Meta-analyses of the efficacy of pharmacotherapies and sublingual allergy immunotherapy tablets for allergic rhinitis in adults and children.

BACKGROUND: Treatment options for seasonal and perennial allergic rhinitis (SAR/PAR) include pharmacotherapies and allergy immunotherapy. These meta-analyses evaluated the efficacy of pharmacotherapies and sublingual immunotherapy tablets (SLIT-tablets) versus placebo on nasal symptoms associated with SAR and PAR. METHODS: Randomized, double-blind, placebo-controlled trials were identified from systematic PubMED/EMBASE searches through 7/18/2019 (PROSPERO protocol CRD42018105632). The primary outcome was mean numerical difference in total nasal symptom score (TNSS; 0-12) between active treatment and placebo at the end of the assessment period. Random-effects meta-analyses estimated the mean difference for each medication group weighted by the inverse of the trial variance. Publication bias assessments and sensitivity analyses were conducted. RESULTS: Rescue symptom-relieving pharmacotherapy was prohibited in most pharmacotherapy trials but was allowed in all SLIT-tablet trials. For adult/adolescent SAR, the mean numerical difference (95% CI) in TNSS versus placebo was: intranasal corticosteroids (INCS)=1.38 (1.18, 1.58; 39 trials); combination intranasal antihistamine/INCS=1.34 (1.15, 1.54; 4 trials); intranasal antihistamines=0.72 (0.56, 0.89; 13 trials); oral antihistamine=0.62 (0.35, 0.90; 18 trials); SLIT-tablets=0.57 (0.41, 0.73; 4 trials); and montelukast=0.48 (0.36, 0.60; 10 trials). For adult/adolescent PAR, mean difference in TNSS versus placebo (95% CI) was: INCS=0.82 (0.66, 0.97; 14 trials); SLIT-tablets=0.65 (0.42, 0.88; 3 trials); and oral antihistamine=0.27 (0.11, 0.42; 3 trials). The number of eligible trials limited meta-analyses for pediatric SAR/PAR. CONCLUSIONS: All treatments significantly improved nasal symptoms versus placebo. SLIT-tablets provided improvement in TNSS despite access to rescue symptom-relieving pharmacotherapy. Extensive trial heterogeneity and strong indications of publication bias preclude the comparison of treatment effects among treatment classes.

Exploring factors associated with health disparities in asthma and poorly controlled asthma among school-aged children in the U.S.

Objective: Certain populations suffer disproportionately from asthma and asthma morbidity. The objective was to provide a national descriptive profile of asthma control and treatment patterns among school-aged children (SAC: aged 6-17) in the U.S. Methods: This was a cross-sectional analysis using the nationally representative 2007-2014 Medical Expenditure Panel Survey. Among SAC with asthma, indicators of poor control included: exacerbation/asthma attack; >3 canisters short-acting beta agonist (SABA)/3 months; and asthma-specific Emergency Department or inpatient visits (ED/IP). Results: Non-Hispanic black, non-Hispanic multiple races, Puerto Rican, obese, Medicaid, poor, ≥2 non-asthma chronic comorbidities (CC), and family average CC ≥ 2 were associated with higher odds of having asthma. The following had significantly higher odds ratios (OR) of excessive SABA use compared to non-Hispanic whites [OR; CI; p < 0.05]: Puerto Rican (3.8; 2.1-6.9), Mexican (3.6; 2.0-6.4), Central/South American (3.0; 1.2-7.7), Hispanic-other (3.1; 1.1-9.0), non-Hispanic black (2.5; 1.6-3.9), and non-Hispanic Asian (4.0; 1.7-9.2). SABA OR were also significant for Spanish spoken at home (2.5; 1.6-3.8), obese (2.1; 1.3-3.3), Medicaid (2.9; 2.0-4.1), no medical insurance (2.1; 1.1-4.1), no prescription insurance (2.5; 1.8-3.5), poor (2.8; 1.7-4.7), CC ≥ 2 (2.1; 1.6-2.8), parent-without high-school degree (2.5; 1.8-3.6), parent-SF-12 Physical Component Scale <50 (1.6; 1.2-2.1) and Mental Component Scale <50 (1.5; 1.1-2.0). Significant differences also existed across subgroups for ED/IP visits. Conclusions: There are disparities in asthma control and prevalence among certain populations in the U.S. These results provide national data on disparities in several indicators of poor asthma control beyond the standard race/ethnicity groupings.

