Early Postoperative Weight-Bearing Ability after Total Hip Arthroplasty versus Bipolar Hemiarthroplasty in Elderly Patients with Femoral Neck Fracture.

Background: Femoral neck fractures are among the most common types of fractures and particularly affect elderly patients. Two of the most common treatment strategies are total hip arthroplasty (THA) and bipolar hemiarthroplasty (BA). However, the role of the different treatment strategies in the postoperative weight-bearing ability in the early postoperative phase is still not entirely clear. Methods: Patients who underwent either THA or BA were consecutively included in our prospective cohort study. Gait analysis was performed during the early postoperative period. The gait analysis consisted of a walking distance of 40 m coupled with the turning movement in between. During the gait analysis, the duration of the measurement, the maximum peak force and the average peak force were recorded. Results: A total of 39 patients were included, 25 of whom underwent BA and 14 of whom underwent THA. The maximum peak force during the gait analysis was, on average, 80.6% ± 19.5 of the body weight in the BA group and 78.9% ± 21.6 in the THA group. The additionally determined average peak force during the entire gait analysis was 66.8% ± 15.8 of the body weight in the BA group and 60.5% ± 15.6 in the THA group. Conclusions: Patients with femoral neck fractures undergoing THA and BA can achieve sufficient weight bearing on the operated leg in the early postoperative period. In our study, BA did not allow for a significantly higher average and maximum loading capacity compared with THA.

Feasibility of High-Fidelity Simulator Models for Minimally Invasive Spine Surgery in a Resource-Limited Setting: Experience From East Africa.

BACKGROUND: Spine surgery is a rapidly evolving specialty with a continuous need to learn new skills. In resource-limited settings such as Africa, the need for training is greater. The use of simulation-based training is important in different stages of skill acquisition, especially for high-stake procedures such as spine surgery. Among the available methods of simulation, the use of synthetic models has gained popularity among trainers. METHOD: Twenty participants of a neurosurgery training course, most of whom (65%) were neurosurgery residents and fellows, were recruited. They had hands-on training sessions using a high-fidelity lumbar degenerative spine simulation model and hands-on theater experience. After this, they completed a survey to compare their experience and assess the effectiveness of the lumbar spine model in stimulating real patient and surgery experiences. RESULTS: The participants were from four African countries, and the majority were neurosurgery residents. There were varying levels of experience among the participants in minimally invasive spine surgery, with the majority either having no experience or having only observed the procedure. All the participants said that the high-fidelity lumbar spine model effectively simulated real minimally invasive spine setup and real bone haptics and was effective in learning new techniques. Most of the participants agreed that the model effectively simulated real dura and nerve roots (95%), real muscle (90%), real bleeding from bones and muscles (95%), and real cerbrospinal fluid in the subarachnoid space. Among them, 95% agreed that the model is effective in lumbar minimally invasive spine training in resource-limited settings. CONCLUSION: With the development of new and better surgical techniques, the use of high-fidelity models provides a good opportunity for learning and training, especially in resource-poor settings where there is a paucity of training facilities and personnel.

The effect of "smoky" coal bans on chronic lung disease among older people in Ireland.

Globally, coal is still widely used for heating. However, there are concerns about its effect on ambient air quality and health. We estimated the effect of bans prohibiting the sale and use of so-called "smoky coal" on the prevalence of chronic lung disease in older people. Our identification strategy relied on the phased extension of smoky coal bans to Irish towns after 2010. We examined five waves of The Irish Longitudinal Study on Ageing (TILDA), a large nationally representative survey containing detailed information on health, housing, and socio-economic status. Controlling for relevant factors, smoky coal bans reduced the probability that an older person reports being diagnosed with chronic lung disease by between three and five percentage points. In models where we estimated the effect of the ban on the incidence of new cases of chronic lung disease, rather than existing cases, we found the effect was between -0.96 and -2.5 percentage points. Our findings were robust to estimating the model using different sub-samples and control variables. Furthermore, to address potential endogeneity of the ban, we examined subsamples defined by whether participants lived in towns within a range of the population threshold at which the ban was imposed. Estimating our model using these subsamples showed a consistently negative effect of the ban. We also showed parallel trends in health outcomes before the treatment, and that the treatment did not affect attrition from the sample.

