Adverse effects and duration of treatment of TB in Canterbury, New Zealand.

BACKGROUND Treatment of TB is often extended beyond the recommended duration. The aim of this study was to assess prevalence of extended treatment and to identify associated risk factors. We also aimed to determine the frequency and type of adverse drug reactions (ADR) experienced by this study population.METHODS We performed a retrospective cohort study of all patients treated for active TB at Christchurch Hospital, Christchurch, New Zealand, between 1 March 2012 and 31 December 2018. Data for 192 patients were collected on patient demographics, disease characteristics and treatment characteristics, including planned and actual duration of treatment and ADRs.RESULTS Of 192 patients, 35 (18.2%) had treatment extended, and 85 (46.5%) of 183 with fully drug-susceptible TB received ≥9 months treatment. The most common reasons for extension were persistent or extensive disease and ADR. Extended treatment duration was not associated with any patient or disease characteristics. We found 35 (18.2%) patients experienced at least one ADR. The most common ADRs were hepatitis, rash and peripheral neuropathy.CONCLUSION TB treatment extension beyond WHO guidelines is common. Further research is needed to guide management of those with slow response to treatment. Methods for early detection of ADR, systems to improve adherence and therapeutic drug monitoring are potentially useful strategies.

Acceptability of Chairside Screening for Racial/Ethnic Minority Older Adults: A Qualitative Study.

An aging and more racially and ethnically diverse population, coupled with changes in the health care policy environment, is demanding that the dental profession both redirect and expand its focus. Challenges include providing comprehensive care for patients with complicated medical needs while improving access to care for underserved groups. The purpose of this study is to examine the acceptability of screening for hypertension and diabetes in the dental setting for African American, Puerto Rican, and Dominican older adults who attend senior centers in northern Manhattan, New York City. Focus groups were conducted with 194 racial/ethnic minority men and women aged 50 y and older living in northern Manhattan who participated in 1 of 24 focus group sessions about improving oral health for older adults. All groups were digitally audio-recorded and transcribed for analysis. Groups that were conducted in Spanish were transcribed first in Spanish and then translated into English. Analysis of the transcripts was conducted using thematic content analysis. Five themes were manifest in the data regarding the willingness of racial/ethnic minority older adults to receive hypertension and diabetes screening as part of routine dental visits: 1) chairside screening is acceptable, 2) screening is routine for older adults, 3) the interrelationship between oral and general health is appreciated, 4) chairside screening has perceived benefits, and 5) chairside screening may reduce dental anxiety. Reservations centered on 4 major themes: 1) dental fear may limit the acceptability of chairside screening, 2) there is a perceived lack of need for dental care and chairside screening, 3) screening is available elsewhere, and 4) mistrust of dental providers as primary care providers. This study provides novel evidence of the acceptability of screening for hypertension and diabetes in the dental setting among urban racial/ethnic minority senior center attendees. Knowledge Transfer Statement: The results of this study may be used by oral health providers when deciding whether to conduct chairside screening for medical conditions such as hypertension and diabetes that could affect, or be affected by, the oral health of their patients. Patient experiences of care-along with clinical outcomes, avoidable hospital admissions, equity of services, and costs-are important outcomes to consider in meeting the needs of an aging and racially and ethnically diverse US population.

Examining the relative effects of fire weather, suppression and fuel treatment on fire behaviour--a simulation study.

Large budgets are spent on both suppression and fuel treatments in order to reduce the risk of wildfires. There is little evidence regarding the relative contribution of fire weather, suppression and fuel treatments in determining the risk posed from wildfires. Here we undertake a simulation study in the Sydney Basin, Australia, to examine this question using a fire behaviour model (Phoenix Rapidfire). Results of the study indicate that fire behaviour is most strongly influenced by fire weather. Suppression has a greater influence on whether a fire reaches 5 ha in size compared to fuel treatments. In contrast, fuel treatments have a stronger effect on the fire size and maximum distance the fire travels. The study suggests that fire management agencies will receive additional benefits from fuel treatment if they are located in areas which suppression resources can respond rapidly and attempt to contain the fires. No combination of treatments contained all fires, and the proportion of uncontained fires increased under more severe fire weather when the greatest number of properties are lost. Our study highlights the importance of alternative management strategies to reduce the risk of property loss.

