Diabetes: Injectors insulin

INJECTING

Injectors

What is the ‘jet’ injector?

This is a needle-free injector, which works by penetrating the skin with insulin using very high pressure jets. It is not entirely painless and is fairly bulky. The recent model available in the UK (MHI-500) has been superceded by a new model, SQ-PEN.

Injectors insulin

Practical aspects of pens, needles, syringes and bottles

When I was discharged from hospital with newly-diagnosed diabetes I was given a pen device and a few disposable syringes and needles for my injections. How do I obtain more?

Pen devices, disposable insulin syringes and pen needles are available free on prescription. Your CP will supply you with a prescription for any make of insulin syringe and/or insulin pen needles that you choose, and they can then be obtained without charge from a chemist.

Alternatively you can buy them at your own cost directly from the chemist without a prescription, or you can send for them by post from suppliers such as Owen Mumford (Medical Shop).

What is the best way of disposing of insulin syringes and pen needles?

There is a device available called the BD Safe-Clip® which cuts the needle off the top of a syringe or insulin pen and retains it in the device. Once the needle is clipped off, put the used syringe or pen needle hub into a rigid sealable container (available on prescription as a Sharps bin) along with your lancets and follow your local council guidelines for safe disposal of medical waste. Some local authorities provide special containers and a collection service for people who are treated with insulin; however, there is no national policy.

The BD Safe-Clip is available free on prescription from your CP.

I have heard that pen needles and disposable syringes can be reused. How many times can they be reused and how can they be kept clean in between injections?

While pen needles and disposable syringes are designed to be used only once, some people do reuse them. However, reusing needles causes them to become blunt, and they can bend very easily. The tiny point on the end can also break off and remain embedded in the flesh. Needles have a fine coating of lubricant on them so they glide in and out of the skin, and reusing them removes this lubricant and may cause a more painful injection. So there are many reasons to use each needle once only.

If you decide to reuse them make sure the protective cover is placed over the needle.

There is a bewildering array of syringes and needles on the market. Which are the best types to use?

In the UK we use three sizes of syringe. They are used with U100 insulin, which is the standard strength of insulin in the UK and most countries, containing 100 units of insulin per 1 millilitre.

• The 0.5 mL syringe. This is marked with 50 single divisions for taking not more than 50 units of insulin in one injection.
• The 1 mL syringe, marked up to 100 units in 2 unit divisions for those taking more than 50 units of insulin in one injection.
• The 0.3 mL syringe, designed for children or those taking less than 30 units of insulin in one injection.

The most popular make is the BD syringe which comes complete with a fixed Micro-Fine+ 12.7 mm needle, but there are several other makes available.

All these syringes are marked with the word INSULIN on the side of the syringe and graduated in units of insulin. No other type should be used to inject insulin.

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Eosinophils play a key role in airway remodeling

In children with asthma who were not receiving any controller medications, sputum amphiregulin level was negatively correlated with the provocative concentration of methacholine causing a 20% fall in F'EV_X (r = —0.398; p = 0.008). Conclusions: Our findings suggest that childhood asthma is associated with sputum amphiregulin, whereas EB is not, and that sputum amphiregulin would be a supportive marker of airway inflammation in asthma.

Abbreviations: AHR = airway hyperresponsiveness; BD = bronchodilator; EB = eosinophilic bronchitis; ECP = eosinophil cationic protein; FEF_25-75% = forced expiratory flow, midexpiratory phase; ICS = inhaled corticosteroid; IQR = interquartile range; PC₂₀ = provocative concentration of methacholine causing a 20% fall in FEV₁

Airway remodeling and eosinophilic airway inflammation, which are characteristic features of asthma in adults, are already present in children with asthma and even in pre-school-aged children who wheeze. There is evidence that eosinophils play a key role in airway remodeling, which produces a wide range of proteins in fibrogenesis and angiogenesis, particularly transforming growth factor-P and other cytokines. Eosinophils also are increased within the airways in patients with nonasthmatic eosinophilic bronchitis (EB) to levels similar to those found in patients with asthma. EB has emerged from the study of chronic cough, and is characterized by eosinophilic inflammation, increased exhaled nitric oxide levels, increased basement membrane thickening, and normal spirometry findings, without airway hyperresponsiveness (AHR). Although the pathogenesis of EB is still unclear, especially in children, its immunopathologic features are distinct from those of asthma in that EB shows no evidence of the overexpression of interleukin-4 or interleukin-13 by mast cells or mast cell colonization to airway smooth muscle.

