The "Difficult" Inpatient, a Qualitative Study of Physician Perspectives.

BACKGROUND: Previous studies exploring difficult inpatients have mostly focused on psychiatric inpatients. OBJECTIVE: To explore the characteristics of difficult medicine inpatients. DESIGN: Qualitative study using focus groups and semi-structured interviews. Transcripts were recorded, transcribed, and coded (MAXQDA) using thematic content analysis. PARTICIPANTS: Medicine inpatient providers at a tertiary care facility. KEY RESULTS: Our sample consisted of 28 providers (6 hospitalists, 10 medicine attendings, 6 medicine residents, and 6 interns). Theme 1: Provider experience: Difficult inpatients were time-consuming and evoked emotional responses including frustration and dysphoria. Theme 2: Patient characteristics: Included having personality disorders or mental health issues, being uncooperative, manipulative, angry, demanding, threatening, or distrustful. Difficult patients also had challenging social situations and inadequate support, unrealistic care expectations, were self-destructive, tended to split care-team messages, and had unclear diagnoses. Theme 3: Difficult families: Shared many characteristics of difficult patients including being distrustful, demanding, manipulative, threatening, or angry. Difficult families were barriers to care, disagreed with the treatment plan and each other, did not act in the patient's best interest, suggested inappropriate treatment, or had unrealistic expectations. STRATEGIES: Approaches to dealing with difficult patients or families included building trust, being calm, and having a consistent message. Communication approaches included naming the emotion, empathetic listening, identifying patient priorities and barriers, and partnering. CONCLUSIONS: Difficult patients induced emotional responses, dysphoria, and self-doubt among providers. Underlying personality disorders were often mentioned. Difficult patients and families shared many characteristics. Communication and training were highlighted as key strategies.

Buprenorphine Use in the United States, 2010-2019.

BACKGROUND: Buprenorphine is effective for the treatment of opioid use disorder and chronic pain, has a safer pharmacological profile than full mu-opioid agonists, and can now be prescribed by any US provider with a Drug Enforcement Administration license. This study aimed to examine a decade of buprenorphine prescribing patterns in the United States. METHODS: We abstracted opioid and buprenorphine prescribing patterns, including patient characteristics, from the 2010-2019 National Ambulatory Medical Care Survey, a national probability sample of non-federal, ambulatory encounters. DISCUSSION: Among 248,164 ambulatory encounters, opioids were prescribed 2.6%-4.3% of the time with a rate that peaked in 2013 and has been steadily declining. Buprenorphine was infrequently prescribed. Patients receiving buprenorphine were predominantly male (59%), white (70%), younger in age, and had higher rates of substance use disorder (72%). CONCLUSION: Buprenorphine is infrequently used, despite being effective for pain and safer than full mu-opioid agonists. The Drug Enforcement Administration recently ended the requirement for prescribers to obtain an X-waiver, which may increase the rate of buprenorphine use among US practitioners.

Two formulations of the agricultural pesticide adjuvant, Toximul, reduce the glycogen content of HepG2 cells.

Young mice exposed dermally to the Toximul (Tox) class of agricultural pesticide adjuvants have reduced levels of hepatic glycogen, a marker of subclinical toxicity. The present study determined whether these effects on glycogen also occurred in cultured HepG2 cells. Exposure (3 hr) to Tox resulted in significant, concentration-dependent glycogen reductions (up to 70%) relative to control values (76 +/- 3 microg glycogen/mg protein). These reductions did not appear to be due to loss of cell viability, and were reversible with Tox removal. Two different formulations of Tox (3409F and MP-A) differed significantly in the magnitudes of glycogen reduction in the HepG2 cells.

The pesticide adjuvant, Toximul, alters hepatic metabolism through effects on downstream targets of PPARalpha.

Previous studies demonstrated that chronic dermal exposure to the pesticide adjuvant (surfactant), Toximul (Tox), has significant detrimental effects on hepatic lipid metabolism. This study demonstrated that young mice dermally exposed to Tox for 12 days have significant increases in expression of peroxisomal acyl-CoA oxidase (mRNA and protein), bifunctional enzyme (mRNA) and thiolase (mRNA), as well as the P450 oxidizing enzymes Cyp4A10 and Cyp4A14 (mRNA and protein). Tox produced a similar pattern of increases in wild type adult female mice but did not induce these responses in PPARalpha-null mice. These data support the hypothesis that Tox, a heterogeneous blend of nonionic and anionic surfactants, modulates hepatic metabolism at least in part through activation of PPARalpha. Notably, all three groups of Tox-treated mice had increased relative liver weights due to significant accumulation of lipid. This could be endogenous in nature and/or a component(s) of Tox or a metabolite thereof. The ability of Tox and other hydrocarbon pollutants to induce fatty liver despite being PPARalpha agonists indicates a novel consequence of exposure to this class of chemicals, and may provide a new understanding of fatty liver in populations with industrial exposure.

