Burden of respiratory syncytial virus disease across the lifespan in Australia and New Zealand: a scoping review.

OBJECTIVES: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection in young children worldwide. RSV is increasingly associated with severe respiratory disease in people aged >65 years. The heterogeneous landscape of RSV in Australia and New Zealand makes generalisation of results from global studies to local contexts difficult. Given the changing landscape of RSV, we aimed to examine the existing literature on the burden of RSV disease and identify evidence gaps in Australia and New Zealand. STUDY DESIGN: Scoping review. METHODS: We designed a scoping review protocol and searched the Web of Science and Scopus databases for eligible peer-reviewed publications. Data from eligible studies were charted and summarised in tabular and narrative form. RESULTS: Of the 153 eligible publications identified, 123 investigated RSV disease in a hospital setting and six in primary care. Only six studies reported the economic burden of disease, all of which estimated direct healthcare costs associated with treatment and/or hospitalisation; no studies quantified the indirect costs or costs to families. CONCLUSIONS: In this scoping review, we describe the effect of RSV disease in several high-risk populations, including children and adults. An improved understanding of the RSV burden of disease, both in primary care settings and economically, within the local context will assist with the implementation of preventative strategies, including vaccination programmes. Future studies to determine the true burden of RSV-associated morbidity, mortality and economic burden across the entire patient journey and among different healthcare settings will help prioritise emerging RSV therapeutics.

Fear of progression in chronic illnesses other than cancer: a systematic review and meta-analysis of a transdiagnostic construct.

Fear of cancer recurrence (FCR) is the most common psychosocial issue amongst cancer survivors. However, fear of progression (FoP) has rarely been studied outside of the cancer context. This review aimed to: (1) meta-synthesise qualitative studies of FoP in illnesses other than cancer; and (2) quantify the relationship between FoP and anxiety, depression, and quality of life (QoL) in non-cancer chronic illnesses. We identified 25 qualitative and 11 quantitative studies in a range of chronic illnesses. Participants described fears of progression and recurrence of their illness, including fears of dying, and fears of becoming a burden to family. Fears were often triggered by downward comparison (i.e., seeing people worse off than themselves). Participants coped in different ways, including by accepting the illness or seeking knowledge. Those for whom these fears caused distress reported hypervigilance to physical symptoms and avoidance. Distress, and seeking information, were associated with adherence. In quantitative analyses, FoP was moderately associated with QoL, and strongly associated with anxiety and depression. These results suggest that FoP in illnesses other than cancer is similar to FCR. FoP appears to be an important transdiagnostic construct associated with distress. Evidence-based FCR interventions could be adapted to better manage FoP in other illnesses.

The impact of the changing pneumococcal national immunisation program among older Australians.

Australia has a universal infant pneumococcal conjugate vaccination program and until recently a universal pneumococcal polysaccharide vaccine program for non-Indigenous adults aged ≥65 years and Indigenous adults aged ≥50 years. We documented the impacts of infant and adult vaccination programs on the epidemiology of invasive pneumococcal disease (IPD) in Indigenous and non-Indigenous adults. IPD notifications from the National Notifiable Disease Surveillance System were analysed from 2002 to 2017, grouped by age, vaccine serotype group and Indigenous status. Since the universal funding of infant and elderly pneumococcal vaccination programs in January 2005, total IPD decreased by 19% in non-Indigenous adults aged ≥65 years but doubled in Indigenous adults aged ≥50 years. Vaccine uptake was suboptimal in both groups but lower in Indigenous adults. IPD due to the serotypes contained in the pneumococcal conjugate vaccines (PCV) except for serotype 3 declined markedly over the study period but were replaced by non-PCV serotypes. Serotype 3 is currently the most common in older adults. In the populations eligible for the adult 23-valent pneumococcal polysaccharide vaccine (23vPPV) program, IPD rates due to its exclusive serotypes increased to a lower extent than non-vaccine types. In 2017, non-vaccine serotypes accounted for most IPD in the older population eligible for the 23vPPV program, while it's eleven exclusive serotypes accounted for the majority of IPD in younger adults. Infant and adult pneumococcal vaccination programs in Australia have shaped the serotype-specific epidemiology of IPD in older adults. IPD remains a significant health burden for the Indigenous population. Herd immunity impact is clear for PCV serotypes excluding serotype 3 and serotype replacement is evident for non-PCV serotypes. The adult 23vPPV immunisation program appears to have partially curbed replacement with IPD due to its eleven exclusive serotypes, highlighting a potential benefit of increasing adult 23vPPV coverage in Australia.

