Safety considerations in the management of allergic diseases: focus on antihistamines.

OBJECTIVE: To conduct a systematic review of evidence supporting the safety profiles of frequently used oral H(1)-antihistamines (AHs) for the treatment of patients with histamine-release related allergic diseases, e.g. allergic rhinitis and urticaria, and to compare them to the safety profiles of other medications, mostly topical corticosteroids and leukotriene antagonists (LTRA). RESEARCH DESIGN AND METHODS: Systematic search of the published literature (PubMed) and of the regulatory authorities databases (EMA and FDA) for oral AHs. RESULTS: Similarly to histamine, antihistamines (AHs) have organ-specific efficacy and adverse effects. The peripheral H(1)-receptor (PrH1R) stimulation leads to allergic symptoms while the brain H(1)-receptor (BrH1R) blockade leads to somnolence, fatigue, increased appetite, decreased cognitive functions (impaired memory and learning), seizures, aggressive behaviour, etc. First-generation oral AHs (FGAHs) inhibit the effects of histamine not only peripherally but also in the brain, and additionally have potent antimuscarinic, anti-α-adrenergic and antiserotonin effects leading to symptoms such as visual disturbances (mydriasis, photophobia, and diplopia), dry mouth, tachycardia, constipation, urinary retention, agitation, and confusion. The somnolence caused by FGAHs interferes with the natural circadian sleep-wake cycle and therefore FGAHs are not suitable to be used as sleeping pills. Second-generation oral AHs (SGAHs) have proven better safety and tolerability profiles, much lower proportional impairment ratios, with at least similar if not better efficacy, than their predecessors. Only SGAHs, and especially those with a proven long-term (e.g., ≥12 months) clinical safety, should be prescribed for young children. Evidence exist that intranasally applied medications, like intranasal antihistamines, have the potential to reach the brain and cause somnolence. CONCLUSIONS: Second-generation oral antihistamines are the preferred first-line treatment option for allergic rhinitis and urticaria. Patients taking SGAHs report relatively little and mild adverse events even after long-term continuous treatments. An antihistamine should ideally possess high selectivity for the H(1)-receptor, high PrH1R occupancy and low to no BrH1R occupancy.

Clinical Pulmonary Infection Score to diagnose ventilator-associated pneumonia in children.

BACKGROUND: There is a need to validate and suggest easy clinical method for diagnosis of ventilator-associated pneumonia (VAP) in developing countries. OBJECTIVES: To validate the use of simplified Clinical Pulmonary Infection Score (CPIS) for the diagnosis of VAP. DESIGN: Prospective study. SETTING: Pediatric intensive care unit of a tertiary care teaching hospital. SUBJECTS: 30 children receiving mechanical ventilation for more than 48 hours and with simplified CPIS=6. METHODS: All patients underwent flexible bronchoscopy to obtain bronchoalveolar lavage which was analyzed quantitatively. Colony count = 10(4) cfu/mL was considered reference standard for definite VAP. RESULTS: Of the five variables used for simplified CPIS, only patients temperature (P=0.013) and PaO2/FiO2 ratio were significant (P<0.001) to differentiate the presence of definite VAP. Patients with definite VAP (BAL colony count = 10(4) cfu/mL) had CPIS of 8.4 while in no definite VAP group it was 6.4 (P=0.007). CPIS of 8 was found to have sensitivity of 80%, specificity 80%, PPV 86.9%, NPV 70.5% and accuracy 80%. The area under Receiver operating characteristic curve of CPIS against reference standard was 0.81± 0.069 (P=0.001). CONCLUSION: Simplified CPIS is useful in patients on mechanical ventilation to diagnose ventilator-associated pneumonia.

Disability and quality of life in schizophrenia and obsessive compulsive disorder: a cross-sectional comparative study.

OBJECTIVE: To assess and compare the quality of life and disability in patients with schizophrenia and obsessive compulsive disorder. METHODS: A cross-sectional study was carried out in the outpatient psychiatry clinics at Jaipur of India. Fifty patients with obsessive compulsive disorder and 47 with schizophrenia (diagnosed as per criteria of the 10th revision of the International Classification of Diseases), and with a minimum duration of 2 years on maintenance treatments, were evaluated. Evaluation was based on the World Health Organization Quality of Life Instrument, the Global Assessment of Functioning scale, and the Indian Disability Evaluation Assessment Scale. The collected data were analysed using descriptive and inferential statistics. RESULTS: Regarding quality of life domains, there was no statistically significant difference between the 2 groups. Obsessive compulsive disorder patients had lower scores on all domains of disability, all such differences being statistically significant. CONCLUSIONS: The deleterious effect of illness on quality of life and functioning occur not only in schizophrenic but also in obsessive compulsive disorder patients. Thus management should be planned with this consideration to yield better outcomes in both conditions.

Blood glutathione levels in head and neck malignancies.

