield was determined on appropriate malignant samples. Logistic regression was used to determine factors predicting successful radial-EBUS. RESULTS: Overall diagnostic yield of radial-EBUS was 55.9% (95% confidence interval (CI): 44.3-67.9). Malignant diagnostic sensitivity was 60.8% (95% CI: 46.1-74.2) and benign diagnostic sensitivity was 50% (95% CI: 23-77). Lesions close to the hilum (P = 0.039), concentric radial-probe positioning (P = 0.008) and the use of forceps as first instrument (P = 0.0049) significantly predicted successful diagnostic yield. Of the malignant cases 81.0% (95% CI: 58.1-94.6) were sufficient for molecular analysis. Pneumothorax occurred in 4.4% (95% CI: 0.9-12.4), none required chest drain intervention. There were no cases of significant pulmonary haemorrhage. CONCLUSION: Radial-EBUS was shown to be safe with diagnostic yield similar to international reports. Important predictors of success include distance from hilum, probe position and forceps as first instrument. We also demonstrated that molecular analysis is possible in radial-EBUS obtained samples.

Novel hybrid cryo-radial method: an emerging alternative to CT-guided biopsy in suspected lung cancer. A prospective case series and description of technique.

In diagnosing peripheral pulmonary lesions (PPL), radial endobronchial ultrasound (R-EBUS) is emerging as a safer method in comparison to CT-guided biopsy. Despite the better safety profile, the yield of R-EBUS remains lower (73%) than CT-guided biopsy (90%) due to the smaller size of samples. We adopted a hybrid method by adding cryobiopsy via the R-EBUS Guide Sheath (GS) to produce larger, non-crushed samples to improve diagnostic capability and enhance molecular testing. We report six prospective patients who underwent this procedure in our institution. R-EBUS samples were obtained via conventional sampling methods (needle aspiration, forceps biopsy, and cytology brush), followed by a cryobiopsy. An endobronchial blocker was placed near the planned area of biopsy in advance and inflated post-biopsy to minimize the risk of bleeding in all patients. A chest X-ray was performed 1 h post-procedure. All the PPLs were visualized with R-EBUS. The mean diameter of cryobiopsy samples was twice the size of forceps biopsy samples. In four patients, cryobiopsy samples were superior in size and the number of malignant cells per high power filed and was the preferred sample selected for mutation analysis and molecular testing. There was no pneumothorax or significant bleeding to report. Cryobiopsy samples were consistently larger and were the preferred samples for molecular testing, with an increase in the diagnostic yield and reduction in the need for repeat procedures, without hindering the marked safety profile of R-EBUS. Using an endobronchial blocker improves the safety of this procedure.

The novel 19G endobronchial USS (EBUS) needle samples processed as tissue "core biopsies" facilitate PD-L1 and other biomarker testing in lung cancer specimens: case report and the view point from the Respiratory Physician and the Pathologist.

The immunohistochemical expression of Programmed Death Ligand (PD-L1) predicts responses to PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC). PD-L1 testing is currently only recommended on tissue specimens; however, in many patients, cytology samples are the only specimens available. The introduction of the novel 19G "core-biopsy" needle has revolutionized the utility of endobronchial USS-guided biopsy (EBUS) by providing solid tissue "microbiopsies" rather than traditional liquid cytology samples. We report a case of metastatic adenocarcinoma with the only accessible site of biopsy being a hilar lymph node. Using the 19G core-biopsy needle and processing the microbiopsy samples in formalin provided more material for predictive biomarker testing, including PD-L1 immunohistochemistry, when traditional processing was inadequate. This case highlights the need for close multidisciplinary discussions between the pathologist and the respiratory physician regarding emerging biomarkers and novel biopsy techniques to obtain maximum utility of the tools and avoid repeated procedures for the patient.

Prophylactic antibiotic therapy in chronic obstructive pulmonary disease.

CLINICAL QUESTION Is prophylactic antibiotic treatment associated with fewer exacerbations or improved health-related quality of life (HRQOL) in patients with chronic obstructive pulmonary disease (COPD)? BOTTOM LINE Continuous macrolide antibiotic use for prophylaxis was associated with a clinically significant reduction in COPD exacerbations. Pulsed antibiotic use was not associated with benefit. Continuous and pulsed antibiotics were associated with improved HRQOL, but this was not clinically significant.

Pulmonary involvement in patients presenting with extra-pulmonary tuberculosis: thinking beyond a normal chest x-ray.