A randomised controlled trial of SMS messaging and calendar reminders to improve vaccination timeliness in infants.

BACKGROUND: The effectiveness of SMS reminders in improving vaccination coverage has been assessed previously, with effectiveness varying between settings. However, there are very few studies on their effect on the timeliness of vaccination. DESIGN: Unblinded, randomised controlled trial with blocked sampling. METHODS: 1594 Australian infants and young children were recruited to assess the impact of (1) SMS reminders only, (2) a personalised calendar, (3) SMS reminder and personalised calendar and (4) no intervention, on receipt of vaccine within 30 days of the due date. Outcomes were measured for receipt of vaccines due at 2, 4, 6, 12 and 18 months of age. A post-hoc assessment was also conducted of the impact of a new national "No jab No Pay" policy introduced during the trial, which removed philosophical objections as an exemption for financial penalties for non-vaccination. RESULTS: There was a statistically significant improvement in on-time vaccination only at the 12 month schedule point amongst infants who received SMS reminders alone (RR 1.09, 95% CI 1.01-1.18) or in combination with a personalised calendar (1.11, CI 1.03-1.20) compared to controls. This impact was limited to participants who had received one or more previous doses late. No statistically significant impacts of calendar interventions alone were seen. There was a high rate of on-time compliance amongst control participants - 95%, 86%, 80%, 74% at the 4, 6, 12 and 18 month schedule points respectively, which increased more than 10 percentage points after implementation of the "No Jab, No Pay" policy. CONCLUSIONS: SMS reminders are more effective in improving timeliness where pre-existing compliance is lower, but the 18 month schedule point appeared to be less amenable to intervention. Australia and New Zealand Clinical Trial Registration No. ACTRN12614000970640.

Retrospective cost-effectiveness of the 23-valent pneumococcal polysaccharide vaccination program in Australia.

BACKGROUND: The Australian infant pneumococcal vaccination program was funded in 2005 using the 7-valent pneumococcal conjugate vaccine (PCV7) and the 13-valent conjugate vaccine (PCV13) in 2011. The PCV7 and PCV13 programs resulted in herd immunity effects across all age-groups, including older adults. Coincident with the introduction of the PCV7 program in 2005, 23-valent pneumococcal polysaccharide vaccine (PPV23) was funded for all Australian adults aged over 65 years. METHODS: A multi-cohort Markov model with a cycle length of one year was developed to retrospectively evaluate the cost-effectiveness of the PPV23 immunisation program from 2005 to 2015. The analysis was performed from the healthcare system perspective with costs and quality-adjusted life years discounted at 5% annually. The incremental cost-effectiveness ratio (ICER) for PPV23 doses provided from 2005 to 2015 was calculated separately for each year when compared to no vaccination. Parameter uncertainty was explored using deterministic and probabilistic sensitivity analysis. RESULTS: It was estimated that PPV23 doses given out over the 11-year period from 2005 to 2015 prevented 771 hospitalisations and 99 deaths from invasive pneumococcal disease (IPD). However, the estimated IPD cases and deaths prevented by PPV23 declined by more than 50% over this period (e.g. from 12.9 deaths for doses given out in 2005 to 6.1 in 2015), likely driven by herd effects from infant PCV programs. The estimated ICER over the period 2005 to 2015 was approximately A$224,000/QALY gained compared to no vaccination. When examined per year, the ICER for each individual year worsened from $140,000/QALY in 2005 to $238,000/QALY in 2011 to $286,000/QALY in 2015. CONCLUSION: The cost-effectiveness of the PPV23 program in older Australians was estimated to have worsened over time. It is unlikely to have been cost-effective, unless PPV23 provided protection against non-invasive pneumococcal pneumonia and/or a low vaccine price was negotiated. A key policy priority should be to review of the future use of PPV23 in Australia, which is likely to be more cost-effective in certain high-risk groups.

Photoionization dynamics of cis-dichloroethene from investigation of vibrationally resolved photoelectron spectra and angular distributions.

