Patient Portal Use and Risk of Readmissions in Decompensated Cirrhosis: Retrospective Study.

BACKGROUND: Patient portals are a common electronic medical record tool that allow for the asynchronous exchange of health information between patients and their health care teams. Patients can leverage patient portals to perform tasks such as viewing test results, reviewing clinical notes, and messaging their health care team. The impact of patient portal use on clinical outcomes in cirrhosis is unknown. OBJECTIVE: In this study, we evaluated the relationship between patient portal use patterns and readmissions in cirrhosis. METHODS: We identified 131 patients with decompensated cirrhosis with an index cirrhosis-related admission between May 1, 2018, and May 1, 2019. We then examined patient portal enrollment and use data during the 6-month period preceding the study period. Portal functions evaluated included sending a message, reading a message, and reading a test result. Use was categorized as active (sending a message) and passive (reading a message or test result) and was further stratified as no, moderate, or frequent use based on the frequency of portal function use compared to the mean. The primary outcomes were 90-day and overall readmissions, adjusted for age, model for end-stage liver disease-sodium, alcohol-related cirrhosis etiology, ascites, and hepatic encephalopathy. Portal functions assessed included sending a message, reading a message, and reading a result; the total number of times a portal function was performed was divided by the number of months the patient was enrolled in the patient portal during the 6-month period. RESULTS: The study population was 50.4% (66/131) female, with a mean age of 58 years. Enrollment in the patient portal was 63.4% (83/131), and there was no significant difference in enrollment based on clinical or demographic characteristics. For the entire cohort, 14.5% (19/131) and 22.1% (29/131) of patients were moderate and frequent active users, respectively. Of those enrolled in the patient portal, 97.6% (81/83) of patients were moderate or frequent passive users for both reading a message and reading a test result. Moderate active users had less 90-day readmissions (odds ratio 0.77, 95% CI 0.60-1.00) and overall readmissions (subdistribution hazard ratio 0.42, 95% CI 0.21-0.84), compared to nonactive users. There was no relationship between readmissions and passive use. CONCLUSIONS: Passive use of the patient portal is very high but is not associated with the risk of readmissions in people with decompensated cirrhosis. However, moderately active use of the patient portal is associated with a reduced risk of readmissions. Further work is needed to identify possible confounders and refine key use behaviors that may be protective with regard to the risk of readmission in this population.

Two Cases of COVID-19 Patients With Associated Purpura Fulminans.

Purpura fulminans (PF) is a life-threatening emergency involving coagulopathy and widespread skin necrosis. Early treatment, especially surgical management, is imperative as prognosis can be very poor. PF is most commonly associated with severe bacterial illness; however, viral causes are also possible. Currently in the literature, there have only been a handful of PF cases associated with COVID-19. We present two cases of PF in the setting of COVID-19 infection. Both patients had a history of underlying coagulopathies. PF can be a sign of underlying coagulopathy in a COVID-19 patient, who is already at increased risk for thromboembolic events due to the inflammatory nature of COVID itself. Due to how quickly PF can develop into life-threatening necrosis and multiorgan failure, it is imperative that these patients are referred early to a burn center for more advanced care.

Rate of Successful Extubation in Mechanically Ventilated Patients with Cirrhosis and Hepatic Coma.