Outcomes of infected abdominal aortic grafts managed with antimicrobial therapy and graft retention in an unselected cohort.

OBJECTIVE: To document the treatment of all patients with infected aortic grafts at Christchurch Hospital between 1999 and 2010, focussing on the mortality and morbidity of those treated without graft explantation. METHODS: Cases of infected aortic grafts were reviewed. Cases required a compatible clinical syndrome, CT imaging and tissue/blood culture results. RESULTS: Eighteen patients were identified. Organisms isolated at diagnosis from blood or graft site were Staphylococcus aureus 6 (MRSA 1), beta haemolytic streptococci 2, enteric organisms 9.There was no isolate from 2. One case had graft explantation and brief antimicrobial therapy. Seventeen patients had the graft retained. Of these, 14 received intravenous antimicrobial therapy for 6 weeks and 14 lifelong oral therapy. None died during their initial admission or within 30 days. During a mean follow-up of 57 months, 10 (59%) relapsed (median time 31 months, range 0--98), 4 (24%) underwent graft explantation and 10 (59%) died (median 40 months, range 1e 198). Four of 10 who relapsed had organisms isolated (all enteric). CONCLUSION: Patients treated with lifelong antimicrobial therapy and graft retention survived a median of 41 months, with low early mortality although over half relapsed. Empiric therapy should cover skin organisms and enteric organisms, even for those outside the post-operative period.

Combination of a fusogenic glycoprotein, pro-drug activation and oncolytic HSV as an intravesical therapy for superficial bladder cancer.

BACKGROUND: There are still no effective treatments for superficial bladder cancer (SBC)/non-muscle invasive bladder cancer. Following treatment, 20% of patients still develop metastatic disease. Superficial bladder cancer is often multifocal, has high recurrences after surgical resection and recurs after intravesical live Bacillus Calmette-Guérin. Oncovex(GALV/CD), an oncolytic herpes simplex virus-1, has shown enhanced local tumour control by combining oncolysis with the expression of a highly potent pro-drug activating gene and the fusogenic glycoprotein. METHODS: In vitro fusion/prodrug/apoptotic cell-based assays. In vivo orthotopic bladder tumour model, visualised by computed microtomography. RESULTS: Treatment of seven human bladder carcinoma cell lines with the virus resulted in tumour cell killing through oncolysis, pro-drug activation and glycoprotein fusion. Oncovex(GALV/CD) and mitomycin C showed a synergistic effect, whereas the co-administration with cisplatin or gemcitabine showed an antagonistic effect in vitro. Transitional cell cancer (TCC) cells follow an apoptotic cell death pathway after infection with Oncovex(GALV/CD) with or without 5-FC. In vivo results showed that intravesical treatment with Oncovex(GALV/CD) + prodrug (5-FC) reduced the average tumour volume by over 95% compared with controls. DISCUSSION: Our in vitro and in vivo results indicate that Oncovex(GALV/CD) can improve local tumour control within the bladder, and potentially alter its natural history.

Ochroconis gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis.

Ochroconis gallopava has rarely been isolated in immunosuppressed patients. We report the first case to our knowledge of O. gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis. A 58-year-old man who had undergone cardiac transplant 8 years earlier alerted his dialysis nurses to the presence of black material in his catheter lumen. Fungal hyphae were seen on direct microscopy of the black material and from the dialysate effluent, and O. gallopava was cultured from both after 1 day. He was treated successfully with a single dose of intravenous voriconazole, followed by 2 weeks of oral voriconazole.

Improved outcomes associated with advances in therapy for invasive fungal infections in immunocompromised hosts.

