Treatment efficacy for rectal Neisseria gonorrhoeae: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Rectal gonorrhoea is a common sexually transmitted infection with increasing antimicrobial resistance requiring optimization of available treatments. OBJECTIVES: This systematic review aimed to assess the efficacy of current treatments, previously trialled treatments and new emerging treatments for rectal Neisseria gonorrhoeae (NG). METHODS: Online bibliographic databases were search from 1 January 1946 to 14 August 2020. All randomized controlled trials (RCTs) with rectal NG data among participants aged 15 years or above and published in English were included. Random effects meta-analyses were used to estimate overall treatment efficacy, defined as microbiological cure. Sub-group analyses included stratifying by diagnostic assay, by dual versus monotherapy, and by currently recommended treatments (e.g. ceftriaxone ± azithromycin) versus previously trialled but not recommended treatments (e.g. amoxicillin) versus emerging treatments (e.g. zoliflodacin). The study protocol was registered on PROSPERO (CRD42020202998). RESULTS: 54 studies including 1813 participants and 44 treatment regimens were identified. The overall summary treatment efficacy for rectal NG was 100.0% (95% CI: 99.9%-100.0%; I2 = 0.0%; P = 0.86). Efficacy estimates for monotherapies (100.0%; 95% CI: 99.88%-100.0%; I2 = 0.00%; P = 0.97) and dual therapies (100.0%; 95% CI: 97.65%-100.0%; I2 = 56.24%; P = 0.03) were similar. Efficacy was highest for current treatments (100.00%; 95% CI: 99.96%-100.00%; I2 = 0.00%; P = 0.98) versus emerging treatments (97.16%; 95% CI: 86.79%-100.00%; I2 = 0.00%; P = 0.84). There were no trials exclusively investigating rectal NG and small sample size was a limitation in most trials. CONCLUSIONS: Currently recommended treatments containing ceftriaxone, as mono or dual therapy, are effective. Emerging drugs such as zoliflodacin may be potentially useful for rectal NG but further data are needed.

Behavior-partitioned diversity reveals differential habitat values of gardens to butterfly communities.

Diversity metrics, essential for habitat evaluation in conservation, are often based on occurrences records with little consideration of behavioral ecology. As species use diverse habitats to perform different behaviors, reliance on occurrence records alone will fail to reveal environmental conditions shaping the behavioral importance of habitats with respect to resource exploitation. Here, we integrated occurrence and behavioral records to quantify diversity and assessed how environmental determinants shape the behavioral importance of gardens to butterflies across Hong Kong. We conducted standardized butterfly sampling and behavioral observation, and recorded environmental variables related to climate, habitat quality, and landscape connectivity. We found differential responses of diversity and behavioral diversity metrics to environmental variables. Connectivity increased taxonomic richness based on occurrence and flying across records, while temperature reduced richness based on occurrence, settling and interaction records. Floral abundance increased richness based on nectaring records only. No environmental variable promoted the average number of behavioral types observed in each taxon. Our results suggest that connectivity and temperature determine the richness of butterflies reaching gardens, while floral abundance determines whether butterflies use the sites as nectaring grounds via modifying species behaviors. Our study demonstrates the utility in integrating behavioral and diversity data to reveal how environmental conditions shape behavioral importance of habitats.

Short term physician visits and medication prescriptions for allergic disease associated with seasonal tree, grass, and weed pollen exposure across the United States.

