Association Between American Board of Surgery Initial Certification and Medical Malpractice Payments.

OBJECTIVE: To measure associations between surgeons' examination performance and obtaining American Board of Surgery certification with the likelihood of having medical malpractice payments. BACKGROUND: Further research is needed to establish a broader understanding of the association of board certification and patient and practice outcomes. METHODS: Retrospective analysis using propensity score-matched surgeons who attempted to obtain American Board of Surgery certification. Surgeons who completed residency between 2000 and 2019 (n=910) and attempted to become certified were categorized as certified or failing to obtain certification. In addition, groups were categorized as either passing or failing their first attempt on the qualifying and certifying examinations. Malpractice payment reports were dichotomized for surgeons who either had a payment report or not. RESULTS: The hazard rate (HR) of malpractice payment reports was significantly greater for surgeons who attempted and failed to obtain certification [HR=1.87; 95% confidence interval (CI), 1.28-2.74] than for surgeons who were certified. Moreover, surgeons who failed either the qualifying (HR=1.64; 95% CI, 1.14-2.37) or certifying examination (HR=1.72; 95% CI, 1.14-2.60) had significantly higher malpractice payment HRs than those who passed the examinations on their first attempt. CONCLUSIONS: Failing to obtain board certification was associated with a higher rate of medical malpractice payments. In addition, failing examinations in the certification examination process on the first attempt was also associated with higher rates of medical malpractice payments. This study provides further evidence that board certification is linked to potential indicators for patient outcomes and practice quality.

Characteristics of Paid Malpractice Claims Among Resident Physicians From 2001 to 2015 in the United States.

PURPOSE: Limited information exists about medical malpractice claims against physicians-in-training. Data on residents' involvement in malpractice actions may inform perceptions about medicolegal liability and influence clinical decision-making at a formative stage. This study aimed to characterize rates and payment amounts of paid malpractice claims on behalf of resident physicians in the United States. METHOD: Using data from the National Practitioner Data Bank, 1,248 paid malpractice claims against resident physicians (interns, residents, and fellows) from 2001 to 2015, representing 1,632,471 residents-years, were analyzed. Temporal trends in overall and specialty-specific paid claim rates, payment amounts, catastrophic (> $1 million) and small (< $100,000) payments, and other claim characteristics were assessed. Payment amounts were compared with attending physicians during the same time period. RESULTS: The overall paid malpractice claim rate was 0.76 per 1,000 resident-years from 2001 to 2015. Among 1,194 unique residents with paid claims, 95.7% had exactly 1 claim, while 4.3% had 2-4 claims during training. Specialty-specific paid claim rates ranged from 0.12 per 1,000 resident-years (pathology) to 2.96 (obstetrics and gynecology). Overall paid claim rates decreased by 52% from 2001-2005 to 2011-2015 (95% confidence interval [CI]: 0.45, 0.59). Median inflation-adjusted payment amount was $199,024 (2015 dollars), not significantly different from payments made on behalf of attending physicians during the same period. Proportions of catastrophic (11.2%) and small (33.1%) claims did not significantly change over the study period. CONCLUSIONS: From 2001 to 2015, paid malpractice claim rates on behalf of resident physicians decreased by 52%, while median payment amounts were stable. Resident paid claim rates were lower than attending physicians, while payment amounts were similar.

Changes in Practice among Physicians with Malpractice Claims.

BACKGROUND: Physicians with poor malpractice liability records may pose a risk to patient safety. There are long-standing concerns that such physicians tend to relocate for a fresh start, but little is known about whether, how, and where they continue to practice. METHODS: We linked an extract of the National Practitioner Data Bank to the Medicare Data on Provider Practice and Specialty data set to create a national cohort of physicians 35 to 65 years of age who practiced during the period from 2008 through 2015. We analyzed associations between the number of paid malpractice claims that physicians accrued and exits from medical practice, changes in clinical volume, geographic relocation, and change in practice-group size. RESULTS: The cohort consisted of 480,894 physicians who had 68,956 paid claims from 2003 through 2015. A total of 89.0% of the physicians had no claims, 8.8% had 1 claim, and the remaining 2.3% had 2 or more claims and accounted for 38.9% of all claims. The number of claims was positively associated with the odds of leaving the practice of medicine (odds ratio for 1 claim vs. no claims, 1.09; 95% confidence interval [CI], 1.06 to 1.11; odds ratio for ≥5 claims, 1.45; 95% CI, 1.20 to 1.74). The number of claims was not associated with geographic relocation but was positively associated with shifts into smaller practice settings. For example, physicians with 5 or more claims had more than twice the odds of moving into solo practice than physicians with no claims (odds ratio, 2.39; 95% CI, 1.79 to 3.20). CONCLUSIONS: Physicians with multiple malpractice claims were no more likely to relocate geographically than those with no claims, but they were more likely to stop practicing medicine or switch to smaller practice settings. (Funded by SUMIT Insurance and the Australian Research Council.).

