Continuous wave terahertz detection using 1550 nm pumped nonlinear photoconductive GaAs metasurfaces.

Terahertz (THz) continuous wave (CW) spectroscopy systems can offer extremely high spectral resolution over the THz band by photo-mixing high-performance telecommunications-band (1530-1565 nm) lasers. However, typical THz CW detectors in these systems use narrow band-gap photoconductors, which require elaborate material growth and generate relatively large detector noise. Here we demonstrate that two-step photon absorption in a nano-structured low-temperature grown GaAs (LT-GaAs) metasurface which enables switching of photoconductivity within approximately one picosecond. We show that LT-GaAs can be used as an ultrafast photoconductor in CW THz detectors despite having a bandgap twice as large as the telecommunications laser photon energy. The metasurface design harnesses Mie modes in LT GaAs resonators, whereas metallic electrodes of THz detectors can be designed to support an additional photonic mode, which further increases photoconductivity at a desired wavelength.

Hospital-Wide Adherence to Postsurgical Opioid Prescribing Guidelines: A Retrospective Cohort Study.

INTRODUCTION: Lowering opioid prescription doses and quantity decreases the risk of chronic opioid usage. A tool was inserted into the brief operative note for the surgeon to assess the severity of pain associated with the procedure. We studied surgeon adherence to current opioid-prescribing recommendations. METHODS: Retrospective cohort study with 5486 patients were included in the study population. Each patient's prescription was scored yes or no for adherence on total morphine milligram equivalents (MMEs) and days prescribed with the selection in the brief operative note. The entire study population was tested for an increase from the null-hypothesis "benchmark" value of 75% using a one-sided exact binomial test of a single proportion with P < 0.05. This procedure was repeated for subgroups, with P < 0.01. RESULTS: Adherence to guidelines was higher than the 75% benchmark for "total MMEs prescribed" (79.5%; P < 0.001), but lower for "number of days prescribed" (63.5%; P > 0.999). Surgeries with severe predicted pain showed the highest adherence toward total MMEs prescribed at 87.1%, followed by moderate (80.5%) and mild (74.5%). Severe cases also showed the highest adherence in number of days prescribed (92.4%). Adherence to total MMEs prescribed was highest among attending physicians (88.1%) and lowest among residents/fellows (76.6%). CONCLUSIONS: Adherence to current guidelines was 79.5% for MMEs prescribed but only 63.5% for days prescribed. Compliance with guidelines was better for severe procedures than mild or moderate. Differences were seen across surgical departments. While an improvement from previous reports, further improvement is needed to reduce the number of days of opioids prescribed and increase compliance with recommended guidelines.

Utilisation of pre-exposure prophylaxis (PrEP) for HIV prevention in the Australian general practice setting: a longitudinal observational study.

BACKGROUND: Pre-exposure prophylaxis (PrEP) became available through the Australian Pharmaceutical Benefits Scheme (PBS) on 1 April 2018 for HIV infection prevention in patients ≥18years at medium-to-high HIV risk. The aims were to investigate PrEP utilisation in general practice since PBS listing, and factors associated with discontinuation. METHODS: This longitudinal study included patients aged 18-74years attending general practices participating in MedicineInsight, a large-scale national primary care database of deidentified electronic health records, between October 2017 and September 2019. RESULTS: PrEP utilisation increased 10-fold following PBS listing. On average, patients had 9.7 PrEP prescriptions per year; a medication possession ratio of 80.8%. Of 1552 patients prescribed PrEP from April 2018, most were male (98.3%), aged 18-39years (59.3%), resided in major cities (86.7%) and in the two most socioeconomically advantaged quintiles (70.0%). Almost half (49.1%) of the patients were identified as new to PrEP. At study end, 65.1% were on active PrEP (16.5%, of whom had non-continuous use), 19.2% had discontinued PrEP and 15.7% were lost to follow up. Patients who discontinued were more likely to attend low rather than high PrEP caseload practices (adjusted odds ratio [aOR] 1.7; 95% CI: 1.0-2.8; P =0.047). The odds of non-continuous therapy was 2.9-fold higher in patients with bipolar disorder (aOR 2.89; 95% CI: 1.10-7.6; P =0.045). CONCLUSIONS: Following PBS listing, PrEP utilisation increased and stopping therapy was associated with attending low caseload practices. General practice education, particularly among low caseload practices, could help address these disparities.