BACKGROUND: The prognosis of critically ill patients with cirrhosis who require mechanical ventilation is guarded. Data are lacking for the optimal therapeutic approach to hepatic encephalopathy (HE) in the ventilated patient. METHODS: Retrospective cohort analysis of 314 encounters (298 patients) with cirrhosis who underwent mechanical ventilation in a medical ICU and were ordered at least 1 dose of lactulose. Hazard of extubation alive was determined using a competing risk model. Primary exposures were HE therapy (lactulose and rifaximin) which were adjusted for the indication for ventilation (HE, procedures, respiratory failure), age, MELD-Na, and compensation status. RESULTS: Indications for ventilation were 22.3% for grade 4 HE, 29.9% for procedures, and 47.8% for respiratory or cardiovascular failure. Median length of intubation was 2.63 days; death rate on ventilator was 31.2%. Relative to intubation for procedure, hazard of extubation for intubation for HE was 0.34 (95% confidence interval (CI): 0.22-0.52) and 0.33 (CI: 0.23-0.47) for respiratory failure. Hazard of extubation for rifaximin administration within 24-h after intubation was significant at 1.74 (1.21-2.50). Lactulose dosing was not significant for hazard of extubation. DISCUSSION: Mortality is high for all patients with cirrhosis requiring mechanical ventilation, including those intubated for grade 4 HE. Efforts to optimize the odds of successful extubation are urgently needed. Our findings suggest improved incidence of extubation associated with rifaximin administration in the first 24-h after intubation. Prospective, multi-center data to confirm these findings in this vulnerable population are warranted.

Follow-up colonoscopy after an abnormal stool-based colorectal cancer screening result: analysis of steps in the colonoscopy completion process.

BACKGROUND: Delays in receiving follow-up colonoscopy after an abnormal fecal immunochemical test (FIT) result are associated with increased colorectal cancer incidence and mortality. Little is known about patterns of follow-up colonoscopy completion in federally qualified health centers. METHODS: We abstracted the medical records of health center patients, aged 50-75 years, who had an abnormal FIT result between August 5, 2017 and August 4, 2018 (N = 711). We assessed one-year rates of colonoscopy referral, pre-procedure visit completion, colonoscopy completion, and time to colonoscopy; associations between these outcomes and patient characteristics; and reasons for non-completion found in the medical record. RESULTS: Of the 711 patients with an abnormal FIT result, 90% were referred to colonoscopy, but only 52% completed a pre-procedure visit, and 43% completed a colonoscopy within 1 year. Median time to colonoscopy was 83 days (interquartile range: 52-131 days). Pre-procedure visit and colonoscopy completion rates were relatively low in patients aged 65-75 (vs. 50-64), who were uninsured (vs. insured) or had no clinic visit in the prior year (vs. ≥ 1 clinic visit). Common reasons listed for non-completion were that the patient declined, or the provider could not reach the patient. DISCUSSION: Efforts to improve follow-up colonoscopy rates in health centers might focus on supporting the care transition from primary to specialty gastroenterology care and emphasize care for older uninsured patients and those having no recent clinic visits. Our findings can inform efforts to improve follow-up colonoscopy uptake, reduce time to colonoscopy receipt, and save lives from colorectal cancer. TRIAL REGISTRATION: National Clinical Trial (NCT) Identifier: NCT03925883.

Peritoneal Dialysis Zoonotic Bacterial Peritonitis with Staphylococcus pseudintermedius.

We present the first reported case of peritoneal dialysis-associated peritonitis caused by Staphylococcus pseudintermedius, an organism that had been misclassified as S. aureus in the past. S. pseudintermedius is well recognized in the veterinary literature and noted as flora in the mouth, nares, and anus of domesticated animals. It has been associated with soft tissue infections in pets and is now being reported in increased frequency as the causative agent in various human infections. It also has a different antibiotic sensitivity profile. The patient had close contact with her pet dog and was successfully treated with intravenous antibiotics in the hospital followed by oral doxycycline for 10 days after discharge. The patient has not had any recurrent infection after obtaining and applying appropriate hygienic education and precautions.

Relative contributions of severe dopaminergic neuron ablation and dopamine depletion to cognitive impairment.

Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons and produces a movement disorder and cognitive impairment that becomes more extensive with the duration of the disease. To what extent cognitive impairment in advanced PD can be attributed to severe loss of dopamine (DA) signaling is not well understood. Furthermore, it is unclear if the loss of DA neurons contributes to the cognitive impairment caused by the reduction in DA signaling. We generated genetic mouse models with equally severe chronic loss of DA achieved by either extensive ablation of DA neurons or inactivation of DA synthesis from preserved neurons and compared their motor and cognitive performance. Motor behaviors were equally blunted in both models, but we observed that DA neuron ablation caused more severe cognitive deficits than DA depletion. Both models had marked deficits in cue-discrimination learning. Yet, deficits in cue-discrimination learning were more severe in mice with DA neuron ablation and only mice with DA neuron ablation had drastically impaired performance in spatial learning, spatial memory and object memory tests. These results indicate that while a severe reduction in DA signaling results in motor and cognitive impairments, the loss of DA neurons promotes more extensive cognitive deficits and suggest that a loss of additional factors that depend on DA neurons may participate in the progressive cognitive decline found in patients with PD.

Dopamine dependency for acquisition and performance of Pavlovian conditioned response.

During Pavlovian conditioning, pairing of a neutral conditioned stimulus (CS) with a reward leads to conditioned reward-approach responses (CRs) that are elicited by presentation of the CS. CR behaviors can be sign tracking, in which animals engage the CS, or goal tracking, in which animals go to the reward location. We investigated CR behaviors in mice with only ∼5% of normal dopamine in the striatum using a Pavlovian conditioning paradigm. These mice had severely impaired acquisition of the CR, which was ameliorated by pharmacological restoration of dopamine synthesis with l-dopa. Surprisingly, after they had learned the CR, its expression decayed only gradually in following sessions that were conducted without l-dopa treatment. To assess specific contributions of dopamine signaling in the dorsal or ventral striatum, we performed virus-mediated restoration of dopamine synthesis in completely dopamine-deficient (DD) mice. Mice with dopamine signaling only in the dorsal striatum did not acquire a CR, whereas mice with dopamine signaling only in in the ventral striatum acquired a CR. The CR in mice with dopamine signaling only in the dorsal striatum was restored by subjecting the mice to instrumental training in which they had to interact with the CS to obtain rewards. We conclude that dopamine is essential for learning and performance of CR behavior that is predominantly goal tracking. Furthermore, although dopamine signaling in the ventral striatum is sufficient to support a CR, dopamine signaling only in the dorsal striatum can also support a CR under certain circumstances.

Acetylcholine encodes long-lasting presynaptic plasticity at glutamatergic synapses in the dorsal striatum after repeated amphetamine exposure.

Locomotion and cue-dependent behaviors are modified through corticostriatal signaling whereby short-term increases in dopamine availability can provoke persistent changes in glutamate release that contribute to neuropsychiatric disorders, including Parkinson's disease and drug dependence. We found that withdrawal of mice from repeated amphetamine treatment caused a chronic presynaptic depression (CPD) in glutamate release that was most pronounced in corticostriatal terminals with a low probability of release and lasted >50 d in treated mice. An amphetamine challenge reversed CPD via a dopamine D1-receptor-dependent paradoxical presynaptic potentiation (PPP) that increased corticostriatal activity in direct pathway medium spiny neurons. This PPP was correlated with locomotor responses after a drug challenge, suggesting that it may underlie the sensitization process. Experiments in brain slices and in vivo indicated that dopamine regulation of acetylcholine release from tonically active interneurons contributes to CPD, PPP, locomotor sensitization, and cognitive ability. Therefore, a chronic decrease in corticostriatal activity during withdrawal is regulated around a new physiological range by tonically active interneurons and returns to normal upon reexposure to amphetamine, suggesting that this paradoxical return of striatal activity to a more stable, normalized state may represent an additional source of drug motivation during abstinence.

Inhalation injury severity and systemic immune perturbations in burned adults.

