Severe hyponatraemia with cerebral oedema after Pfizer BNT162b2 mRNA vaccination against COVID-19.

Background: Severe hyponatraemia can lead to serious neurological complications including coma, seizure and death. Hyponatraemia and the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) has been previously described in cases of COVID-19, however there have been few reports post vaccination. We describe a case of severe hyponatraemia post second Pfizer BNT162b2 mRNA vaccination against COVID-19. Case presentation: A 48-year-old previously well woman presented to the emergency department with severe headaches and confusion one day after she received her second Pfizer COVID-19 vaccination. She reported no more than 2.5 L fluid intake. Vital signs were normal. Laboratory investigation revealed serum sodium 113 mmol/L, potassium 3.4 mmol/L, urea 3.5 mmol/L and serum osmolality 266 mmol/kg. TSH, random cortisol and C-reactive protein levels were normal. She was found to be in urinary retention and developed marked polyuria post in dwelling catheter insertion. Following this she underwent spontaneous and rapid correction of serum sodium without intervention. Retrospective analysis showed an inappropriately high copeptin of 4.4 pmol/L. Conclusions: It is important to be cautioned and aware of hyponatraemia as an immediate side effect of COVID-19 vaccination. The exact mechanism is unknown and further research is required to understand the acute endocrine effects which may arise in response to COVID-19 vaccination.

Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions.

OBJECTIVE: To assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DESIGN: A prospective observational cohort study. PARTICIPANTS: All inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital. MAIN OUTCOMES: We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2. RESULTS: Of 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18-1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20-1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03-1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01-1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05-1·18;p < 0·001). CONCLUSIONS: In patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

Beta-blockers are under-prescribed in patients with chronic obstructive pulmonary disease and co-morbid cardiac disease.

The use of beta-blockers in patients with chronic obstructive pulmonary disease and co-morbid cardiovascular disease is controversial, despite increasing evidence to support their use as safe and efficacious. This study retrospectively assessed the rates of beta-blocker prescription in patients admitted to two Australian tertiary hospitals for acute exacerbation of chronic obstructive pulmonary disease. This revealed that less than half of patients (45%) with known cardiac indications were receiving beta-blocker therapy, evident across all degrees of airways disease severity. Further work is needed to ensure that medical management of this patient group is optimised.

Outcomes of exertional rhabdomyolysis following high-intensity resistance training.

BACKGROUND: High-intensity resistance training (HIRT) programmes are increasingly popular amongst personal trainers and those attending gymnasiums. We report the experience of exertional rhabdomyolysis (ER) at two tertiary hospitals in Melbourne, Australia. AIMS: To compare the clinical outcomes of ER with other causes of rhabdomyolysis. METHODS: Retrospective cross-sectional study of patients presenting with a serum creatine kinase (CK) of greater than 25 000 units/L from 1 September 2013 to 31 August 2014 at two tertiary referral hospitals in Melbourne, Australia. Records were examined to identify care measures implemented during hospital stay, clinical outcomes during admission and on subsequent follow up. RESULTS: Thirty four cases of rhabdomyolysis with a CK of greater than 25 000 units/L (normal range: 20-180 units/L) were identified during the 12-month study period. Twelve of the 34 cases (35%) had ER with 10 of 12 related to HIRT. No acute kidney injury, intensive care admission or death were seen among those with ER. All cases were managed conservatively, with 11 admitted and 9 receiving intravenous fluids only. In contrast, patients with rhabdomyolysis from other causes experienced significantly higher rates of intensive care admission (64%, P = 0.0002), acute kidney injury (82%, P = 0.0001) and death (27%, P = 0.069). CONCLUSION: ER resulting from HIRT appears to have a benign course compared with rhabdomyolysis of other aetiologies in patients with a serum CK greater than 25 000 units/L. Conservative management of ER appears to be adequate, although this requires confirmation in future prospective studies.

Relapse more common than reinfection in recurrent tuberculosis 1-2 years post treatment in urban Uganda.