Telemedical Support Using Smartphones for Spine Surgery in Low- and Middle-Income Countries.

Objective: Low- and middle-income countries (LMICs) face many challenges compared to industrialized nations, most notably in regard to the health care system. Patients often have to travel long distances to receive medical care with few reliable transportation mechanisms. In time-critical emergencies, this is a significant disadvantage. One specialty that is particularly affected by this is spine surgery. Within this field, traumatic injuries and acutely compressive pathologies are often time-critical. Increasing global networking capabilities through internet access offers the possibility for telemedical support in remote regions. Recently, high-performance cameras and processors became available in commercially available smartphones. Due to their wide availability and ease of use, this could provide a unique opportunity to offer telemedical support in LMICs. Methods: We conducted a feasibility study with a neurosurgical institution in east Africa. To ensure telemedical support, a commercially available smartphone was selected as the experimental hardware. Preoperatively, resolution, contrast, brightness, and color reproduction were assessed under theoretical conditions using a test chart. Intraoperatively, the image quality was assessed under different conditions. In the first step, the instrumentation table was displayed, and the mentor surgeon marked an instrument that the mentee surgeon should recognize correctly. In the next evaluation step, the surgical field was shown on film and the mentor surgeon marked an anatomical structure, and in the last evaluation step, the screen of the X-ray machine was captured, and the mentor surgeon again marked an anatomical structure. Subjective image quality was rated by two independent reviewers using the similar modified Likert scale as before on a scale of 1-5, with 1 indicating inadequate quality and 5 indicating excellent quality. Results: The image quality during the video calls was rated as sufficient overall. When evaluating the test charts, a quality of 97% ± 5 on average was found for the chart with the white background and a quality of 84% ± 5 on average for the chart with the black background. The color reproduction, the contrast, and the reproduction of brightness were rated excellent. Intraoperatively, the visualization of the instrument table was also rated excellent. Visualization of the operative site was rated 1.5 ± 0.5 on average and it was not possible to recognize relevant anatomical structures with the required confidence for surgical procedures. Image quality of the X-ray screen was rated 1.5 ± 0.9 on average. Conclusion: Current generation smartphones have high imaging performance, high computing power, and excellent connectivity. However, relevant anatomical structures during spine surgery procedures and on the X-ray screen in the operating room could not be identified with reliability to provide adequate surgical support. Nevertheless, our study showed the potential in smartphones supporting surgical procedures in LMICs, which could be helpful in other surgical fields.

Does caring for others affect our mental health? Evidence from the COVID-19 pandemic.

Despite a growing literature about the mental health effects of COVID-19, less is known about the psychological costs of providing informal care during the pandemic. We examined longitudinal data from the UK's Understanding Society Survey, including eight COVID surveys, to estimate fixed effects difference-in-differences models combined with matching, to explore the causal effects of COVID-19 among informal carers. While matching accounts for selection on observables into caregiving, multiple period difference-in-differences specifications allow investigation of heterogeneous mental health effects of COVID-19 by timing and duration of informal care. The estimates suggest that while mental health fluctuated following the imposition of social restrictions, informal carers who started caregiving during the pandemic show the largest mental health deterioration, especially during lockdowns. Policies to mitigate the psychological burden of caregiving might be more effective if targeted at those starting to provide care for the first time.

Indoor particulate air pollution from open fires and the cognitive function of older people.