Dopamine Transporter Dynamics of N-Substituted Benztropine Analogs with Atypical Behavioral Effects.

Atypical dopamine transporter (DAT) inhibitors, despite high DAT affinity, do not produce the psychomotor stimulant and abuse profile of standard DAT inhibitors such as cocaine. Proposed contributing features for those differences include off-target actions, slow onsets of action, and ligand bias regarding DAT conformation. Several 3α-(4',4''-difluoro-diphenylmethoxy)tropanes were examined, including those with the following substitutions: N-(indole-3''-ethyl)- (GA1-69), N-(R)-2''-amino-3''-methyl-n-butyl- (GA2-50), N-2''aminoethyl- (GA2-99), and N-(cyclopropylmethyl)- (JHW013). These compounds were previously reported to have rapid onset of behavioral effects and were presently evaluated pharmacologically alone or in combination with cocaine. DAT conformational mode was assessed by substituted-cysteine accessibility and molecular dynamics (MD) simulations. As determined by substituted-cysteine alkylation, all BZT analogs except GA2-99 showed bias for a cytoplasmic-facing DAT conformation, whereas cocaine stabilized the extracellular-facing conformation. MD simulations suggested that several analog-DAT complexes formed stable R85-D476 "outer gate" bonds that close the DAT to extracellular space. GA2-99 diverged from this pattern, yet had effects similar to those of other atypical DAT inhibitors. Apparent DAT association rates of the BZT analogs in vivo were slower than that for cocaine. None of the compounds was self-administered or stimulated locomotion, and each blocked those effects of cocaine. The present findings provide more detail on ligand-induced DAT conformations and indicate that aspects of DAT conformation other than "open" versus "closed" may facilitate predictions of the actions of DAT inhibitors and may promote rational design of potential treatments for psychomotor-stimulant abuse.

Behavioral economic analysis of the effects of N-substituted benztropine analogs on cocaine self-administration in rats.

RATIONALE AND OBJECTIVES: Benztropine (BZT) analogs and other atypical dopamine uptake inhibitors selectively decrease cocaine self-administration at doses that do not affect responding maintained by other reinforcers. Those effects were further characterized in the current study using a behavioral economic assessment of how response requirement (price) affects reinforcers obtained (consumption) in rats. METHODS: Two groups of rats were trained to press levers with food (45-mg pellet) or cocaine (0.32 mg/kg/injection) reinforcement under fixed-ratio (FR) 5-response schedules. In selected sessions, the FR requirement was increased (5-80) during successive 20-min components to determine demand curves, which plot consumption against price. An exponential function was fitted to the data to derive the consumption at zero price (Q 0) and the rate of decrease in consumption (essential value, EV) with increased price. The BZT analogs, AHN1-055, AHN2-005, JHW007 (3.2-10 or 17.8 mg/kg, each), vehicle, or comparison drugs (methylphenidate, ketamine), were administered i.p. before selected demand-curve determinations. RESULTS: Consumption of cocaine or food decreased with increased FR requirement. Each drug shifted the demand curve rightward at the lowest doses and leftward/downward at higher doses. The effects on EV and Q 0 were greater for cocaine than for food-reinforced responding. Additionally, the effects of the BZT analogs on EV and Q 0 were greater than those obtained with a standard dopamine transport inhibitor, methylphenidate, and the NMDA antagonist, ketamine (1.0-10.0 mg/kg, each). With these latter drugs, the demand-curve parameters were affected similarly with cocaine and food-maintained responding. CONCLUSIONS: The current findings, obtained using a behavioral economic assessment, suggest that BZT analogs selectively decrease the reinforcing effectiveness of cocaine.

