Hemodialysis using a low bicarbonate dialysis bath: Implications for acid-base homeostasis.

The low bath bicarbonate concentration ([ HCO3- ]) used by a nephrology group in Japan (25.5 mEq/L), coupled with a bath [acetate] of 8 mEq/L, provided an opportunity to study the acid-base events occurring during hemodialysis when HCO3- flux is from the patient to the bath. We used an analytic tool that allows calculation of HCO3- delivery during hemodialysis and the physiological response to it in 17 Japanese outpatients with an average pre-dialysis blood [ HCO3- ] of 25 mEq/L. Our analysis demonstrates that HCO3- addition is markedly reduced and that all of it comes from acetate metabolism. The HCO3- added to the extracellular fluid during treatment (19.5 mEq) was completely consumed by H+ mobilization from body buffers. In contrast to patients dialyzing with higher bath [ HCO3- ] values in the US and Europe, organic acid production was suppressed rather than stimulated. Dietary analysis indicates that these patients are in acid balance due to the alkaline nature of their diet. In a larger group of patients using the same bath solution, pre-dialysis blood [ HCO3- ] was lower, 22.2 mEq/L, but still in an acceptable range. Our studies indicate that a low bath [ HCO3- ] is well tolerated and can prevent stimulation of organic acid production.

Assessing Residents' Skills in Psychiatric Reasoning: the Tufts Test of Formulation and Treatment Planning.

OBJECTIVE: The authors aimed to develop an easily administered and scored written test of clinical reasoning for psychiatry residents and to explore its internal reliability and correlation with parameters of training. METHODS: The authors developed a case-based, multiple-choice test comprising 83 questions related to data gathering and interpretation, diagnosis, hypothesis generation and testing, and treatment planning. Postgraduate years 1-4 residents at 18 diverse residency programs, along with their Program Directors and/or Associate Program Directors, took the test. Outcome measures included internal reliability statistics, performance across levels of training, performance in different test categories, performance in programs with high vs. low emphasis on integrative case formulation, and performance in native English speakers vs. others. RESULTS: A total of 359 residents and 23 faculty members participated. The KR-20 statistic of 0.78 indicated that the test was internally reliable. Faculty performed better than residents, who began to approach faculty level only in their fourth year. Residents in programs with high emphasis on formulation and treatment planning tended to score better than those from low emphasis programs on hypothesis generation and testing, but not other categories of question. There was no evidence that non-native English speakers were at a disadvantage on the test. CONCLUSIONS: A novel test of formulation and treatment planning has met criteria for internal reliability and provided preliminary data about development of reasoning skills in residents. The authors hope that taking and discussing it will also be useful as a training exercise in integrative case formulation.

Changing dialysate composition to optimize acid-base therapy.

In response to rapid alkali delivery during hemodialysis, hydrogen ions (H+ ) are mobilized from body buffers and from stimulation of organic acid production in amounts sufficient to convert most of the delivered bicarbonate to CO2 and water. Release of H+ from nonbicarbonate buffers serves to back-titrate them to a more alkaline state, readying them to buffer acids that accumulate in the interval between treatments. By contrast, stimulation of organic acid production only serves to remove added bicarbonate (HCO3 - ) from the body; the organic anions produced by this process are lost into the dialysate, irreversibly acidifying the patient as well as diverting metabolic activity from normal homeostasis. We have developed an analytic tool to quantify these acid-base events, which has shown that almost two-thirds of the H+ mobilized during hemodialysis comes from organic acid production when bath bicarbonate concentration ([HCO3 - ]) is 32 mEq/L or higher. Using data from the hemodialysis patients we studied with our analytical model, we have simulated the effect of changing bath solute on estimated organic acid production. Our simulations demonstrate that reducing bath [HCO3 - ] should decrease organic acid production, a change we propose as beneficial to the patient. They also highlight the differential effects of variations in bath acetate concentration, as compared to [HCO3 - ], on the amount and rate of alkali delivery. Our results suggest that transferring HCO3 - delivery from direct influx to acetate influx and metabolism provides a more stable and predictable rate of HCO3 - addition to the patient receiving bicarbonate-based hemodialysis. Our simulations provide the groundwork for the clinical studies needed to verify these conclusions.

