Stabilisation of the [SiH6]2- Anion within a Supramolecular Assembly.

The hypercoordinate [SiH6]2- anion is not stable in solution. Here, we report the room temperature, solution stable molecular [SiH6]2- complex, [{KCa(NON)(OEt2)}2][SiH6] (NON=4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethyl-xanthene)), where the [SiH6]2- anion is stabilised within a supramolecular assembly that mimics the solid-state environment of the anion in the lattice of K2SiH6. Solution-state reactivity of the complex towards carbon monoxide, benzaldehyde, azobenzene and acetonitrile is reported, yielding a range of reduction and C-C coupled products.

The Ambiguous Origin of Thermochromism in Molecular Crystals of Dichalcogenides: Chalcogen Bonds versus Dynamic Se-Se/Te-Te Bonds.

We report thermochromism in crystals of diphenyl diselenide (dpdSe) and diphenyl ditelluride (dpdTe), which is at variance with the commonly known mechanisms of thermochromism in molecular crystals. Variable temperature neutron diffraction studies indicated no conformational change, tautomerization or phase transition between 100 K and 295 K. High-pressure crystallography studies indicated no associated piezochromism in dpdSe and dpdTe crystals. The evolution of the crystal structures and their electronic band structure with pressure and temperature reveal the contributions of intramolecular and intermolecular factors towards the origin of thermochromism-especially the intermolecular Se⋅⋅⋅Se and Te⋅⋅⋅Te chalcogen bonds and torsional modes of vibrations around the dynamic Se-Se and Te-Te bonds. Further, a co-crystal of dpdSe with iodine (dpdSe-I2 ) and an alloy crystal of dpdSe and dpdTe implied a predominantly intramolecular origin of the observed thermochromism associated with vibronic coupling.

Magnesium(I) Reduction of Aluminum(III) Hydride Complexes: Generation of Mixed Valence Aluminum (AlI /Al0 ) Hydride Cluster Compounds, [Al6 H8 (NR3 )2 {Mg(ß-diketiminate)}4 ].

Reduction of a range of amido- and aryloxy-aluminum dihydride complexes, e.g. [AlH2 (NR3 ){N(SiMe3 )2 }] (NR3 =NMe3 or N-methylpiperidine (NMP)), with ß-diketiminato dimagnesium(I) reagents, [{(Ar Nacnac)Mg}2 ] (Ar Nacnac=[HC(MeCNAr)2 ]- , Ar=mesityl (Mes) or 2,6-xylyl (Xyl)), have afforded deep red mixed valence aluminum hydride cluster compounds, [Al6 H8 (NR3 )2 {Mg(Ar Nacnac)}4 ], which have an average Al oxidation state of +0.66, the lowest for any well-defined aluminum hydride compound. In the solid-state, the clusters are shown to have distorted octahedral Al6 cores, having zero-valent Al axial sites and mono-valent AlH2 - equatorial units. Several novel by-products were isolated from the reactions that gave the clusters, including the Mg-Al bonded magnesio-aluminate complexes, [(Ar Nacnac)(Me3 N)Mg-Al(µ-H)3 [{Mg(Ar Nacnac)}2 (µ-H)]]. Computational analyses of one aluminum hydride cluster revealed its Al6 core to be electronically delocalized, and to possess one unoccupied, and six occupied, skeletal molecular orbitals.

Anionic Magnesium and Calcium Hydrides: Transforming CO into Unsaturated Disilyl Ethers.

The synthesis, characterisation and reactivity of two isostructural anionic magnesium and calcium complexes is reported. By X-ray and neutron diffraction techniques, the anionic hydrides are shown to exist as dimers, held together by a range of interactions between the two anions and two bridging potassium cations. Unlike the vast proportion of previously reported dimeric group 2 hydrides, which have hydrides that bridge two group 2 centres, here the hydrides are shown to be "terminal", but stabilised by interactions with the potassium cations. Both anionic hydrides were found to insert and couple CO under mild reaction conditions to give the corresponding group 2 cis-ethenediolate complexes. These cis-ethenediolate complexes were found to undergo salt elimination reactions with silyl chlorides, allowing access to small unsaturated disilyl ethers with a high percentage of their mass originating from the C1 source CO.