Exposure to indoor air pollution is known to affect respiratory and cardiovascular health, but little is known about its effects on cognitive function. We measured the concentrations and magnetite content of airborne particulate matter (PM) in the indoor environment arising from burning peat, wood or coal in residential open fires. Highest indoor PM2.5 concentrations (60 µg/m3 i.e. 2.4 times the WHO-recommended 24-h mean) occurred when peat was burned, followed by burning of coal (30 µg/m3) and wood (17 µg/m3). Conversely, highest concentrations of coarser PM (PM10-2.5) were associated with coal burning (20 µg/m3), with lower concentrations emitted during burning of wood (10 µg/m3) and peat (8 µg/m3). The magnetic content of the emitted PM, greatest (for both PM size fractions) when coal was burned, is similar to that of roadside airborne PM. Exposure to PM, and to strongly magnetic airborne PM, can be greater for individuals spending ~5 h/day indoors with a coal-burning open fire for 6 months/year compared to those commuting via heavily-trafficked roads for 1 h/day for 12 months/year. Given these high indoor PM and magnetite concentrations, and the reported associations between (outdoor) PM and impaired neurological health, we used individual-level data from The Irish Longitudinal Study on Ageing (TILDA) to examine the association between the usage of open fires and the cognitive function of older people. Using a sample of nearly seven thousand older people, we estimated multi-variate models of the association between cognitive function and open fire usage, in order to account for relevant confounders such as socio-economic status. We found a negative association between open fire usage and cognitive function as measured by widely-used cognitive tests such as word recall and verbal fluency tests. The negative association was largest and statistically strongest among women, a finding explained by the greater exposure of women to open fires in the home because they spent more time at home than men. Our findings were also robust to stratifying the sample between old and young, rich and poor, and urban and rural.

Disabilities moderate the association between neighbourhood urbanity and cognitive health: Results from the Irish longitudinal study on ageing.

BACKGROUND: Geographical variations in cognitive health have been extensively explored, but the evidence on adult individuals with disabilities is inconclusive. While urban living is suggested as more cognitively stimulating than rural dwelling in epidemiological research, both rurality and urbanity can present barriers that may negatively impact cognitive health, the former due to limited accessibility to stimulation, and the latter because presenting environmental stressors. OBJECTIVE: To bridge this gap in the literature, we investigated geographical variations in multiple cognitive skills in adult age based on neighbourhood urbanity and having disabilities. METHODS: Data on global cognition, memory, speed of processing and executive functions, as well as reported functional limitations, was taken from 4127 individuals aged 50 + participating in the first wave of The Irish Longitudinal Study on Ageing (TILDA). Neighbourhood urbanity was measured using Census data on population density. Multivariate regression analyses controlled for socio-demographic, health and lifestyle covariates. RESULTS: Residence in medium-high densely populated areas was significantly associated with better cognitive performance across all measures, after controlling for covariates. However, having disabilities was linked to worse global cognitive functioning (MoCA, p = .005), immediate recall (p = .022) and executive functions (CTT2, p = .009) in the least and most densely populated areas. CONCLUSIONS: Living in urbanised areas may provide more mental stimulation than rural places; however, functional limitations moderate this association, suggesting potential environmental challenges both in rural and urban areas. Considering both individual and environmental circumstances can enrich investigations of geographical variations in cognitive health.

Environment and cognitive aging: A cross-sectional study of place of residence and cognitive performance in the Irish longitudinal study on aging.

OBJECTIVE: Stimulating environments foster cognitive vitality in older age. However, it is not known whether and how geographical and physical characteristics of lived environments contribute to cognitive aging. Evidence of higher prevalence of dementia in rural rather than urban contexts suggests that urban environments may be more stimulating either cognitively, socially, or in terms of lifestyle. The present study explored urban/rural differences in cognition for healthy community-dwelling older people while controlling for a comprehensive spectrum of confounding factors. METHOD: Cognitive performance of 3,765 healthy Irish people aged 50+ years participating in Wave 1 of The Irish Longitudinal Study on Aging was analyzed in relation to current location of residence-urban, other settlements, or rural areas-and its interaction with childhood residence. Regression models controlled for sociodemographic, health, and lifestyle factors. RESULTS: Urban residents showed better performance than the other 2 residence groups for global cognition and executive functions after controlling for covariates. Childhood urban residence was associated with a cognitive advantage especially for currently rural participants. CONCLUSION: Our findings suggest higher cognitive functioning for urban residents, although childhood residence modulates this association. Suggestions for further developments of these results are discussed. (PsycINFO Database Record

Seasonal and meteorological associations with depressive symptoms in older adults: A geo-epidemiological study.