BACKGROUND: While year-round exposure to pollen is linked to a large burden of allergic diseases, location-specific risk information on pollen types and allergy outcomes are limited. We characterize the relationship between acute exposure to tree, grass and weed pollen taxa and two allergy outcomes (allergic rhinitis physician visit and prescription allergy medication fill) across 28 metropolitan statistical areas (MSA) in the United States. METHODS: We obtained daily pollen data from National Allergy Bureau (NAB) monitors at these 28 MSAs for 2008-2015. We revised the NAB guidelines to classify taxa-specific pollen severity each day. Daily information on allergic rhinitis and prescribed allergy medications for individuals with employer-based health insurance from the IBM MarketScan Research database for these MSAs. We combined the daily pollen and health data for each MSA into a longitudinal dataset. We conducted a MSA-specific conditional quasi-Poisson regression analysis to assess how different levels of pollen concentration impact the health outcomes, controlling for local air pollution, meteorology and Influenza-like illness (ILI). We used a random effects meta-analysis to produce an overall risk estimate for each pollen type and health outcome. RESULTS: The seasonal distribution of pollen taxa and associated health impacts varied across the MSAs. Relative risk of allergic rhinitis visits increased as concentrations increased for all pollen types; relative risk of medication fills increased for tree and weed pollen only. We observed an increase in health risk even on days with moderate levels of pollen concentration. 7-day average concentration of pollen had stronger association with the health outcomes compared to the same-day measure. Controlling for air pollution and ILI had little impact on effect estimates. CONCLUSION: This analysis expands the catalogue of associations between different pollen taxa and allergy-related outcomes across multiple MSAs. The effect estimates we present can be used to project the burden of allergic disease in specific locations in the future as well inform patients with allergies on impending pollen exposure.

Pollen calendars and maps of allergenic pollen in North America.

Pollen is a common allergen that causes significant health and financial impacts on up to a third of the population of the USA. Knowledge of the main pollen season can improve diagnosis and treatment of allergic diseases. Our objective in this study is to provide clear, quantitative visualizations of pollen data and make information accessible to many disciplines, in particular to allergy sufferers and those in the health field. We use data from 31 National Allergy Bureau (NAB) pollen stations in the continental USA and Canada from 2003 to 2017 to produce pollen calendars. We present pollen season metrics relevant to health and describe main pollen season start and end dates, durations, and annual pollen integrals for specific pollen taxa. In most locations, a small number of taxa constitute the bulk of the total pollen concentration. Start dates for tree and grass pollen season depend strongly on latitude, with earlier start dates at lower latitudes. Season duration is correlated with the start dates, such that locations with earlier start dates have a longer season. NAB pollen data have limited spatiotemporal coverage. Increased spatiotemporal monitoring will improve analysis and understanding of factors that govern airborne pollen concentrations.

Racial and ethnic disparities in survival of US children with acute lymphoblastic leukemia: evidence from the SEER database 1988-2008.

PURPOSE: Prior studies have shown poorer survival from childhood acute lymphoblastic leukemia (ALL) among some minorities compared to non-Hispanic whites (NHW). Here, we examine whether these survival disparities have persisted and to see whether they also exist for Asian and Hispanic subgroups. METHODS: Using data from the US National Cancer Institute's Surveillance, Epidemiology and End Results program from 1988 to 2008, we compared all natural-cause survival for children aged 19 years or under diagnosed with ALL using Cox proportional hazards models adjusted for age, diagnosis year, gender and disease immunophenotype. RESULTS: Black, Hispanic and Native American children continue to have significantly poorer survival than NHW. Unlike previous studies, we found that Asian Americans also had significantly worse survival. Among Asian subgroups, Vietnamese (relative risk [RR] = 2.44, 95 % CI = 1.50-3.97) and Filipinos (RR = 1.64, 95 % CI = (1.13-2.38) had significantly poorer survival, while other East Asian groups, except Chinese, had non-significantly worse survival. Most Hispanic subgroups had RRs around 2. CONCLUSION: Previously observed poorer prognosis for childhood ALL for some minority groups appears to be shared by most Asians as well. Further research is needed to find explanations for the poorer survival of minority children with ALL and possible treatment implications.

Development of a Random Forest model for forecasting allergenic pollen in North America.

Pollen allergies have negative impacts on health. Information about airborne pollen concentration can improve symptom management by guiding choices affecting timing of medicines and pollen exposure. Observations provide accurate pollen concentrations at point locations. However, in the contiguous United States and southern Canada (CUSSC), observations are sparse, and sampling is often seasonal, intermittent or both. Modeling pollen concentration can fill in the gaps with estimates where direct observations are unavailable and also provide much-needed forecasts. The goal of this study is to develop and evaluate statistical models that predict daily pollen concentrations using a machine learning Random Forest algorithm. To evaluate our methods, we made retrospective forecasts of four pollen types (Quercus, Cupressaceae, Ambrosia and Poaceae), each in one of four CUSSC locations. Meteorological and vegetation conditions were input to the models at city and regional scales. A data augmentation technique was investigated and found to improve model skill. Models were also developed to forecast pollen in locations where there are no observations. Forecast skill in these models were found to be greater than in previous models. Nevertheless, the skill is limited by the spatiotemporal resolution of the pollen observations.

