Mediating Photochemical Reaction Rates at Lewis Acidic Rare Earths by Selective Energy Loss to 4f-Electron States.

Manifesting chemical differences in individual rare earth (RE) element complexes is challenging due to the similar sizes of the tripositive cations and the corelike 4f shell. We disclose a new strategy for differentiating between similarly sized Dy3+ and Y3+ ions through a tailored photochemical reaction of their isostructural complexes in which the f-electron states of Dy3+ act as an energy sink. Complexes RE(hfac)3(NMMO)2 (RE = Dy (2-Dy) and Y (2-Y), hfac = hexafluoroacetylacetonate, and NMMO = N-methylmorpholine-N-oxide) showed variable rates of oxygen atom transfer (OAT) to triphenylphosphine under ultraviolet (UV) irradiation, as monitored by 1H and 19F NMR spectroscopies. Ultrafast transient absorption spectroscopy (TAS) identified the excited state(s) responsible for the photochemical OAT reaction or lack thereof. Competing sensitization pathways leading to excited-state deactivation in 2-Dy through energy transfer to the 4f electron manifold ultimately slows the OAT reaction at this metal cation. The measured rate differences between the open-shell Dy3+ and closed-shell Y3+ complexes demonstrate that using established principles of 4f ion sensitization may deliver new, selective modalities for differentiating the RE elements that do not depend on cation size.

Isolable fluorinated triphenylmethyl cation salts of [HCB11Cl11]-: demonstration of remarkable hydride affinity.

Significantly fluorinated triarylmethyl cations have long attracted attention as potentially accessible highly reactive carbocations, but their isolation in a convenient form has proved elusive. We show that abstraction of chloride with a cationic silylium reagent leads to the facile formation of di-, tetra-, and hexafluorinated trityl cations, which could be isolated as analytically pure salts with the [HCB11Cl11]- counterion and are compatible with (halo)arene solvents. The F6Tr+ cation carrying six meta-F substituents was computationally predicted to possess up to 20% higher hydride affinity than the parent triphenylmethyl cation Tr+. We report that indeed F6Tr+ displays reactivity unmatched by Tr+. F6Tr+ at ambient temperature abstracts hydrides from the C-H bonds in tetraethylsilane, mesitylene, methylcyclohexane, and catalyzes Friedel-Crafts alkylation of arenes with ethylene, while Tr+ does none of these.

Relationships of capsular polysaccharides belonging to Campylobacter jejuni HS1 serotype complex.

The Campylobacter jejuni capsule type HS1 complex is one of the most common serotypes identified worldwide, and consists of strains typing as HS1, HS1/44, HS44 and HS1/8. The capsule structure of the HS1 type strain was shown previously to be composed of teichoic-acid like glycerol-galactosyl phosphate repeats [4-)-α-D-Galp-(1-2)-Gro-(1-P-] with non-stoichiometric fructose branches at the C2 and C3 of Gal and non-stoichiometric methyl phosphoramidate (MeOPN) modifications on the C3 of the fructose. Here, we demonstrate that the capsule of an HS1/44 strain is identical to that of the type strain of HS1, and the capsule of HS1/8 is also identical to HS1, except for an additional site of MeOPN modification at C6 of Gal. The DNA sequence of the capsule locus of an HS44 strain included an insertion of 10 genes, and the strain expressed two capsules, one identical to the HS1 type strain, but with no fructose branches, and another composed of heptoses and MeOPN. We also characterize a HS1 capsule biosynthesis gene, HS1.08, as a fructose transferase responsible for the attachment of the ß-D-fructofuranoses residues at C2 and C3 of the Gal unit. In summary, the common component of all members of the HS1 complex is the teichoic-acid like backbone that is likely responsible for the observed sero-cross reactivity.

Synthetic Strategies for Trapping the Elusive trans-Dirhodium(II,II) Formamidinate Isomer: Effects of Cis versus Trans Geometry on the Photophysical Properties.