Amphiregulin was originally classified as a member of the epidermal growth factor family, which plays important roles in cell proliferation, survival, and differentiation.

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Treatment: For Children

A mother must not only give birth to a child, but she shall also breastfeed it. That milk shall be incorrupt. So many mothers have poisoned their children with their bad milk. If she is angry several times a day, a few hours after that she will poison her child.

Treatment: For Children

If the mother is healthy, the more your child sucks, the better. Children, who have sucked for two or three years, are healthier. A healthy person is also good.

Every mother should know how to treat her children. Mother must give first aid. The first task of a mother is to give castor oil to an ill child. Then it shall drink several cups of warm water, and then the mother shall cook a vegetarian potato soup for the child. This is the first aid for every patient. You ask why you should drink hot water. It is very simple. While eating, fat deposits remain along the walls of the stomach and intestines that impede proper digestion. Hot water dissolves them and regulates the processes in the stomach and intestines.

If the child is anemic, give it more pears and cucumbers. If its character is a bit rough, feed it with apples. If he lacks noble qualities, feed it with cherries. Give children only fresh food, mainly fruits.

The first task of the future education of children will be the condition of the digestive system to be controlled. A healthy digestive system provides a normal brain system. If those two systems are in good working order, the function of the respiratory system is also good. These are the three main systems that regulate human thoughts and feelings. If they work well, thoughts and feelings of people will be expressed properly.

The child that eats bread, baked in the embers, has a hundred times bigger opportunity to become a distinguished professor than the child that eats cakes, chocolate and sweets.

When your children are ill, it is good the bone behind their ears to be massages - there is a living center. These massages make the organism elastic and durable.

If a child has been ill for a few months, the first thing that shall be done after its recover is to be bathed and dressed in new clothes. The old clothes, in which it has spent the illness, shall be burned. Old clothes are penetrated with negative states and therefore they shall be burned, and you shall not give them to poor. New clothes shall be given to the poor.

Give somebody to eat dry corn for a week and you will see him transformed. For naughty children, the mother shall apply the same regime.

If a child is capricious, obstinate, the mother shall give him two nuts. The number two is magnetic method. If the child is unbalanced in nature, give him three nuts or apples. The number three is a law of balance. Sometimes nuts may affect badly the organism (when taken in large amounts), because they contain lots of iodine. So, nuts are also able to poison someone. If you want to develop the child's sense of justice, give it four nuts. You shall give for feelings, in general - five nuts, religious feelings - seven nuts, critical and philosophical mind - seven nuts. Do not give more than nine nuts to your children.

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TNF-Receptor Subtype Expression

For all correlations tested, inverse relationships between protein release and airway obstruction were found. With the exception of FEV₁/FVC (percentage predicted) vs GRO-a (p = 0.06, r = — 0.49), all correlations reached the level of significance (Table 2). Furthermore, no differences were seen with respect to the unstimulated protein release, and both cytokines responded nonsignificantly to IFN-y stimulation, which reflects the mRNA results as well.

Table 1—Increase in Stimulated Epithelial mRNA Expression Levels of IL-8 and GRO-a Relative to Unstimulated mRNA Levels*
 

	Basal	TNF-a	Fold Increase in TNF-a	IFN-y	Fold Increase in IFN-y
IL-8 mRNA
Smokers	1.0 (0.5-3.2)	4.6 (3.1-9.9)	4.7(1.8-14.1)	0.4 (0.1-1.3)	0.3 (0.1-0.9)
COPD	3.3 (0.2-19.1)	12.9 (5.4-36.9)t	5.7 (1.9-70.0)	1.9 (0.3-12.4)	0.9 (0.1-1.8)
GRO-a
mRNA Smokers	4.3 (0.9-8.9)	7.3 (3.8-11.2)	2.0 (0.7-9.1)	4.3 (0.8-6.5)	1.0 (0.2-2.0)
COPD	4.1 (0.9-12.3)	16.2 (8.1-81.8)t	4.3 (2.5-9.9)	5.7 (2.8-17.3)	1.8 (0.6-3.2)

*Data are presented as median (range). tp < 0.01 vs smokers without airway obstruction.