Decreased Epicardial CTRP3 mRNA Levels in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease Undergoing Elective Cardiac Surgery: A Possible Association with Coronary Atherosclerosis.

(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.

Lifting effect of onabotulinumtoxinA in patients treated for glabellar and crow's feet rhytids.

OnabotulinumtoxinA injection can enhance the appearance of the eyes. This study evaluated the lifting effect of onabotulinumtoxinA treatment of the eye area. A retrospective, single-center audit of patients treated for glabellar and crow's feet rhytids was undertaken. Standardized photographs taken before and 2-4 weeks after treatment were assessed. Computer-based measurements were made of the height of the visible superior tarsal plate (STP) and brow (measured from upper eyelid lash edge to eyebrow base) at rest and maximum frown. One hundred patients were included (96 females; mean age: 46.2 ± 8.8 years). Mean onabotulinumtoxinA doses were 14.95 ± 0.61 units (glabella) and 17.83 ± 2.74 units (crow's feet). There were significant post-treatment increases in mean STP height at rest (left side, 0.76 ± 0.99 mm, p = .02; right side, 0.79 ± 0.94 mm, p = .01) and maximum frown (left, 2.25 ± 1.52 mm, p < .0001; right, 1.87 ± 1.34 mm, p < .0001), and mean brow height at rest (left side, 1.54 ± 1.49 mm, p = .0006; right side, 1.47 ± 1.84 mm, p = .0009) and maximum frown (left, 4.37 ± 2.29 mm, p < .0001; right, 4.16 ± 1.88 mm, p < .0001). OnabotulinumtoxinA injection is effective for elevating brow position and increasing STP show.

Osteoporosis management in Australian general practice: an analysis of current osteoporosis treatment patterns and gaps in practice.

BACKGROUND: Among Australians aged 50 and over, an estimated 1 in 4 men and 2 in 5 women will experience a minimal trauma fracture during their remaining lifetime. Effective fracture prevention is hindered by substantial undertreatment, even of patients who clearly warrant pharmacological therapy. Poor adherence to osteoporosis treatment is also a leading cause of repeat fractures and hospitalisation. The aim of this study was to identify current osteoporosis treatment patterns and gaps in practice in Australia, using general practice data, and to explore general practitioners' (GPs') attitudes to osteoporosis treatment and their views on patient factors affecting osteoporosis management. METHODS: The study was conducted in two phases. Phase 1 was a longitudinal retrospective cohort study which utilised data from MedicineInsight - a national general practice data program that extracts longitudinal, de-identified patient data from clinical information systems (CISs) of participating general practices. Phase 2 included semi-structured, in-depth telephone interviews with a sample of MedicineInsight practice GPs. Data were analysed using an inductive thematic analysis method informed by the theory of planned behaviour. RESULTS: A diagnosis of osteoporosis was recorded in 12.4% of patients over the age of 50 years seen in general practice. Of those diagnosed with osteoporosis, almost a quarter were not prescribed osteoporosis medicines. From 2012 to 17, there was a progressive increase in the number of denosumab prescriptions, while prescriptions for bisphosphonates and other osteoporosis medicines decreased. More than 80% of patients who ceased denosumab treatment had no subsequent bisphosphonate prescription recorded. Interviews with GPs revealed beliefs and attitudes that may have influenced their intentions towards prescribing and osteoporosis management. CONCLUSIONS: This study suggests that within the Australian general practice setting, osteoporosis is underdiagnosed and undertreated. In addition, it appears that most patients who ceased denosumab treatment had no record of subsequent antiresorptive therapy, which would place them at risk of further fractures. The study supports the need for the development of clinical education programs addressing GP knowledge gaps and attitudes, and the implementation of specific interventions such as good reminder/recall systems to avoid delays in reviewing and treating patients with osteoporosis.

Polypyridyl Zinc(II)-Indomethacin Complexes with Potent Anti-Breast Cancer Stem Cell Activity.