Acid-base homeostasis during hemodialysis: New insights into the mystery of bicarbonate disappearance during treatment.

In patients receiving hemodialysis, it has long been recognized that much more bicarbonate is delivered during treatment than ultimately appears in the blood. To gain insight into this mystery, we developed a model that allows a quantitative analysis of the patient's response to rapid alkalinization during hemodialysis. Our model is unique in that it is based on the distribution of bicarbonate in the extracellular fluid and assesses its removal from this compartment by mobilization of protons (H+ ) from buffers and other sources. The model was used to analyze the pattern of rise in blood bicarbonate concentration ([HCO3- ]), calculated from measurements of pH and PCO2 , in patients receiving standard bicarbonate hemodialysis. Model analysis demonstrated two striking findings: (1) 35% of the bicarbonate added during hemodialysis was due to influx and metabolism of acetate, despite its low concentration in the bath solution, because of the rapidly collapsing gradient for bicarbonate influx. (2) Almost 90% of the bicarbonate delivered to the patients was neutralized by H+ generation. Virtually all the new H+ came from intracellular sources and included both buffering and organic acid production. The small amount of added bicarbonate retained in the extracellular fluid increased blood [HCO3- ], on average, by 6 mEq/L in our patients. Almost all this rise occurred during the first 2 hours. Thereafter, blood [HCO3- ] changed minimally and always remained less than bath [HCO3- ]. This lack of equilibrium was due to the continued production of organic acid. Release of H+ from buffers is a reversible physiological response, restoring body alkali stores. By contrast, organic acid production is an irreversible process during hemodialysis and is metabolically inefficient and potentially catabolic. Our analysis underscores the need to develop new approaches for alkali repletion during hemodialysis that minimize organic acid production.

Conservation of Mass: An Important Tool in Renal Research.

The dialytic treatment of end-stage renal disease (ESRD) patients is based on control of solute concentrations and management of fluid volume. The application of the principal of conservation of mass, or mass balance, is fundamental to the study of such treatment and can be extended to chronic kidney disease (CKD) in general. This review discusses the development and use of mass conservation and transport concepts, incorporated into mathematical models. These concepts, which can be applied to a wide range of solutes of interest, represent a powerful tool for quantitatively guided studies of dialysis issues currently and into the future. Incorporating these quantitative concepts in future investigations is key to achieving positive control of known solutes, and in the analysis of such studies; to relate future research to known results of prior studies; and to help in the understanding of the obligatory physiological perturbations that result from dialysis therapy.

Experiences in global mental health.

Participating in Global Mental Health program development and education and training efforts is rewarding and exciting work. The author describes several global experiences he has engaged in over the past 30 years, which has focused on teaching and encouraging family therapy and mental health care that support human rights and promote human development as innovated and promoted by the Global Alliance for Behavioral Health, formerly the American Orthopsychiatric Association. The author learned through participation that merely presenting mental health information and treatment approaches through lecture presentation was not adequate to help professionals and advocates in low- and middle-income countries to build sustainable mental health care systems in their home regions. The author engaged in several collaborative program development efforts with local professionals at their invitation. These programs, consisting of multiyear partnerships based on the needs and culture of the home region, will be described in the article. The programs, based on relationships between local professionals and a U.S. team of experts in child mental health care, had long-term positive effects and were highly rewarding. The basis for these programs was an invitation by local professionals, followed by collaboration in setting the agenda for the U.S. professionals' visits, an on-going relationship in which local professionals trusted that the visitors want and need to understand the local cultural environment, and improvements that will be most helpful and sustainable. In this process, the author learned about the cultures he worked in and was a part of extremely meaningful and enlightening relationships and experiences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Understanding Families as Essential in Psychiatric Practice.