OBJECTIVE: To determine the proportion of recurrent tuberculosis (TB) due to relapse with the patient's initial strain or reinfection with a new strain of Mycobacterium tuberculosis 1-2 years after anti-tuberculosis treatment in Uganda, a sub-Saharan TB-endemic country. DESIGN: Records of patients with culture-confirmed TB who completed treatment at an urban Ugandan clinic were reviewed. Restriction fragment length polymorphism (RFLP) patterns were used to determine relapse or reinfection. Associations between human immunodeficiency virus (HIV) positivity and type of TB recurrence were determined. RESULTS: Of 1701 patients cured of their initial TB episode with a median follow-up of 1.24 years, 171 (10%) had TB recurrence (8.4 per 100 person-years). Rate and risk factors for recurrence were similar to other studies from sub-Saharan Africa. Insertion sequence (IS) 6110-based RFLP of paired isolates from 98 recurrences identified 80 relapses and 18 reinfections. Relapses among HIV-positive and -negative patients were respectively 79% and 85% of recurrences. CONCLUSIONS: Relapse was more common and presented earlier than reinfection in both HIV-positive and -negative TB patients 1-2 years after completing treatment. These findings impact both the choice of retreatment drug regimen, as relapsing patients are at higher risk for acquired drug resistance, and clinical trials of new TB regimens with relapse as clinical endpoint.

Concordance of a positive tuberculin skin test and an interferon gamma release assay in bacille Calmette-Guérin vaccinated persons.

BACKGROUND: False-positive tuberculin skin test (TST) results due to prior bacille Calmette-Guérin (BCG) vaccination may lead to unnecessary treatment of presumed latent tuberculosis infection (LTBI). Recently approved interferon-gamma release assays (IGRAs) are more specific for LTBI in this group. METHODS: A total of 316 BCG-vaccinated foreign-born individuals with a positive TST had a commercially available IGRA (QuantiFERON®-TB Gold In-Tube) performed as part of a two-step procedure to determine the need for isoniazid therapy. Baseline demographic information and TST size were recorded and analyzed for characteristics associated with an increased likelihood of having a positive IGRA. RESULTS: Increasing age, male sex, origin from a country with a high prevalence of tuberculosis (TB), shorter time since arrival in the United States, and increasing TST size were all independently associated with a positive IGRA. CONCLUSION: Patient characteristics and TST size can help determine those at highest risk for LTBI. A two-step procedure for LTBI screening should be considered for foreign-born persons with prior BCG vaccination and a positive TST.

Incidence of bacteraemia following endobronchial ultrasound-guided transbronchial needle aspiration.

Few data exist concerning possible infectious complications associated with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The present prospective evaluation was undertaken in order to determine the incidence of bacteraemia and infectious complications associated with EBUS-TBNA. Consecutive patients undergoing EBUS-TBNA for evaluation of mediastinal or hilar lymph node lesions were studied. Venesection was performed within 60 s of TBNA for aerobic and anaerobic blood culture. Sterile saline washing of TBNA needles was also performed. Patients with positive blood cultures were reviewed immediately, and all patients underwent clinical review within 1 week of EBUS-TBNA. A total of 43 patients underwent EBUS-TBNA, with bacteraemia demonstrated in three (7%). All bacterial isolates were typical oropharyngeal commensal organisms. The TBNA needle washing culture was positive in 15 (35%) patients. None of the three bacteraemic patients had clinical features suggestive of infection, and no complications were seen among the cohort. The incidence of bacteraemia following EBUS-TBNA is comparable to that following routine flexible bronchoscopy. Performance of TBNA does not appear to measurably increase the risk of bacteraemia over that associated with insertion of the bronchoscope into the airway. Contamination of the TBNA needle with oropharyngeal commensal bacteria is common; however, clinically significant infection following EBUS-TBNA appears rare.

A quantitative assessment of the efficacy of surgical and N95 masks to filter influenza virus in patients with acute influenza infection.

We assessed the in vivo efficacy of surgical and N95 (respirator) masks to filter reverse transcription-polymerase chain reaction (RT-PCR)-detectable virus when worn correctly by patients with laboratory-confirmed acute influenza. Of 26 patients with a clinical diagnosis of influenza, 19 had the diagnosis confirmed by RT-PCR, and 9 went on to complete the study. Surgical and N95 masks were equally effective in preventing the spread of PCR-detectable influenza.

Galanin and alcohol dependence: neurobehavioral research.

It is known that microinjection of galanin (GAL) intraventricularly or in specific hypothalamic sites increases food consumption and, conversely, the intake of food increases the expression of GAL in hypothalamic sites. Ethanol (EtOH) is a calorie-rich food as well as a drug of abuse. The research reviewed here shows that GAL may play a similar role in alcohol intake. First, experiments in which GAL was microinjected into the third ventricle or the paraventricular nucleus (PVN) showed increases in EtOH consumption. The increase in EtOH consumption occurred during both the light and dark cycles after GAL injection in the third ventricle in rats with limited EtOH access. Injection of GAL did not increase food intake in rats that had been chronically drinking alcohol. GAL receptor blockade reversed these increases. Microinjection of GAL directly into the PVN also increased ad libitum EtOH intake and blockade of these receptors in the PVN inhibited ad libitum EtOH consumption. Secondly, rats administered EtOH showed increases in GAL in the PVN and related hypothalamic sites. EtOH injection and voluntary intake, both ad libitum and limited access, increased GAL gene and peptide expression in the PVN consistently across administration procedures. These experiments show that GAL injection increases alcohol intake and that the intake of alcohol increases GAL, suggesting a positive feedback relationship between alcohol intake and specific hypothalamic GAL systems. Such a relationship may contribute to the motivation to consume excessive alcoholic beverages and the development of alcohol dependence.

