Raymond G. Murphy VA Medical Center

Previously, two reports proposed a four-stream dialysis fluid delivery system consisting of an acid concentrate, a base concentrate, a sodium chloride concentrate, and product water for correcting dysnatremias and metabolic acid-base disorders separately, by hemodialysis. This report describes a new method for the clinical use of the previously reported four-stream dialysis fluid delivery system to treat concurrently dysnatremias and metabolic acid-base disturbances by hemodialysis. Pumps attached to each concentrate are designed to control its flow rate. Formulas were derived to determine the flow rate of each of the pumps controlling the flows of the product water ( W ), the base concentrate ( B ), and the sodium chloride concentrate ( S ) for any prescribed combination of sodium and bicarbonate concentrations is the final dialysis fluid. In this scheme, the flow rate of the acid concentrate ( A ), the concentrations of its contents in the final dialysis fluid remain constant. The flow rate ratio W:S:B:A remains also constant at 45 (i.e., 45X). The formulas were entered in an EXCEL flow sheet which determines the flow rate ratio W:S:B:A for any desired combination of sodium and bicarbonate concentrations in the dialysis fluid. The upper and lower limits of the concentrations of sodium and bicarbonate in the dialysis fluid were computed. The system has not been applied clinically. Measurements of any electrolyte concentrations have not been made. This system makes the treatment of profound dysnatremias, metabolic acid-base disorders, and combined dysnatremias and metabolic acid-base disorders feasible. The clinical application of the system demands prior invitro or exvivo studies plus fastidious and expert attention to ensure safe and dependable application.

Editorial on the Research Topic Dysnatremias and related disordersKheetan et al. reviewed the following issues encountered in hyponatremia: (a) The pathophysiological mechanisms involved in reversing the swelling of brain cells, which is the source of the clinical manifestations of hyponatremia, in acute and chronic hyponatremia.(b) The changes in various osmolytes during and following the development of hyponatremia.These changes define acute and chronic hyponatremia.Hyponatremia lasting longer than 48 h is chronic.The changes in brain organic osmolytes during development of hyponatremia determine the distinction between acute and chronic hyponatremia.(c) The influence of patient gender on the severity of hyponatremia.(d) The adverse effects of rapid correction of chronic hyponatremia on brain astrocytes, which may lead to myelinolysis.And (e) the methods for treating hyponatremia.They concluded that distinction between acute hyponatremia, which requires rapid correction, and chronic hyponatremia, which should be corrected slowly, is critical.

Isolated lateral-sided knee pain is a unique problem following total knee arthroplasty (TKA). Reported causes include soft tissue impingement against extruded cement, an overhanging tibial tray, remnant osteophytes rubbing against the iliotibial band (ITB), popliteal tendon impingement, fabella syndrome, and synovial tissue impingement in the lateral gutter. In addition, iliotibial band traction syndrome secondary to guided motion Bi-cruciate stabilizing knee arthroplasty has been recognized as a new clinical entity. Initial work up should include ruling out the most common causes of painful TKA including infection, aseptic loosening, and instability. Radiographs and CT scan are utilized to identify potential source of pain. Ultrasound evaluation (with elicited probe tenderness) can increase diagnostic accuracy. Ultrasound guided local anesthetic injections can confirm the source of pain. Anti-inflammatory medications, physical therapy with ITB stretches, and therapeutic local steroid injections are initial treatment modalities. Satisfactory resolution of symptoms may require surgical intervention directed at the specific cause and may avoid the morbidity associated with revision TKA.