The influence of vibronic coupling on the outer valence ionic states of cis-dichloroethene has been investigated by recording photoelectron spectra over the excitation range 19-90 eV using plane polarized synchrotron radiation, for two polarization orientations. The photoelectron anisotropy parameters and electronic state branching ratios derived from these spectra have been compared to theoretical predictions obtained with the continuum multiple scattering approach. This comparison shows that the photoionization dynamics of the Ã2B2, B̃2A1, C̃2A2, and D̃2B1 states, all of which are formed through the ejection of an electron from a nominally chlorine lone-pair orbital, exhibit distinct evidence of the Cooper minimum associated with the halogen atom. While retaining a high degree of atomic character, these orbital ionizations nevertheless display clear distinctions. Simulations, assuming the validity of the Born-Oppenheimer and the Franck-Condon approximations, of the X̃2B1, Ã2B2, and D̃2B1 state photoelectron bands have allowed some of the vibrational structure observed in the experimental spectra to be assigned. The simulations provide a very satisfactory interpretation for the X̃2B1 state band but appear less successful for the Ã2B2 and D̃2B1 states, with irregularities appearing in both. The B̃2A1 and C̃2A2 state photoelectron bands exhibit very diffuse and erratic profiles that cannot be reproduced at this level. Photoelectron anisotropy parameters, ß, have been evaluated as a function of binding energy across the studied photon energy range. There is a clear step change in the ß values of the Ã2B2 band at the onset of the perturbed peak intensities, with ß evidently adopting the value of the B̃2A1 band ß. The D̃2B1 band ß values also display an unexpected vibrational level dependence, contradicting Franck-Condon expectations. These various behaviors are inferred to be a consequence of vibronic coupling in this system.

An experimental and theoretical study of the photoelectron spectra of cis-dichloroethene: Valence shell vertical ionization and vibronic coupling in the low-lying cationic states.

The valence shell photoelectron spectrum of cis-dichloroethene has been studied both experimentally and theoretically. Photoelectron spectra have been recorded with horizontally and vertically plane polarized synchrotron radiation, thereby allowing the anisotropy parameters, characterizing the angular distributions, to be determined. The third-order algebraic-diagrammatic construction approximation scheme for the one-particle Green's function has been employed to compute the complete valence shell ionization spectrum. In addition, the vertical ionization energies have been calculated using the outer valence Green's function (OVGF) method and the equation-of-motion coupled-cluster, with single and double substitutions for calculating ionization potentials (EOM-IP-CCSD) model. The theoretical results have enabled assignments to be proposed for most of the structure observed in the experimental spectra, including the inner-valence regions dominated by satellite states. The linear vibronic coupling model has been employed to study the vibrational structure of the lowest photoelectron bands, using parameters obtained from ab initio calculations. The ground state optimized geometries and vibrational frequencies have been computed at the level of the second-order Møller-Plesset perturbation theory, and the dependence of the ionization energies on the nuclear configuration has been evaluated using the OVGF method. While the adiabatic approximation holds for the X̃2B1 state photoelectron band, the Ã2B2, B̃2A1, and C̃2A2 states interact vibronically and form a complex photoelectron band system with four distinct maxima. The D̃2B1 and Ẽ2B2 states also interact vibronically with each other. The potential energy surface of the D̃2B1 state is predicted to have a double-minimum shape with respect to the out-of-plane a2 deformations of the molecular structure. The single photoelectron band resulting from this interaction is characterized by a highly irregular structure, reflecting the non-adiabatic nuclear dynamics occurring on the two coupled potential energy surfaces forming a conical intersection close to the minimum of the Ẽ2B2 state.

The role of timeliness in the cost-effectiveness of older adult vaccination: A case study of pneumococcal conjugate vaccine in Australia.

While the impact of the timeliness of vaccine administration has been well-studied for childhood vaccinations, there has been little detailed quantitative analysis on the potential impact of the timeliness of vaccinations in older adults. The aim of this study was to explore the impact of implementing more realistic observed uptake distributions, taking into the account reduced vaccine efficacy but higher pneumococcal disease burden with increasing age beyond 65 years. A multi-cohort Markov model was constructed to evaluate the cost-effectiveness of a pneumococcal (PCV13) immunisation program in Australia, assuming two different uptake modelling approaches. The approach using an estimate of observed uptake was compared with a scenario in which the total cumulative uptake was delivered at the recommended age of vaccination. We found these two approaches produced different results both in terms of cases prevented and cost-effectiveness. The impact of the non-timely uptake in adult programs may sometimes have positive and other times negative effects, depending on several factors including the age-specific disease rates and the duration of vaccine protection. Our study highlights the importance of using realistic assumptions around uptake (including non-timely vaccination) when estimating the impact of vaccination in adults.

