Health state utility values measured using the EuroQol 5-dimensions questionnaire in adults with chronic hepatitis C: a systematic literature review and meta-analysis.

PURPOSE: Chronic hepatitis C infection and its treatment can considerably affect patients' health-related quality-of-life (HRQoL). This study aimed to identify and summarise the current evidence base for health state utility values (HSUVs) in patients with chronic hepatitis C infection, generated using the EuroQol 5-dimensions (EQ-5D) questionnaire. METHODS: MEDLINE, Embase, the Cochrane Library and EconLit were searched from database inception through 31 August 2017. Eligible studies reported HSUVs elicited using the EQ-5D questionnaire in adults with chronic hepatitis C infection. Study quality and risk of bias were assessed. RESULTS: Of 1480 records identified, 26 studies were included. The most commonly defined health states described different stages of chronic hepatitis C infection and specific liver-related disease states, including METAVIR score, compensated and decompensated cirrhosis, hepatocellular carcinoma and liver transplantation. Patients with higher METAVIR scores tended to have lower EQ-5D scores compared to patients with lower METAVIR scores. Patients that achieved sustained virologic responses tended to have higher EQ-5D scores compared to those that did not. A meta-analysis conducted on three studies confirmed that patients with decompensated cirrhosis have significantly lower HSUVs than patients with compensated cirrhosis [mean difference - 0.11 (95% CI - 0.19 to - 0.04)], implying worse HRQoL. However, there was not sufficient evidence to compare how different treatments for chronic hepatitis C infection affect EQ-5D scores. CONCLUSIONS: This study provides a summary of EQ-5D HSUVs for patients with chronic hepatitis C infection, and demonstrates that clinically important disease stages associated with treatment decisions are associated with differences in HRQoL.

Seasonal fluxes of carbon monoxide from an intensively grazed grassland in Scotland.

Fluxes of carbon monoxide (CO) were measured using a fast-response quantum cascade laser absorption spectrometer and the eddy covariance method at a long-term intensively grazed grassland in southern Scotland. Measurements lasted 20 months from April 2016 to November 2017, during which normal agricultural activities continued. Observed fluxes followed a regular diurnal cycle, peaking at midday and returning to values near zero during the night, with occasional uptake observed. CO fluxes correlated well with the meteorological variables of solar radiation, soil temperature and soil moisture content. Using a general additive model (GAM) we were able to gap fill CO fluxes and estimate annual fluxes of 0.38 ±â€¯0.046 and 0.35 ±â€¯0.045 g C m-2 y-1g C m-2 y-1 for 2016 and 2017, respectively. If the CO fluxes reported in this study are representative of UK grasslands, then national annual emissions could be expected to be in the order of 61.91 (54.3-69.5) Gg, which equates to 3.8% (3.4-4.3%) of the current national inventory total.

Antimicrobial Stewardship in the Microbiology Laboratory: Impact of Selective Susceptibility Reporting on Ciprofloxacin Utilization and Susceptibility of Gram-Negative Isolates to Ciprofloxacin in a Hospital Setting.

The objective of this study was to determine the impact of selective susceptibility reporting on ciprofloxacin utilization and Gram-negative susceptibility to ciprofloxacin in a hospital setting. Historically at our institution, the microbiology laboratory practice was to report ciprofloxacin susceptibility for all Enterobacteriaceae regardless of susceptibility to other agents. A selective reporting policy was implemented which involved the suppression of ciprofloxacin susceptibility to Enterobacteriaceae when there was lack of resistance to the antibiotics on the Gram-negative panel. Ciprofloxacin utilization (measured in defined daily doses [DDD] per 1,000 patient days) was collected before and after the intervention and compared to moxifloxacin, trimethoprim-sulfamethoxazole, nitrofurantoin, and amoxicillin-clavulanate. Monthly susceptibility of Pseudomonas aeruginosa and Escherichia coli to ciprofloxacin was tabulated. An interrupted time series analysis using segmented regression was performed. The mean monthly ciprofloxacin utilization decreased from 87 (95% CI, 83.7 to 91.2) to 39 (95% CI, 35.0 to 44.0) DDD per 1,000 patient days before and after the implementation of selective reporting, respectively. There was an immediate and sustained reduction in ciprofloxacin usage at 1, 3, 6, 12, and 24 months postintervention (P < 0.001). A compensatory increase in amoxicillin-clavulanate use was noted starting at 6 months postintervention and persisted for the study period (P < 0.027). Susceptibility of E. coli, but not that of P. aeruginosa, to ciprofloxacin was higher than predicted starting 12 months after the intervention (P < 0.05). In conclusion, selective reporting of ciprofloxacin susceptibly may be a useful intervention to reduce targeted antimicrobial utilization and improve Gram-negative susceptibility to ciprofloxacin. This approach should be considered as part of a broader multimodal antimicrobial stewardship program.