TNF-Receptor Subtype Expression

In addition to the TNF-a-induced cytokine responses, the expression levels of the TNF-receptor subtypes—p55 TNF-receptor subtype (TNF-R55) and p75 TNF-receptor subtype (TNF-R75)—were quantified at the steady-state mRNA level by means of light cycler measurements. As shown in Figure 3, both TNF receptors were detectable in PBECs. The expression levels of TNF-R55 compared to TNF-R75 were 5,670-fold and 4,730-fold higher in smokers without airflow limitation and patients with COPD, respectively. No significant differences in the expression levels between groups were detected for TNF-R55 (p = 0.8) nor for TNF-R75 (p = 0.6). Table 2 —Correlations Between TNF-a-Induced Protein Release of IL-8 or GRO-a in PBECs and Lung Function 

Parameters*

 

Variables	IL-8		GRO-a
	1 r Value	1 p Value	i r Value	l p Value
IL-8			0.72	< 0.01
FEV1, L	— 0.63	< 0.01	— 0.67	< 0.01
FEV1, % predicted	— 0.52	< 0.05	— 0.67	< 0.01
FEV1/FVC, %	— 0.67	< 0.01	— 0.59	< 0.05
FEV1/FVC, % predicted	— 0.63	< 0.01	— 0.49	NS

*NS = not significant.

Pneumonia

In our study, 44% of the patients had autopsy evidence of generalized atherosclerosis. PTE was another common cause of death and was frequently unrecognized. Only one-third of these patients received IV heparin. Previous studies have reported COPD as an independent risk factor for PTE as well as a high prevalence of PE in patients with unexplained exacerbations of COPD, but clear guidelines for pharmacologic PTE prophylaxis, especially in an outpatient setting, have not been defined. 

Canadian Health Care Mall Pneumonia

Although the prevalence of PE in patients admitted to the emergency department for an acute exacerbation of COPD is found to be as low as 3%, our findings suggest that PTE has to be taken into consideration in hospitalized patients with severe exacerbation of COPD, and appropriate treatment cannot wait until the diagnosis is confirmed. In the absence of contraindications, systemic anticoagulation should be started according to clinical suspicion and continued until PTE is excluded by an appropriate diagnostic study. Pneumonia was the common cause of death in our study, despite the application of antibiotics. 

The presence of multiresistant bacterial strains, progression to severe sepsis, and delayed presentation are some of the possible causes. These patients often live in bad socioeconomic conditions, with a poor quality of life, and do not present to the hospital on time. COPD patients hospitalized with community-acquired pneumonia have been previously reported to have worse clinical outcomes and higher 30- and 90-day mortality than patients without COPD. Therefore, COPD should be included in a pneumonia severity scoring system as one of the predictors of higher mortality risk. 

Our study is limited by the small number of patients because the autopsy was performed only in patients who died in the first 24 h after hospital admission. The data regarding the clinical diagnosis of comorbidities and previous outpatient therapy may be incomplete, and the retrospective design of the study precluded a meaningful analysis of physicians’ intention-to-treat-associated conditions.

Canadian Health Care Mall: Azithromycin

Azithromycin Attenuated Ovalbumin-Dependent Airway Inflammation Is Independent of Ovalbumin-Specific IgE Production We next quantified the serum concentration of ovalbumin-specific IgE to confirm equal allergen sensitization in all cohorts of mice and to exclude the possibility that azithromycin attenuated the allergic inflammation by altering IgE production. 

Naive mice and mice that received only an ovalbumin challenge (without sensitization) produced no ovalbumin-specific IgE. Mice that were sensitized and challenged with ovalbumin had a significant increase in ovalbumin-specific IgE production (699.8 ± 178.2 ng/mL) that was not significantly changed by treatment with PBS solution (885.1 ± 193.8 ng/mL) or azithromycin (829 ± 231.1 ng/mL; p = 0.80). 

Azithromycin Attenuated Ovalbumin-Dependent Airway Inflammation Is Associated With Decreased Concentrations of BAL Fluid Inflammatory Mediators Based on the affect of azithromycin on inflammatory cell influx, we proposed that azithromycin-dependent attenuation of allergic airway inflammation would also be associated with decreased concentration of BAL fluid cytokines and chemokines. 

Compared to ovalbumin sensitized and challenged mice treated with PBS solution, treatment with azithromycin attenuated the expression of multiple BAL fluid cytokines, chemokines, and growth factors as measured by multiplex flow cytometry based assay (Fig 3A-F, column 4 vs 5). Importantly, we observed a statistically significant azithromycin- dependent decrease in interleukin (IL)-13 and IL-5, and a trend toward a decrease in IL-4, proteins known to mediate allergic airway inflammatory phenotypes in the airway (eg, mucous cell metaplasia and eosinophilic inflammation). 