BACKGROUND: Given increased social and physiological vulnerabilities, older adults may be particularly susceptible to environmental influences on mood. Whereas the impact of season on mood is well described for adults, studies rarely extend to elders or include objective weather data. We investigated the impact of seasonality and meteorological factors on risk of current depressive symptoms in older adults. METHODS: We used data on 8027 participants from the first wave of The Irish Longitudinal Study of Ageing, a population-representative cohort of adults aged 50+. Depressive symptoms were recorded using the Centre for Epidemiological Studies Depression Scale. Season was defined according to the World Meteorological Organisation. Data on climate over the preceding thirty years, and temperature and rain over the preceding month, were provided by the Irish Meteorological Service and linked using Geographic Information Systems techniques to participant's geo-coded locations at a resolution of one kilometre. RESULTS: The highest levels of depressive symptoms were reported in winter and the lowest in spring (mean 6.56 [CI95% 6.09, 7.04] vs. 5.81 [CI95%: 5.40, 6.22]). In fully adjusted linear regression models, participants living in areas with higher levels of rainfall in the preceding and/or current calendar month had greater depressive symptoms (0.04 SE 0.02; p=0.039 per 10mm additional rainfall per month) while those living in areas with sunnier climates had fewer depressive symptoms (-2.67 SE 0.88; p=0.003 for every additional hour of average annual daily sunshine). LIMITATIONS: This was a cross-sectional analysis thus causality cannot be inferred; monthly rain and temperature averages were available only on a calendar month basis while monthly local levels of sunshine data were not available. CONCLUSIONS: Environmental cues may influence mood in older adults and thus have relevance for the recognition and treatment of depression in this age group.

Water fluoridation, dentition status and bone health of older people in Ireland.

OBJECTIVE: To examine some of the potential benefits and risks of water fluoridation for older adults. METHODS: This study used 'The Irish Longitudinal Study on Ageing', to access a nationally representative sample of 4977 people aged 50 and older. The sample was used to estimate associations between the percentage of households in a respondent's local area with a currently fluoridated water supply and the probability of two binary outcomes: the respondent having all their own teeth and having normal bone density. Past exposure of individuals to fluoridated water was not assessed; the prevalence of fluoridated water in local supplies was obtained from the 2006 Census of Ireland. The Census data indicated that there was considerable variation in the proportion of households with fluoridated water supplies, especially in rural areas. Bone mineral density was estimated from a heel ultrasound of each respondent, and their number of teeth was self-reported. A range of individual variables, such as educational attainment, housing wealth, age and health behaviours, was controlled for. RESULTS: It was found that the greater the percentage of households with a fluoridated water supply in an area, the higher the probability that respondents had all their own teeth. There was no significant relationship between the proportion of households with a fluoridated water supply in an area and bone health. CONCLUSION: This study suggests that water fluoridation provides a net health gain for older Irish adults, though the effects of fluoridation warrant further investigation.

Rapid deamidation of recombinant protective antigen when adsorbed on aluminum hydroxide gel correlates with reduced potency of vaccine.

Deamidation of the recombinant protective antigen (rPA) correlates with decreased effectiveness of the vaccine in protecting against infection by Bacillus anthracis. We present data demonstrating dramatic deamidation of amino acid positions 713 and 719 of rPA adsorbed onto aluminum hydroxide gel, an adjuvant, relative to rPA stored in solution without adjuvant. Although deamidation did not impact total levels of rPA-specific antibodies in a mouse model, it did correlate with a decrease in toxin-neutralizing antibodies. On the basis of these data, we hypothesize that interactions of rPA with aluminum hydroxide gel are destabilizing and are the direct cause of reduced vaccine efficacy.

Deposition of albuterol aerosol generated by pneumatic nebulizer in the Sophia Anatomical Infant Nose-Throat (SAINT) model.