The national burden of poorly controlled asthma, school absence and parental work loss among school-aged children in the United States.

OBJECTIVE: The degree of poorly controlled asthma and its association with missed school days and parental missed work days is not well understood. METHODS: This was a retrospective analysis of missed school days and missed work days for school-aged children (SAC; aged 6-17) and their caregivers in the nationally representative 2007-2013 Medical Expenditure Panel Survey (MEPS). Indicators of poor asthma control included: exacerbation in previous 12 months; use of >3 canisters of short-acting beta agonist (SABA) in 3 months; and annual asthma-specific (AS) Emergency Department (ED) or inpatient (IP) visits. Negative binomial regression was used for missed school days, and a Heckman two-step selection model was used for missed work days. All analyses controlled for sociodemographics and other covariates. RESULTS: There were 44,320 SAC in MEPS, of whom 5,890 had asthma. SAC with asthma and an indicator of poor control missed more school days than SAC without asthma: exacerbation (1.8 times more; p < 0.001); >3 canisters SABA (2.7 times more; p < 0.001) and ED/IP visit (3.8 times more; p < 0.001). The parents/caregivers of SAC with asthma and an exacerbation missed 1.2 times more work days (p < 0.05), while those with SAC with asthma and an ED/IP visit missed 1.8 times more work days (p < 0.01) than the parents of SAC without asthma. CONCLUSIONS: This study provides evidence of the significant national burden of poorly controlled asthma due to missed school and work days in the United States. More effective and creative asthma management strategies, with collaboration across clinical, community and school-based outreach, may help address this burden.

Assessment of treatment patterns associated with injectable disease-modifying therapy among relapsing-remitting multiple sclerosis patients.

BACKGROUND: Availability of oral disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS) may affect injectable DMT (iDMT) treatment patterns. OBJECTIVE: The objective of this paper is to evaluate iDMT persistency, reasons for persistency lapses, and outcomes among newly diagnosed RRMS patients. METHODS: Medical records of 300 RRMS patients initiated on iDMT between 2008 and 2013 were abstracted from 18 US-based neurology clinics. Eligible patients had ≥3 visits: pre-iDMT initiation, iDMT initiation (index), and ≥1 visit within 24 months post-index. MS-related symptoms, relapses, iDMT treatment patterns (i.e. persistency, discontinuation, switching, and restart), and reasons for non-persistency were tracked for 24 months. RESULTS: At 24 months, iDMT persistency was 61.0%; 28.0% of patients switched to another DMT, 8.0% discontinued, and 3.0% stopped and restarted the same iDMT. The most commonly identified reasons for non-persistency were perceived lack of efficacy (22.2%), adverse events (18.8%), and fear of needles/self-injecting (9.4%). At 24 months, 38.0% of patients had experienced a relapse and 11.0% had changes in MRI lesion counts. Patients without MS-related symptoms at index reported increases in the incidence of these symptoms at 24 months. CONCLUSIONS: Non-persistency with iDMT remains an issue in the oral DMT age. Many patients still experienced relapses and disease progression, and should consider switching to more effective therapies.

The impact of adherence and disease control on resource use and charges in patients with mild asthma managed on inhaled corticosteroid agents.