INTRODUCTION: Recognition of pulmonary involvement in extra-pulmonary tuberculosis (TB) may be an important public health issue, as smear-negative pulmonary TB is responsible for about 17% of new infections. Pulmonary TB can be present despite a normal chest x-ray (CXR), even in human immunodeficiency virus (HIV)-negative patients. In this retrospective clinical audit, we reviewed a case series of HIV-negative patients with extra-pulmonary tuberculosis to identify the proportion with concurrent pulmonary TB despite an unremarkable CXR. METHODS: Clinical notes, microbiology results and CXR reports were reviewed from consecutive patients treated at Auckland City Hospital for extra-pulmonary TB from January 2007 to July 2010. RESULTS: Of the sample of 103 patients with extra-pulmonary TB, the majority of patients were born in an Asian country (n=70; 68%). The commonest presentation of extra-pulmonary TB was lymphadenopathy (n=51; 50%), followed by pleural (n=24; 23%) and bone (n=6; 6%) disease. Extra-pulmonary TB was diagnosed by biopsy or excision of the extra-pulmonary site in the majority (n=74; 72%), and by sputum testing alone in 26 (25%). The majority had CXR abnormalities (n=76; 74%). In the group with a normal CXR (n=27), 55% (n=15) had sputum cultures performed. In total, 18% (n=5) of patients with extra-pulmonary TB and a normal CXR had pulmonary TB, of whom two were smear positive. DISCUSSION: In patients with extra-pulmonary TB, sputum testing should be considered to detect concurrent pulmonary TB even if a CXR is normal, especially in immunosuppressed or symptomatic patients. This may aid diagnosis and determine infectivity and consequent public health action.

Increasing awareness of Rhodococcus equi pulmonary infection in the immunocompetent adult: a rare infection with poor prognosis.

The aim of this case report and review is to increase awareness of this uncommon infection with Rhodococcus equi (R. equi), in immunocompetent adults. R. equi is a soil-dwelling Gram-positive bacillus that frequently causes infection in grazing livestock. Human infection is rare and mostly limited to the immunocompromised hosts. We present a case of pneumonia caused by R. equi infection in a 55-year-old male builder who presented with cough, dyspnoea and night sweats, initially suspected to have pulmonary tuberculosis. Following biopsy of the mediastinal lymph nodes, R. equi was cultured, which is usually not a contaminant. Despite extensive investigations a host immune defect was not identified. The patient recovered after three months of combination antibiotic treatment, initially with intravenous vancomycin and meropenem followed by oral clarithromycin and rifampicin. To further clarify this rare disease we did a literature review that identified 26 adult patients with R. equi infection, without an identified host immunosuppressive condition. In this cohort, the median age at presentation was 53 years and infection holds a strong male predominance 19 (73%). An environmental exposure (e.g. farming, horse breeder) was found in 13 (50%). Ten (38%) of these patients had pulmonary infection. All deaths 3 (12%) occurred in the patients had pulmonary infection. R.equi is an infection that is difficult to diagnose and carries a high mortality if prompt treatment is not established. It is important to realise the potential for this disease to be misdiagnosed as pulmonary tuberculosis or community acquired pneumonia. Clinical suspicion is important especially if an environmental exposure is suspected.

Prophylactic antibiotic therapy for chronic obstructive pulmonary disease (COPD).