Nitrogen management is essential to prevent tropical oil palm plantations from causing ground-level ozone pollution.

More than half the world's rainforest has been lost to agriculture since the Industrial Revolution. Among the most widespread tropical crops is oil palm (Elaeis guineensis): global production now exceeds 35 million tonnes per year. In Malaysia, for example, 13% of land area is now oil palm plantation, compared with 1% in 1974. There are enormous pressures to increase palm oil production for food, domestic products, and, especially, biofuels. Greater use of palm oil for biofuel production is predicated on the assumption that palm oil is an "environmentally friendly" fuel feedstock. Here we show, using measurements and models, that oil palm plantations in Malaysia directly emit more oxides of nitrogen and volatile organic compounds than rainforest. These compounds lead to the production of ground-level ozone (O(3)), an air pollutant that damages human health, plants, and materials, reduces crop productivity, and has effects on the Earth's climate. Our measurements show that, at present, O(3) concentrations do not differ significantly over rainforest and adjacent oil palm plantation landscapes. However, our model calculations predict that if concentrations of oxides of nitrogen in Borneo are allowed to reach those currently seen over rural North America and Europe, ground-level O(3) concentrations will reach 100 parts per billion (10(9)) volume (ppbv) and exceed levels known to be harmful to human health. Our study provides an early warning of the urgent need to develop policies that manage nitrogen emissions if the detrimental effects of palm oil production on air quality and climate are to be avoided.

A real-world assessment of procalcitonin combined with antimicrobial stewardship in a community ICU.

PURPOSE: We evaluated the feasibility and impact of PCT-guided antibiotic duration combined with an established antibiotic stewardship program (ASP) in a community hospital intensive care unit (ICU). METHODS: We implemented daily PCT levels for ICU patients receiving antibiotics. Our protocol recommended stopping antibiotic therapy if PCT met an absolute or relative stopping threshold. We evaluated the adherence to stopping criteria within 48 h, antibiotic use [days of therapy (DOT) per 1000 patient-days (PD)], length of stay and ICU-mortality. We performed interrupted time series analysis to compare 24 months before and 12 months after implementation. RESULTS: A total of 297 antibiotic courses were monitored with PCT in 217 patients. Protocol adherence was 34% (absolute threshold: 39%, relative threshold: 12%). Antibiotic use pre-PCT was 935 DOTs/1000 PDs and post-PCT was 817 DOTs/1000 PDs (RRadj 0.73, 95% CI: 0.62 to 0.86). No statistically significant changes in clinical outcomes were noted. CONCLUSION: In the context of an established ASP in a community hospital ICU, PCT monitoring was feasible and associated with an adjusted overall decrease of 27% in antibiotic use with no adverse impact on clinical outcomes. Incorporating PCT testing to guide antibiotic duration can be successful if integrated into workflow and paired with ASP guidance.

The second-hand effects of antibiotics: communicating the public health risks of drug resistance.

Antimicrobial resistance (AMR) poses a threat to modern medicine, but there are challenges in communicating its urgency and scope and potential solutions to this growing problem. It is recognized that AMR has a 'language problem' and the way in which healthcare professionals communicate about AMR may not always resonate with patients. Many patients are unaware that antibiotics can have detrimental effects to those beyond the recipient, due to transmission of drug-resistant organisms. The overestimation of benefits and underestimation of risks helps to fuel demand for antibiotic use in situations where they may be of little or no benefit. To better communicate risks, clinicians may borrow the term 'second-hand' from efforts to reduce smoking cessation. We present several examples where antibiotics themselves have second-hand effects beyond the individual recipient in hospitals, long-term care homes and the community. Incorporation of the concept of the second-hand effects of antibiotics into patient counselling, mass messaging and future research may help facilitate a more balanced discussion about the benefits and risks of antibiotic use in order to use these agents more appropriately.

Predictors of blood pressure fall with continuous positive airway pressure (CPAP) treatment of obstructive sleep apnoea (OSA).