The Continuum Between Hexagonal Planar and Trigonal Planar Geometries.

New heterometallic hydride complexes that involve the addition of {Mg-H} and {Zn-H} bonds to group 10 transition metals (Pd, Pt) are reported. The side-on coordination of a single {Mg-H} to Pd forms a well-defined σ-complex. In contrast, addition of three {Mg-H} or {Zn-H} bonds to Pd or Pt results in the formation of planar complexes with subtly different geometries. We compare their structures through experiment (X-ray diffraction, neutron diffraction, multinuclear NMR), computational methods (DFT, QTAIM, NCIPlot), and theoretical analysis (MO diagram, Walsh diagram). These species can be described as snapshots along a continuum of bonding between ideal trigonal planar and hexagonal planar geometries.

Nickel and Palladium Complexes of a PP(O)P Pincer Ligand Based upon a peri-Substituted Acenaphthyl Scaffold and a Secondary Phosphine Oxide.

A PP(O)P pincer ligand based upon a peri-substituted acenaphthyl (Ace) scaffold and a secondary phosphine oxide, (5-Ph2P-Ace-6-)2P(O)H, was prepared and fully characterized including a neutron diffraction study. The reaction with [Ni(H2O)6]Cl2 and PdCl2 produced ionic metal(II) complexes [κ3-P,P',P''((5-Ph2P-Ace-6-)2P(OH))MCl]Cl, which upon addition of Et3N gave rise to zwitterionic metal(II) complexes κ3-P,P',P''((5-Ph2P-Ace-6-)2P(O))MCl (M = Ni, Pd). The reaction with Ni(COD)2 (COD = cyclooctadiene) provided the η3-cyclooctenyl Ni(II) complex κ3-P,P',P''((5-Ph2P-Ace-6-)2P(O))Ni(η3-C8H13). A detailed complementary bonding analysis of the P-H, P-O, and P-M interactions was carried out (M = Ni, Pd).

Three year clinical outcomes in a nationwide, observational, siteless clinical trial of atrial fibrillation screening-mHealth Screening to Prevent Strokes (mSToPS).

BACKGROUND: Atrial fibrillation (AF) is common, often without symptoms, and is an independent risk factor for mortality, stroke and heart failure. It is unknown if screening asymptomatic individuals for AF can improve clinical outcomes. METHODS: mSToPS was a pragmatic, direct-to-participant trial that randomized individuals from a single US-wide health plan to either immediate or delayed screening using a continuous-recording ECG patch to be worn for two weeks and 2 occasions, ~3 months apart, to potentially detect undiagnosed AF. The 3-year outcomes component of the trial was designed to compare clinical outcomes in the combined cohort of 1718 individuals who underwent monitoring and 3371 matched observational controls. The prespecified primary outcome was the time to first event of the combined endpoint of death, stroke, systemic embolism, or myocardial infarction among individuals with a new AF diagnosis, which was hypothesized to be the same in the two cohorts but was not realized. RESULTS: Over the 3 years following the initiation of screening (mean follow-up 29 months), AF was newly diagnosed in 11.4% (n = 196) of screened participants versus 7.7% (n = 261) of observational controls (p<0.01). Among the screened cohort with incident AF, one-third were diagnosed through screening. For all individuals whose AF was first diagnosed clinically, a clinical event was common in the 4 weeks surrounding that diagnosis: 6.6% experienced a stroke,10.2% were newly diagnosed with heart failure, 9.2% had a myocardial infarction, and 1.5% systemic emboli. Cumulatively, 42.9% were hospitalized. For those diagnosed via screening, none experienced a stroke, myocardial infarction or systemic emboli in the period surrounding their AF diagnosis, and only 1 person (2.3%) had a new diagnosis of heart failure. Incidence rate of the prespecified combined primary endpoint was 3.6 per 100 person-years among the actively monitored cohort and 4.5 per 100 person-years in the observational controls. CONCLUSIONS: At 3 years, screening for AF was associated with a lower rate of clinical events and improved outcomes relative to a matched cohort, although the influence of earlier diagnosis of AF via screening on this finding is unclear. These observational data, including the high event rate surrounding a new clinical diagnosis of AF, support the need for randomized trials to determine whether screening for AF will yield a meaningful protection from strokes and other clinical events. TRAIL REGISTRATION: The mHealth Screening To Prevent Strokes (mSToPS) Trial is registered on ClinicalTrials.gov with the identifier NCT02506244.