Blood glutathione was estimated in fifty patients of head and neck cancer in the age group of 18-76 years and the results were compared with a group of normal healthy controls. Mean blood glutathione level was found to be significantly lowered in patients than the controls. Irrespective of the site, TNM classification, histopathology, and character of lesion, fall in blood glutathione was nearly same in all the patients. The mean level was significantly increased after radiotherapy when compared with the levels before radiotherapy. The decreased levels of GSH in-patients with head and neck cancer, observed in the present study, may be due to its increased utilization by the cells. The results suggest that patients with head and neck cancer have increased oxidative stress.

Clinical approach to a patient with cough.

A number of disorders of the respiratory tract and some even outside the respiratory tract can cause cough. A systematic approach towards a patient of chronic cough consisting of detailed history, physical examination of upper as well as lower respiratory tract, complete blood counts, tuberculin test, chest X-ray, and peak flow rate testing will give the diagnosis in majority of children. Pulmonary tuberculosis and asthma are the two commonest conditions diagnosed. If the initial work up is inconclusive, further laboratory testing and imaging studies should be considered. Thus, radiolabelled milk scan, barium swallow and 24-hour pH monitoring would diagnose gastroesophageal reflux. Spirometry, methacholine/exercise challenge test or a therapeutic trial may be required for confirming bronchial asthma. Flexible bronchoscopy is useful for evaluation for suspected aspiration syndromes and any anatomical or dynamic problem of the airway (e.g. tracheomalacia). Spiral and high resolution computed tomography (HRCT) along with magnetic resonance imaging are the modern day imaging techniques used for studying mediastinal masses, airway obstruction and even lung parenchyma (HRCT). Sputum examination for type of cells and bacteria can be useful, especially if pseudomonas or acid-fast bacilli are identified. Pseudomonas suggests cystic fibrosis (an uncommon disease in India) which can be confirmed by sweat chloride test and gene mutation studies.

Difficult asthma.

Children with asthma who are not well controlled in spite of optimum therapy outlined in Asthma Management Guidelines are said to have 'difficult-to manage asthma' or 'difficult asthma'. Several phenotypes of this subset of asthma have been described. However, before any child is labeled as difficult asthma a thorough search for an alternative diagnosis should be made. Thus, one should look for recurrent aspiration pneumonia, tuberculosis, foreign body aspiration, tracheomalacia, bronchomalacia, cystic fibrosis etc. Causes of treatment failure range from unidentified exacerbating factors, noncompliance, inappropriate inhalers and spacers and true steroid dependence or resistance. Economics of the treatment and social beliefs should also be taken into consideration at the time of finalizing the management plan. Management involves recognizing and correcting the above factors. However, steroids form the main pillar of treatment. Majority of the patients can be controlled by optimizing inhaled steroid therapy and possibly adding steroid sparing agents. Thus, long acting bata-2 agonists, long acting theophyllines and leukotriene inhibiters may be useful. A few children will require continuous oral steroid therapy and an occasional one may be actually steroid steroid resistant. Such children are best managed at asthma specialist centers where experimental drugs like, methotrexate cyclosporin or IVIG may be tried on an individual basis under close monitoring.

Management of dengue fever in ICU.

Dengue virus infection can cause a wide spectrum of illness. Thrombocytopenia with concurrent haemoconcentration differentiates dengue haemorrhagic fever from classical dengue fever. Only cases with shock or unstable vitals signs need admission in the pediatric intensive care. The management is essentially supportive and symptomatic. The key to success is frequent monitoring and changing strategies. A rise in hematocrit of 20% along with a continuing drop in platelet count is an important indicator for the onset of shock. Patients in grade I and II should be closely monitored for signs of shock. The management of dengue shock syndrome (grade III and IV) is a medical emergency needing prompt and adequate fluid replacement for the rapid and massive plasma losses through increased capillary permeability. Early and effective replacement of plasma losses with plasma expanders or fluid and electrolyte solutions results in a favourable outcome in most cases. The ideal fluid management should include both cystalloids and colloids (including albumin). Cystalloids are given as boluses as rapidly as possible, and as many as 2 to 3 boluses may be needed in profound shock. Colloidal fluids are indicated in patients with massive plasma leakage and in whom a large volume of cystalloids has been given. Frequent recording of vital signs and determinations of haematocrit are important in evaluating the results of treatment. Apart from correction of electrolyte and metabolic disturbances, oxygen is mandatory in all patients of shock. Some patients develop DIC and need supportive therapy with blood products (blood, FFP and platelet transfusions). Polyserositis, in the form of pleural effusion and ascitis, are common in cases of dengue shock syndrome, and if possible, drainage should be avoided as it can lead to severe hemorrhages and sudden circulatory collapse. The prognosis depends mainly on the early recognition and treatment of shock.

ICU management of severe malaria.