Invasive fungal infections cause substantial morbidity and mortality in immunocompromised hosts. The response rate to therapy, in particular for invasive aspergillosis and invasive mould infections, has been poor. Recently a number of techniques to facilitate early diagnosis of these infections, in parallel with the development of a number of antifungals with increased potency and lower toxicity, have raised optimism that outcomes for invasive fungal infection can be improved upon. The availability of lipid formulations of amphotericin B, azoles with extended spectrum against filamentous fungi and the development of a new class of antifungal agents, the echinocandins, presents the clinician with a range of therapeutic choices. Recent clinical trials have provided important insights into how these agents should be used. In particular, voriconazole has demonstrated superior efficacy to amphotericin B in the management of invasive aspergillosis, posaconazole has been shown to have significant efficacy in the prophylaxis of invasive fungal infection in high-risk individuals and a role in salvage therapy of invasive aspergillosis, caspofungin has demonstrated efficacy in salvage therapy of invasive aspergillosis, and each of the echinocandins show activity without significant toxicity in invasive candidiasis. Nevertheless, many therapeutic areas of uncertainty remain, including the role of combination therapy, and will provide the focus for future studies.

Invasive pneumococcal disease and the potential for prevention by vaccination in the United Kingdom.

OBJECTIVES: Invasive pneumococcal disease (IPD) is associated with a high mortality despite antimicrobial therapy, but may be preventable by pneumococcal vaccination. The extent of previous exposure to pneumococcal capsular polysaccharide vaccination prior to an episode of IPD in hospitalised adults in the United Kingdom is unclear. METHODS: We conducted a retrospective cohort study in adults with IPD admitted to either of two teaching hospitals in Sheffield, United Kingdom during 1992-2000. Receipt of pneumococcal vaccination, risk factors for IPD, death and disability were determined. RESULTS: The number of cases of IPD was 552 and 187/230 patient records from one site were reviewed. According to UK pneumococcal vaccination guidelines 59% of patients should have received the vaccine and 76% of patients if updated guidelines, which include age>65 years as an indication, are applied. In patients with known risk factors, excluding age, only 8% had been vaccinated. The mortality from IPD was 21% and an additional 6% suffered major complications. CONCLUSIONS: In patients hospitalised with IPD there is a high rate of pre-existing risk factors and a low rate of administration of pneumococcal vaccination. IPD incurs significant mortality, morbidity and economic cost and there is potential for reducing this by improved uptake of pneumococcal vaccination.

Physiological effects of kaolin applications in well-irrigated and water-stressed walnut and almond trees.

BACKGROUND AND AIMS: Kaolin applications have been used to mitigate the negative effects of water and heat stress on plant physiology and productivity with variable results, ranging from increased to decreased yields and photosynthetic rates. The mechanisms of action of kaolin applications are not clear: although the increased albedo reduces leaf temperature and the consequent heat stress, it also reduces the light available for photosynthesis, possibly offsetting benefits of lower temperature. The objective of this study was to investigate which of these effects are prevalent and under which conditions. METHODS: A 6% kaolin suspension was applied on well-irrigated and water-stressed walnut (Juglans regia) and almond (Prunus dulcis) trees. Water status (i.e. stem water potential, psi(s)), gas exchange (i.e. light-saturated CO2 assimilation rate, Amax; stomatal conductance, g(s)), leaf temperature (T(l)) and physiological relationships in treated and control trees were then measured and compared. KEY RESULTS: In both species, kaolin did not affect the daily course of psi(s) whereas it reduced Amax by 1-4 micromol CO2 m(-2) s(-1) throughout the day in all combinations of species and irrigation treatments. Kaolin did not reduce g(s) in any situation. Consequently, intercellular CO2 concentration (C(i)) was always greater in treated trees than in controls, suggesting that the reduction of Amax with kaolin was not due to stomatal limitations. Kaolin reduced leaf temperature (T(l)) by about 1-3 degrees C and leaf-to-air vapour pressure difference (VPD(l)) by about 0.1-0.7 kPa. Amax was lower at all values of g(s), T(l) and VPD(l) in kaolin-treated trees. Kaolin affected the photosynthetic response to the photosynthetically active radiation (PAR) in almond leaves: kaolin-coated leaves had similar dark respiration rates and light-saturated photosynthesis, but a higher light compensation point and lower apparent quantum yield, while the photosynthetic light-response curve saturated at higher PAR. When these parameters were used to model the photosynthetic response curve to PAR, it was estimated that the kaolin film allowed 63% of the incident PAR to reach the leaf. CONCLUSIONS: The main effect of kaolin application was the reduction, albeit minor, of photosynthesis, which appeared to be related to the shading of the leaves. The reduction in T(l) and VPD(l) with kaolin did not suffice to mitigate the adverse effects of heat and water stress on Amax.