OBJECTIVE: We aimed to determine whether the severity of inhalation injury evokes an immune response measurable at the systemic level and to further characterize the balance of systemic pro- and anti-inflammation early after burn and inhalation injury. BACKGROUND: Previously, we reported that the pulmonary inflammatory response is enhanced with worse grades of inhalation injury and that those who die of injuries have a blunted pulmonary immune profile compared with survivors. METHODS: From August 2007 to June 2011, bronchoscopy was performed on 80 patients admitted to the burn intensive care unit when smoke inhalation was suspected. Of these, inhalation injury was graded into 1 of 5 categories (0, 1, 2, 3, and 4), with grade 0 being the absence of visible injury and grade 4 corresponding to massive injury. Plasma was collected at the time of bronchoscopy and analyzed for 28 immunomodulating proteins via multiplex bead array or enzyme-linked immunosorbent assay. RESULTS: The concentrations of several plasma immune mediators were increased with worse inhalation injury severity, even after adjusting for age and % total body surface area (TBSA) burn. These included interleukin (IL)-1RA (P = 0.002), IL-6 (P = 0.002), IL-8 (P = 0.026), granulocyte colony-stimulating factor (P = 0.002), and monocyte chemotactic protein 1 (P = 0.007). Differences in plasma immune mediator concentrations in surviving and deceased patients were also identified. Briefly, plasma concentrations of IL-1RA, IL-6, IL-8, IL-15, eotaxin, and monocyte chemotactic protein 1 were higher in deceased patients than in survivors (P < 0.05 for all), whereas IL-4 and IL-7 were lower (P < 0.05). After adjusting for the effects of age, % TBSA burn, and inhalation injury grade, plasma IL-1RA remained significantly associated with mortality (odds ratio, 3.12; 95% confidence interval, 1.03-9.44). Plasma IL-1RA also correlated with % TBSA burn, inhalation injury grade, fluid resuscitation, Baux score, revised Baux score, Denver score, and the Sequential Organ Failure Assessment score. CONCLUSIONS: The severity of smoke inhalation injury has systemically reaching effects, which argue in favor of treating inhalation injury in a graded manner. In addition, several plasma immune mediators measured early after injury were associated with mortality. Of these, IL-1RA seemed to have the strongest correlation with injury severity and outcomes measures, which may explain the blunted pulmonary immune response we previously found in nonsurvivors.

Regulating molecular diagnostic assays: developing a new regulatory structure for a new technology.

Molecular diagnostics are playing an increasingly important part in the practice of medicine. However, molecular diagnostics have not yet made the clinical impact that many had predicted. Multiple factors affect the uptake and utilization of molecular diagnostics, including government regulation. Current regulatory systems were not developed to optimize regulation of molecular diagnostics. This article recommends areas that should be carefully evaluated and appropriately revised, including risk assessment, review criteria and facilitating product improvements. The adoption of molecular diagnostics will be advanced as regulatory criteria become more predictable and their application becomes more consistent between products and over time.

Litigating the legality of compounding: the medical center pharmacy case.

The question of whether all compounded drugs are "new drugs" has been disputed in the United states for over 15 years. The Federal Food, Drug, and Cosmetic Act generally requires that "new drugs" obtain U.S. Food and Drug Administration approval before being sold in the U.S. Between 1938 and the late 1980s, the U.S. Food and Drug Adminsitration did not asert that compounded drugs are subject to the drug provisions. Then the U.S.Food and Drug Administration developed and advanced a new theory. As articulated in a 1989 memorandum by a U.S. Food and Drug Administration attorney, the U.S. Food and Drug Administration could take the position that compounded drugs were new drugs and therefore subject to new drug approval requirements. Although the memorandum acknowledged that this represented a significant change in policy, the U.S.Food and Drug Administration adopted this legal theory. Their position that compounded drugs are new drugs led to a clash between the agency and compounding pharmacies. Congress appeared to settle this dispute in 1997 when it passed the Food and Drug Administration Modernization Act. This law contained a provision expempting pharmacies from the new drug approval requirements (and two other requirements) if they met certain critieria. Although the U.S. Food and Drug Administration has continued to maintain that is will not assert the "unapproved new drug" theory against the traditional compounding of drugs, it has invoked the "new drug" theory in many warning letters to pharmacies, including a series of heavily publicized warning letters issued the day before oral argument in the Medical Center Pharmacy case to the validity of the U.S. Food and Drug Administration's interpretation. The Fifth Circuit decision in the Medical Center Pharmcy case will provide an answer. It may not, however, be the final answer.