PURPOSE: To quantify distribution of albuterol aerosol generated by a pneumatic nebulizer within the nose and lungs of a model of a 9-month-old child (SAINT) and aerosol loss to the environment, during simulated breathing at increasing tidal volumes (TVs). METHODS: (99m)technetium-labeled albuterol aerosol was generated by an IPI nebulizer with face-mask. Deposition was quantified as a percentage of emitted dose using gamma scintigraphy. RESULTS: Lung deposition was similar for all TVs, averaging 7.17 +/- 0.01%, 9.34 +/- 0.01% and 9.41 +/- 0.02% at 50, 100 and 200 mL TV, respectively. In contrast, nose deposition increased significantly with TV, averaging 4.40 +/- 0.02%, 11.39 +/- 0.02% and 22.12 +/- 0.02% at 50 mL, 100 mL and 200 mL TV, respectively (all p < 0.0167). Aerosol loss to the environment was significantly lower at 200 mL TV (53.81 +/- 0.04%), compared to 50 mL (71.99 +/- 0.02%) (p < 0.0167). CONCLUSIONS: Our results suggest that nasal deposition of albuterol aerosol generated by a pneumatic nebulizer in 9-month-old infants may be significantly affected by changes in TV, ranging between 50 to 200 mL, whereas total lung deposition may not be affected. These results also predict that environmental losses would be highest when administering to a child breathing at 50 mL TV. These data should be useful to companies who are working to improve aerosol delivery systems to treat infants.

Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection. We evaluated a spray-freeze-dried powder vaccine containing a recombinant F1-V fusion protein of Y. pestis for vaccination against plaque in a mouse model. Mice were immunized with reconstituted spray-freeze-dried F1-V powder via intramuscular injection, microneedle-based intradermal delivery, or noninvasive intranasal administration. By intramuscular injection, the reconstituted powder induced serum antibody responses and provided protection against lethal subcutaneous challenge with 1,000 50% lethal doses of Y. pestis at levels equivalent to those elicited by unprocessed liquid formulations (70 to 90% protection). The feasibility of intradermal and intranasal delivery of reconstituted powder F1-V vaccine was also demonstrated. Overall, microneedle-based intradermal delivery was shown to be similar in efficacy to intramuscular injection, while intranasal administration required an extra dose of vaccine to achieve similar protection. In addition, the results suggest that seroconversion against F1 may be a better predictor of protection against Y. pestis challenge than seroconversion against either F1-V or V. In summary, we demonstrate the preclinical feasibility of using a reconstituted powder F1-V formulation and microneedle-based intradermal delivery to provide protective immunity against plague in a mouse model. Intranasal delivery, while feasible, was less effective than injection in this study. The potential use of these alternative delivery methods and a powder vaccine formulation may result in substantial health and economic benefits.

Intranasal administration of dry powder anthrax vaccine provides protection against lethal aerosol spore challenge.

The use of an aerosolizable form of anthrax as a biological weapon is considered to be among the most serious bioterror threats. Intranasal (IN) delivery of a dry powder anthrax vaccine could provide an effective and non-invasive administration alternative to traditional intramuscular (IM) or subcutaneous (SC) injection. We evaluated a dry powder vaccine based on the recombinant Protective Antigen (rPA) of Bacillus anthracis for vaccination against anthrax via IN immunization in a rabbit model. rPA powders were formulated and administered IN using a prototype powder delivery device. We compared serum IgG and toxin neutralizing antibody (TNA) titers of rabbits immunized IN with 10 microg rPA of a powder formulation with those immunized with the same dose of liquid rPA vaccine, delivered either IN or by IM injection. In addition, each group was tested for survival after aerosol spore challenge. Our results showed that IN vaccination with rPA powders elicited serum PA-specific IgG and TNA titers that were equivalent to those raised by liquid rPA administered IN. Serum PA-specific IgG and TNA titers after IN delivery were lower than for IM injection, however, after aerosol spore challenge, rabbits immunized IN with powders displayed 100% protection versus 63% for the group immunized IN with the liquid vaccine and 86% for the group immunized by IM injection. The results suggest that an IN powder vaccine based on rPA is at least as protective as a liquid delivered by IM injection.

Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine.

The recombinant protective antigen (rPA) of Bacillus anthracis is a promising anthrax vaccine. We compared serum immunoglobulin G levels and toxin-neutralizing antibody titers in rabbits following delivery of various doses of vaccine by microneedle-based intradermal (i.d.) delivery or intramuscular (i.m.) injection using conventional needles. Intradermal delivery required less antigen to induce levels of antibody similar to those produced via i.m. injection during the first 2 weeks following primary and booster inoculation. This dose-sparing effect was less evident at the later stages of the immune response. Rabbits immunized i.d. with 10 mug of rPA displayed 100% protection from aerosol spore challenge, while i.m. injection of the same dose provided slightly lower protection (71%). Groups immunized with lower antigen doses were partially protected (13 to 29%) regardless of the mode of administration. Overall, our results suggest rPA formulated with aluminum adjuvant and administered to the skin by a microneedle-based device is as efficacious as i.m. vaccination.