In alcohol-treated rats, naloxone decreases extracellular dopamine and increases acetylcholine in the nucleus accumbens: evidence of opioid withdrawal.

Withdrawal from ethanol is aversive. The question is why. As with the withdrawal from morphine, nicotine, diazepam and sugar, the ethanol withdrawal state may involve an increase in nucleus accumbens (NAc) acetylcholine (ACh) causing an alteration of the dopamine (DA)-ACh balance in favor of ACh. Therefore the effects of acute and chronic alcohol (1 gm/kg/day i.p.) treatment on extracellular concentrations of NAc ACh and DA were determined before and after naloxone-precipitated withdrawal. Ethanol initially increased DA to 119% of baseline as measured by microdialysis. This was still the case on the 21st day of ethanol injection when DA increased to 126%. There was no effect of ethanol on ACh. However, naloxone (3 mg/kg s.c.) injected the next day decreased extracellular DA to 83% of baseline and caused a significant rise in ACh to 119%. This state of high ACh combined with low DA may contribute to the aversive aspects of alcohol withdrawal.

Taste, intake rate, and food choice in rats.

The contribution of taste to the food choices of foraging rats was examined. Rats in a laboratory foraging paradigm searched for sequential opportunities to eat at two feeders containing chow-based food pellets that were plain or flavored with saccharin or citric acid. Pellets cost the same number of bar presses at both feeders. Saccharin adulteration had no effect on intake parameters. Citric-acid-flavored pellets were eaten more slowly and in smaller meals. If there was no alternative food, daily intake was slightly reduced. When the alternative food was plain, fewer meals and fewer pellets were taken of the citric-acid-flavored than plain pellets. When we gradually increased the price of the plain pellets at one feeder, while the price at the alternative feeder (which contained either plain or citric-acid-flavored pellets) remained low, the rate of eating (profitability) decreased at the higher-price feeder, and the rats shifted their intake toward the less-costly, more profitable pellets. We compared the relationship between the relative eating rate at each feeder and the relative meal size (or daily intake) at each feeder when the low-priced food was plain and when it was flavored with citric acid, and found no differences. This indicates that taste may influence choice via its effect on rate of intake.

Sucrose intake as a function of its cost and the cost of chow.

The avid consumption of pure carbohydrate solutions, which often results in a distortion of nutrient balance, is generally presumed to be driven by their taste. In the first of two experiments, we examined the effect of consumption cost on rats' intake of three concentrations of sucrose solution (8%, 16%, and 32%) when a nutritionally complete chow was concurrently freely available. In the second experiment, we examined the intake of 24% sucrose solution and chow as the consumption costs of both were varied. Increasing the cost of sucrose resulted in a reduction in the percent calories taken from sucrose; the steepness of the decline in intake with price was inversely related to the sucrose concentration and to the cost of chow. Chow calories were substituted for relatively expensive sucrose calories. An increase in the cost of chow resulted in a reduction in the percent of calories taken from chow and a protein-poor diet. The cost of sucrose did not affect the slope of the chow intake curve, presumably because, despite its sweet taste, sucrose was not a substitute for the protein, fat, and micronutrients in chow. Total caloric intake was conserved in all cases.Thus, the avid consumption of sucrose solution is curtailed when it is costly; but the degree of change in intake with cost depends on the cost of an alternative food. These results suggest that diet selection involves a comparison not only of the taste and post-ingestive consequences of available foods, but also of the cost of calories and nutrients in the foods. Selection appears to be guided first by caloric requirements and the relative cost of calories, then by nutrient requirements and the relative cost of nutrients, and finally by taste.

Dermal hypoesthesia after total knee arthroplasty.

Dermal hypoesthesia is a well-recognized sequelae of total knee arthroplasty (TKA). However, it is poorly documented. Thirty-five knees were evaluated for hypoesthesia among 26 patients after TKA to determine the incidence, area affected, and change over time in situ. All knees sustained an area of hypoesthesia, showing diminution over time. All were affected lateral to the medial parapatellar incision. A 71% decline of the area affected was seen over the first 2 years after surgery. All patients had some residual hypoesthesia with a mean of 33 cm2 at 2 years.