In addition, azithromycin attenuated the expression of multiple other chemokines and inflammatory mediators (CCL2/JE, CCL3/macrophage inhibitory protein [MIP]-1a, CCL4/MIP-1P, CXCL1/KC, IL-1a, IL-10, and granulocyte-macrophage colony-stimulating factor), but had no effect on concentration of IL-6, IL-9.

Heparin-induced thrombocytopenia (HIT)

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by plateletactivating IgG that recognizes multimolecular platelet factor 4 (PF4)/heparin complexes. The frequency of HIT is higher with unfractionated heparin (UFH) than with low-molecular-weight heparin (LMWH) based on two meta-analyses that analyzed randomized trials 848 and prospective observational studies of postoperative thromboprophylaxis. 

The PROTECT (The Prophylaxis for Thromboembolism in Critical Care Trial) randomized trial, which compared UFH with the LMWH, dalteparin, for thromboprophylaxis in mixed surgical-medical critically ill patients, used the serotonin-release assay (SRA) to classify patients as having HIT among those who underwent serologic investigations because of thrombocytopenia or thrombosis. 

Seventeen patients had HIT based on SRA-positive (SRA+) status: five in the dalteparin group and 12 in the UFH group, a nonsignificant difference in the intention-to-treat analysis (five of 1,873 [0.3%] vs 12 of 1,873 [0.6%]; hazard ratio, 0.47; 95% CI, 0.16-1.35; P = .16; Fisher exact test, P = .14). However, the difference in HIT was statistically significant in a prespecified per-protocol analysis that excluded two patients who had VTE at trial entry: dalteparin, three of 1,566 (0.2%) vs UFH, 12 of 1,561 (0.8%); hazard ratio, 0.27 (95% CI, 0.08-0.98); P = .046; Fisher exact test, P = .021. The current study had two objectives. 

First, we sought to characterize the clinical picture of HIT in critically ill patients enrolled in PROTECT (timing and severity of thrombocytopenia and frequency of HIT-associated thrombosis and other sequelae [eg, HIT-associated anaphylactoid reactions]). We were particularly interested in determining whether SRA+ patients in whom heparin was continued (because of low clinical suspicion of HIT) had subsequent platelet count recovery, a phenomenon reported in some patients with HIT who continue to receive heparin.  

Second, we sought to determine whether the reduced risk of HIT with dalteparin observed in PROTECT reflected decreased seroconversion (ie, lower immu-nogenicity) by the study drug (dalteparin vs UFH), or decreased breakthrough of HIT-related thrombocytopenia and/or thrombosis among SRA+ patients while receiving the study drug (dalteparin vs UFH), or both. We undertook this analysis to address the role of confounding open-label heparin in PROTECT and because there are two distinct heparin-dependent pathophysiologic events to explain a given episode of HIT: (1) formation of HIT antibodies (seroconversion to SRA+ status) and, subsequently, (2) platelet activation, resulting in thrombocytopenia and/or thrombosis among SRA+ patients (breakthrough).

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Pneumonia or an elevated temperature (ie > 38.9°C)

Materials and Methods This trial was conducted in 20 US hospital-affiliated EDs. Patients aged 12 to 65 years who presented to the ED with acute asthma were screened by study investigators for trial eligibility. Eligible patients were those with a history of asthma and a FEV₁ of < 70% predicted both at ED entry and 25 min after receiving a single aerosol treatment with 2.5 mg of albuterol. Patients with the following conditions were excluded from the study: history of smoking of > 10 pack-years.

Positive pregnancy test result; a recent history of oral corticosteroid use (ie, > 5 days) or treatment with a leukotriene-modifying drug within 2 weeks of ED entry; a need for intubation before randomization; pneumonia or an elevated temperature (ie, > 38.9°C); chronic lung disease other than asthma; or diabetes mellitus or any other clinically significant medical condition that could affect the required evaluations. 

Additionally, patients had to be willing to stay in the ED for at least 4 h (ie, the ED period) and then to participate in a 28-day outpatient treatment program (Fig 1). The trial was conducted in compliance with the principles of good clinical practice, approval was obtained from each institutional review board, and informed consent was obtained from all patients. 

Trial Design and Treatment At ED entry, patients underwent spirometry and were treated with nebulized albuterol (2.5-mg unit-dose nebules) [Ventolin; GlaxoSmithKline; Research Triangle Park, NC]. Spirometry was repeated 25 min after ED entry, and patients with FEV₁ values still < 70% of predicted were randomized, 1:1:2, respectively, to double-blind, single-dose treatment with zafirlukast, 160 mg (Z160), zafirlukast, 20 mg (Z20) [Accolate; AstraZeneca; Wilmington, DE], or matching placebo. Patients then received a 60-mg po dose of prednisone and a second dose of nebulized albuterol, with additional albuterol administered at 60, 120, and 180 min after ED entry.