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Randomised controlled trials have shown that, on average, treatment of OSA with continuous positive airway pressure (CPAP) reduces blood pressure (BP) by 3-5 mm Hg, although with considerable variation between individuals. No predictors of the change in BP with CPAP have been convincingly identified. This prospective study aimed to determine predictors of BP change, which might provide an insight into the aetiology of the raised BP seen in untreated OSA. METHODS: Eighty-six patients with daytime hypersomnolence warranting treatment with CPAP were recruited. 24 h mean BP (24 hMBP), subjective sleepiness, fasting venous blood samples and anthropometric measurements were assessed at baseline and after 6 months of CPAP treatment. RESULTS: The mean (SD) 24 hMBP fell at 6 months from 101.0 (10.3) mm Hg to 96.1 (9.1) mm Hg (change -4.92 mm Hg (95% CI -2.8 to -7.1)). The Epworth Sleepiness Score (ESS) fell from a median of 16 (IQR 12-18) to 4 (2-7) with a mean fall of 9.7 (95% CI 8.6 to 10.8). Several factors correlated with the fall in 24 hMBP but, after allowing for the baseline 24 hMBP, only the fall in ESS and the body mass index (BMI) remained significant independent predictors (p = 0.006 and 0.007, respectively). There was also a correlation between the fall in 24 hMBP and the fall in pulse rate (r = 0.44, p<0.001). Baseline severity of OSA, overnight hypoxia, caffeine intake or being on antihypertensive drugs were not independent predictors of a fall in 24 hMBP. CONCLUSION: Improvement in hypersomnolence and the BMI are independent correlates of the fall in 24 hMBP following CPAP therapy. Markers of initial OSA severity did not predict the fall in 24 hMBP. This suggests that sleep fragmentation and its effects may be more important than hypoxia in the pathogenesis of the hypertension associated with human sleep apnoea.

Bringing home unwelcome souvenirs: Travel and drug-resistant bacteria.

Antimicrobial resistance poses a significant threat to public health globally and in Canada. Wide regional variability in antimicrobial resistance and ongoing increases in global travel present an important risk for the acquisition and transmission of drug-resistant organisms. Travel from high-income to low- and middle-income countries, particularly the Indian subcontinent, present the greatest risks for acquiring a drug-resistant Enterobacteriaceae. Risk factors for returning from travel with drug-resistant organisms include seeking medical care while abroad, travellers' diarrhea and antibiotic use. Health care professionals can play an important role in preventing harm for travellers by counselling patients on the risks of acquiring drug-resistant organisms, appropriate antibiotic prescribing for travellers' diarrhea and tailored empiric therapy for patients presenting with infection after travel.

The atmospheric chemistry of trace gases and particulate matter emitted by different land uses in Borneo.

We report measurements of atmospheric composition over a tropical rainforest and over a nearby oil palm plantation in Sabah, Borneo. The primary vegetation in each of the two landscapes emits very different amounts and kinds of volatile organic compounds (VOCs), resulting in distinctive VOC fingerprints in the atmospheric boundary layer for both landscapes. VOCs over the Borneo rainforest are dominated by isoprene and its oxidation products, with a significant additional contribution from monoterpenes. Rather than consuming the main atmospheric oxidant, OH, these high concentrations of VOCs appear to maintain OH, as has been observed previously over Amazonia. The boundary-layer characteristics and mixing ratios of VOCs observed over the Borneo rainforest are different to those measured previously over Amazonia. Compared with the Bornean rainforest, air over the oil palm plantation contains much more isoprene, monoterpenes are relatively less important, and the flower scent, estragole, is prominent. Concentrations of nitrogen oxides are greater above the agro-industrial oil palm landscape than over the rainforest, and this leads to changes in some secondary pollutant mixing ratios (but not, currently, differences in ozone). Secondary organic aerosol over both landscapes shows a significant contribution from isoprene. Primary biological aerosol dominates the super-micrometre aerosol over the rainforest and is likely to be sensitive to land-use change, since the fungal source of the bioaerosol is closely linked to above-ground biodiversity.

Continuous positive airway pressure does not reduce blood pressure in nonsleepy hypertensive OSA patients.