Cancer stem cells (CSCs) are thought of as a clinically pertinent subpopulation of tumors, partly responsible for cancer relapse and metastasis. Research programs aimed at discovering anti-CSC agents have largely focused on biologics and purely organic molecules. Recently, we showed that a family of redox-active copper(II) complexes with phenanthroline-based ligands and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, are capable of potently and selectively killing breast CSCs. Herein we present analogous redox-inactive, zinc(II)-phenanthroline-indomethacin complexes with the ability to kill breast CSCs and bulk breast cancer cells with equal potency (in the submicro- or micromolar range). A single dose of the zinc(II) complexes could theoretically be administered to eliminate whole tumor populations. Excitingly, some of the zinc(II) complexes decrease the growth and viability of mammospheres to a comparable or higher degree than salinomycin, a compound known to effectively kill breast CSCs. As far as we are aware this is the first report to examine the anti-breast CSC activity of zinc(II)-containing compounds.

Blood Pressure and Heart Rate Changes During Clozapine Treatment.

People with schizophrenia are 3-4 times more likely to die from cardiovascular disease than the general population. Clozapine (CLZ) is the gold standard of treatment for refractory schizophrenia. It has been associated with tachycardia and recent evidence shows individuals prescribed CLZ may develop blood pressure (BP) elevation and hypertension. The purpose of this study was to examine the effects of CLZ on BP and heart rate (HR). This was a retrospective chart review of patients 18-75 years old with a DSM IV diagnosis of Schizophrenia or Schizoaffective disorder. Primary outcomes were systolic blood pressure (SBP), diastolic blood pressure (DBP), and HR measured 12 weeks before and 24 weeks during CLZ treatment. Eighteen patient records were included in this study. The mean stabilized CLZ dose was 441.7 ± 171.8 mg/day. DBP (t = 1.02, df = 79.5, = 2.00, 0.049) and HR (t = 1.32, df = 355  = -4.61, < 0.0001) were significantly higher after CLZ initiation. A trend was noted for increase in SBP (p = 0.071). 22 % of patients met criteria for hypertension before CLZ and 67 % during CLZ treatment (Chi Square = 6.25, df = 1, p = 0.0124). No significant changes in weight or renal function occured during CLZ treatment. No patients had evidence of cardiomyopathy. The data suggest CLZ may be associated with a rise in BP and HR. The results of this study support previous literature that found an increase in SBP/DBP regardless of CLZ dose, occurring early in treatment. Due to high risk of cardiovascular morbidity and mortality, more work is needed to determine risk factors and understand the mechanism of action that may cause this side effect.

Solvation Structure of Uracil in Ionic Liquids.

The local solvation environment of uracil dissolved in the ionic liquid 1-ethyl-3-methylimidazolium acetate has been studied using neutron diffraction techniques. At solvent:solute (ionic liquid:uracil) ratios of 3:1 and 2:1, little perturbation of the ion-ion correlations compared to those of the neat ionic liquid are observed. We find that solvation of the uracil is driven predominantly by the acetate anion of the solvent. While short distance correlations exist between uracil and the imidazolium cation, the geometry of these contacts suggest that they cannot be considered as hydrogen bonds, in contrast to other studies by Araújo et al. (J. M. Araújo, A. B. Pereiro, J. N. Canongia-Lopes, L. P. Rebelo, I. M. Marrucho, J. Phys. Chem. B 2013, 117, 4109-4120). Nevertheless, this combination of interactions of the solute with both the cation and anion components of the solvents helps explain the high solubility of the nucleobase in this media. In addition, favourable uracil-uracil contacts are observed, of similar magnitude to those between cation and uracil, and are also likely to aid dissolution.

Direct measurements of ionic liquid layering at a single mica-liquid interface and in nano-films between two mica-liquid interfaces.

The layering of ionic liquids close to flat, charged interfaces has been identified previously through theoretical and some experimental measurements. Here we present evidence for oscillations in ion density ('layering') in a long chain ionic liquid (1-decyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide) near the interface with mica using two complementary approaches. Neutron reflection at the ionic liquid-mica interface is used to detect structure at a single interface, and surface force balance (SFB) measurements carried out with the same ionic liquid reveal oscillatory density in the liquid confined between two mica sheets. Our findings imply the interfacial structure is not induced by confinement alone. Structural forces between two mica surfaces extend to approximately twice the distance of the density oscillations measured at a single interface and have similar period in both cases.

The electrochemical reduction of 1-bromo-4-nitrobenzene at zinc electrodes in a room-temperature ionic liquid: a facile route for the formation of arylzinc compounds.