BackgroundHydroxychloroquine (HCQ) is commonly used for patients with autoimmune conditions. Long-term use of HCQ can cause retinal toxicity, but this risk can be reduced if high doses are avoided.ObjectiveWe developed and piloted an electronic health record–based dashboard to improve the safe prescribing of HCQ within the Veterans Health Administration (VHA). We observed pilot facilities over a 1-year period to determine whether they were able to improve the proportion of patients receiving inappropriate doses of HCQ.MethodsPatients receiving HCQ were identified from the VHA corporate data warehouse. Using PowerBI (Microsoft Corp), we constructed a dashboard to display patient identifiers and the most recent HCQ dose and weight (flagged if ≥5.2 mg/kg/day). Six VHA pilot facilities were enlisted to test the dashboard and invited to participate in monthly webinars. We performed an interrupted time series analysis using synthetic controls to assess changes in the proportion of patients receiving HCQ ≥5.2 mg/kg/day between October 2020 and November 2021.ResultsAt the start of the study period, we identified 18,525 total users of HCQ nationwide at 128 facilities in the VHA, including 1365 patients at the 6 pilot facilities. Nationwide, at baseline, 19.8% (3671/18,525) of patients were receiving high doses of HCQ. We observed significant improvements in the proportion of HCQ prescribed at doses ≥5.2 mg/kg/day among pilot facilities after the dashboard was deployed (–0.06; 95% CI –0.08 to –0.04). The difference in the postintervention linear trend for pilot versus synthetic controls was also significant (–0.06; 95% CI –0.08 to –0.05).ConclusionsThe use of an electronic health record–based dashboard reduced the proportion of patients receiving higher than recommended doses of HCQ and significantly improved performance at 6 VHA facilities. National roll-out of the dashboard will enable further improvements in the safe prescribing of HCQ.

Chimeric antigen receptor (CAR) T-cells are now a well-established treatment for hematologic malignancies. Their use in clinical practice has expanded quite rapidly and hospitals have developed CAR T-cell protocols to evaluate patients for associated toxicities, and particularly for neurotoxicity. There are many variables that influence the risk for developing this complication, many of which are not fully understood. The severity can be related to a particular product. Clinical vigilance is critical to facilitate early recognition of neurotoxicity, hence the importance of pre-CAR T-cell neurological evaluation of each patient. While details of such an evaluation may slightly differ between institutions, generally a comprehensive neurological evaluation including assessment of cognitive abilities along with magnetic resonance imaging (MRI) of the brain is a gold standard. Management of neurotoxicity requires a well-orchestrated team approach with specialists from oncology, neurology, oftentimes neurosurgery and neuro-intensive care. Diagnostic work-up frequently includes detailed neurologic evaluation with comparison to the baseline assessment, imaging of the brain, electroencephalogram, and lumbar puncture. While steroids are uniformly used for treatment, many patients also receive tocilizumab for an underlying and frequently concomitant cytokine release syndrome (CRS) in addition to symptom-driven supportive care. Novel CAR T-cell constructs and other agents allowing for potentially lower risk of toxicity are being explored. While neurotoxicity is predominantly an early, and reversible, event, a growing body of literature suggests that late neurotoxicity with variable clinical presentation can also occur.