Obstructive sleep apnoea (OSA) is associated with high cardiovascular morbidity and mortality. Several randomised controlled trials have shown that continuous positive airway pressure (CPAP) treatment of OSA reduces blood pressure (BP). This randomised, sham-placebo controlled crossover trial assesses whether CPAP produces a similar clinically significant fall in BP in hypertensive OSA patients, but without hypersomnolence. Thirty-five, nonsleepy, hypertensive patients with OSA were treated with CPAP for 1 month, randomised first to either therapeutic or sham-placebo (subtherapeutic CPAP, about 1 cmH(2)O pressure). The second months' alternative treatment followed a 2-week washout period. BP was measured over 24 h, before and at the end of the two treatment periods: mean 24-h BP was the primary outcome variable. There was no overall significant difference in mean 24-h BP: the change in mean 24-h BP on therapeutic CPAP was -2.1 mmHg (sd 8.1), and -1.1 mmHg (sd 8.1) on subtherapeutic CPAP, with a difference of 0.7 mmHg (95% confidence interval (CI) +2.9- -4.4). There was a small significant fall in Epworth Sleepiness Score, therapeutic (-1.4) versus sham (-0.3), and difference -1.2 (95% CI -2.0- -0.4), but no change in objective sleepiness. In nonhypersomnolent hypertensive patients with obstructive sleep apnoea, there is no significant fall in mean 24-h blood pressure with continuous positive airway pressure, in contrast to the fall seen in hypersomnolent patients with obstructive sleep apnoea.

Prevalence of sleepiness and its relation to autonomic evidence of arousals and increased inspiratory effort in a community based population of men and women.

Degrees of sleep apnoea and daytime sleepiness are quite common in community populations. However the relationship between the two is poor, although sleepiness does correlate better with a history of snoring. It has been suggested that sleep can be fragmented by upper airways obstructive events, short of full apnoeas or hypopnoeas, and that these events may not provoke full cortical arousal, but be detectable through activation of the autonomic system. Failure to detect both these could mask a relationship between 'sleep apnoea' and daytime sleepiness. We have therefore measured sleepiness (Epworth Sleepiness Scale) in addition to both autonomic 'arousals' and inspiratory effort (using pulse transit time) in 473 men and women at home. Although sleepiness was related to a history of snoring, it was not significantly predicted by the measures of autonomic 'arousal', or inspiratory effort. Reported snoring and objectively measured snoring correlated poorly. As in other studies, nocturnal hypoxic dips were correlated with obesity, age, alcohol consumption, drug usage and a history of snoring. These data make it unlikely that sleep fragmentation from subtle variants of sleep apnoea and 'autonomic' (or 'subcortical') arousals are an important source of daytime sleepiness in the community.

Which aspects of breathing during sleep influence the overnight fall of blood pressure in a community population?

BACKGROUND: Obstructive sleep apnoea (OSA) causes recurrent rises in blood pressure during sleep, and recent community surveys have suggested a link between mild OSA and diurnal hypertension. The fact that OSA and hypertension share some risk factors, as well as problems accurately quantifying OSA severity, have diluted the power of such studies. This study tries to circumvent some of these problems by measuring the overnight change in blood pressure and relating it to relevant measures of the severity of upper airway obstruction on the same night. METHODS: Men born between 1930 and 1960 and their wives living in a market town north of Oxford were identified from a GP practice register. Enough couples were recruited to provide approximately 10 (20 individuals) per year of birth. Subjects were visited at home where a questionnaire was administered, anthropometric measurements made, blood pressures taken (including by the subject), and sensors applied for a subsequent overnight sleep study. The sleep study measured indices of hypoxia, snoring, autonomic arousal, degree of respiratory effort; the last two of these derived from measurements of pulse transit time (indirect beat to beat blood pressure). After waking the following morning, the subjects took their own blood pressures again. RESULTS: Data were available from 224 couples (448 subjects). On average, systolic BP fell 8 mm Hg from evening to morning. Only hypoxic dips (>4% SaO(2) dips/h) and the measure of degree of respiratory effort were significant independent predictors of this overnight change in systolic BP, together accounting for 7-10% of the variation (p<0.0001). Dividing the subjects into quartiles according to the respiratory effort overnight showed a progressive reduction in the fall of systolic BP overnight: 13.6, 10.8, 7.3, and 5.6 mm Hg, lowest to highest quartiles. CONCLUSIONS: This study suggests that increased respiratory effort during sleep (seen in OSA and related syndromes of increased upper airway resistance during sleep) offsets the normal fall in BP that occurs overnight, even within this community population. This may be one of the mechanisms by which hypertension is carried over into the waking hours in patients with OSA.