The electrochemical reduction of 1-bromo-4-nitrobenzene (p-BrC6H4NO2) at zinc microelectrodes in the [C4mPyrr][NTf2] ionic liquid was investigated via cyclic voltammetry. The reduction was found to occur via an EC type mechanism, where p-BrC6H4NO2 is first reduced by one electron, quasi-reversibly, to yield the corresponding radical anion. The radical anions then react with the Zn electrode to form arylzinc products. Introduction of carbon dioxide into the system led to reaction with the arylzinc species, fingerprinting the formation of the latter. This method thus demonstrates a proof-of-concept of the formation of functionalised arylzinc species.

Incidence of Acute Kidney Injury in Trough and AUC/MIC Vancomycin Dosing Strategies in a Large Tertiary Care Center: A Retrospective Cohort.

Acute kidney injury (AKI) is a complication associated with vancomycin use. There is evidence that this was related to the presence of supratherapeutic vancomycin levels rather than the drug itself. The area under the curve over 24 h to minimum inhibitory concentration (AUC/MIC) dosing for vancomycin has replaced trough-based dosing, but the impact of this change on AKI rates remains unclear. A retrospective cohort study was conducted in a tertiary care teaching hospital. Patients from the trough cohort were recruited from January 1, 2019, to June 30, 2019, and the AUC/MIC cohort from July 1, 2021, to January 1, 2022. Sociodemographics, clinical characteristics, and concomitant medications were obtained. AKI was defined by The Kidney Disease Improving Global Outcomes. A total of 1056 patients were included, 509 in the trough cohort and 547 in the AUC/MIC cohort. The baseline rates of chronic kidney disease were 15.4% and 9.9%, respectively. The AKI rates were 15.9% and 11.9% for trough and AUC/MIC cohorts, respectively (P-value .045). The most frequent nephrotoxins were piperacillin/tazobactam (TZP), diuretics, and IV contrast for both groups. The rates of supratherapeutic levels were higher in the trough cohort (20.7%) than in the AUC/MIC cohort (6.6%). The multivariate logistic regression analysis showed that trough dosing was not associated with increased rates of AKI (OR = 0.96 CI 0.64-1.44). Supratherapeutic levels (OR = 4.64), diuretics (OR = 1.62), TZP (OR = 2.01), and ICU admission (OR = 1.72) were associated with AKI. Vancomycin AUC/MIC dosing strategy was associated with decreased rates of supratherapeutic levels of this drug compared to trough dosing, with a trend toward lower rates of AKI.

The Protective Effect of Abortion on Preeclampsia: An Analysis of Current Research.

A review of the current literature on preeclampsia (PE) confirms that this pregnancy complication remains a common cause of maternal mortality. Within the last several decades, obstetric and gynecological researchers worldwide have indicated an association between prior abortions and the development of PE. Different studies have debated whether abortion is a protective or risk factor for PE. However, the most current literature demonstrates a stronger likelihood that a positive history of abortions will offer a protective effect against PE. This association has been supported by advancements in the reproductive immunology literature, which states complex fetal and paternal pathological mechanisms help to build maternal immunological tolerance, thus protecting expectant mothers from pregnancy complications. This literature review will compare studies supporting prior abortions offering a protective effect against PE with those stating prior abortions are a risk factor for the development of PE. Additionally, this critical review will discuss the advancements and current understanding of reproductive immunology and how it pertains to this association between positive abortion history and PE.

The electroreduction of benzoic acid: voltammetric observation of adsorbed hydrogen at a platinum microelectrode in room temperature ionic liquids.

The electrochemical reduction of benzoic acid in the presence and absence of hydrogen (H(2)) has been investigated using a 10 µm diameter platinum microelectrode in four different room temperature ionic liquids (RTILs), namely [C(4)mim][NTf(2)], [C(4)mpyrr][NTf(2)], [C(4)mim][OTf] and [C(4)mim][BF(4)], versus Ag/Ag(+). In all cases, reductive voltammetry is observed, and is suggested to occur via a CE mechanism in which dissociation of benzoic acid is followed by electron transfer to H(+) ultimately forming adsorbed hydrogen. Furthermore, the adsorbed H atoms, formed from the reduction of benzoic acid, could be used to achieve the rapid hydrogenolysis of the organic compound (bis(benzyloxycarbonyl)-l-lysine) on the timescale of the voltammetric technique under moderate conditions (25 °C).