The cis- and trans-dirhodium(II,II) complexes cis-[Rh2(µ-DTolF)2(µ-np)(MeCN)4][BF4]2 (1; DTolF = N,N'-di-p-tolylformamidinate and np = 1,8-naphthyridine), cis- and trans-[Rh2(µ-DTolF)2(µ-qxnp)(MeCN)3][BF4]2 [2 and 3, respectively, where qxnp = 2-(1,8-naphthyridin-2-yl)quinoxaline], and trans-[Rh2(µ-DTolF)2(µ-qxnp)2][BF4]2 (4) were synthesized and characterized. A new synthetic methodology was developed that consists of the sequential addition of π-accepting axially blocking ligands to favor formation of the first example of a bis-substituted formamidinate-bearing trans product. Isolation of the intermediates 2 and 3 provides insight into the mechanistic requirements for obtaining 4 and the cis analogue, cis-[Rh2(µ-DTolF)2(µ-qxnp)2][BF4]2 (5). Density functional theory calculations provide support for the synthetic mechanism and proposed intermediates. The metal/ligand-to-ligand charge-transfer (ML-LCT) absorption maximum of the trans complex 4 at 832 nm is red-shifted by 1173 cm-1 and exhibits shorter lifetimes of the 1ML-LCT and 3ML-LCT excited states, 3 ps and 0.40 ns, respectively, compared to those of the cis analogue 5. The shorter excited-state lifetimes of 4 are attributed to the longer Rh-Rh bond of 2.4942(8) Å relative to that in 5, 2.4498(2) Å. A longer metal-metal bond reflects a decreased overlap of the Rh atoms, which leads to more accessible metal-centered excited states for radiationless deactivation. The 3ML-LCT excited states of 4 and 5 undergo reversible bimolecular charge transfer with the electron donor p-phenylenediamine when irradiated with low-energy light. These results indicate that trans isomers are a source of unexplored tunability for potential p-type semiconductor applications and, given their distinct geometric arrangement, constitute useful building blocks for supramolecular architectures with potentially interesting photophysical properties.

A Contemporary Analysis of Medicolegal Issues in Obstetric Anesthesia Between 2005 and 2015.

BACKGROUND: Detailed reviews of closed malpractice claims have provided insights into the most common events resulting in litigation and helped improve anesthesia care. In the past 10 years, there have been multiple safety advancements in the practice of obstetric anesthesia. We investigated the relationship among contributing factors, patient injuries, and legal outcome by analyzing a contemporary cohort of closed malpractice claims where obstetric anesthesiology was the principal defendant. METHODS: The Controlled Risk Insurance Company (CRICO) is the captive medical liability insurer of the Harvard Medical Institutions that, in collaboration with other insurance companies and health care entities, contributes to the Comparative Benchmark System database for research purposes. We reviewed all (N = 106) closed malpractice cases related to obstetric anesthesia between 2005 and 2015 and compared the following classes of injury: maternal death and brain injury, neonatal death and brain injury, maternal nerve injury, and maternal major and minor injury. In addition, settled claims were compared to the cases that did not receive payment. χ, analysis of variance, Student t test, and Kruskal-Wallis tests were used for comparison between the different classes of injury. RESULTS: The largest number of claims, 54.7%, involved maternal nerve injury; 77.6% of these claims did not receive any indemnity payment. Cases involving maternal death or brain injury comprised 15.1% of all cases and were more likely to receive payment, especially in the high range (P = .02). The most common causes of maternal death or brain injury were high neuraxial blocks, embolic events, and failed intubation. Claims for maternal major and minor injury were least likely to receive payment (P = .02) and were most commonly (34.8%) associated with only emotional injury. Compared to the dropped/denied/dismissed claims, settled claims more frequently involved general anesthesia (P = .03), were associated with delays in care (P = .005), and took longer to resolve (3.2 vs 1.3 years; P < .0001). CONCLUSIONS: Obstetric anesthesia remains an area of significant malpractice liability. Opportunities for practice improvement in the area of severe maternal injury include timely recognition of high neuraxial block, availability of adequate resuscitative resources, and the use of advanced airway management techniques. Anesthesiologists should avoid delays in maternal care, establish clear communication, and follow their institutional policy regarding neonatal resuscitation. Prevention of maternal neurological injury should be directed toward performing neuraxial techniques at the lowest lumbar spine level possible and prevention/recognition of retained neuraxial devices.