A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age.

OBJECTIVE: To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. METHODS: Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). RESULTS: Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed. CONCLUSION: This pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment.

An experimental and theoretical study of the valence shell photoelectron spectra of 2-chloropyridine and 3-chloropyridine.

The valence shell photoelectron spectra of 2-chloropyridine and 3-chloropyridine have been studied both experimentally and theoretically. Synchrotron radiation has been employed to record angle resolved photoelectron spectra in the photon energy range 20-100 eV, and these have enabled anisotropy parameters and branching ratios to be derived. The experimental results have been compared with theoretical predictions obtained using the continuum multiple scattering Xα approach. This comparison shows that the anisotropy parameter associated with the nominally chlorine lone-pair orbital lying in the molecular plane is strongly affected by the atomic Cooper minimum. In contrast, the photoionization dynamics of the second lone-pair orbital, orientated perpendicular to the molecular plane, seem relatively unaffected by this atomic phenomenon. The outer valence ionization has been studied theoretically using the third-order algebraic-diagrammatic construction (ADC(3)) approximation scheme for the one-particle Green's function, the outer valence Green's function method, and the equation-of-motion (EOM) coupled cluster (CC) theory at the level of the EOM-IP-CCSD and EOM-EE-CC3 models. The convergence of the results to the complete basis set limit has been investigated. The ADC(3) method has been employed to compute the complete valence shell ionization spectra of 2-chloropyridine and 3-chloropyridine. The relaxation mechanism for ionization of the nitrogen σ-type lone-pair orbital (σN LP) has been found to be different to that for the corresponding chlorine lone-pair (σCl LP). For the σN LP orbital, π-π* excitations play the main role in the screening of the lone-pair hole. In contrast, excitations localized at the chlorine site involving the chlorine πCl LP lone-pair and the Cl 4p Rydberg orbital are the most important for the σCl LP orbital. The calculated photoelectron spectra have allowed assignments to be proposed for most of the structure observed in the experimental spectra. The theoretical work also highlights the formation of satellite states, due to the breakdown of the single particle model of ionization, in the inner valence region.

Cost-effectiveness of 13-valent pneumococcal conjugate vaccine (PCV13) in older Australians.

BACKGROUND: The 23-valent pneumococcal polysaccharide vaccine (PPV23) has been funded under the Australia National Immunisation Program (NIP) since January 2005 for those aged >65years and other risk groups. In 2016, PCV13 was accepted by the Pharmaceutical Benefits Advisory Committee (PBAC) as a replacement for a single dose of PPV23 in older Australian adults. METHODS: A single-cohort deterministic multi-compartment (Markov) model was developed describing the transition of the population between different invasive and non-invasive pneumococcal disease related health states. We applied a healthcare system perspective with costs (Australian dollars, A$) and health effects (measured in quality adjusted life-years, QALYs) attached to model states and discounted at 5% annually. We explored replacement of PPV23 with PCV13 at 65years as well as other age based vaccination strategies. Parameter uncertainty was explored using deterministic and probabilistic sensitivity analysis. RESULTS: In a single cohort, we estimated PCV13 vaccination at the age of 65years to cost ∼A$11,120,000 and prevent 39 hospitalisations and 6 deaths from invasive pneumococcal disease and 180 hospitalisations and 10 deaths from community acquired pneumonia. The PCV13 program had an incremental cost-effectiveness ratio of ∼A$88,100 per QALY gained when compared to a no-vaccination, whereas PPV23 was ∼A$297,200 per QALY gained. To fall under a cost-effectiveness threshold of A$60,000 per QALY, PCV13 would have to be priced below ∼A$46 per dose. The cost-effectiveness of PCV13 in comparison to PPV23 was ∼A$35,300 per QALY gained. CONCLUSION: In comparison to no-vaccination, we found PCV13 use in those aged 65years was unlikely to be cost-effective unless the vaccine price was below A$46 or a longer duration of protection can be established. However, we found that in comparison to the PPV23, vaccination with PCV13 was cost-effective. This partly reflects the poor value for money estimated for PPV23 use in Australia.