BACKGROUND: There has been renewal of interest in the use of prophylactic antibiotics to reduce the frequency of exacerbations and improve quality of life in chronic obstructive pulmonary disease (COPD). OBJECTIVES: To determine whether or not regular treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. SEARCH METHODS: We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was August 2013. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. DATA COLLECTION AND ANALYSIS: We used the standard methods of The Cochrane Collaboration. Data were extracted and analysed by two independent review authors. MAIN RESULTS: Seven RCTs involving 3170 patients were included in this systematic review. All studies were published between 2001 and 2011. Five studies were of continuous antibiotics and two studies were of intermittent antibiotic prophylaxis (termed 'pulsed' for this review). The antibiotics investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin. Azithromycin, erythromycin and clarithromycin are macrolides while moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the results were of moderate quality. The risk of bias of the included studies was generally low, and we did not downgrade the quality of evidence for risk of bias.The trials recruited participants with a mean age of 66 years and with at least a moderate severity of COPD. Three trials included participants with frequent exacerbations and two trials recruited participants requiring systemic steroids or antibiotics, or both, or who were at the end stage of their disease and required oxygen.The primary outcomes for this review were the number of exacerbations and quality of life.With use of continuous prophylactic antibiotics the number of patients experiencing an exacerbation was reduced (odds ratio (OR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, 3 studies, 1262 participants, high quality). This represented a reduction from 69% of participants in the control group compared to 54% in the treatment group (95% CI 46% to 63%) and the number needed to treat to prevent one exacerbation (NNTb) was therefore 8 (95% CI 5 to 18). The frequency of exacerbations was also reduced with continuous prophylactic antibiotic treatment (rate ratio 0.73; 95% CI 0.58 to 0.91).Use of pulsed antibiotic treatment showed a non-significant reduction in the number of people with exacerbations (OR 0.87; 95% CI 0.69 to 1.09, 1 study, 1149 participants, moderate quality) and the test for interaction showed that this result was significantly different from the effect on exacerbations with continuous antibiotics.There was a statistically significant improvement in quality of life with both continuous and pulsed antibiotic treatment but this was smaller than the four unit improvement that is regarded as being clinically significant (MD -1.78; 95% CI -2.95 to -0.61, 2 studies, 1962 participants, moderate quality).Neither pulsed nor continuous antibiotics showed a significant effect on the secondary outcomes of frequency of hospital admissions, change in lung function, serious adverse events or all-cause mortality (moderate quality evidence).The adverse events that were recorded varied among the trials depending on the different antibiotics used. Azithromycin was associated with a significant hearing loss in the treatment group. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice.The development of antibiotic resistance in the community is of major concern. One study found newly colonised patients to have higher rates of antibiotic resistance. Patients colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. AUTHORS' CONCLUSIONS: Use of continuous prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All trials of continuous antibiotics used macrolides hence the noted benefit applies only to the use of continuous macrolide antibiotics. The impact of pulsed antibiotics remains uncertain and requires further research.The trials in this review included patients who were frequent exacerbators and needed treatment with antibiotics or systemic steroids, or who were on supplemental oxygen. There were also older individuals with a mean age of 66 years. The results of these trials apply only to the group of patients who were studied in these trials and may not be generalisable to other groups.Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse.

Use of postictal respiratory pattern to discriminate between convulsive psychogenic nonepileptic seizures and generalized tonic-clonic seizures.

Distinguishing between generalized tonic-clonic seizures (GTCSs) and convulsive psychogenic nonepileptic seizures (PNESs) can be difficult at the bedside, and this distinction has important implications for patient care. This study used a fully blinded method to examine postictal breathing parameters to identify features distinguishing between generalized tonic-clonic seizures (GTCSs) and convulsive psychogenic nonepileptic seizures (PNESs). Three blinded readers examined edited video recordings of the postictal phase of 72 convulsive seizure episodes recorded from 56 patients. There were 59 GTCS episodes and 13 PNES episodes. Postictal breathing after a PNES episode was more rapid than after a GTCS episode and, thereafter, normalized more rapidly. Postictal breathing after a GTCS episode was more likely to be characterized by stertorous respirations. Postictal breathing after a PNES episode was very unlikely to be characterized by stertorous respirations. Postictal respiratory pattern can assist in discriminating between GTCS and convulsive PNES.

Is walking barefoot a risk factor for diabetic foot disease in developing countries?

INTRODUCTION: Walking barefoot is common in poorer developing countries which have large rural populations. Although high rates of foot injury could be expected among those who walk barefoot, walking barefoot as a risk factor for diabetic foot disease is rarely documented in the literature. METHODS: Two preliminary clinical studies were undertaken to investigate whether there is a causal link between walking barefoot and diabetic foot ulcers. The first study investigated whether being barefoot was a factor in initiating foot ulceration. In the second study, 204 consecutive diabetic outpatients were studied to further investigate the association between diabetic foot disease and walking barefoot. RESULTS: In the first study, of the 75 consecutive diabetics admitted for foot ulceration of less than 4 weeks, 32 (42.4%) had foot ulcers resulting from injuries by sharp or hard objects. Of those injured, 27 (84%) were barefoot at the time of the injury. This suggested that walking barefoot is a risk factor for foot ulcers, and that using footwear has the potential to prevent foot ulcers. In the second study, the relative risk of foot ulcers among barefoot diabetics was 2.21 (95% CI 1.55 to 3.14) compared with those using some form of footwear. A history of foot ulcers was more frequent in the group who wore footwear less than 10 hours per day, compared with those who used footwear more than 10 hours. The prevalence of web space and nail infections was also higher in the group who wore footwear less than 10 hours per day, compared with those who used footwear for more than 10 hours. CONCLUSION: The data suggest that walking barefoot is a risk factor for diabetic foot disease. Thus, public health messages in developing countries with large rural populations who walk barefoot should strongly advise diabetics to use footwear for a greater part of the day. This may be overlook in literature originating from affluent countries where footwear use is the norm. Further studies are indicated to investigate potential associations between walking barefoot, rurality and cultural factors.