Slow magnetization dynamics in a six-coordinate Fe(ii)-radical complex.

A new paramagnetic ligand, betaDTDA, and its coordination complex with Fe(hfac)2 are reported (betaDTDA = 4-(benzothiazol-2'-yl)-1,2,3,5-dithiadiazolyl; hfac = 1,1,1,5,5,5-hexafluoroacetylacetonato-). The neutral radical betaDTDA is the first dithiadiazolyl ligand designed to include an electropositive sulphur moiety outside the thiazyl heterocycle, increasing the capacity for supramolecular, structure-directing electrostatic contacts and enabling new pathways for magnetic exchange. The Fe(hfac)2(betaDTDA) complex is composed of a hs-Fe(ii) center with the three bidentate ligands arranged about the ion in a distorted octahedral 6-coordinate environment. The magnetic properties of crystalline Fe(hfac)2(betaDTDA) are consistent with strong antiferromagnetic (AF) coupling between the metal and ligand moments, giving rise to a well-defined Stotal = 3/2 ground state that is the only thermally populated state below 40 K. Below 4 K, this complex exhibits slow relaxation of the magnetization detected by ac susceptibility measurements consistent with a single-molecule magnet (SMM) behaviour.

Magnetic Bistability in Crystalline Organic Radicals: The Interplay of H-bonding, Pancake Bonding, and Electrostatics in 4-(2'-Benzimidazolyl)-1,2,3,5-dithiadiazolyl.

The neutral radical 4-(2'-benzimidazolyl)-1,2,3,5-dithiadiazolyl (HbimDTDA) exhibits a first order phase transition around 270 K without symmetry breaking, preserving its orthorhombic Pbca space group between 340 and 100 K. Associated with this reversible single-crystal-to-single-crystal phase transition, thermal hysteresis of the magnetic susceptibility is observed. The low temperature (LT) phase is diamagnetic owing to pancake bonding between the π-radicals. In the paramagnetic high temperature (HT) phase, the pancake bonds are broken, and new electrostatic contacts are apparent. As a result of the dense 3D network of supramolecular contacts, which includes H-bonds, the HbimDTDA system provides the first example of magnetic bistability for a DTDA radical.

Comparison of Emergency Medicine Malpractice Cases Involving Residents to Nonresident Cases.

BACKGROUND: Data are lacking on how emergency medicine (EM) malpractice cases with resident involvement differs from cases that do not name a resident. OBJECTIVES: The objective was to compare malpractice case characteristics in cases where a resident is involved (resident case) to cases that do not involve a resident (nonresident case) and to determine factors that contribute to malpractice cases utilizing EM as a model for malpractice claims across other medical specialties. METHODS: We used data from the Controlled Risk Insurance Company (CRICO) Strategies' division Comparative Benchmarking System (CBS) to analyze open and closed EM cases asserted from 2009 to 2013. The CBS database is a national repository that contains professional liability data on > 400 hospitals and > 165,000 physicians, representing over 30% of all malpractice cases in the United States (>350,000 claims). We compared cases naming residents (either alone or in combination with an attending) to those that did not involve a resident (nonresident cohort). We reported the case statistics, allegation categories, severity scores, procedural data, final diagnoses, and contributing factors. Fisher's exact test or t-test was used for comparisons (alpha set at 0.05). RESULTS: A total of 845 EM cases were identified of which 732 (87%) did not name a resident (nonresident cases), while 113 (13%) included a resident (resident cases). There were higher total incurred losses for nonresident cases. The most frequent allegation categories in both cohorts were "failure or delay in diagnosis/misdiagnosis" and "medical treatment" (nonsurgical procedures or treatment regimens, i.e., central line placement). Allegation categories of safety and security, patient monitoring, hospital policy and procedure, and breach of confidentiality were found in the nonresident cases. Resident cases incurred lower payments on average ($51,163 vs. $156,212 per case). Sixty-six percent (75) of resident versus 57% (415) of nonresident cases were high-severity claims (permanent, grave disability or death; p = 0.05). Procedures involved were identified in 32% (36) of resident and 26% (188) of nonresident cases (p = 0.17). The final diagnoses in resident cases were more often cardiac related (19% [21] vs. 10% [71], p < 0.005) whereas nonresident cases had more orthopedic-related final diagnoses (10% [72] vs. 3% [3], p < 0.01). The most common contributing factors in resident and nonresident cases were clinical judgment (71% vs. 76% [p = 0.24]), communication (27% vs. 30% [p = 0.46]), and documentation (20% vs. 21% [p = 0.95]). Technical skills contributed to 20% (22) of resident cases versus 13% (96) of nonresident cases (p = 0.07) but those procedures involving vascular access (2.7% [3] vs 0.1% [1]) and spinal procedures (3.5% [4] vs. 1.1% [8]) were more prevalent in resident cases (p < 0.05 for each). CONCLUSIONS: There are higher total incurred losses in nonresident cases. There are higher severity scores in resident cases. The overall case profiles, including allegation categories, final diagnoses, and contributing factors between resident and nonresident cases are similar. Cases involving residents are more likely to involve certain technical skills, specifically vascular access and spinal procedures, which may have important implications regarding supervision. Clinical judgment, communication, and documentation are the most prevalent contributing factors in all cases and should be targets for risk reduction strategies.