Changed reactivity of the 1-bromo-4-nitrobenzene radical anion in a room temperature ionic liquid.

Radical anions of 1-bromo-4-nitrobenzene (p-BrC6H4NO2) are shown to be reactive in the room temperature ionic liquid N-butyl-N-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide, ([C4mPyrr][NTf2]), by means of voltammetric measurements. In particular, they are shown to react via a DISP type mechanism such that the electrolysis of p-BrC6H4NO2 occurs consuming between one and two electrons per reactant molecule, leading to the formation of the nitrobenzene radical anion and bromide ions. This behaviour is a stark contrast to that in conventional non-aqueous solvents such as acetonitrile, dimethyl sulfoxide or N,N-dimethylformamide, which suggests that the ionic solvent promotes the reactivity of the radical anion, probably via stabilisation of the charged products.

Examining the 100-year floodplain as a metric of risk, loss, and household adjustment.

An understudied, but central aspect in understanding flood impacts is the way we conceptualize, identify, and delineate risk. The 100-year floodplain is the longstanding metric in the United States for determining and acting upon the possibility of an area being inundated. This spatial delineation guides local planning and development decisions, triggers insurance purchases and other household adjustments, and serves as the fundamental indicator for whether it is safe to build a structure on a particular site. However, increasing evidence suggests that the 100-year floodplain is neither accurate nor sufficient in guiding communities and household decisions to mitigate the adverse economic impacts of floods. In this perspective, we examine the effectiveness of the 100-year floodplain as an appropriate marker of risk. First, we review existing studies on location and flood damage. Next, we apply these concepts to repetitive flood losses data in Harris County, Texas. We conclude that the apparent inability of the floodplain designation to effectively capture the likelihood of property damage and potential loss of human life in coastal areas has left potentially millions of property owners unaware of the flood risk and unprepared to mitigate their adverse impacts. Relying on traditional 100-year floodplain boundaries, local decision makers are hampered in their ability to ensure community development occurs in a resilient manner. Finally, we set forth an agenda for future research to better capture the conditions associated with flood risk and account for the large percentage of damage outside the designated floodplain.

A simultaneous voltammetric temperature and humidity sensor.

We report the simultaneous measurement of temperature and humidity by analysing square wave voltammetric responses of two ferrocene derivatives, decamethylferrocene (DmFc) and 1,2-diferrocenylethylene (bisferrocene, BisFc) in 1-(2-methoxyethyl)-1-methyl-pyrrolidinium tris(pentafluoroethyl)trifluorophosphate ([Moepyrr][FAP]). These two molecules produce three peaks in square wave voltammetry. Through study of the peak potentials of BisFc/BisFc(+) (vs. DmFc/DmFc(+)) and BisFc(+)/BisFc(2+) (vs. DmFc/DmFc(+)) over a temperature range of 298 K to 318 K and humidity range of 1% to 50% using square wave voltammetry, the temperature and humidity dependences of the relative peak potentials were investigated. A reliable method to calculate the humidity and temperature based on the voltammetric experiment is characterised and demonstrated.

Reach in a pragmatic hypertension trial: A critical RE-AIM component.

BACKGROUND: Hypertension control is falling in the US yet efficacious interventions exist. Poor patient reach has limited the ability of pragmatic trials to demonstrate effectiveness. This paper uses quantitative and qualitative data to understand factors influencing reach in Hyperlink 3, a pragmatic hypertension trial testing an efficacious pharmacist-led Telehealth Care intervention in comparison to a physician-led Clinic-based Care intervention. Referrals to both interventions were ordered by physicians. METHODS: A sequential-explanatory mixed methods approach was used to understand barriers and facilitators to reach. Reach was assessed quantitatively using EHR data, defined as the proportion of eligible patients attending intended follow-up hypertension care and qualitatively, via semi-structured interviews with patients who were and were not reached. Quantitative data were analyzed using descriptive and inferential statistics. Qualitative data were analyzed via combined deductive and inductive content analysis. RESULTS: Of those eligible, 27% of Clinic-based (n = 532/1945) and 21% of Telehealth patients (n = 385/1849) were reached. In both arms, the largest drop was between physician-signed orders and patients attending initial intended follow-up care. Qualitative analyses uncovered patient barriers related to motivation, capability, and opportunity to attend follow-up care. CONCLUSIONS: Although the proportion of eligible patients with signed orders was high in both arms, the proportion ultimately reached was lower. Patients described barriers related to the influence of one's own personal beliefs or priorities, decision making processes, logistics, and patient perceptions on physician involvement on reach. Addressing these barriers in the design of pragmatic interventions is critical for future effectiveness. TRIAL REGISTRATION: NCT02996565.