Ionization of pyridine: Interplay of orbital relaxation and electron correlation.

The valence shell ionization spectrum of pyridine was studied using the third-order algebraic-diagrammatic construction approximation scheme for the one-particle Green's function and the outer-valence Green's function method. The results were used to interpret angle resolved photoelectron spectra recorded with synchrotron radiation in the photon energy range of 17-120 eV. The lowest four states of the pyridine radical cation, namely, 2A2(1a2-1), 2A1(7a1-1), 2B1(2b1-1), and 2B2(5b2-1), were studied in detail using various high-level electronic structure calculation methods. The vertical ionization energies were established using the equation-of-motion coupled-cluster approach with single, double, and triple excitations (EOM-IP-CCSDT) and the complete basis set extrapolation technique. Further interpretation of the electronic structure results was accomplished using Dyson orbitals, electron density difference plots, and a second-order perturbation theory treatment for the relaxation energy. Strong orbital relaxation and electron correlation effects were shown to accompany ionization of the 7a1 orbital, which formally represents the nonbonding σ-type nitrogen lone-pair (nσ) orbital. The theoretical work establishes the important roles of the π-system (π-π* excitations) in the screening of the nσ-hole and of the relaxation of the molecular orbitals in the formation of the 7a1(nσ)-1 state. Equilibrium geometric parameters were computed using the MP2 (second-order Møller-Plesset perturbation theory) and CCSD methods, and the harmonic vibrational frequencies were obtained at the MP2 level of theory for the lowest three cation states. The results were used to estimate the adiabatic 0-0 ionization energies, which were then compared to the available experimental and theoretical data. Photoelectron anisotropy parameters and photoionization partial cross sections, derived from the experimental spectra, were compared to predictions obtained with the continuum multiple scattering approach.

Investigating adverse events following immunisation with pneumococcal polysaccharide vaccine using electronic General Practice data.

BACKGROUND: In early 2011, following an increased number of reports of severe vaccine-related injection site reactions, Australian authorities recommended against administering repeat doses of the 23-valent pneumococcal polysaccharide vaccine (23vPPV) in otherwise healthy adults. The aim of this study was to assess a source of electronic medical record data from primary care providers (General Practitioners, GPs), for validity and ability to retrospectively detect this adverse event signal. METHODS: The General Practice Research Network (GPRN) holds data routinely collected from a representative sample of Australian GPs. Data were extracted on persons 18years or older who had received at least one dose of 23vPPV or influenza vaccine (as comparator) between January 2002 and June 2012. Increases above background levels were assessed using 95% confidence intervals of reaction rates, calculated from the Poisson distribution of counts. RESULTS: There was an average of 253 practices and 532 GPs contributing data per year. Over the study period there were 95,760 recorded 23vPPV administrations and 823 reactions, of which 233 were local. For influenza vaccine the numbers were 683,829 doses, 3001 and 387 respectively. Patterns of vaccinations and reactions were consistent with known safety profiles. There were 3 local reactions following 23vPPV in early 2011 (235/100,000 doses, 95% CI 49-717), which was not significantly different to the historical average (260, 225-298). We estimate that this system could have detected a 3-fold increase over background levels. CONCLUSIONS: Using GP consultation data, we were unable to confirm an increase in local reactions detected by passive surveillance, suggesting that this apparent signal was artefactual. GP consultation data captures large numbers of vaccine recipients and medically attended adverse reactions at low cost. If available in a timely manner and expanded, this system has significant potential for use in validation of apparent signals from passive surveillance.

Beyond expectations: Post-implementation data shows rotavirus vaccination is likely cost-saving in Australia.