Dissociation of tolerance and nicotine withdrawal-associated deficits in contextual fear.

Nicotine addiction is associated with the development of tolerance and the emergence of withdrawal symptoms upon cessation of chronic nicotine administration. Changes in cognition, including deficits in learning, are one of the most common withdrawal symptoms reported by smokers. However, the neural substrates of tolerance to the effects of nicotine on learning and the substrates of withdrawal deficits in learning are unknown, and in fact it is unclear whether a common mechanism is involved in both. The present study tested the hypothesis that tolerance and withdrawal are separate processes and that nicotinic acetylcholine receptor (nAChR) upregulation underlies changes in learning associated with withdrawal but not tolerance. C57BL/6 male mice were administered a dose of nicotine (3, 6.3, 12, or 24 mg/kg/d) chronically for varying days and tested for the onset of tolerance to the effects of nicotine on learning. Follow up experiments examined the number of days of chronic nicotine treatment required to produce withdrawal deficits in learning and a significant increase in [(3)H] epibatidine binding in the hippocampus indicative of receptor upregulation. The results indicate that tolerance onset was influenced by dose of chronic nicotine, that tolerance occurred before withdrawal deficits in learning emerged, and that nAChR upregulation in the dorsal hippocampus was associated with withdrawal but not tolerance. This suggests that for the effects of nicotine on learning, tolerance and withdrawal involve different substrates. These findings are discussed in terms of implications for development of therapeutics that target symptoms of nicotine addiction and for theories of addiction.

2-isoxazol-3-phenyltropane derivatives of cocaine: molecular and atypical system effects at the dopamine transporter.

The present study examined RTI-371 [3ß-(4-methylphenyl)-2ß-[3-(4-chlorophenyl)-isoxazol-5-yl]tropane], a phenyltropane cocaine analog with effects distinct from cocaine, and assessed potential mechanisms for those effects by comparison with its constitutional isomer, RTI-336 [3ß-(4-chlorophenyl)-2ß-[3-(4-methylphenyl)-isoxazol-5-yl]tropane]. In mice, RTI-371 was less effective than cocaine and RTI-336 in stimulating locomotion, and incompletely substituted (∼60% maximum at 5 minutes or 1 hour after injection) in a cocaine (10 mg/kg i.p.)/saline discrimination procedure; RTI-336 completely substituted. In contrast to RTI-336, RTI-371 was not self-administered, and its pretreatment (1.0-10 mg/kg i.p.) dose-dependently decreased maximal cocaine self-administration more potently than food-maintained responding. RTI-336 pretreatment dose-dependently left-shifted the cocaine self-administration dose-effect curve. Both RTI-336 and RTI-371 displaced [(3)H]WIN35,428 [[(3)H](-)-3ß-(4-fluorophenyl)-tropan-2ß-carboxylic acid methyl ester tartrate] binding to striatal dopamine transporters (DATs) with Ki values of 10.8 and 7.81 nM, respectively, and had lower affinities at serotonin or norepinephrine transporters, or muscarinic and σ receptors. The relative low affinity at these sites suggests the DAT as the primary target of RTI-371 with minimal contributions from these other targets. In biochemical assays probing the outward-facing DAT conformation, both RTI-371 and RTI-336 had effects similar to cocaine, suggesting little contribution of DAT conformation to the unique pharmacology of RTI-371. The locomotor-stimulant effects of RTI-371 (3.0-30 mg/kg i.p.) were comparable in wild-type and knockout cannabinoid CB1 receptor (CB1R) mice, indicating that previously reported CB1 allosteric effects do not decrease cocaine-like effects of RTI-371. DAT occupancy in vivo was most rapid with cocaine and least with RTI-371. The slow apparent association rate may allow compensatory actions that in turn dampen cocaine-like stimulation, and give RTI-371 its unique pharmacologic profile.

Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term, but not short-term, hippocampus-dependent memory.