Hemoglobin A1C testing frequency among patients with type 2 diabetes within a US payer system: a retrospective observational study.

OBJECTIVE: The American Diabetes Association (ADA) guidelines recommend A1C testing schedules for patients with type 2 diabetes; however, level of real-world guideline adherence remains unclear. The current study evaluated A1C testing frequency and its association with glycemic control and cardiovascular outcomes. METHODS: A retrospective study was conducted utilizing Aetna's Enterprise Data Warehouse. Adult patients with a medical claim for type 2 diabetes in 2017 (index date) were included. Patients had continuous enrollment through December 2019 and ≥1 reported A1C measurement from 2017 to 2019. Follow-up was up to 36 months post-index date. RESULTS: Of the 112,572 eligible patients, 50.0% were female and median age was 70 years; 32.9% of patients with controlled baseline A1C (<8%, 64 mmol/mol) received less than the 2 tests/year recommended by the ADA, while 60.6% of patients with uncontrolled baseline A1C received less than the quarterly testing recommended by the ADA. More frequent testing was associated with age (65-75 years), uncontrolled baseline A1C and presence of comorbidities. In separate multivariable models, 2-3 A1C tests/year were associated with greater likelihood of A1C < 8% (64 mmol/mol) vs. <2 tests/year (OR = 1.07, 95% confidence interval [CI] 1.02-1.12), while >3 tests/year was associated with a modestly increased risk of cardiovascular events vs. <2 tests/year (OR = 1.08, 95% CI 1.01-1.15). CONCLUSIONS: A large proportion of type 2 diabetes patients were not tested per guideline recommendations. The relationship between A1C testing frequency and glycemic control was inconsistent, though there was a significant association between more frequent testing and experiencing a CV event.

Evaluating the relationship between clinical and demographic characteristics of insulin-using people with diabetes and their health outcomes: a cluster analysis application.

BACKGROUND: The aim of this study was to determine how clusters or subgroups of insulin-treated people with diabetes, based upon healthcare resource utilization, select social demographic and clinical characteristics, and diabetes management parameters, are related to health outcomes including acute care visits and hospital admissions. METHODS: This was a non-experimental, retrospective cluster analysis. We utilized Aetna administrative claims data to identify insulin-using people with diabetes with service dates from 01 January 2015 to 30 June 2018. The study included adults over the age of 18 years who had a diagnosis of type 1 (T1DM) or type 2 diabetes mellitus (T2DM) on insulin therapy and had Aetna medical and pharmacy coverage for at least 18 months (6 months prior and 12 months after their index date, defined as either their first insulin prescription fill date or their earliest date allowing for 6 months' prior coverage). We used K-means clustering methods to identify relevant subgroups of people with diabetes based on 13 primary outcome variables. RESULTS: A total of 100,650 insulin-using people with diabetes were identified in the Aetna administrative claims database and met study criteria, including 11,826 (11.7%) with T1DM and 88,824 (88.3%) with T2DM. Of these 79,053 (78.5%) people were existing insulin users. Seven distinct clusters were identified with different characteristics and potential risks of diabetes complications. Overall, clusters were significantly associated with differences in healthcare utilization (emergency room visits, inpatient admissions, and total inpatient days) after multivariable adjustment. CONCLUSIONS: This analysis of healthcare claims data using clustering methodologies identified meaningful subgroups of patients with diabetes using insulin. The subgroups differed in comorbidity burden, healthcare utilization, and demographic factors which could be used to identify higher risk patients and/or guide the management and treatment of diabetes.

C-H and C-F coordination of arenes in neutral alkaline earth metal complexes.