BACKGROUND: Universal vaccination against rotavirus was included in the funded Australian National Immunisation Program in July 2007. Predictive cost-effectiveness models assessed the program before introduction. METHODS: We conducted a retrospective economic evaluation of the Australian rotavirus program using national level post-implementation data on vaccine uptake, before-after measures of program impact and published estimates of excess intussusception cases. These data were used as inputs into a multi-cohort compartmental model which assigned cost and quality of life estimates to relevant health states, adopting a healthcare payer perspective. The primary outcome was discounted cost per quality adjusted life year gained, including or excluding unspecified acute gastroenteritis (AGE) hospitalisations. RESULTS: Relative to the baseline period (1997-2006), over the 6years (2007-2012) after implementation of the rotavirus program, we estimated that ∼77,000 hospitalisations (17,000 coded rotavirus and 60,000 unspecified AGE) and ∼3 deaths were prevented, compared with an estimated excess of 78 cases of intussusception. Approximately 90% of hospitalisations prevented were in children <5years, with evidence of herd protection in older age groups. The program was cost-saving when observed changes (declines) in both hospitalisations coded as rotavirus and as unspecified AGE were attributed to the rotavirus vaccine program. The adverse impact of estimated excess cases of intussusception was far outweighed by the benefits of the program. CONCLUSION: The inclusion of herd impact and declines in unspecified AGE hospitalisations resulted in the value for money achieved by the Australian rotavirus immunisation program being substantially greater than predicted bypre-implementation models, despite the potential increased cases of intussusception. This Australian experience is likely to be relevant to high-income countries yet to implement rotavirus vaccination programs.

Treatment of non-cavitary pulmonary tuberculosis with shortened fluoroquinolone-based regimens: a meta-analysis.

SETTING: Several recent trials evaluating 4-month fluoroquinolone (FQ) containing regimens found that none of the experimental regimens were non-inferior to standard 6-month therapy in treating patients with drug-susceptible pulmonary tuberculosis (PTB). OBJECTIVE: To answer whether FQ-containing duration-shortened regimens are non-inferior to standard therapy in the treatment of patients with non-cavitary PTB. DESIGN: Systematic review of all randomized and quasi-randomized trials that substituted an FQ into standard therapy for less than 6 months' duration to treat drug-susceptible, non-cavitary PTB. Non-inferiority was based on a 6% margin of difference. RESULTS: Of 4594 total participants in the three trials that met the inclusion criteria, 1066 patients had non-cavitary disease. The pooled difference in unfavorable outcomes was 5% (95%CI -3 to 13) in patients with non-cavitary disease treated with FQ-containing regimens vs. standard therapy. In subgroup analyses, the pooled difference in unfavorable outcomes was 1% (95%CI -3 to 5) when comparing the daily form of intervention regimen with standard therapy, and -1% (95%CI -5 to 4) between regimens replacing ethambutol (EMB) with an FQ and standard therapy. No difference in risk of adverse events was noted. CONCLUSION: Daily administered 4-month regimens with substitution of EMB by an FQ may be non-inferior to standard therapy in patients with culture-confirmed, non-cavitary, drug-susceptible PTB.

Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis

The American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Diseases Society of America jointly sponsored the development of this guideline for the treatment of drug-susceptible tuberculosis, which is also endorsed by the European Respiratory Society and the US National Tuberculosis Controllers Association. Representatives from the American Academy of Pediatrics, the Canadian Thoracic Society, the International Union Against Tuberculosis and Lung Disease, and the World Health Organization also participated in the development of the guideline. This guideline provides recommendations on the clinical and public health management of tuberculosis in children and adults in settings in which mycobacterial cultures, molecular and phenotypic drug susceptibility tests, and radiographic studies, among other diagnostic tools, are available on a routine basis. For all recommendations, literature reviews were performed, followed by discussion by an expert committee according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. Given the public health implications of prompt diagnosis and effective management of tuberculosis, empiric multidrug treatment is initiated in almost all situations in which active tuberculosis is suspected. Additional characteristics such as presence of comorbidities, severity of disease, and response to treatment influence management decisions. Specific recommendations on the use of case management strategies (including directly observed therapy), regimen and dosing selection in adults and children (daily vs intermittent), treatment of tuberculosis in the presence of HIV infection (duration of tuberculosis treatment and timing of initiation of antiretroviral therapy), as well as treatment of extrapulmonary disease (central nervous system, pericardial among other sites) are provided. The development of more potent and better-tolerated drug regimens, optimization of drug exposure for the component drugs, optimal management of tuberculosis in special populations, identification of accurate biomarkers of treatment effect, and the assessment of new strategies for implementing regimens in the field remain key priority areas for research. See the full-text online version of the document for detailed discussion of the management of tuberculosis and recommendations for practice.