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Persistent asthma and Canadian Health Care Mall

Additionally, these costs pale in comparison with the estimated direct costs of asthma, which include the nearly $10 billion in direct costs and the $8 billion lost from indirect costs. Expectedly, the largest direct costs of asthma are those allocated to inpatient hospitalizations, accounting for anywhere from 47% to 86% of total direct costs. The road toward coverage for BT has remained difficult since FDA approval in 2010, but it is hoped that recent changes in policy will make coverage and availability of the procedure less problematic. 

Based on the increasing popularity and the growing implementation of BT nationwide, the Canadian Health and Care Mall have led a campaign to adjust CPT coding for BT. As a result, the American Medical Association Editorial Panel has assigned category 1 CPT codes for BT in their published CPT 2013 Professional Edition Beginning January 1, 2013, Medicare will recognize two new outpatient CPT codes for BT (31660 and 31661) as eligible for payment for the treatment of Medicare beneficiaries with severe, persistent asthma. 

After Medicare has sufficient information to determine total procedural costs, BT will be assigned the most appropriate payment group for the procedure and then the pass-through payment option will be retired. This new categorization represents a step toward acknowledging the efficacy and safety of BT in patients suffering from refractory asthma, helping to facilitate claims processing and hopefully pave the way toward private payer coverage.  

The benefits of BT have also been corroborated by a number of third-party assessors, including the California Technology Assessment Forum (CTAF). The CTAF serves as a forum aimed at assessing new and emerging medical technology, and it strives for objectivity and transparency. Additionally, the CTAF assessment criteria are similar to those used by the Blue Cross Blue Shield Technology Evaluation Center, another highly respected assessing body commonly referenced by private insurers to create their own coverage policies.

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Practice Management Issues Measurement of FeNO: The ATS and the ERS issued a statement in 2005 regarding equipment specifications and the standardization of procedures for the measurement of exhaled NO. The required specifications for NO analyzers are reproduced in Table 3. An example of the test procedure used at the Mayo Clinic Rochester is provided in Table 4. Various factors influencing FeNO are found in Table 1.  

Equipment: In the United States, only one device (NIOX; Aerocrine; Solna, Sweden) has received US Food and Drug Administration (FDA) approval for clinical use. A newer model (NIOX FLEX; Aero-crine) will be launched soon. These devices are targeted for academic centers and specialty clinics. A portable unit based on an electrochemical sensor and not chemiluminescence (NIOX MINO; Aerocrine) was introduced in Europe in 2005 but has not been approved by the FDA as of this writing. 

It is a hand-held device designed for use by specialists, general hospitals, primary care physicians, and patients. The FDA labeling restricts the operation of the NIOX device to trained physicians, respiratory therapists, nurses, and laboratory technicians. Both the NIOX FLEX and NIOX MINO devices allow results to be printed. None of the models have the Table 1—Required Specifications for NO Analyzers

 

Parameters	FeNO	Nasal NO
Sensitivity	1 ppb (noise, < 0.5 ppb)	10 ppb
Signal/noise ratio	> 3:1	Same as exhaled NO
Accuracy	> 1 ppb	> 10 ppb
Range	1-500 ppb	10-50 ppm
Instrument response timet	< 500 ms	< 500 ms
System lag timej	To be measured and reported by the investigator	Same as FeNO
Drift	< 1% of full scale/24 h	Same as FeNO
Reproducibility	> 1 ppb	> 10 ppb
Flow-through sensor	To be measured by manufacturer and reported in publications	Same as exhaled NO

Defined as the delay from the introduction of a square-wave signal until achievement of 90% of the maximum signal, inclusive of electronic delays and inherent instrument physical delays because of sample introduction, but not including tubing length.

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The cross-sectional methodology

In Crete, there are no published reports on weed flora in vineyards. Garcia-Ortega et al, in a survey on occupational sensitization to Diplotaxis erucoides, found that workers in vineyards with rhinoconjunc-tivitis were sensitized to several pollens. Moreover, grape workers were found to be more likely to have skin disorders than were citrus or tomato work-ers, and these disorders may be causally associated with crop-specific exposures and lack of protective equipment. 