OBJECTIVE: Inadequate asthma control may affect asthma resource use and treatment charges, consequently contributing to the growing economic burden of asthma. The study objective was to determine the impact of medication adherence and asthma control on resource use and charges in mild asthmatic patients treated with inhaled corticosteroids (ICSs). RESEARCH DESIGN AND METHODS: A claims database was analyzed retrospectively from October 2001-December 2007 to identify mild asthmatic patients aged 12-65 years who began ICS treatment. Demographics, drug utilization, and resource use for each patient were identified for the 365-day period before and after the index date (pre-index and post-index periods, respectively). Patients were designated as having high control high adherence (HCHA) or low control low adherence (LCLA) based on post-index exacerbations and the percentage of days covered; not all patients who qualified for study inclusion met adherence designation requirements. Differences between the HCHA and LCLA cohorts in resource use (eg, asthma treatment days) and asthma-related treatment charges were assessed. RESULTS: Compared with the HCHA cohort (n = 483), the LCLA cohort (n = 258) had more asthma treatment days (2.9 vs 3.9, respectively; P < 0.0001) and higher overall asthma treatment charges ($2655 vs $3345, respectively; P < 0.0001) in the post-index period. An adjusted odds ratio suggested that patients receiving mometasone furoate (MF) were approximately 5 times more likely to belong to the HCHA cohort than patients receiving any other ICS (P < 0.0001). CONCLUSIONS: Better asthma control and adherence to prescribed ICSs are associated with lower asthma-related resource use and charges. Mild asthmatic patients receiving MF were more likely to be in the HCHA cohort than patients receiving other ICSs, perhaps due to the once-daily dosing of MF. Current NAEPP guidelines recommend low-dose ICS monotherapy for mild persistent asthma; thus, it is critical to optimize mild persistent asthma control and limit unnecessary resource use and charges.

Molecular characterization of genes encoding the quinolone resistance determining regions of Malaysian Streptococcus pneumoniae strains.

Genes encoding the quinolones resistance determining regions (QRDRs) in Streptococcus pneumoniae were detected by PCR and the sequence analysis was carried out to identify point mutations within these regions. The study was carried out to observe mutation patterns among S. pneumoniae strains in Malaysia. Antimicrobial susceptibility testing of 100 isolates was determined against various antibiotics, out of which 56 strains were categorised to have reduced susceptibility to ciprofloxacin (>or=2 microg/mL). These strains were subjected to PCR amplification for presence of the gyrA, parC , gyrB and parE genes. Eight representative strains with various susceptibilities to fluoroquinolones were sequenced. Two out of the eight isolates that were sequenced were shown to have a point mutation in the gyrA gene at position Ser81. The detection of mutation at codon Ser81 of the gyrA gene suggested the potential of developing fluoroquinolone resistance among S. pneumoniae isolates in Malaysia. However, further experimental work is required to confirm the involvement of this mutation in the development of fluoroquinolone resistance in Malaysia.

Rapid detection of non-enterobacteriaceae directly from positive blood culture using fluorescent in situ hybridization.

Fluorescent in situ hybridization (FISH) was carried out using two different oligonucleotide probes specific for Pseudomonas spp. and Acinetobacter spp. These probes were tested against different organisms and were found to be highly specific. Sensitivity testing showed that the probes were able to detect as low as 10 3 CFU/mL. In addition, FISH was carried out directly on positive blood culture samples and the detection of microorganisms took less than 2 h. We believe that FISH is a rapid method that can be used as a routine laboratory diagnostic technique for the detection of Acinetobacter spp. and Pseudomonas spp. in clinical samples.

SHV-5 extended-spectrum beta-lactamases in clinical isolates of Escherichia coli in Malaysia.

Escherichia coli isolates resistant to ceftazidime isolated in the University Malaya Medical Center (UMMC) Kuala Lumpur, Malaysia, between the years 1998 and 2000 were studied for extended-spectrum beta-lactamase (ESBL) production. All strains were analysed phenotypically and genotypically and found to be ESBL-producing organisms harbouring SHV-5 beta-lactamase. This was confirmed by PCR-SSCP and nucleotide sequencing of the blaSHV amplified gene. As there was no evidence of ESBL activity in E. coli prior to this, coupled with the fact that there was a predominance of SHV-5 beta-lactamases in Klebsiella pneumoniae isolates in UMMC, we postulate that the E. coli obtained the SHV-5 beta-lactamase genes by plasmid transfer from the ESBL-producing K. pneumoniae.