Retrospective economic evaluation of childhood 7-valent pneumococcal conjugate vaccination in Australia: Uncertain herd impact on pneumonia critical.

BACKGROUND: Retrospective cost-effectiveness analyses of vaccination programs using routinely collected post-implementation data are sparse by comparison with pre-program analyses. We performed a retrospective economic evaluation of the childhood 7-valent pneumococcal conjugate vaccine (PCV7) program in Australia. METHODS: We developed a deterministic multi-compartment model that describes health states related to invasive and non-invasive pneumococcal disease. Costs (Australian dollars, A$) and health effects (quality-adjusted life years, QALYs) were attached to model states. The perspective for costs was that of the healthcare system and government. Where possible, we used observed changes in the disease rates from national surveillance and healthcare databases to estimate the impact of the PCV7 program (2005-2010). We stratified our cost-effectiveness results into alternative scenarios which differed by the outcome states included. Parameter uncertainty was explored using probabilistic sensitivity analysis. RESULTS: The PCV7 program was estimated to have prevented ∼5900 hospitalisations and ∼160 deaths from invasive pneumococcal disease (IPD). Approximately half of these were prevented in adults via herd protection. The incremental cost-effectiveness ratio was ∼A$161,000 per QALY gained when including only IPD-related outcomes. The cost-effectiveness of PCV7 remained in the range A$88,000-$122,000 when changes in various non-invasive disease states were included. The inclusion of observed changes in adult non-invasive pneumonia deaths substantially improved cost-effectiveness (∼A$9000 per QALY gained). CONCLUSION: Using the initial vaccine price negotiated for Australia, the PCV7 program was unlikely to have been cost-effective (at conventional thresholds) unless observed reductions in non-invasive pneumonia deaths in the elderly are attributed to it. Further analyses are required to explore this finding, which has significant implications for the incremental benefit achievable by adult PCV programs.

The Video Interaction Guidance approach applied to teaching communication skills in dentistry.

PURPOSE: To examine dentists' views of a novel video review technique to improve communication skills in complex clinical situations. MATERIALS AND METHODS: Dentists (n = 3) participated in a video review known as Video Interaction Guidance to encourage more attuned interactions with their patients (n = 4). Part of this process is to identify where dentists and patients reacted positively and effectively. Each dentist was presented with short segments of video footage taken during an appointment with a patient with intellectual disabilities and communication difficulties. Having observed their interactions with patients, dentists were asked to reflect on their communication strategies with the assistance of a trained VIG specialist. RESULTS: Dentists reflected that their VIG session had been insightful and considered the review process as beneficial to communication skills training in dentistry. They believed that this technique could significantly improve the way dentists interact and communicate with patients. The VIG sessions increased their awareness of the communication strategies they use with their patients and were perceived as neither uncomfortable nor threatening. DISCUSSION: The VIG session was beneficial in this exploratory investigation because the dentists could identify when their interactions were most effective. Awareness of their non-verbal communication strategies and the need to adopt these behaviours frequently were identified as key benefits of this training approach. One dentist suggested that the video review method was supportive because it was undertaken by a behavioural scientist rather than a professional counterpart. CONCLUSION: Some evidence supports the VIG approach in this specialist area of communication skills and dental training.

Control of varicella in the post-vaccination era in Australia: a model-based assessment of catch-up and infant vaccination strategies for the future.

In Australia, varicella vaccine was universally funded in late 2005 as a single dose at 18 months. A school-based catch-up programme for children aged 10-13 years without a history of infection or vaccination was funded until 2015, when those eligible for universal infant vaccination would have reached the age of high school entry. This study projects the impact of discontinuing catch-up vaccination on varicella and zoster incidence and morbidity using a transmission dynamic model, in comparison with alternative policy options, including two-dose strategies. At current vaccine coverage (83% at 2 years and 90% at 5 years), ceasing the adolescent catch-up programme in 2015 was projected to increase varicella-associated morbidity between 2035 and 2050 by 39%. Although two-dose infant programmes had the lowest estimated varicella morbidity, the incremental benefit from the second dose fell by 70% if first dose coverage increased from 83% to 95% by age 24 months. Overall zoster morbidity was predicted to rise after vaccination, but differences between strategies were small. Our results suggest that feasibility of one-dose coverage approaching 95% is an important consideration in estimating incremental benefit from a second dose of varicella vaccine.