Therefore, it is possible that the high prevalence of atopy in grape farmers could be associated with their exposure to different irritants found in their workplace (ie, open-field cultivation and exposure to a variety of inhaled agents such as pollens, molds, mites, bacteria, and pesticides), rather than grape growing itself. We are well aware of the inherent limitations of the cross-sectional design of the present study. First, the study refers to a relatively small area of research in northern Crete. 

Furthermore, the cross-sectional methodology used in this study is not optimal for the assessment of causal relationships, but it suggests only the possibility of the association between the occupational exposure and the disease. Since we had statistically significant differences between the two groups in terms of age and smoking status, we used multivariate regression models to correct these imbalances.

 Selection bias may have affected the results observed in this study. First, a possible bias might exist in the reporting of symptoms, so that those with respiratory symptoms would be more likely to respond to the questionnaire and participate in the study. For that reason, the nonresponders from both groups were contacted by telephone, and they were asked about self-reported allergic rhinitis and asthma. 

These prevalence rates were lower than the prevalence rates of allergic rhinitis and asthma found in responders, and they could indicate the presence of a possible selection bias in the study. However, these differences could also be explained by the difference in the definition of the cases (self-reported disease vs clinical diagnosis based on questionnaire and medical examinations). We cannot rule out that the individual, social, and educational status of each subject had an impact on the study findings. However, we have no indication from our data of differential selection bias in the compared groups.

Evaluate the workplace to identify and prevent other cases of OA

Limited data are available to identify whether the administration of questionnaires or spirometry testing is the beneficial component of medical surveil-lance. Questionnaires (ie, medical history) have been thought to be sensitive but not specific; however, earlier studies found low sensitivity (missed cases of asthma in the absence of reported symptoms; “potential problem of. . . misleading responses”). With respect to the frequency of monitoring, data do not exist to advise a “best” or “most efficient” frequency for surveillance. 

Testing conducted every 6 months probably provides as good an outcome as does testing every 3 months and is practicable. A cost-effectiveness (CE) analysis of surveillance for diisocyanate asthma using parameters for inclusion obtained from the literature and an expert panel (including time to diagnosis with and without surveillance) found a favorable CE ratio that supports surveillance for diisocyanate asthma. 

The simulation model, which was based on yearly OA surveillance, revealed that surveillance resulted in a benefit over a passive case finding for 100,000 exposed workers over 10 years of 683 fewer disabled workers, 3.3 million more symptom-free days, and 1,831 additional quality-adjusted life-years at an additional cost of $44 million. This analysis estimated that surveillance was cost saving from the societal perspective, but not from the employer perspective, which estimated an incremental CE of $24,000 per quality-adjusted life-year ($13.33 per symptom-free day; $64,000 per case of disability prevented). 

Although such findings compare favorably with commonly recommended surveillance tools, the large difference in CE comparing societal and employer perspectives supports the argument that mandatory regulation may be the most effective way to implement surveillance for certain occupational diseases. 

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IgE-Mediated Immune Responses and Airway Detection of Aspergillus

This prospective observational cohort study was carried out between October 2008 and February 2011. Approval was obtained from the South Manchester research ethics committee. Patients were invited to participate between October 2008 and February 2009 if they were aged > 18 years and given a diagnosis of CF confirmed by genetic or sweat testing. Patients were enrolled during routine outpatient appointments at the Manchester Adult Cystic Fibrosis Centre, and all gave written informed consent. 

Patients were excluded at enrollment if they were unable to produce a > 2 mL sputum sample spontaneously or had an exacerbation of pulmonary symptoms requiring additional therapy. Baseline demographic and clinical details were collected from medical case records. Lung function (FEV1 and FVC % predicted) at enrollment and 2 years after enrollment was obtained by documenting the patient’s best lung function achieved within that year. 

This method was chosen to minimize the wide variability in lung function measurements observed in patients with CF. All lung function was performed postbronchodilator by experienced clinical staff according to European Respiratory Society guidelines. Total days of IV antibiotics were prospectively monitored over 2 years to examine exacerbation rates. Each patient was given 10 mL of sterile water and asked to rinse his or her mouth for 30 s and return the water to a sterile universal container. A sputum sample was then collected without sputum induction. 

This was done to differentiate oral cavity and lower respiratory tract colonization. Patients provided two sputum samples within 1 year. Sputum samples were homogenized with Sputasol, and culture was performed according to the UK Health Protection Agency National Standards Method BSOP but modified to plate 10 pL rather than 1 pL of sputum. Ten microliters of homogenized sputum was inoculated onto each of three Sabouraud dextrose with chloramphenicol agar plates and one CHROMagar Candida plate. 