Comparison of explanatory and pragmatic design choices in a cluster-randomized hypertension trial: effects on enrollment, participant characteristics, and adherence.

BACKGROUND: Explanatory trials are designed to assess intervention efficacy under ideal conditions, while pragmatic trials are designed to assess whether research-proven interventions are effective in "real-world" settings without substantial research support. METHODS: We compared two trials (Hyperlink 1 and 3) that tested a pharmacist-led telehealth intervention in adults with uncontrolled hypertension. We applied PRagmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2) scores to describe differences in the way these studies were designed and enrolled study-eligible participants, and the effect of these differences on participant characteristics and adherence to study interventions. RESULTS: PRECIS-2 scores demonstrated that Hyperlink 1 was more explanatory and Hyperlink 3 more pragmatic. Recruitment for Hyperlink 1 was conducted by study staff, and 2.9% of potentially eligible patients enrolled. Enrollees were older, and more likely to be male and White than non-enrollees. Study staff scheduled the initial pharmacist visit and adherence to attending this visit was 98%. Conversely for Hyperlink 3, recruitment was conducted by clinic staff at routine encounters and 81% of eligible patients enrolled. Enrollees were younger, and less likely to be male and White than non-enrollees. Study staff did not assist with scheduling the initial pharmacist visit and adherence to attending this visit was only 27%. Compared to Hyperlink 1, patients in Hyperlink 3 were more likely to be female, and Asian or Black, had lower socioeconomic indicators, and were more likely to have comorbidities. Owing to a lower BP for eligibility in Hyperlink 1 (>140/90 mm Hg) than in Hyperlink 3 (>150/95 mm Hg), mean baseline BP was 148/85 mm Hg in Hyperlink 1 and 158/92 mm Hg in Hyperlink 3. CONCLUSION: The pragmatic design features of Hyperlink 3 substantially increased enrollment of study-eligible patients and of those traditionally under-represented in clinical trials (women, minorities, and patients with less education and lower income), and demonstrated that identification and enrollment of a high proportion of study-eligible subjects could be done by usual primary care clinic staff. However, the trade-off was much lower adherence to the telehealth intervention than in Hyperlink 1, which is likely to reflect uptake under real-word conditions and substantially dilute intervention effect on BP. TRIAL REGISTRATION: The Hyperlink 1 study (NCT00781365) and the Hyperlink 3 study (NCT02996565) are registered at ClinicalTrials.gov.

Use of Pamidronate for Hypercalcemia of Malignancy in Renal Dysfunction.

BACKGROUND: Few studies have been conducted investigating the use of bisphosphonates in hypercalcemia of malignancy (HCM) in the setting of renal dysfunction. OBJECTIVE: The primary objective was to compare the incidence of acute kidney injury (AKI) within 7 days of receiving pamidronate for the treatment of HCM with pre-existing renal dysfunction versus normal renal function at the time of pamidronate administration. The secondary objectives explored the effects of pamidronate doses and infusion rates on the safety and efficacy in those with pre-existing renal dysfunction for the treatment of HCM. METHODS: A retrospective chart review was conducted on patients who received pamidronate for the treatment of HCM at a community teaching hospital in Indianapolis, Indiana, from January 1, 2013, to May 31, 2017. RESULTS: A total of 141 pamidronate administrations were included (116 patients had normal baseline renal function, and 25 patients had pre-existing renal dysfunction before pamidronate administration for the treatment of HCM). Two (8%) patients developed AKI in the pre-existing renal dysfunction group, compared with 4 (3.4%) patients in those without pre-existing renal dysfunction (P = .288). For those with pre-existing renal dysfunction, the incidence of AKI did not differ based on the dosage of pamidronate given (P = .762) or infusion rates (P = .373). CONCLUSION: Pamidronate appears to have limited impact on renal function at doses up to 90 mg in the setting of pre-existing renal dysfunction for the treatment of HCM.