Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis.

AIM: To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before (iii) combining results with prior studies using meta-analysis. METHODS: A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) was conducted from 331 375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n = 45 854) or bisphosphonates (control, n = 285 521), across 83 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 45 851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed the association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality were assessed using Cochrane-endorsed tools. RESULTS: Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78-0.88]). Secondary analysis showed significant risk reduction in all-cause mortality (0.79 [0.72-0.87]) and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomized controlled trial) following meta-analysis showed a reduced relative risk (RR [95% CI]) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I2 = 10.76%). CONCLUSIONS: This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all-cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D.

Solar energy development and aquatic ecosystems in the southwestern United States: potential impacts, mitigation, and research needs.

The cumulative impacts of utility-scale solar energy facilities on aquatic ecosystems in the Southwestern United States are of concern, considering the many existing regional anthropogenic stressors. We review the potential impacts of solar energy development on aquatic habitat and biota. The greatest potential for impacts is related to the loss, fragmentation, or prolonged drying of ephemeral water bodies and drainage networks resulting from the loss of desert washes within the construction footprint of the facility. Groundwater-dependent aquatic habitat may also be affected by operational groundwater withdrawal in the case of water-intensive solar technologies. Solar panels have also been found to attract aquatic insects and waterbirds, potentially resulting in mortality. Avoiding construction activity near perennial and intermittent surface waters is the primary means of reducing impacts on aquatic habitats, followed by measures to minimize erosion, sedimentation, and contaminant inputs into waterways. Currently, significant data gaps make solar facility impact assessment and mitigation more difficult. Examples include the need for more regional and site-specific studies of surface-groundwater connectivity, more detailed maps of regional stream networks and riparian vegetation corridors, as well as surveys of the aquatic communities inhabiting ephemeral streams. In addition, because they often lack regulatory protection, there is also a need to develop valuation criteria for ephemeral waters based on their ecological and hydrologic function within the landscape. By addressing these research needs, we can achieve the goal of greater reliance on solar energy, while at the same time minimizing impacts on desert ecosystems.

Quantifying the sensitivity of ephemeral streams to land disturbance activities in arid ecosystems at the watershed scale.

Large areas of public lands administered by the Bureau of Land Management and located in arid regions of the southwestern United States are being considered for the development of utility-scale solar energy facilities. Land-disturbing activities in these desert, alluvium-filled valleys have the potential to adversely affect the hydrologic and ecologic functions of ephemeral streams. Regulation and management of ephemeral streams typically falls under a spectrum of federal, state, and local programs, but scientifically based guidelines for protecting ephemeral streams with respect to land-development activities are largely nonexistent. This study developed an assessment approach for quantifying the sensitivity to land disturbance of ephemeral stream reaches located in proposed solar energy zones (SEZs). The ephemeral stream assessment approach used publicly-available geospatial data on hydrology, topography, surficial geology, and soil characteristics, as well as high-resolution aerial imagery. These datasets were used to inform a professional judgment-based score index of potential land disturbance impacts on selected critical functions of ephemeral streams, including flow and sediment conveyance, ecological habitat value, and groundwater recharge. The total sensitivity scores (sum of scores for the critical stream functions of flow and sediment conveyance, ecological habitats, and groundwater recharge) were used to identify highly sensitive stream reaches to inform decisions on developable areas in SEZs. Total sensitivity scores typically reflected the scores of the individual stream functions; some exceptions pertain to groundwater recharge and ecological habitats. The primary limitations of this assessment approach were the lack of high-resolution identification of ephemeral stream channels in the existing National Hydrography Dataset, and the lack of mechanistic processes describing potential impacts on ephemeral stream functions at the watershed scale. The primary strength of this assessment approach is that it allows watershed-scale planning for low-impact development in arid ecosystems; the qualitative scoring of potential impacts can also be adjusted to accommodate new geospatial data, and to allow for expert and stakeholder input into decisions regarding the identification and potential avoidance of highly sensitive stream reaches.

Enhancement and inhibition of denitrification by fluid-flow and dissolved oxygen flux to stream sediments.

Microscale measurements of nitrate (NO3-) and dissolved oxygen (DO) concentrations in sediments were made in a laboratory channel under turbulent fluid-flow conditions to examine the effects of DO flux on denitrification rates. DO concentrations and flux within sediments increased with increasing velocity in the surface water. Under low fluid-flow conditions (shear stress velocity, u* < 0.23 cm s(-1)), increasing velocity increased NO3- loss from the bulk flow. For high fluid-flow conditions (u* > 0.39 cm s(-1)), increasing velocity inhibited NO3-loss. Sediment cores were collected and sliced to measure the depth distribution of denitrifying biomass in sediments. Quantities of nirK and nirS genes were higher within the surface layer and decreased with depth in the sediments. Microscale concentration profiles of DO and NO3- revealed that denitrification occurs within a thin region just below the oxic-anoxic interface in sediments. The interplay of mass transfer and DO flux generated threshold conditions for NO3- loss by denitrification. These results suggest that for a given sediment and environmental conditions (chemical, physical, microbiological), there exists an optimal range in velocities for enhancing denitrification in aquatic systems.