IMPORTANCEPosttraumatic stress disorder (PTSD) is a prevalent and seriousmental health problem. Although there are effective psychotherapies forPTSD, there is little information about their comparative effectiveness.OBJECTIVETo compare the effectiveness of prolonged exposure (PE) vs cognitiveprocessing therapy (CPT) for treating PTSD in veterans.DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial assessed the comparativeeffectiveness of PE vs CPT among veterans with military-related PTSDrecruited from outpatient mental health clinics at 17 Department of VeteransAffairs medical centers across the US from October 31, 2014, to February 1,2018, with follow-up through February 1, 2019. The primary outcome wasassessed using centralized masking. Tested hypotheses were prespecifiedbefore trial initiation. Data were analyzed from October 5, 2020, to May 5,2021.INTERVENTIONSParticipants were randomized to 1 of 2 individualcognitive-behavioral therapies, PE or CPT, delivered according to a flexibleprotocol of 10 to 14 sessions.MAIN OUTCOMES AND MEASURESThe primary outcome was change in PTSD symptom severity on theClinician-Administered PTSD Scale for DSM-5 (CAPS-5) frombefore treatment to the mean after treatment across posttreatment and 3- and6-month follow-ups. Secondary outcomes included other symptoms, functioning,and quality of life.RESULTSAnalyses were based on all 916 randomized participants (730 [79.7%]men and 186 [20.3%] women; mean [range] age 45.2 [21–80] years), with455 participants randomized to PE (mean CAPS-5 score at baseline, 39.9 [95%CI, 39.1–40.7] points) and 461 participants randomized to CPT (meanCAPS-5 score at baseline, 40.3 [95% CI, 39.5–41.1] points). PTSDseverity on the CAPS-5 improved substantially in both PE (standardized meandifference [SMD], 0.99 [95% CI, 0.89–1.08]) and CPT (SMD, 0.71 [95%CI, 0.61–0.80]) groups from before to after treatment. Meanimprovement was greater in PE than CPT (least square mean, 2.42 [95% CI,0.53–4.31]; P = .01), but the difference was notclinically significant (SMD, 0.17). Results for self-reported PTSD symptomswere comparable with CAPS-5 findings. The PE group had higher odds ofresponse (odds ratio [OR], 1.32 [95% CI, 1.00–1.65];P < .001), loss of diagnosis (OR, 1.43 [95% CI,1.12–1.74]; P < .001), and remission (OR,1.62 [95% CI, 1.24–2.00]; P < .001) comparedwith the CPT group. Groups did not differ on other outcomes. Treatmentdropout was higher in PE (254 participants [55.8%]) than in CPT (215participants [46.6%]; P < .01). Three participantsin the PE group and 1 participant in the CPT group were withdrawn fromtreatment, and 3 participants in each treatment dropped out owing to seriousadverse events.CONCLUSIONS AND RELEVANCEThis randomized clinical trial found that although PE wasstatistically more effective than CPT, the difference was not clinicallysignificant, and improvements in PTSD were meaningful in both treatmentgroups. These findings highlight the importance of shared decision-making tohelp patients understand the evidence and select their preferredtreatment.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT01928732

IntroductionPositive airway pressure (PAP) compliance for the treatment of sleep apnea at the Albuquerque Veterans Affairs (VA) Sleep Medicine clinic has been observed to be lower in new setup patients after the onset of the COVID-19 pandemic. The reasons for decreased PAP compliance during the COVID-19 pandemic are unclear. The primary outcome will be to identify if there is a common reason that patients at the Albuquerque VA were less compliant with PAP after the onset of the COVID-19 pandemic.MethodsCompliance data for 4/1/2020 through 9/30/2020 was compared to compliance data for 4/1/2019 through 9/30/2019. Compliance after PAP machine setup was confirmed to be lower during the 2020 time period. Noncompliant patients will be selected by setup type, new versus machine replacement, and surveyed for reasons for noncompliance. The survey will be conducted at the Albuquerque VA Sleep Center and will include questions regarding beliefs, barriers, and challenges with the use of PAP therapy during the coronavirus pandemic. The definition for initial PAP compliance will be the use of PAP therapy for greater than or equal to four hours per night on at least 70% of nights.ResultsFor the 6-month time period of 4/1/2019 through 9/30/2019, there were 758 PAP setups at the Albuquerque VA. The 30-day compliance for the 758 setups was found to be 61.4%. Comparatively, for the six-month period of 4/1/2020 through 9/30/2020, there were 462 setups with a 30-day compliance result of 49.7%. A survey consisting of questions designed to elicit barriers to use as well as beliefs regarding PAP and COVID-19 will be administered to 20% (n = 46) of the non-compliant patients who were set up with a PAP machine during the 2020 study period.ConclusionPAP compliance after machine setup was lower at the Albuquerque VA sleep center in 2020 versus 2019 (49.7% versus 61.4%). The reasons for the lower observed compliance are attributed to the effects of the coronavirus pandemic. A random sampling of the non-compliant patients during the 2020 time period will be performed and the results will be presented once available.Support (if any)None