A series of neutral magnesium and calcium complexes bearing an extremely bulky diamido ligand have been synthesised and crystallographically characterised. A number of these complexes feature rare group 2 metalaromatic interactions, such as the η6-coordination of benzene and 'agostic-like' C-H coordination, the latter previously unseen in neutral Mg and Ca complexes.

N-Heterocyclic carbene, carbodiphosphorane and diphosphine adducts of beryllium dihalides: synthesis, characterisation and reduction studies.

Reaction of several N-heterocyclic carbenes, a carbodiphosphorane, and bis(diphenylphosphino)ethane (DPPE) with [BeX2(OEt2)2] (X = Br or I) have yielded a variety of beryllium dihalide adduct complexes, all of which were crystallographically characterised. Attempts to reduce the compounds to low oxidation state beryllium complexes using a variety of reducing agents have been carried out, but were of limited success. However, reaction of [(IPr)BeBr2] (IPr = :C{(DipNCH)2}; Dip = 2,6-diisopropylphenyl) with the aluminium(i) heterocycle, [:Al(DipNacnac)] (DipNacnac = [HC(MeCNDip)2]-) afforded the adduct complex, [{(IPr)(Br)Be(µ-H)}2], while reduction of [(IPr)BeBr2] with potassium naphthalenide gave the beryllium naphthalenediyl complex, [(IPr)Be(C10H8)]. Furthermore, reaction of [{(DPPE)BeI2}∞], with [:Al(DipNacnac)] led to insertion of the Al centre of the heterocycle into a Be-I bond, and formation of a rare example of an Al-Be bonded complex, [(DPPE)(i)Be-Al(i)(DipNacnac)].

Treatment Patterns and Health Care Costs of Lupus Nephritis in a United States Payer Population.

OBJECTIVE: To describe the characteristics, treatment patterns, health care resource utilization (HCRU), and cost of care for members of a large United States (US) health insurance plan with lupus nephritis (LN). METHODS: A retrospective observational study was conducted using a health insurance plan database to identify adult members with a diagnosis of LN. Medical and pharmacy claims were used to describe demographics, comorbidities, HCRU, and cost patterns over a 12-month follow-up period for each patient, between January 1, 2014, and December 31, 2016. All study variables were examined descriptively. RESULTS: A total of 1039 patients were available for analysis (median age, 47 years; 83% female). The median Charlson Comorbidity Index (CCI) was 3.3. Less than half (41%) of patients received immunosuppressive therapies commonly used to treat LN. Evidence indicated that 58% of the study population were prescribed corticosteroid therapy, in most cases (73%) for more than 60 days. Adverse events known to be associated with corticosteroid therapy were recorded in 58% of patients. Guideline-recommended preventive therapy with hydroxychloroquine was prescribed for 54% of members with LN. Nearly half (47%) of members with LN did not see a nephrologist and more than one-third (36%) did not see a rheumatologist over 1 year of follow-up. Rates of all-cause hospitalization and emergency department (ED) use were 25% and 35%, respectively. The mean all-cause per-member-per-month (PMPM) medical cost for the study population was $2801, with LN-specific costs accounting for $1147 PMPM. CONCLUSION: Patients with LN who are insured through a large US health plan appeared to underutilize outpatient specialist services and guideline-recommended hydroxychloroquine therapy. Corticosteroid use and adverse events known to be associated with corticosteroids were common in this cohort.

Effect of Probiotic Use on Antibiotic Administration Among Care Home Residents: A Randomized Clinical Trial.