Surveillance study of bacteraemic episodes in febrile neutropenic children.

We prospectively studied the type, frequency and outcome of infections in 513 patients with 762 consecutive episodes of febrile neutropenia (FN) over a five-year period between 1995 and 1999 in a single paediatric oncology unit. The findings were then compared with a similar study carried out in our unit between 1990 and 1994. The types of bacterial isolates and sensitivity patterns were also studied to identify trends and to gauge the suitability of antibiotics chosen for empirical therapy. Bacteraemia was documented in 35.4% of FN episodes, although 70% of patients did not have an obvious site of sepsis. The majority of isolates (61.9%) were gram-negative bacteria, a consistent finding throughout the study period. Resistance to ceftazidime, amikacin and imipenem among gram-negative bacteria was 26.3%, 21.2% and 0.7%, respectively. Methicillin resistance among gram-positive bacteria was 26.3%, while no vancomycin-resistant bacteria were encountered. There were 36 sepsis-related deaths. Factors associated with a fatal outome were prolonged capillary refill time, hypotension, fever above 39 degrees C and pneumonia. Rapid neutrophil recovery was associated with a good prognosis. A change to our current choice of empirical antibiotics for FN, comprising ceftazidime/ceftriaxone and amikacin appears necessary because of the relatively high resistance rates found.

Ceftazidime-resistant Klebsiella pneumoniae bloodstream infection in children with febrile neutropenia.

OBJECTIVES: To evaluate prevalence of ceftazidime-resistant Klebsiella pneumoniae (CRKP) in the pediatric oncology unit of University Hospital, Kuala, Lumpur, and to identify differences between febrile neutropenic pediatric patients with CRKP and ceftazidime-sensitive K. pneumoniae (CSKP) bacteremia. MATERIALS AND METHODS: Febrile neutropenic patients treated between January 1996 and December 1997 at the pediatric oncology unit of University Hospital, Kuala Lumpur, were prospectively studied. Empirical antibiotic therapy consisted of ceftazidime and amikacin. Those who developed K. pneumoniae bacteremia were identified, and clinical features analyzed. Ceftazidime-resistance was documented via disk-diffusion testing. Production of extended-spectrum beta-lactamase (ESBL) was inferred on the basis of synergy between ceftazidime and amoxicillin-clavulanic acid. The different features between the two groups and variables associated with the development of CRKP bacteremia were analyzed using chi-square and t-tests and calculation of odds ratios. A multivariate analysis was used to identify independent factors for CRKP development. RESULTS: Ceftazidime-resistance was seen in 51.6% of all K. pneumoniae isolates, and all these isolates were inferred to be ESBL producers. All isolates were sensitive to imipenem. Susceptibility to gentamicin was 90.5%. The mean continuous hospital stay prior to the detection of bacteremia was 13.7 days overall, but significantly longer in the CRKP group (21.9 d) compared to the CSKP group (4.3 d) (P = 0.003). Children with CRKP were more likely to have received antibiotics in the 2 weeks prior to detection of bacteremia (87.5% of cases) than the CSKP group (20.0% of cases) (P = 0.0008). Sepsis-related mortality was higher in those with CRKP (50.0%) than in the CSKP group (13.3%) (P = 0.02). Patients who did not receive CRKP-directed antibiotics within 48 hours of admission were more likely to have a fatal outcome than those who did (P = 0.009). Logistic regression analysis identified use of third-generation cephalosporins 2 weeks prior to presentation and a hospital stay of 2 weeks or more as independent risk factors for development of CRKP. CONCLUSIONS: More than half of total K. pneumoniae isolated from blood cultures in the unit were ceftazidime-resistant. Children with febrile neutropenia with prolonged hospital stay and recent prior antibiotic exposure are at high risk of developing CRKP bacteremia. Mortality was significantly higher in this group. Early commencement of appropriate antibiotics (e.g., imipenem with or without gentamicin), according to susceptibility study results, may be beneficial in such circumstances.