Formulation of a dry powder influenza vaccine for nasal delivery.

The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (WIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery. Chitosan flakes were reduced in size using a cryo-milling technique. Milled powders were sieved between 45 and 125 microm aggregate sizes and characterized for particle size and distribution, morphology, and flow properties. Powders were blended in the micro-ball mill without the ball. Lyophilization followed by milling produced irregularly shaped, polydisperse particles with a median primary particle diameter of approximately 21 microm and a yield of approximately 37% of particles in the 45 to 125 microm particle size range. Flow properties of lactose and trehalose powders after lyophilization followed by milling and sieving were similar. Cryo-milling produced a small yield of particles in the desired size range (<10%). Lyophilization followed by milling and sieving produced particles suitable for nasal delivery with different physicochemical properties as a function of processing conditions and components of the formulation. Further optimization of particle size and morphology is required for these powders to be suitable for clinical evaluation.

Noninvasive delivery technologies: respiratory delivery of vaccines.

This paper reviews the developments in noninvasive methods of drug delivery, with a focus on the delivery of vaccines via the respiratory tract. Recent results indicate that the respiratory system, and the nasal mucosa in particular, provide a valuable target site for immunisation against respiratory and mucosal pathogens. Vaccine delivery via the nasal and pulmonary routes each present distinct sets of performance requirements. Current delivery systems in development for both routes are reviewed herein. The storage and respiratory delivery of drugs and vaccines in powder form has been shown to provide improved stability and extended retention time in the respiratory mucosa. These features, in addition to the noninvasive nature of respiratory delivery, can provide benefits to public health vaccination campaigns, facilitating mass vaccination without the high cost of maintaining cold-chain storage.

Anthrax vaccine powder formulations for nasal mucosal delivery.

Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6-8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7-8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization.

Formulation of a dry powder influenza vaccine for nasal delivery.

The purpose of this research was to prepare a dry powder vaccine formulation containing whole inactivated influenza virus (VIIV) and a mucoadhesive compound suitable for nasal delivery. Powders containing WIIV and either lactose or trehalose were produced by lyophilization. A micro-ball mill was used to reduce the lyophilized cake to sizes suitable for nasal delivery. Chitosan flakes were reduced in size using a cryo-milling technique. Milled powders were sieved between 45 and 125 µm aggregate sizes and characterized for particle size and distribution, morphology, and flow properties. Powders were blended in the micro-ball mill without the ball. Lyophilization followed by milling produced irregularly shaped, polydisperse particles with a median primary particle diameter of ≈21 µm and a yield of ≈37% of particles in the 45 to 125 µm particle size range. Flow properties of lactose and trehalose powders after lyophilization followed by milling and sieving were similar. Cryo-milling produced a small yield of particles in the desired size range (<10%). Lyophilization followed by milling and sieving produced particles suitable for nasal delivery with different physicochemical properties as a function of processing conditions and components of the formulation. Further optimization of particle size and morphology is required for these powders to be suitable for clinical evaluation.

Protective immunization against inhalational anthrax: a comparison of minimally invasive delivery platforms.

A new anthrax vaccine under clinical investigation is based on recombinant Bacillus anthracis protective antigen (rPA). Here, we investigated microneedle-based cutaneous and nasal mucosal delivery of rPA in mice and rabbits. In mice, intradermal (id) delivery achieved up to 90% seroconversion after a single dose, compared with 20% after intramuscular (im) injection. Intranasal (inl) delivery of a liquid formulation required 3 doses to achieve responses that were comparable with those achieved via the id or im routes. In rabbits, id delivery provided complete protection against aerosol challenge with anthrax spores; in addition, novel powder formulations administered inl provided complete protection, whereas a liquid formulation provided only partial protection. These results demonstrate, for the first time, that cutaneous or nasal mucosal administration of rPA provides complete protection against inhalational anthrax in rabbits. The novel vaccine/device combinations described here have the potential to improve the efficacy of rPA and other biodefense vaccines.