Importance: Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited. Objective: To determine whether a daily oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 compared with placebo reduces antibiotic administration in care home residents. Design, Setting, and Participants: Placebo-controlled randomized clinical trial of 310 care home residents, aged 65 years and older, recruited from 23 care homes in the United Kingdom between December 2016 and May 2018, with last follow-up on October 31, 2018. Interventions: Study participants were randomized to receive a daily capsule containing a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 (total cell count per capsule, 1.3 × 1010 to 1.6 × 1010) (n = 155), or daily matched placebo (n = 155), for up to 1 year. Main Outcomes and Measures: The primary outcome was cumulative antibiotic administration days for all-cause infections measured from randomization for up to 1 year. Results: Among 310 randomized care home residents (mean age, 85.3 years; 66.8% women), 195 (62.9%) remained alive and completed the trial. Participant diary data (daily data including study product use, antibiotic administration, and signs of infection) were available for 98.7% randomized to the probiotic group and 97.4% randomized to placebo. Care home residents randomized to the probiotic group had a mean of 12.9 cumulative systemic antibiotic administration days (95% CI, 0 to 18.05), and residents randomized to placebo had a mean of 12.0 days (95% CI, 0 to 16.95) (absolute difference, 0.9 days [95% CI, -3.25 to 5.05]; adjusted incidence rate ratio, 1.13 [95% CI, 0.79 to 1.63]; P = .50). A total of 120 care home residents experienced 283 adverse events (150 adverse events in the probiotic group and 133 in the placebo group). Hospitalizations accounted for 94 of the events in probiotic group and 78 events in the placebo group, and deaths accounted for 33 of the events in the probiotic group and 32 of the events in the placebo group. Conclusions and Relevance: Among care home residents in the United Kingdom, a daily dose of a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 did not significantly reduce antibiotic administration for all-cause infections. These findings do not support the use of probiotics in this setting. Trial Registration: ISRCTN Identifier:16392920.

Molecular Thorium Trihydrido Clusters Stabilized by Cyclopentadienyl Ligands.

Hydrogenolysis of alkyl-substituted cyclopentadienyl (CpR ) ligated thorium tribenzyl complexes [(CpR )Th(p-CH2 -C6 H4 -Me)3 ] (1-6) afforded the first examples of molecular thorium trihydrido complexes [(CpR )Th(µ-H)3 ]n (CpR =C5 H2 (t Bu)3 or C5 H2 (SiMe3 )3 , n=5; C5 Me4 SiMe3 , n=6; C5 Me5 , n=7; C5 Me4 H, n=8; 7-10 and 12) and [(Cp# )12 Th13 H40 ] (Cp# =C5 H4 SiMe3 ; 13). The nuclearity of the metal hydride clusters depends on the steric profile of the cyclopentadienyl ligands. The hydrogenolysis intermediate, tetra-nuclear octahydrido thorium dibenzylidene complex [(Cpttt )Th(µ-H)2 ]4 (µ-p-CH-C6 H4 -Me)2 (Cpttt =C5 H2 (t Bu)3 ) (11) was also isolated. All of the complexes were characterized by NMR spectroscopy and single-crystal X-ray analysis. Hydride positions in [(CpMe4 )Th(µ-H)3 ]8 (CpMe4 =C5 Me4 H) were further precisely confirmed by single-crystal neutron diffraction. DFT calculations strengthen the experimental assignment of the hydride positions in the complexes 7 to 12.

Effects of conformance to type 2 diabetes guidelines on health care resource utilization, clinical outcomes, and cost: A retrospective claims analysis.

OBJECTIVES: To determine if there is a difference in the outcomes of diabetes patients managed with high, intermediate, or low conformance to diabetes guidelines. STUDY DESIGN: Retrospective database analysis. METHODS: This was a retrospective database analysis of adults diagnosed with type 2 diabetes and with glycated hemoglobin (HbA1c) ≥7% (53 mmol/mol) who were commercially insured by, or receiving Medicare benefits through, Aetna. Subjects were classified as having high, intermediate, or low conformance to current guidelines. Six, 12, and 18 months later, health care resource utilization, clinical outcomes, and costs were assessed using multivariable regression analysis to determine whether differences existed between patients with high, intermediate, and low conformance. Regression models were adjusted using pre-index variables, and the results were expressed as incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: A total of 21,171 individuals were included in the analysis. In analyses of patients with low versus high conformance, pharmacy costs were significantly lower over 18 months of outcome assessment (P < 0.001), but diabetes-related outpatient costs were significantly higher (P < 0.001). In analyses of patients with intermediate versus high conformance, diabetes-related outpatient costs were significantly greater at 12 and 18 months (P < 0.001 for both). CONCLUSIONS: Reduced conformance to guidelines leads to higher diabetes-related costs.

Healthcare resource utilization following ECG sensor patch screening for atrial fibrillation.