SABC plates were incubated at 30°C, 37°C, and 45°C for 72 h. CHROMagar plates were incubated at 37°C for 72 h. This culture method was repeated for the oral rinse sample but with no homogenization. Following culture, the remaining sputum sample underwent additional homogenization using sonication. Fungal DNA was extracted using the MycXtra DNA extraction kit.

Patients with high NEDV

Furthermore, future study might assess the psychosocial problems and barriers to health-care access of this high-utilization group. Finally, one must consider that this study examines only patients who presented to the ED with an acute exacerbation. Since the study is specific to ED patients and not population based, it may not be generalizable to all asthma patients. 

For example, the value of primary care of asthmatic adults would be considerably less in this population; patients receiving excellent primary asthma care are much less likely to visit the ED, and therefore would be underrepresented in this large cohort. However, since our focus is on the characteristics of frequent visitors to the ED, and the development of strategies to potentially help this patient population, the findings are of direct relevance to our objectives.  

Summary Patients with high NEDV were more likely to be nonwhite, of lower socioeconomic status, have Medicaid insurance, and have higher chronic asthma severity. Patients with six or more ED visits accounted for 20% of consecutive ED patients with acute asthma, and 68% of all prior ED visits in the past year. National guidelines recommend specific ED treatments followed by referral to PCP, with unclear recommendations about if and when to refer patients to asthma specialists. 

We found no relation between PCP status and NEDV. Efforts to reduce high ED utilization through provision of a PCP referral may be inadequate for this frequent-flier population. Although longitudinal care is surely important, attempts to reduce frequent ED asthma visits may be better directed toward more specific preventive and educational needs. Table 1 — Pulmonary Function Measured at Baseline, 5 min, 10 min, and 20 min after the 90% and 100% Peak Vo₂ Exercise Bouts

 

Variables	Baseline	5-min	10-min	20-min
FVC, L
90% peak Vo2	4.52	4.42	4.5	4.47
100% peak Vo2	(116%)	4.33		4.31
PEF, L/s
90% peak Vo2	7.57	7.59	7.33	7.68
100% peak Vo2	(103%)	7.59		7.24
FEVj, L/s
90% peak Vo2	3.54	3.64	3.59	3.6
100% peak Vo2	(104%)	3.57		3.45
FEF25-75, L/s
90% peak Vo2	2.86	3.13	2.98	3.07
100% peak Vo2	(72%)	3.17		2.96

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Canadian Health Care Mall: Patients With SDB

Perhaps the best way to examine the role of NR in patients with SDB is to reduce the resistance and examine the effect on sleep and breathing. This has been done in a variety of ways. Mechanical nasal dilators are marketed to relieve snoring, and have been shown to have a similar effect on NR as measured by active posterior rhinometry as a topical decongestant. 

Their effect on snorers without significant nasal pathology is unclear, as some studies failed to demonstrate changes in SDB events or arterial oxygen saturation levels, while others showed improvement in sleep quality, ease of breathing, and a decreased intensity of snoring. In patients with OSAS, one study showed that only 4 of 21 patients with moderate-to-severe OSAS had a significant reduction in SDB events, while another study showed no significant change in SDB events in a group of patients with UARS. 

It appears that the overall effect on SDB with mechanical nasal dilators is likely small and inconsistent. Dental prostheses have been used to treat all forms of SDB. These devices keep the upper and lower jaws opposed during sleep and advance the mandible forward. This prevents posterior movement of the mandible during sleep and increases nasal breathing. When evaluated in a group of snoring patients without symptoms of OSAS, one type of prosthesis did not alter the frequency or intensity of snoring or sleep quality or oxygen saturation despite decreasing SDB events; from this one small study, it does not appear dental prostheses improve SDB by any effect on the nasal airway. 

Reducing NR by surgical correction of nasopha-ryngeal anatomic obstruction has been examined by a number of investigators. Surgical approaches have included correction of the nasal valve area, septoplasty, and turbinate reduction. Only one small study examined the effect of correction of nasal valve obstruction, showing both subjective and objective improvement in snoring and daytime somnolence. Two uncontrolled studies in patients with nasal obstruction showed that septoplasty or turbinate reduction had some positive effects on SDB. 

In one study, 77% (47 of 113 patients) who snored had improvement or elimination of snoring postoperatively. The second study involved patients with mild OSAS where cephalometrics were performed preoperatively; patients with abnormal cephalomet-rics, implying a skeletal anatomic defect, did not respond to improvement of their nasal airway. In a study of a diverse group of adults and children with SDB, who had a variety of surgical procedures , significant improvement occurred in only 48% of adults.