Internet searches offer insight into early-season pollen patterns in observation-free zones.

Tracking concentrations of regional airborne pollen is valuable for a variety of fields including plant and animal ecology as well as human health. However, current methods for directly measuring regional pollen concentrations are labor-intensive, requiring special equipment and manual counting by professionals leading to sparse data availability in select locations. Here, we use publicly available Google Trends data to evaluate whether searches for the term "pollen" can be used to approximate local observed early-season pollen concentrations as reported by the National Allergy Bureau across 25 U.S. regions from 2012-2017, in the context of site-specific characteristics. Our findings reveal that two major factors impact the ability of internet search data to approximate observed pollen: (1) volume/availability of internet search data, which is tied to local population size and media use; and (2) signal intensity of the seasonal peak in searches. Notably, in regions and years where internet search data was abundant, we found strong correlations between local search patterns and observed pollen, thus revealing a potential source of daily pollen data across the U.S. where observational pollen data are not reliably available.

Spray freeze drying of small nucleic acids as inhaled powder for pulmonary delivery.

The therapeutic potential of small nucleic acids such as small interfering RNA (siRNA) to treat lung diseases has been successfully demonstrated in many in vivo studies. A major barrier to their clinical application is the lack of a safe and efficient inhaled formulation. In this study, spray freeze drying was employed to prepare dry powder of small nucleic acids. Mannitol and herring sperm DNA were used as bulking agent and model of small nucleic acid therapeutics, respectively. Formulations containing different solute concentration and DNA concentration were produced. The scanning electron microscope (SEM) images showed that the porosity of the particles increased as the solute concentration decreased. Powders prepared with solute concentration of 5% w/v were found to maintain a balance between porosity and robustness. Increasing concentration of DNA improved the aerosol performance of the formulation. The dry powder formulation containing 2% w/w DNA had a median diameter of 12.5 µm, and the aerosol performance study using next generation impactor (NGI) showed an emitted fraction (EF) and fine particle fraction (FPF) of 91% and 28% respectively. This formulation (5% w/v solute concentration and 2% w/w nucleic acid) was adopted subsequently to produce siRNA powder. The gel retardation and liquid chromatography assays showed that the siRNA remained intact after spray freeze drying even in the absence of delivery vector. The siRNA powder formulation exhibited a high EF of 92.4% and a modest FPF of around 20%. Further exploration of this technology to optimise inhaled siRNA powder formulation is warranted.

Inhaled powder formulation of naked siRNA using spray drying technology with l-leucine as dispersion enhancer.

Pulmonary delivery of short interfering RNA (siRNA) has been widely studied in both animal and clinical studies to treat various respiratory diseases by gene silencing through RNA interference. Some of these studies showed that the administration of naked siRNA (without the use of any delivery vectors) could achieve satisfactory gene silencing effect, a unique feature to pulmonary delivery. Liquid aerosols were mostly used with very limited studies on the use of powder aerosols for siRNA. In this study, siRNA was co-spray dried with mannitol and l-leucine, the latter being a dispersion enhancer. To the best of our knowledge, this is the first time that siRNA in its naked form was formulated into an inhalable dry powder using spray drying technology. The aerosol performance of the powder was evaluated by Next Generation Impactor (NGI). The presence of l-leucine in the formulation could improve the aerosolization of siRNA-containing powders. Results from the X-ray photoelectron spectroscopy (XPS) suggested that l-leucine was enriched on the particle surface and promote powder dispersion. Among the different siRNA formulations being examined, the one that contained 50% w/w of l-leucine exhibited the best aerodynamic performance, with a high emitted fraction (EF) of around 80% and a modest fine particle fraction (FPF) of 45%. Importantly, the integrity of siRNA was successfully retained as evaluated by gel retardation assay and high performance liquid chromatography (HPLC).