Malaria is very common in India. First step in management of malaria is to establish the diagnosis. It is established by using traditional smear or method like dipstick antigen captures assay which is simpler, accurate and doesn't require expertise. Next step is to look for signs and symptoms, which help cases of severe malaria should be admitted in intensive care unit (ICU) and antimalarial chemotherapy should be started through parenteral route. Complications like coma, anemia, renal failure, pulmonary edema, disseminated intravascular coagulation are not very uncommon. These complications should be anticipated and treated in time. There is no role of corticosteroids, mannitol in the treatment of cerebral edema. Therapeutic monitoring of severe malaria should involve quantitative estimation of parasite load.

Glibenclamide vs gliclazide in reducing oxidative stress in patients of noninsulin dependent diabetes mellitus--a double blind randomized study.

OBJECTIVE: Parameters of oxidative stress were quantitated in 50 patients with type 2 diabetes mellitus in uncontrolled state and after control using oral glibenclamide or gliclazide. The estimates were further compared between the two groups irrespective of drug used to evaluate the difference, if any. METHODS: The study was a double blind, uncontrolled, noncrossover and randomized trial. Fifty patients of uncontrolled type 2 diabetes were divided in to two groups. Group I (25 patients) received capsule A (glibenclamide) while Group II (25 patients) received capsule B (gliclazide). The parameters studied were Superoxide dismutase (SOD), malonyl-dialdehyde (MDA) and reduced glutathione (GSH). They were done at (a) uncontrolled stage (FBS--165 +/- 16.7 mg/dl, PP--240 +/- 30.1 mg/dl and HbA1--10.5 +/- 0.9% in group I and FBS--150 +/- 15.8 mg/dl, PP--246 +/- 29.1 mg/dl HbA1 10.6 +/- 0.8% in group II) and during controlled stage at 12 weeks (FBS--120 +/- 18.5 mg/dl, PP--180 +/- 19.1 mg/dl and HbA1--8.4 +/- 0.29% in group I and FBS--118 +/- 17.6 mg/dl, PP--176 +/- 20.1 mg/dl and HbA1--8.5 +/- 0.39% in group II patients). RESULTS: The significantly raised levels of MDA and SOD, and decreased levels of reduced glutathione (GSH) during uncontrolled stage of diabetes indicated free radical stress induced lipid peroxidation. The significant fall of MDA and SOD and increased levels of GSH in blood in both groups after control revealed beneficial effects of glycemic control on oxidative stress. The levels were not normalized and stayed higher than those in controls. On intergroup comparison; the control of diabetes with gliclazide (group II) showed improvement in oxidative stress (MDA, GSH) better (p < 0.001) than glibenclamide (group I). CONCLUSION: Oxidative stress in uncontrolled diabetes is decreased with glycemic control. The control of diabetes with gliclazide reduced oxidative stress more than glibenclamide, indicating higher antioxidant properties of gliclazide. Normalization of oxidative stress was not achieved. Further studies are required to see long-term effect of drug therapy in combating oxidative stress after achieving acceptable control of diabetes.

Material property determination of sub-surface objects in a viscoelastic environment.

Modeling human organs and soft tissue or anatomic regions for the purpose of medical training and simulation is a relatively new area. The data presented here is the groundwork for our ongoing development of a real-time haptic virtual environment for abdominal soft tissue palpation. The purpose of modeling the human abdomen is twofold. First, to provide a mathematical description of soft tissue and organs and second, to simulate the behavior of realistic interactions in real-time within a virtual environment. We have developed a, non-invasive, system that will allow us to determine mathematical functions that model the deformation of individual layers of soft tissue within the human abdomen. This system has been tested, experimentally, with a viscoelastic polyester foam model. We have been able to determine the stiffness and force/displacement function of an object beneath two layers of foam having different material characteristics. These experimental results correlate well with known polyester foam material characteristics. In general, the calculated stiffness constants were within 5% of the actual value. The data presented in this study shows that this system may be a viable tool for accurate measurement of human soft tissue properties and behavioral response to palpation.

Pneumonia due to unusual organisms in children.

Generally antimicrobials for treatment of pneumonia are chosen to target the usual bacterial etiological agents. Such regimens are unable to cure patients of pneumonia caused by 'unusual organisms' mycoplasma, chlamydia, Pneumocystis carinii and Legionella pneumophilus). Thus, there is a need to anticipate their presence in appropriate cases and to plan the initial antimicrobial therapy accordingly. Studies in Europe as well as India have shown that such infections form a fairly substantial percentage of community acquired pneumonia in children. Mycoplasma pneumoniae and Chlamydia pneumoniae are common in school age children while Chlamydia trachomatis occurs in early infancy. Pneumocystis carinii is an important pathogen in immunocompromised children. Routine laboratory tests and radiological features are not specific enough to give accurate diagnosis of these infections for which one has to depend on sophisticated culture techniques, immunological tests for the antigens or antibodies and polymerase chain reaction. Mycoplasma, chlamydia and legionella infections respond to macrolide antibiotics and for pneumocystis infections, trimethoprim-sulfamethaxozole or pentamidine is the drug of choice. Overall prognosis with appropriate treatment is good except for P. carinii infection in immunocompromised host which carries a high mortality and recurrence rate.