A simple method to estimate photosynthetic radiation use efficiency of canopies.

BACKGROUND AND AIMS: Photosynthetic radiation use efficiency (PhRUE) over the course of a day has been shown to be constant for leaves throughout a general canopy where nitrogen content (and thus photosynthetic properties) of leaves is distributed in relation to the light gradient. It has been suggested that this daily PhRUE can be calculated simply from the photosynthetic properties of a leaf at the top of the canopy and from the PAR incident on the canopy, which can be obtained from weather-station data. The objective of this study was to investigate whether this simple method allows estimation of PhRUE of different crops and with different daily incident PAR, and also during the growing season. METHODS: The PhRUE calculated with this simple method was compared with that calculated with a more detailed model, for different days in May, June and July in California, on almond (Prunus dulcis) and walnut (Juglans regia) trees. Daily net photosynthesis of 50 individual leaves was calculated as the daylight integral of the instantaneous photosynthesis. The latter was estimated for each leaf from its photosynthetic response to PAR and from the PAR incident on the leaf during the day. KEY RESULTS: Daily photosynthesis of individual leaves of both species was linearly related to the daily PAR incident on the leaves (which implies constant PhRUE throughout the canopy), but the slope (i.e. the PhRUE) differed between the species, over the growing season due to changes in photosynthetic properties of the leaves, and with differences in daily incident PAR. When PhRUE was estimated from the photosynthetic light response curve of a leaf at the top of the canopy and from the incident radiation above the canopy, obtained from weather-station data, the values were within 5 % of those calculated with the more detailed model, except in five out of 34 cases. CONCLUSIONS: The simple method of estimating PhRUE is valuable as it simplifies calculation of canopy photosynthesis to a multiplication between the PAR intercepted by the canopy, which can be obtained with remote sensing, and the PhRUE calculated from incident PAR, obtained from standard weather-station data, and from the photosynthetic properties of leaves at the top of the canopy. The latter properties are the sole crop parameters needed. While being simple, this method describes the differences in PhRUE related to crop, season, nutrient status and daily incident PAR.

Population of the HLA ligand database.

We have established an HLA ligand database to provide scientists and clinicians with access to Major Histocompatibility Complex (MHC) class I and II motif and ligand data. The HLA Ligand Database is available on the world wide web at http://hlaligand.ouhsc.edu and contains ligands that have been published in peer-reviewed journals. HLA peptide datasets prove useful in several areas: ligands are important as targets for various immune responses while algorithms built upon ligand datasets allow identification of new peptides without time-consuming experimental procedures. A review of the HLA class I ligands in the database identifies strengths and deficiencies in the database and, therefore, the utility of the dataset for identifying new peptides. For instance, 212 HLA-A phenotypes exist of which 23 have a motif determined and 43 have peptides characterized. In terms of number of ligands, HLA-A*0201 has 258 characterized ligands, A*1101 has 25 peptides, while the remaining two-thirds of the HLA-A phenotypes have less than 10 associated peptide sequences. Characterization of ligands and motifs remains roughly the same at the HLA-B locus while the peptides of the HLA-C locus tend to be less characterized. These data show that 74% of HLA class I molecules do not have ligands represented in the database and thus algorithms based on the dataset could not predict ligands for a majority of the US population. Building upon this dataset and knowledge of HLA allelic frequencies, it is possible to plan a systematic expansion of the HLA class I ligand database to better identify ligands useful throughout the population.

Human exposure to polychlorinated biphenyls in a residential community.

Blood serum concentrations of polychlorinated biphenyls (PCBs) were measured in members of a residential community who lived near a chemical plant that formerly manufactured PCBs. Elevated blood serum PCB concentrations were detected in some of the older adults who were long-term residents of the community. Congener-specific analyses indicated that PCB congeners 153, 138/158, 180, 118, and 187 contributed 60-67% of the total PCBs detected in blood from adults and children. Blood PCB concentrations correlated strongly with age and length of residency in the neighborhood. However, blood PCB concentrations did not correlate with PCB concentrations in soil or house dust samples from the homes. Past exposures to PCBs may be a significant contributor to the elevated PCB concentrations detected in some adult members of the community.