Health status in obstructive sleep apnea: relationship with sleep fragmentation and daytine sleepiness, and effects of continuous positive airway pressure treatment.

Patients with obstructive sleep apnea (OSA) have impaired health status that improves with nasal continuous positive airway pressure (nCPAP). The study reported here explored the relationships between health status, its improvement with nCPAP, sleep fragmentation, and daytime sleepiness. In the study, 51 patients (46 male, five female) ranging from nonsnorers to individuals with severe OSA (median apnea/hypopnea index [AHI] 25, 90% central range: 1 to 98) had polysomnography with microarousal scoring, respiratory arousal scoring, and measurement of pulse transit time. The Short Form-36 Health Survey (SF-36) questionnaire was administered before and after 4 wk of nCPAP treatment; daytime sleepiness was also measured before starting nCPAP. Relationships between pretreatment health status and sleep fragmentation were weak, but significant associations were found between all sleep fragmentation indices and health status improvement with nCPAP (e.g., arousals according to the criteria of the American Sleep Disorders Association versus change in the physical component summary, r = 0.44, p < 0.001). Compared with general population data, the dimensions of energy and vitality and physical role limitation were abnormal before nCPAP (p < 0.05) and normalized with treatment. Sleepiness and pretreatment SF-36 values correlated significantly (Epworth Sleepiness Scale versus energy and vitality, r = -0.47, p < 0.001; modified Maintenance of Wakefulness Test versus energy and vitality, r = 0.32, p < 0.05). We conclude that the health status of patients with OSA improves with nCPAP and this improvement correlates with sleep fragmentation severity. However, the correlation is not very close, which may reflect the improvement with nCPAP of other symptoms not directly related to disease severity.

Sleep fragmentation indices as predictors of daytime sleepiness and nCPAP response in obstructive sleep apnea.

Sleep fragmentation and respiratory disturbance measures are used in the assessment of obstructive sleep apnea (OSA) but have proved to be disappointingly poor correlates of daytime sleepiness. This study investigates the ability of electroencephalograph (EEG) and non-EEG sleep fragmentation indices to predict both presenting sleepiness and the improvement in sleepiness with subsequent nasal continuous positive airway pressure (nCPAP) therapy (nCPAP responsive sleepiness). Forty-one patients (36 men, 5 women), ranging from nonsnorers to severe OSA (> 4% O2 dip rate, median 11.1, range 0.4 to 76.5), had polysomnography with microarousal scoring, computerized EEG analysis, autonomic arousal detection, and body movement analysis. All patients received a trial of nCPAP regardless of sleep study outcome. Spearman's correlation analysis showed significant and similar associations between all sleep fragmentation indices with both pretreatment and nCPAP responsive sleepiness. There was no deterioration in sleepiness on nCPAP in the nonsnorers. Using stepwise multiple regression analysis, the best predictor of nCPAP responsive subjective and objective sleepiness was body movement index, explaining 38% and 43% of the variance, respectively. Variability in EEG sleep depth, quantified from computerized EEG analysis, was the only other index to contribute to these models. Together these indices explained 44% and 51% of the subjective and objective response to nCPAP, respectively. These results suggest that sleep fragmentation indices are useful for identifying OSA patients with sleepiness likely to respond to nCPAP.

Mandibular advancement devices for the control of snoring.

Patients presenting with the complaint of antisocial snoring have very few options available to them of proven efficiency. Mandibular advancement devices worn intra-orally at night, have recently been shown in controlled trials to help mild to moderate obstructive sleep apnoea. However, there are no properly controlled studies with objective measurements on the use of such appliances for the management of antisocial snoring. Fifteen patients, already established on mandibular advancement devices for the control of snoring, were asked to participate in this study. They were studied over two nights, using a portable sleep monitoring device at home, both with and without their mandibular advancement devices in place (in randomized order). Snoring was measured using a surface throat microphone. In addition oxygen saturation and indirect beat to beat blood pressure were measured. The latter (using pulse transit time) provided an index of autonomic "arousals" and a measure of inspiratory effort. In nearly all of these highly selected patients the mandibular advancement devices reduced significantly the amount of snoring from a median of 193 to 20 snores x h(-1) (p<0.0001). In addition there was a reduction in respiratory effort, implying enlargement of the upper airway whilst wearing the appliance. These patients only represent those who were able to tolerate the appliance. With such clear evidence of their potential efficacy, and no suggestion from other studies of any harm, it would seem reasonable to introduce this approach into the management of antisocial snoring.