BACKGROUND: Screening for asymptomatic, undiagnosed atrial fibrillation (AF) has the potential to allow earlier treatment, possibly resulting in prevention of strokes, but also to increase medical resource utilization. OBJECTIVE: To compare healthcare utilization rates during the year following initiation of screening among participants screened for AF by electrocardiogram (ECG) sensor patch compared with a matched observational control group. METHODS: A total of 1718 participants recruited from a health care plan based on age and comorbidities who were screened with an ECG patch (actively monitored group) as part of a prospective, pragmatic research trial were matched by age, sex, and CHA2DS2-VASc score with 3371 members from the same health plan (observational control group). Healthcare utilization, including visits, prescriptions, procedures, and diagnoses, during the 1 year following screening was compared between the groups using health plan claims data. RESULTS: Overall, the actively monitored group had significantly higher rates of cardiology visits (adjusted incidence rate ratio [aIRR] [95% confidence interval (CI)]: 1.43 [1.27, 1.60]), no difference in primary care provider visits (aIRR [95% CI]: 1.0 [0.95, 1.05]), but lower rates of emergency department (ED) visits and hospitalizations (aIRR [95% CI]: 0.80 [0.69, 0.92]) compared with controls. Among those with newly diagnosed AF, the reduction in ED visits and hospitalizations was even greater (aIRR [95% CI]: 0.27 [0.17, 0.43]). CONCLUSION: AF screening in an asymptomatic, moderate-risk population with an ECG patch was associated with an increase in cardiology outpatient visits but also significantly lower rates of ED visits and hospitalizations over the 1 year following screening.

The partial dehydrogenation of aluminium dihydrides.

The reactions of a series of ß-diketiminate stabilised aluminium dihydrides with ruthenium bis(phosphine), palladium bis(phosphine) and palladium cyclopentadienyl complexes is reported. In the case of ruthenium, alane coordination occurs with no evidence for hydrogen loss resulting in the formation of ruthenium complexes with a pseudo-octahedral geometry and cis-relation of phosphine ligands. These new ruthenium complexes have been characterised by multinuclear and variable temperature NMR spectroscopy, IR spectroscopy and single crystal X-ray diffraction. In the case of palladium, a series of structural snapshots of alane dehydrogenation have been isolated and crystallographically characterised. Variation of the palladium precursor and ligand on aluminium allows kinetic control over reactivity and isolation of intermetallic complexes that contain new Pd-Al and Pd-Pd interactions. These complexes differ by the ratio of H : Al (2 : 1, 1.5 : 1 and 1 : 1) with lower hydride content species forming with dihydrogen loss. A combination of X-ray and neutron diffraction studies have been used to interrogate the structures and provide confidence in the assignment of the number and position of hydride ligands. 27Al MAS NMR spectroscopy and calculations (DFT, QTAIM) have been used to gain an understanding of the dehydrogenation processes. The latter provide evidence for dehydrogenation being accompanied by metal-metal bond formation and an increased negative charge on Al due to the covalency of the new metal-metal bonds. To the best of our knowledge, we present the first structural information for intermediate species in alane dehydrogenation including a rare neutron diffraction study of a palladium-aluminium hydride complex. Furthermore, as part of these studies we have obtained the first SS 27Al NMR data on an aluminium(i) complex. Our findings are relevant to hydrogen storage, materials chemistry and catalysis.

Correction to: Effects of workload, work complexity, and repeated alerts on alert fatigue in a clinical decision support system.

Following publication of the original article [1], the authors reported that the article erroneously stated that Dr. Ancker was affiliated with the Tehran University of Medical Sciences. Dr. Ancker is not affiliated with that institution.

Proximity Enforced Agostic Interactions Involving Closed-Shell Coinage Metal Ions.

A proximity enforcing diarylsilane ligand is reported, which gives rise to unusual Si-H···M interactions with the d10 metal ions Cu+ and Ag+ upon complexation. These interactions are studied in detail both experimentally and computationally and can be classified to be weakly agostic in nature for the Si-H···Cu interaction. The Si-H···Ag interaction has more signatures of an electrostatic contact.