Acute nicotine enhances hippocampus-dependent learning through nicotine binding to ß2-containing nicotinic acetylcholine receptors (nAChRs), but it is unclear if nicotine is targeting processes involved in short-term memory (STM) leading to a strong long-term memory (LTM) or directly targeting LTM. In addition, the molecular mechanisms involved in the effects of nicotine on learning are unknown. Previous research indicates that protein kinase A (PKA), extracellular signal-regulated kinase 1/2 (ERK1/2), and protein synthesis are crucial for LTM. Therefore, the present study examined the effects of nicotine on STM and LTM and the involvement of PKA, ERK1/2, and protein synthesis in the nicotine-induced enhancement of hippocampus-dependent contextual learning in C57BL/6J mice. The protein synthesis inhibitor anisomycin impaired contextual conditioning assessed at 4 h but not 2 h post-training, delineating time points for STM (2 h) and LTM (4 h and beyond). Nicotine enhanced contextual conditioning at 4, 8, and 24 h but not 2 h post-training, indicating nicotine specifically enhances LTM but not STM. Furthermore, nicotine did not rescue deficits in contextual conditioning produced by anisomycin, suggesting that the nicotine enhancement of contextual conditioning occurs through a protein synthesis-dependent mechanism. In addition, inhibition of dorsal hippocampal PKA activity blocked the effect of acute nicotine on learning, and nicotine shifted the timing of learning-related PKA and ERK1/2 activity in the dorsal and ventral hippocampus. Thus, the present results suggest that nicotine specifically enhances LTM through altering the timing of PKA and ERK1/2 signaling in the hippocampus, and suggests that the timing of PKA and ERK1/2 activity could contribute to the strength of memories.

Withdrawal from chronic nicotine and subsequent sensitivity to nicotine challenge on contextual learning.

Nicotine withdrawal is associated with numerous symptoms including impaired hippocampus-dependent learning. Theories of nicotine withdrawal suggest that nicotinic acetylcholine receptors (nAChRs) are hypersensitive during withdrawal, which suggests enhanced sensitivity to nicotine challenge. Research indicates that prior exposure to nicotine enhances sensitivity to nicotine challenge, but it is unclear if this is due to prior nicotine exposure or specific to nicotine withdrawal. Therefore, the present experiments examined if prior nicotine exposure or nicotine withdrawal altered the effects of nicotine challenge on hippocampus-dependent learning. C57BL/6J mice were trained and tested in contextual conditioning following saline or nicotine challenge either during (24h after cessation) or after (14 days after cessation) a period of nicotine withdrawal symptoms. Nicotine challenge produced a greater enhancement of contextual conditioning relative to control withdrawal state in mice withdrawn from chronic nicotine for 24h compared to 14 days and corresponding saline controls. These experiments support the suggestion that during periods of abstinence, smokers may perceive tobacco providing a large boost in cognition.

Divergent functional effects of sazetidine-a and varenicline during nicotine withdrawal.

Smoking is the largest preventable cause of death in the United States. Furthermore, a recent study found that <10% of quit attempts resulted in continuous abstinence for 1 year. With the introduction of pharmacotherapies like Chantix (varenicline), a selective α4ß2 nicotinic partial agonist, successful quit attempts have significantly increased. Therefore, novel subtype-specific nicotinic drugs, such as sazetidine-A, present a rich area for investigation of therapeutic potential in smoking cessation. The present studies examine the anxiety-related behavioral and functional effects of the nicotinic partial agonists varenicline and sazetidine-A during withdrawal from chronic nicotine in mice. Our studies indicate that ventral hippocampal-specific infusions of sazetidine-A, but not varenicline, are efficacious in reducing nicotine withdrawal-related anxiety-like phenotypes in the novelty-induced hypophagia (NIH) paradigm. To further investigate functional differences between these partial agonists, we utilized voltage-sensitive dye imaging (VSDi) in ventral hippocampal slices to determine the effects of sazetidine-A and varenicline in animals chronically treated with saline, nicotine, or undergoing 24 h withdrawal. These studies demonstrate a functional dissociation of varenicline and sazetidine-A on hippocampal network activity, which is directly related to previous drug exposure. Furthermore, the effects of the nicotinic partial agonists in VSDi assays are significantly correlated with their behavioral effects in the NIH test. These findings highlight the importance of drug history in understanding the mechanisms through which nicotinic compounds may be aiding smoking cessation in individuals experiencing withdrawal-associated anxiety.