Family work is a critical component of psychiatric practice. It is important for psychiatrists to be able to understand the role of family relationships and family systems in individual development across the lifespan. Assessing family factors is an important part of developing a biopsychosocial formulation. Understanding family relationships provides a context for an individual's values and beliefs, which are important components of assessing the patient's mental health challenges. Dysfunctional family relationships can be precipitating or perpetuating factors for mental illness. On the other hand, positive family relationships can offer support, be protective, alleviate emotional and behavioral problems, and lead to improved outcomes. It is important for psychiatrists to be able to work effectively with families by providing support, understanding families' needs, assessing families' strengths and limitations, identifying issues requiring family-based intervention, and facilitating referral to a family therapist when necessary. By engaging families as resources and essential partners in treatment planning, the psychiatrist is able to enhance the quality and success of patient care. This article discusses the role of the psychiatrist in assessing family factors implicated in psychiatric illness; offers general context for understanding the response required by families for improving various emotional and behavioral challenges; and provides an overview of family-based interventions, including family psychoeducation and support, parent management training, and family therapy.

Dialog Across Cultures: Therapy for Diverse Families.

Child and adolescent psychiatrists (CAPs) work at the intersections of families, cultures, and systems, which affect engagement in care, assessment, and treatment planning. There are several practical strategies that CAPs can apply to practice cultural humility, to join with families, to facilitate difficult conversations and to work through misalignment. Culturally inclusive family-based care can promote greater understanding and lead to stronger outcomes with families as well as help mitigate mental health impact of structural racism and social inequities.

A cluster randomized controlled trial of child-focused psychiatric consultation and a school systems-focused intervention to reduce aggression.

BACKGROUND: While school-based anti-bullying programs are widely used, there have been few controlled trials of effectiveness. This study compared the effect of manualized School Psychiatric Consultation (SPC), CAPSLE (a systems and mentalization focused whole school intervention), and treatment-as-usual (TAU) in reducing aggression and victimization among elementary school children. METHOD: Participants were 1,345 third to fifth graders in nine elementary schools in a medium-sized Midwestern city who took part in a cluster-level randomized controlled trial with stratified restricted allocation, to assess efficacy after two years of active intervention and effectiveness after one year of minimal input maintenance intervention. Outcome measures included peer and self-reports of bullying, bystanding, and mentalizing behavior and classroom behavioral observations of disruptive and off-task behavior. RESULTS: CAPSLE moderated the developmental trend of increasing peer-reported victimization (p < .01), aggression (p < .05), self-reported aggression (p < .05) and aggressive bystanding (p < .05), compared to TAU schools. CAPSLE also moderated a decline in empathy and an increase in the percent of children victimized compared to SPC (p < .01) and TAU conditions (p < .01). Results for self-reported victimization, helpful bystanding, and beliefs in the legitimacy of aggression did not suggest significantly different changes among the study conditions over time. CAPSLE produced a significant decrease in off-task (p < .001) and disruptive classroom behaviors (p < .01), while behavioral change was not observed in SPC and TAU schools. Superiority with respect to TAU for victimization (p < .05), aggression (p < .01), and helpful (p < .05) and aggressive bystanding (p < .01) were maintained in the follow-up year. CONCLUSIONS: A teacher-implemented school-wide intervention that does not focus on disturbed children substantially reduced aggression and improved classroom behavior.

Structural basis for ether-a-go-go-related gene K+ channel subtype-dependent activation by niflumic acid.

Niflumic acid [2-((3-(trifluoromethyl)phenyl)amino)-3-pyridinecarboxylic acid, NFA] is a nonsteroidal anti-inflammatory drug that also blocks or modulates the gating of a wide spectrum of ion channels. Here we investigated the mechanism of channel activation by NFA on ether-a-go-go-related gene (ERG) K(+) channel subtypes expressed in Xenopus laevis oocytes using two-electrode voltage-clamp techniques. NFA acted from the extracellular side of the membrane to differentially enhance ERG channel currents independent of channel state. At 1 mM, NFA shifted the half-point for activation by -6, -18, and -11 mV for ERG1, ERG2, and ERG3 channels, respectively. The half-point for channel inactivation was shifted by +5 to +9 mV by NFA. The structural basis for the ERG subtype-specific response to NFA was explored with chimeric channels and site-directed mutagenesis. The molecular determinants of enhanced sensitivity of ERG2 channels to NFA were isolated to an Arg and a Thr triplet in the extracellular S3-S4 linker.

Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.

BACKGROUND: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death. METHODS AND RESULTS: Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits. CONCLUSIONS: This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.

Analyzing the true cost of delivering medications.

Reimbursement to providers for delivering medications in the dialysis field is a subject of current concern, with some payors limiting payment to an amount equaling the provider's acquisition cost. At the same time, some providers arbitrarily mark up medications by a large factor. For dialysis, as well as for the general medical field, an objective approach is required for both providers and payors to fairly set prices and reimbursement levels. This analysis evaluated all cost elements involved in the delivery of medications and determined that an increase over the acquisition cost is appropriate for pricing and reimbursement. The increase has 2 parts: a fixed cost associated with resources required for a medication irrespective of its cost and a markup on the acquisition price. The conclusion of this analysis is that an increase over acquisition cost in reimbursement of providers for delivering medications is required to fairly compensate them for their actual costs and avoid compelling them to either incur a loss or cost shift by overcharging some payors to compensate for underpayment by others. Planned adjustments in Medicare reimbursement for dialysis may not recognize this reality.

Tailoring of Atlantic salmon (Salmo salar L.) flesh lipid composition and sensory quality by replacing fish oil with a vegetable oil blend.

Atlantic salmon (Salmo salar L.) juveniles were fed either 100% fish oil (FO), 75% vegetable oil (VO), or 100% VO throughout their life cycle to harvest weight followed by a finishing diet period when all groups were fed 100% FO. The two experimental VO diets were tested at two different locations (Scotland and Norway) against the same control diet (100% FO). The VO blend was composed of rapeseed oil, palm oil, and linseed oil using capelin oil as a control for fatty acid class compositions. Flesh fatty acid profiles were measured regularly throughout the experiment, with the times of sampling determined by changes in pellet size/lipid content and fish life stage. Growth and mortality rates were not significantly affected by dietary fatty acid compositions throughout the life cycle, except during the seawater winter period in Norway when both growth and protein utilization were increased in salmon fed 100% VO compared to 100% FO. Flesh fatty acid composition was highly influenced by that of the diet, and after the finishing diet period the weekly intake recommendations of very long chain n-3 polyunsaturated fatty acid (VLCn-3 PUFA) for human health were 80 and 56% satisfied by a 200 g meal of 75% VO and 100% VO flesh, respectively. No effect on flesh astaxanthin levels was observed in relation to changing dietary oil sources. Sensory evaluation showed only minor differences between salmon flesh from the dietary groups, although prior to the finishing diet period, flesh from 100% VO had less rancid and marine characteristics and was preferred over flesh from the other dietary groups by a trained taste panel. After the finishing diet period, the levels of typical vegetable oil fatty acids in flesh were reduced, whereas those of VLCn-3 PUFA increased to levels comparable with a 100% FO fed salmon. No differences in any of the sensory characteristics were observed between dietary groups. By blending VOs to provide balanced levels of dietary fatty acids, up to 100% of the fish oil can be replaced by the VO blend without compromising growth or flesh quality. At the same time, 75% of the dietary fish oil can be replaced without compromising flesh VLCn-3 PUFA content, thereby providing a beneficial nutritional profile for human consumption.

A family approach to severe mental illness in post-war Kosovo.

This study describes the effects of a psychoeducational multiple-family group program for families of people with severe mental illness in post-war Kosovo that was developed by a Kosovar-American professional collaborative. The subjects were 30 families of people with severe mental illnesses living in two cities in Kosovo. All subjects participated in multiple-family groups and received family home visits. The program documented medication compliance, number of psychiatric hospitalizations, family mental health services use, and several other characteristics, for the year prior to the groups and the first year of the groups. The families attended an average of 5.5 (out of 7) groups, and 93% of these families attended four or more meetings. The uncontrolled pre- to post-intervention comparison demonstrated decreases in medication non-compliance and hospitalizations, and increases in family mental health service use. The program provided training for mental health professionals, led to policy change in the Ministry of Health, and resulted in dissemination to other community mental health centers. This study provides preliminary evidence that a collaboratively designed and implemented psychoeducational, multiple-family program is a feasible and beneficial intervention for families of people with severe mental illness in impoverished post-war settings.