Dioxin exposure in a residential community.

The Agency for Toxic Substances and Disease Registry (ATSDR) conducted biological testing to assess dioxin exposure in residents of a community who lived in an area with heavy chemical industry. Dioxin concentrations were measured in blood serum samples from 28 adult residents of the community. Fourteen of those tested had blood dioxin concentrations that exceeded the 95th percentile prediction level of an age-matched comparison population. Specific congener analyses indicated that the elevated dioxin concentrations were primarily due to high concentrations of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8 pentachlorodibenzo-p-dioxin (PeCDD), and hexachlorodibenzo-p-dioxins (HxCDs). Principal components analysis (PCA) indicated that the profiles of dioxin congeners were different in people with elevated blood dioxin concentrations compared to those with background concentrations. Elevated blood dioxin concentrations were detected only in older members of the population, which suggests that dioxin exposures were higher in the past. The sources of the dioxin exposure have not been identified.

Three methoxy-substituted diethyl 4-phenyl-2,6-dimethyl-1, 4-dihydropyridine-3,5-dicarboxylate compounds.

Diethyl 4-(2,5-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3, 5-dicarboxylate, C(21)H(27)NO(6), (I), diethyl 4-(3, 4-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3, 5-dicarboxylate, C(21)H(27)NO(6), (II), and diethyl 2, 6-dimethyl-4-(3,4,5-trimethoxyphenyl)-1,4-dihydropyridine-3, 5-dicarboxylate, C(22)H(29)NO(7), (III), crystallize with hydrogen-bonding networks involving the H atom bonded to the N atom of the 1,4-dihydropyridine ring and carbonyl O atoms in (I) and (II). Unusually, (III) shows O atoms of methoxy groups serving as hydrogen-bond acceptors.

The value of book distribution in a clinic-based literacy intervention program.

The purpose of this study was to determine whether anticipatory guidance at well-child visits (WCV) that included early literacy development and the provision of books by the examining physician changed family literacy practices. It was conducted in an inner-city pediatric clinic that serves as the continuity practice site for pediatric and pediatric/internal medicine residents. There were 352 children (181 treatment: 171 control), aged 2 to 24 months, enrolled in this prospective, controlled study. The health care providers underwent training on literacy and on how to incorporate this information during WCV. Anticipatory guidance on safety, development, and early literacy was given to all parents. Additionally, the treatment group received an age-appropriate book at each WCV. There were 1,263 visits made (686 treatment, 577 control). Questionnaires were completed by parents on physician helpfulness and by physicians on parental receptiveness. Parental ratings on physician helpfulness were higher in the treatment group than in the control group (p<0.05). Physician's rating of parental receptiveness was also higher in the treatment group than in the control group (p<0.05). Two years after enrollment, mother-child pairs who received guidance and a book were two times more likely to report enjoyment in reading together than the controls who received guidance but no book. We conclude that anticipatory guidance that included early literacy development and distribution of books at WCV resulted in increased family literacy orientation, parental receptiveness, and perception of physician helpfulness.

The utilisation of shared governance to improve vascular access catheter care.

This article looks at the implementation of shared governance at directorate level and its role in improving vascular access catheter care.

Antibodies to toluene diisocyanate in an environmentally exposed population.

Residents living near a polyurethane foam manufacturing facility expressed concern to health officials over chemical emissions from the plant. Environmental monitoring of ambient air near the plant indicated the presence of toluene diisocyanate (TDI), which was used in foam production. Health officials collected blood samples from 113 residents and analyzed the blood sera for antibodies to TDI and related diisocyanates. Ten of the 113 residents (9%) had elevated levels of IgG or IgE antibodies specific for one or more diisocyanates. Exposure histories were taken from antibody-positive individuals to identify possible occupational exposure to TDI or the use of diisocyanate-containing consumer products. Exposure to TDI in ambient air may be responsible for the positive antibody responses detected in some residents of the community.

Guidelines for the management of anaphylaxis in the emergency department.

An algorithm for the emergency treatment of anaphylaxis is presented. The need for early hands-on involvement of senior personnel is stressed. Continuous assessment, monitoring of response to treatment, and a low threshold for hospital admission for observation and further treatment if necessary are required.