Effects of insulin-like growth factor-type 1 on weight gain and hepatic glycogen during early development in a surfactant/virus mouse model of acute liver failure: correlation with mortality.

Acute liver failure (ALF) was reproduced in young mice exposed daily for 12 days to the industrial surfactant, Toximul 3409F (Tox), and infected on postnatal day (P) 14 with sublethal doses of mouse-adapted human influenza B (Lee) virus (FluB). Combined Tox + FluB treatment potentiated mortality due to non-necrotic ALF. This study tested the hypothesis that mortality would decline if the known losses in energy production due to compromised fatty-acid beta-oxidation were compensated by pharmacological manipulation of hepatic glycogen stores. Glycogen levels, body weights, and mortality were determined without and with injections of insulin-like growth factor-1 (IGF-1). On P25, 13 days after Tox exposure ceased, glycogen levels (mg/100mg) were: 4.0 (control), 1.7 (Tox), 4.3 (FluB), and 2.9 (Tox + FluB). Corresponding cumulative mortalities were 0, 14, 2, and 38%. Following daily IGF-1 injections from P12 to P17, liver glycogen levels on P25 were: 3.5 (IGF-1), 3.9 (IGF-1 + Tox), 12.3 (IGF-1 + FluB), and 5.6 (IGF-1 + Tox + FluB). Unexpectedly, IGF-1 treatment increased mortality to 67% (IGF-1), 89% (IGF-1 + Tox), 63% (IGF-1 + FluB), and 81% (IGF-1 + Tox + FluB). For all groups there was a significant correlation between mortality and poor weight gain. This is the first report of persistent glycogen reductions after surfactant exposure and withdrawal. Their role in potentiating FluB-induced mortality remains to be established.

Fish oil containing phytosterol esters alters blood lipid profiles and left ventricle generation of thromboxane a(2) in adult guinea pigs.

This study was designed to investigate the lipid-lowering ability of a novel dietary ingredient composed of phytosterols esterified to (n-3) polyunsaturated fatty acids (PUFA) [PS(n-3)]. Adult guinea pigs were fed a test diet supplemented with PS(n-3) (25 g/kg) and corn oil (CO, 5 g/kg), whereas the diet fed to control guinea pigs was supplemented with CO only (30 g/kg). Cholesterol was added to both diets (0.8 g/kg). After 3-4 wk of consuming the diets, serum total cholesterol (TC) and triacylglycerol (TAG) in the PS(n-3) group were 36 and 29% lower, respectively, than levels in controls (P < 0.05). The lower TC levels in the PS(n-3) group reflected a 38% reduction in non-HDL cholesterol (non-HDL-C), whereas the HDL-C concentration was unaffected. Analysis of cardiac left ventricle indicated that generation of the proaggregatory, arrhythmic eicosanoid, thromboxane A(2), was >60% lower in the PS(n-3)-supplemented guinea pigs than in CO controls (P < 0.001). This study demonstrates that the TAG-lowering and eicosanoid-modifying properties of the fish oil (n-3) PUFA are retained when they are provided in the diet in ester linkage with hypocholesterolemic phytosterols.

Differential effects of docosahexaenoic acid on contractions and L-type Ca2+ current in adult cardiac myocytes.

UNLABELLED: Beneficial effects of n-3 polyunsaturated fatty acids in Ca2+ overload have been attributed to blockade of L-type Ca2+ current (I(Ca-L)). However, cardiac contractions may be maintained despite block of I(Ca-L). OBJECTIVE: This study investigates the cellular basis by which docosahexaenoic acid (DHA), a representative n-3 polyunsaturated fatty acid, inhibits I(Ca-L) while preserving contraction. METHODS: Experiments were conducted in adult guinea pig ventricular myocytes with Na+ currents blocked. Contractions initiated by the voltage-sensitive release mechanism (VSRM) and calcium-induced calcium release (CICR) triggered by I(Ca-L), were activated separately with voltage clamp techniques. RESULTS: DHA (10 microM) inhibited I(Ca-L) and CICR contractions but not VSRM contractions. CICR contractions exhibited a bell-shaped voltage-dependence. However, in the presence of DHA, only contractions with a sigmoidal voltage-dependence characteristic of the VSRM remained. These contractions exhibited inactivation properties characteristic of the VSRM. DHA abolished I(Ca-L) elicited by test steps from -40 mV. Block was voltage-dependent, as residual I(Ca-L) was elicited by steps from -70 mV. Cd2+ inhibited residual current, but not contractions initiated by the same activation steps. CONCLUSION: Preservation of VSRM contractions during block of I(Ca-L), may explain the ability of n-3 polyunsaturated fatty acids to inhibit Ca2+ influx while preserving cardiac contractile function.