A Contemporary Medicolegal Analysis of Outpatient Medication Management in Chronic Pain.

BACKGROUND: Opioids are frequently used in chronic pain management but are associated with significant morbidity and mortality in some patient populations. An important avenue for identifying complications-including serious or rare complications-is the study of closed malpractice claims. The present study is intended to complement the existing closed claims literature by drawing on claims from a more recent timeframe through a partnership with a large malpractice carrier, the Controlled Risk Insurance Company (CRICO). The goal of this study was to identify patient medical comorbidities and aberrant drug behaviors, as well as prescriber practices associated with patient injury and malpractice claims. Another objective was to identify claims most likely to result in payments and use this information to propose a strategy for reducing medicolegal risk. METHODS: The CRICO Strategies Comparative Benchmarking System is a database of claims drawing from >350,000 malpractice claims from Harvard-affiliated institutions and >400 other academic and community institutions across the United States. This database was queried for closed claims from January 1, 2009, to December 31, 2013, and identified 37 cases concerning noninterventional, outpatient chronic pain management. Each file consisted of a narrative summary, including expert witness testimony, as well as coded fields for patient demographics, medical comorbidities, the alleged damaging event, the alleged injurious outcome, the total financial amount incurred, and more. We performed an analysis using these claim files. RESULTS: The mean patient age was 43.5 years, with men representing 59.5% of cases. Payments were made in 27% of cases, with a median payment of $72,500 and a range of $7500-$687,500. The majority of cases related to degenerative joint disease of the spine and failed back surgery syndrome; no patients in this series received treatment of malignant pain. Approximately half (49%) of cases involved a patient death. The use of long-acting opioids and medical conditions affecting the cardiac and pulmonary systems were more closely associated with death than with other outcomes. The nonpain medical conditions present in this analysis included obesity, obstructive sleep apnea, chronic obstructive pulmonary disease, hypertension, and coronary artery disease. Other claims ranged from alleged addiction to opioids from improper prescribing to alleged abandonment with withdrawal of care. The CRICO analysis suggested that patient behavior contributed to over half of these claims, whereas deficits in clinical judgment contributed to approximately 40% of the claims filed. CONCLUSIONS: Claims related to outpatient medication management in pain medicine are multifactorial, stemming from deficits in clinical judgment by physicians, noncooperation in care by patients, and poor clinical documentation. Minimization of both legal risk and patient harm can be achieved by carefully selecting patients for chronic opioid therapy and documenting compliance and improvement with the treatment plan. Medical comorbidities such as obstructive sleep apnea and the use of long-acting opioids may be particularly dangerous. Continuing physician education on the safest and most effective approaches to manage these medications in everyday practice will lead to both improved legal security and patient safety.