Reinfection and duodenal ulcer relapse in south-east Asian patients following successful Helicobacter pylori eradication: results of a 2-year follow-up.

OBJECTIVES: To determine the reinfection rate of Helicobacter pylori and duodenal ulcer relapse rate in a group of patients followed up long term. DESIGN: Prospective study. PATIENTS AND METHODS: Patients were followed up endoscopically at 3, 6, 12 and 24 months after successful H. pylori eradication and duodenal ulcer healing. H. pylori status was determined by culture, rapid urease test, Gram's stain of a fresh tissue smear and histological examination of antral biopsies and rapid urease test and histological examination of corpus biopsies. MAIN OUTCOME MEASURES: Duodenal ulcer healing, H. pylori reinfection. RESULTS: Thirty-eight patients with duodenal ulcer disease (35 active, 3 healed) had successfully eradicated H. pylori following treatment with omeprazole/amoxycillin (n = 11), omeprazole/amoxycillin/metronidazole (n = 16) and colloidal bismuth subcitrate/ amoxycillin/metronidazole (n = 11). All patients with active duodenal ulcer had healed ulcers at the end of therapy. Thirty-five of 38 patients were seen according to schedule up to 2 years; two patients were seen up to 12 months and one up to 6 months only. Reinfection with H. pylori was not recorded in any of our patients. Shallow duodenal ulcers were noted in three patients at 1-year follow-up, two of whom admitted to taking non-steroidal anti-inflammatory drugs (NSAIDs); H. pylori status was negative in all three. Subsequent follow-up revealed spontaneous healing of the ulcers in all three patients. At 2 years, one patient whose H. pylori status was negative had recurrence of duodenal ulcer. All of the three patients who defaulted subsequent to follow-up were negative for H. pylori and had healed ulcers on follow-up endoscopy at 6 and 12 months. CONCLUSION: Reinfection rate with H. pylori was zero in a group of South-East Asian patients who had successfully eradicated the infection. Duodenal ulcer relapse was also low (2.9%) in this group of patients at 2 years.

Helicobacter pylori eradication with short-term therapy leads to duodenal ulcer healing without the need for continued acid suppression therapy.

OBJECTIVE: To determine whether duodenal ulcers continue to heal following successful Helicobacter pylori eradication with short-term eradication therapy without further acid suppression therapy. METHODS: Patients with endoscopically proven duodenal ulcers who were H. pylori positive were randomized to receive omeprazole 40 mg each morning and clarithromycin 500 mg three times daily or famotidine 40 mg twice daily and clarithromycin 500 mg three times daily for 2 weeks. No acid-suppressing agents nor ulcerhealing drugs such as bismuth compounds or sucralfate were prescribed after that. Patients were re-examined endoscopically at week 2 at the end of treatment, and at week 6, 4 weeks after the completion of treatment. RESULTS: Thirty of 44 (68.2%) patients from both treatment arms, in whom the bacteria were subsequently noted to have been eradicated, had healed ulcers at week 2; at Week 6, 42 of 44 (95.5%) were noted to have healed ulcers without further acid-suppressing or ulcer-healing treatment. CONCLUSION: Although a short-term acid-suppressing treatment is insufficient to heal ulcers, where an important putative factor such as H. pylori is eliminated, the ulcer healing process continues without further need for acid-suppressing or ulcer-healing agents.

Molecular analysis of Salmonella enteritidis by pulsed-field gel electrophoresis and ribotyping.