Cultivating the field of psychology. Psychological journals at the turn of the century and beyond.

Prominent psychologists, including G. Stanley Hall, James Mark Baldwin, and James McKeen Cattell, cultivated the field of psychological publishing with privately owned and managed journals. Hall's journals, including the American Journal of Psychology and Pedagogical Seminary, reflected his view of psychology as the empirical study of human nature and his support for applied psychology. Baldwin and Cattell's periodicals, including Psychological Review and Psychological Monographs, reflected a narrower scientific and academic view of psychology. Baldwin and Cattell were more successful editors than Hall and strategically linked their journals to the American Psychological Association (APA). The Psychological Review journals were purchased by APA in 1925. The narrower vision represented in these journals may have contributed to applied psychologists' dissatisfaction with APA during the late 1920s and early 1930s.

Increasing osteopathic manipulative treatment skills and confidence through mastery learning.

Several recent studies document the declining use of osteopathic manipulative treatment (OMT) in clinical practice. In this article, the authors contend that developing new teaching materials based on the mastery learning approach can augment time-tested methods of teaching OMT and help to stop or reverse this decline. The Spencer technique for shoulder manipulation is used to demonstrate the development and evaluation of OMT mastery learning materials. These materials could be developed as part of a progressive teaching sequence requiring increasing diagnostic acumen, palpatory skill, and therapeutic subtlety. Such a program could be used throughout osteopathic medical training and for continuing medical education to increase skills and confidence in the use of OMT.

The relation between meal size and the time between meals: effects of cage complexity and food cost.

Certain popular models of the regulation of food intake predict a positive correlation between the size of a meal and the preceding and/or following intermeal interval. However, the reported strength of these prandial correlations has varied widely in the literature. To determine what factors may influence the strength of these relationships, we measured the timing of and amount consumed in meals of laboratory rats as a function of 1) whether they were housed in isolation or with partial access to peers or a running wheel, 2) whether they were disturbed daily or weekly for maintenance procedures, and 3) whether food was free or contingent on operant responding. We also compared two definitions of "meal" and "intermeal interval." Strong prandial correlations were found only occasionally. Caging, food cost, and maintenance frequency did not affect the size of the correlations, although these factors did influence the rats' meal patterns. We conclude the regulation of food intake cannot be explained by models relying on a regular relationship between meal size and intermeal interval.

Behavioral strategies in the cold: effects of feeding and nesting costs.

Animals can meet energetic challenges by acquiring or conserving energy. In the present experiment, we pitted these strategies against each other by housing rats in a cold environment and requiring them to bar press for food pellets and for access to a heated nest. Our question was how rats would exploit these resources to meet the added energetic demand of the cold when food was abundant or scarce. Results showed that rats' allocation of time and effort between competing activities was a function of demand. Feeding and nesting were partially substitutable in the cold: rats traded food for warmth and vice versa, economizing on both time and energy by adjusting their feeding and nesting patterns. Depending upon food abundance and the cost of nesting, rats acquired calories from food, conserved calories by nesting, and borrowed calories from the defense of body weight.

Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications.

PURPOSE: Aminoglycoside-induced ototoxicity appears to have a genetic susceptibility in some individuals, and the A1555G mutation in the mitochondrial 12S ribosomal RNA gene has been shown to be responsible for this susceptibility in all familial cases. An Italian family with 5 family members who became deaf after aminoglycoside exposure presented to us, and molecular analysis excluded the A1555G mutation. The purpose of this study is to identify the molecular basis for the aminoglycoside susceptibility in this family. PATIENTS AND METHODS: Two sisters and three of their children developed severe to profound high-frequency hearing loss after aminoglycoside exposure. DNA was extracted from the blood of these individuals and their unaffected relatives, and analyzed for mitochondrial DNA mutations. The region around nucleotide 961 was also cloned and individual clones were sequenced. RESULTS: Sequencing of the 12S ribosomal RNA gene revealed a thymidine deletion at position 961, with a complex pattern of sequence around this mutation. Sequencing of individual clones around the 961 mutation demonstrated a varying number of inserted cytosines in different mitochondrial molecules. CONCLUSION: This family establishes the nucleotide 961 thymidine deletion associated with a varying number of inserted cytosines in the mitochondrial 12S ribosomal RNA gene as the second pathogenic mutation that can predispose to aminoglycoside ototoxicity. It demonstrates the clinical relevance of taking a family history before administering aminoglycosides to any patient. In addition, it would be desirable for sporadic patients with aminoglycoside-induced hearing loss to be screened with molecular tests for the presence of the 1555 and 961 mutations. Such screening could significantly decrease the prevalence of aminoglycoside-induced hearing loss.