Missed Diagnosis of Cardiovascular Disease in Outpatient General Medicine: Insights from Malpractice Claims Data.

BACKGROUND: Diagnostic errors are an underrecognized source of patient harm, and cardiovascular disease can be challenging to diagnose in the ambulatory setting. Although malpractice data can inform diagnostic error reduction efforts, no studies have examined outpatient cardiovascular malpractice cases in depth. A study was conducted to examine the characteristics of outpatient cardiovascular malpractice cases brought against general medicine practitioners. METHODS: Some 3,407 closed malpractice claims were analyzed in outpatient general medicine from CRICO Strategies' Comparative Benchmarking System database-the largest detailed database of paid and unpaid malpractice in the world-and multivariate models were created to determine the factors that predicted case outcomes. RESULTS: Among the 153 patients in cardiovascular malpractice cases for whom patient comorbidities were coded, the majority (63%) had at least one traditional cardiac risk factor, such as diabetes, tobacco use, or previous cardiovascular disease. Cardiovascular malpractice cases were more likely to involve an allegation of error in diagnosis (75% vs. 47%, p <0.0001), have high clinical severity (86% vs. 49%, p <0.0001) and result in death (75% vs. 27%, p <0.0001), as compared to noncardiovascular cases. Initial diagnoses of nonspecific chest pain and mimics of cardiovascular pain (for example, esophageal disease) were common and independently increased the likelihood of a claim resulting in a payment (p <0.01). CONCLUSION: Cardiovascular malpractice cases against outpatient general medicine physicians mostly occur in patients with conventional risk factors for coronary artery disease and are often diagnosed with common mimics of cardiovascular pain. These findings suggest that these patients may be high-yield targets for preventing diagnostic errors in the ambulatory setting.

A Contemporary Medicolegal Analysis of Implanted Devices for Chronic Pain Management.

BACKGROUND: Analysis of closed malpractice claims allows the study of rare but serious complications and likely results in improved patient safety by raising awareness of such complications. Clinical studies and closed claims analyses have previously reported on the common complications associated with intrathecal drug delivery systems (IDDS) and spinal cord stimulators (SCS). This study provides a contemporary analysis of claims from within the past 10 years. METHODS: We performed a closed claims analysis for a period January 1, 2009 to December 31, 2013 for cases with pain medicine as the primary service. These cases were identified using the Controlled Risk Insurance Company (CRICO) Comparative Benchmarking System (CBS), a database containing more than 300,000 malpractice claims from more than 400 academic and community institutions, representing approximately 30% of malpractice cases in the United States. The clinical narratives, which included medical files, claims files, depositions, and expert witness testimony, were reviewed by the authors, as were the CRICO coded variables, which included algorithmically determined contributing factors to the patient injury. RESULTS: Intrathecal drug delivery systems represented 17 of the closed claims; spinal cord stimulators represented 11 of the closed claims. The most common chronic pain diagnoses for which a device was implanted included failed back surgery syndrome and spasticity. The average total incurred for pain medicine claims was $166,028. Damaging events included IDDS refill errors (eg, subcutaneous administration of medication, reprogramming errors), intraoperative nerve damage, and postoperative infection (eg, epidural abscess, meningitis). High-severity outcomes included nerve damage (eg, paraplegia) and death. Medium-severity outcomes included drug reactions (eg, respiratory arrest from opioid overdose) and the need for reoperation. For both IDDS and SCS, deficits in technical skill were the most common contributing factor to injury, followed by deficits in clinical judgment, communication, and documentation. CONCLUSIONS: Implanted devices used for pain management involve a significant risk of morbidity and mortality. Proper education of providers and patients is essential. Providers must acquire the technical skills required for the implantation and refilling of these devices and the clinical skills required for the identification and management of complications such as intrathecal granuloma. Proper patient selection and clear communication between the provider and the patient about these possible complications are of paramount importance.