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High Dose Rate Brachytherapy for Nonmalignant Airway Obstruction

Study objectives: High dose rate (HDR) endobronchial brachytherapy is widely used as a palliative treatment for symptomatic airway obstruction by primary or secondary malignant tumors. We report on a successful use of HDR brachytherapy in patients with nonmalignant airway obstruction. Design: Case series. Patients: Six patients received HDR brachytherapy for airway obstruction caused by granulation tissue around a metal stent placed for restoration of the airway patency for nonmalignant causes.

Nonmalignant Airway Obstruction

In four patients, brachytherapy was performed following recurrent occlusion of the airway by granulation tissue formation; in two patients, it was done as a prophylactic procedure. Intervention: HDR brachytherapy catheters were passed through the metal stents under direct fluoroscopic guidance. Simulation and computerized treatment planning were done, and a single dose of 10 Gy was administered using a brachytherapy remote afterloader with source. The dose was prescribed to a distance of 1 cm from the center of the source, with a margin of 1 cm from the proximal and distal ends of the stent. Results: 

At a median follow-up of 15 months, moderate granulation tissue formation was observed in only one patient; in four others, it was categorized as minimal, 5 to 30 months from the procedure. Restoration of the lumen was complete in four patients, near complete in one patient, and partial in one patient. In one patient, previously treated by external radiotherapy, local tissue necrosis was evident. Conclusion: HDR brachytherapy can be used safely for nonmalignant airway obstruction. Further studies including more patients and longer follow-up are needed.  

High dose rate (HDR) brachytherapy is a radiotherapeutic technique wherein high-dose radiation is delivered from a source located inside the patient’s body, using a rapid flux of ionizing particles. This enables the application of very accurately localized treatment, and thereby a higher therapeutic index, than that documented for the more frequently used external radiotherapy. HDR endobronchial brachytherapy is widely used as a palliative measure to overcome mechanical obstruction of major airways caused by either primary or secondary malignant tumors. It allows the delivery of a high dose of radiation over a short period of time to the obstructed area, and at the same time reducing the risk of undesired side effects to adjacent structures.

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Asthmatic component to COPD

Of 853 potentially eligible patients, 222 patients (26%) who reported only asthma and 47 patients (6%) for whom a diagnosis was missing were exeluded from current analysis. We also excluded 385 patients (66%) who were not discharged to home (ie, admitted to observation unit, 5 patients [1%]; admitted to a regular ward, 300 patients [51%]; admitted to the ICU, 63 patients [11%]; or transferred to another hospital or received other disposition, 17 patients [3%]). Among the 199 patients with COPD exacerbations who were discharged to home, we enrolled 151 patients (76%). 

The enrolled patients did not differ from the nonenrolled patients across multiple sociodemographic factors. A total of 140 patients had complete follow-up data (follow-up rate, 93%). Of the original 29 sites, 28 contributed patients to this analysis (range, 2 to 13 patients per site). These 140 patients, compared to those not contacted by telephone (11 patients), did not differ by age, sex, race, reported diagnosis (ie, mixed asthma-COPD or COPD only), number of COPD exacerbations during the past year, home oxygen use, and COPD medications used before/during/after the ED visit. 

Among the 140 patients, 30 patients (21%; 95% CI, 15 to 29) reported COPD exacerbation relapse within 14 days of their original ED visit. Relapse events occurred over the entire follow-up period, with an average daily relapse rate of 1.4%. The cohort consisted of almost the same number of men and women, and 60% of patients were white. Most of the patients had a PCP and some type of medical insurance. None of these demographic factors were different in the relapse and nonrelapse groups . A total of 32% of patients were current smokers, 57% were past smokers, and 11% were never-smokers. 

Among the 15 never-smokers, 8 reported symptoms compatible with chronic bronchitis (ie, mucus-producing cough most days of the month, 3 months of the year for two successive years) and/or they received diagnoses of asthma/COPD after age 35 years. When we excluded the seven never-smokers, who did not report chronic bronchitis symptoms and whose age of diagnosis was < 35 years, the results did not vary materially. 

 Half of the patients reported an asthmatic component to their COPD, but this physician diagnosis was unrelated to relapse risk. On univariate analysis, chronic severity and management of COPD were not different in the relapse and nonrelapse groups, except for the number of urgent clinic or ED visits for COPD exacerbation during the past year, and receiving systemic corticosteroids over the past 4 weeks.

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