A total of 61 isolates of Salmonella enteritidis were analyzed by the techniques of pulsed-field gel electrophoresis (PFGE) and ribotyping. Twenty-three of the isolates were from Zurich, Switzerland, and 38 isolates were from the University Hospital, Kuala Lumpur, Malaysia. Five of the Malaysian isolates were hospital-related outbreak strains and were shown to be indistinguishable by PFGE analysis following digestion with three different restriction endonucleases, XbaI (5'-TCTAGA-3'), SpeI (5'-ACTAGT-3'), and AvrII (5'-CCTAGG-3'). The PFGE pattern of an isolate from a suspected carrier staff nurse was found to be identical to those of the hospital outbreak isolates. These isolates were also indistinguishable by ribotyping with SmaI and SphI. The same single PFGE pattern was also detected in 29 of 32 sporadic isolates of S. enteritidis. Four closely related ribotypes were detected among these 29 isolates. Similarly, outbreak-related strains from Switzerland showed close genetic identity by PFGE and ribotyping. Strains obtained from poultry showed more variations in their PFGE patterns and ribotypes, although the patterns were still closely related. In addition, SphI ribotypes A and D among the Swiss strains correlated with phage types 4 and 8, respectively. No correlation of phage types with PFGE pattern was noted. Both PFGE and ribotyping indicate that the S. enteritidis strains circulating in Malaysia and Switzerland are very similar and may be clonally related. Comparison of the PFGE patterns with the ribotypes for 23 Swiss and 16 Malaysian isolates showed that there was a 69% concordance in the grouping of isolates. We conclude that the close genetic similarity observed between epidemiologically unrelated and outbreak-related isolates of S. enteritidis suggests that both PFGE and ribotyping are of limited value in the epidemiological analysis of these particular isolates, possibly because of the highly clonal nature of pathogenic strains of S. enteritidis.

Comparison of two assays for the detection of haemolysins of Aeromonas species.

The haemolysins produced by Aeromonas species were detected and compared by two assay methods--a modified blood agar plate assay and the rabbit erythrocyte haemolysin method. Both assays showed a high level of agreement (86%). The titres of the rabbit erythrocyte haemolysin assay correlated with the haemolytic zone diameter of the ox blood agar assay. In addition the agar haemolysin assay had simple media requirements, was easy to perform and results were well defined.

Exotoxin profiles of clinical isolates of Aeromonas hydrophila.

Eighty-six clinical isolates of Aeromonas hydrophila were studied for their ability to produce four exotoxins: a haemolysin active against rabbit erythrocytes, cytotoxin and enterotoxin detectable with Vero cell cultures, and the cholera toxin-like factor detected by an enzyme-linked immunosorbent assay. At least one exotoxin was produced by 80% of enteric and 96% of non-enteric isolates. The exotoxin profiles of non-enteric isolates were more restricted than those of enteric isolates, with haemolysin and cytotoxin producers preponderant. Although haemolysin and cytotoxin were produced by isolates from all sources, the enterotoxin and cholera toxin-like factor were more common amongst enteric isolates. The production of haemolysin and cytotoxin were closely related but the association between the enterotoxin and the cholera toxin-like factor was not significant.

Culture-positive thoracic empyema in adults.

Twenty-nine adult patients with culture-positive thoracic empyema were seen at the University Hospital Kuala Lumpur from 1984 to 1988. Cough, fever, chest pain, dyspnoea and weight loss were the common presenting symptoms. The empyema in 16 patients was associated with primary bronchopulmonary infections, nine occurred following thoracentesis of culture-sterile pleural effusions, two occurred as post-thoracic surgery complications, one following a subdiaphragmatic abscess and one as a result of a stab wound. The most common culture isolates were Streptococcus milleri, Pseudomonas aeruginosa and Klebsiella pneumoniae. Closed tube thoracostomy, the most common form of drainage procedure employed, was able to effect a cure or control of the empyema in 11 out of 19 patients in whom it was used.