Overview of the Evidence Base for Family Interventions in Child Psychiatry.

This article provides updated information about evidence-based family interventions for child and adolescent mental health issues. The article reviews randomized controlled trials for family-based interventions carried out over the last 15 years. The studies were selected from an evidence-based clearinghouse search for family therapy, and specific child and adolescent psychiatric disorders. It is hoped this review guides clinical treatment and encourages clinicians to consider family involvement in treatment. This is specifically necessary when there is a limited response to psychopharmacologic and individual or group psychotherapy treatment.

Examining Trends and Coexisting Conditions Among Children Qualifying for SSI Under ADHD, ASD, and ID.

OBJECTIVE: To examine the prevalence trends and coexisting conditions in attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and intellectual disability (ID) in the pediatric Supplemental Security Income (SSI) population and general population. METHODS: The Social Security Administration (SSA) provided data on primary and secondary diagnoses of children qualifying for SSI for years 2000 to 2011. We compared SSA data with 2000-2011 National Health Interview Survey data on the prevalence of mental health diagnoses among children in the general population living between 0 and 199% of the federal poverty line. We utilized linear regression analysis to test the statistical significance of differences in the trends of the conditions' prevalence. RESULTS: Over this time period, the SSI population experienced increases in ADHD (5.8%) and ASD (7.2%) and a decrease in ID (-10.3%). Comparison with change in the general population indicated no significant difference in ADHD but significant differences in ASD and ID. Relative percentage changes reflect similar changes. The SSI population qualifying for SSI with ADHD (70.8%) had higher rates of coexisting conditions than the general population (66.1%), but lower rates of coexisting conditions for ASD and ID. CONCLUSIONS: ADHD is on the rise among children receiving SSI and in the general population. This suggests that the rise of ADHD in the SSI population is expected and does not represent a misallocation of resources. Changes described among the SSI population in ASD and ID may allude to diagnostic/coding trends and/or true changes in prevalence. Limitations arise from the comparability of the 2 data sets.

Replacement of dietary fish oil with increasing levels of linseed oil: modification of flesh fatty acid compositions in Atlantic salmon (Salmo salar) using a fish oil finishing diet.

Five groups of salmon, of initial mean weight 127 +/- 3 g, were fed increasing levels of dietary linseed oil (LO) in a regression design. The control diet contained capelin oil (FO) only, and the same oil was blended with LO to provide the experimental diets. After an initial period of 40 wk, all groups were switched to a finishing diet containing only FO for a further 24 wk. Growth and flesh lipid contents were not affected by dietary treatment. The FA compositions of flesh total lipids were linearly correlated with dietary FA compositions (r2 = 0.88-1.00, P < 0.0001). LO included at 50% of added dietary lipids reduced flesh DHA and EPA (20:5n-3) concentrations to 65 and 58%, respectively, of the concentrations in fish fed FO. Feeding 100% LO reduced flesh DHA and EPA concentrations to 38 and 30%, respectively, of the values in fish fed FO. Differences between diet and flesh FA concentrations showed that 16:0, 18:1n-9, and especially DHA were preferentially retained in flesh, whereas 18:2n-6, 18:3n-3, and 22:1n-11 were selected against and presumably utilized for energy. In fish previously fed 50 and 100% LO, feeding a finishing diet containing FO for 16 wk restored flesh DHA and EPA concentrations, to approximately 80% of the values in fish fed FO throughout. Flesh DHA and EPA concentrations in fish fed up to 50% LO were above recommended intake values for humans for these EFA. This study suggests that LO can be used as a substitute for FO in seawater salmon feeds and that any reductions in DHA and EPA can be largely overcome with a finishing diet high in FO before harvest.