Impact of cardiovascular disease and cardiovascular risk factors in hospitalised COVID-19 patients.

BACKGROUND: Hospitalised COVID-19 patients with underlying cardiovascular disease (CVD) and cardiovascular risk factors appear to be at risk of poor outcome. It is unknown if these patients should be considered a vulnerable group in healthcare delivery and healthcare recommendations during the COVID-19 pandemic. METHODS: A systematic literature search was performed to answer the following question: In which hospitalised patients with proven COVID-19 and with underlying CVD and cardiovascular risk factors should doctors be alert to a poor outcome? Relevant outcome measures were mortality and intensive care unit admission. Medline and Embase databases were searched using relevant search terms until 9 June 2020. After systematic analysis, 8 studies were included. RESULTS: Based on the literature search, there was insufficient evidence that CVD and cardiovascular risk factors are significant predictors of mortality and poor outcome in hospitalised patients with COVID-19. Due to differences in methodology, the level of evidence of all studies was graded 'very low' according to the Grading Recommendations Assessment, Development and Evaluation methodology. It is expected that in the near future, two multinational and multicentre European registries (CAPACITY-COVID and LEOSS) will offer more insight into outcome in COVID-19 patients. CONCLUSION: This literature review demonstrated there was insufficient evidence to identify CVD and cardiovascular risk factors as important predictors of poor outcome in hospitalised COVID-19 patients. However, patients with CVD and cardiovascular risk factors remain vulnerable to infectious disease outbreaks. As such, governmental and public health COVID-19 recommendations for vulnerable groups apply to these patients.

How often and to what extent do admitted COVID-19 patients have signs of cardiac injury?

BACKGROUND: COVID-19 can cause myocardial injury in a significant proportion of patients admitted to the hospital and seems to be associated with worse prognosis. The aim of this review was to study how often and to what extent COVID-19 causes myocardial injury and whether this is an important contributor to outcome with implications for management. METHODS: A literature search was performed in Medline and Embase. Myocardial injury was defined as elevated cardiac troponin (cTn) levels with at least one value > 99th percentile of the upper reference limit. The primary outcome measure was mortality, whereas secondary outcome measures were intensive care unit (ICU) admission and length of hospital stay. RESULTS: Four studies and one review were included. The presence of myocardial injury varied between 9.6 and 46.3%. Myocardial injury was associated with a higher mortality rate (risk ratio (RR) 5.54, 95% confidence interval (CI) 3.48-8.80) and more ICU admissions (RR 3.78, 95% CI 2.07-6.89). The results regarding length of hospital stay were inconclusive. CONCLUSION: Patients with myocardial injury might be classified as high-risk patients, with probably a higher mortality rate and a larger need for ICU admission. cTn levels can be used in risk stratification models and can indicate which patients potentially benefit from early medication administration. We recommend measuring cTn levels in all COVID-19 patients admitted to the hospital or who deteriorate during admission.

Effect of anticoagulant therapy in COVID-19 patients.

BACKGROUND: In patients hospitalised with COVID-19, an increased incidence of thromboembolic events, such as pulmonary embolism, deep vein thrombosis and stroke, has been reported. It is unknown whether anticoagulation can prevent these complications and improve outcome. METHODS: A systematic literature search was performed to answer the question: What is the effect of (prophylactic and therapeutic dose) anticoagulation therapy in COVID-19 patients on cardiovascular and thromboembolic complications and clinical outcome? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Medline and Embase databases were searched with relevant search terms until 17 July 2020. After systematic analysis, eight studies were included. Analysis was stratified for the start of anticoagulation before or during hospital admission. RESULTS: There was insufficient evidence that therapeutic anticoagulation could improve the outcome in patients hospitalised with COVID-19. None of the studies demonstrated improved mortality, except for one very small Italian study. Furthermore, none of the studies showed a positive effect of anticoagulation on other outcome measures in COVID-19, such as ICU admission, length of hospital stay, thromboembolic complications, need for mechanical ventilation, acute kidney failure or need for renal replacement therapy, except for two studies demonstrating an association between anticoagulation and a lower incidence of pulmonary embolism. However, the level of evidence of all studies varied from 'low' to 'very low', according to the GRADE methodology. CONCLUSION: Analysis of the literature showed that there was insufficient evidence to answer our objective on the effect of anticoagulation on outcome in COVID-19 patients, especially due to the low scientific quality of the described studies. Randomised controlled studies are needed to answer this question.

Material properties of Thera-Band Tubing.

BACKGROUND AND PURPOSE: Thera-Band Tubing has been used in rehabilitation to provide resistance for exercise and splinting. However, the forces required to stretch the tubing have not been thoroughly quantified. Therefore, the therapist cannot assess, with certainty, how much force is applied when using a given length and type of Thera-Band Tubing. The purpose of this study was to quantify the material properties of Thera-Band Tubing. METHODS: Force versus percentage of strain for all types of Thera-Band Tubing was measured during elongation in a mechanical testing machine. RESULTS: The material is very compliant and displays nonlinear behavior in the initial stretching phase and linear behavior after 50% elongation. DISCUSSION AND CONCLUSION: From the data obtained in this project, plots that can provide the therapist with information about the forces needed for exercises with Thera-Band Tubing were generated. These data should allow therapists to make better choices about which size of tubing to use for each patient.

Effects of fingernail length on finger and hand performance.

The purpose of this study was to investigate effects of fingernail length on active range of motion (AROM) of the fingers, speed of finger manipulation, number of words typed, and grip strength. Fifteen normal women (mean age, 30 years) performed measurements under four conditions--with no attached fingernails and with fingernails extending 2, 1, and 0.5 cm beyond the tip of the finger. Analyses of variance showed that: 1) with fingernails of all extended lengths, grip strength measured on the first setting of the Jamar hand dynamometer decreased; 2) with fingernails 1 and 2 cm in length, AROM, grip strength on the second dynamometer setting, and finger manipulation decreased; and 3) with fingernails 2 cm in length, typing speed decreased (p < 0.05). Long fingernails limit flexion of the finger joints, particularly the metacarpophalangeal joints. Lack of finger flexion will limit excursion of long flexors and extensors in patients. It is recommended that patients cut their fingernails to a length of 0.5 cm to achieve optimal functional outcomes.

Case reports and case studies: a discussion of theory and methodology in pocket format.

Issues of the theory and methodology of case reports and case studies have been presented. Examples of applications of techniques used in the rehabilitation of the upper extremity conclude this report in pocket format on the theory and methodology of case reports and case studies. Case reports and studies enhance our knowledge about practice in ways that are unique to each case, which are not possible when investigations are performed through group comparison. Case inquiries help us share our practice, sharpen our theoretical reasoning, develop our good habits of applying reliable and valid measurements, and above all help us explore and discuss our treatments.

The effect of use of a wrist orthosis during functional activities on surface electromyography of the wrist extensors in normal subjects.

Wrist orthoses are advocated for patients with lateral epicondylitis on the assumption that use of the orthosis decreases muscle activity of the wrist extensors during activities. The purpose of this study was to compare the amount of electrical activity, root mean square (RMS) calculated from surface EMG recorded over the wrist extensors, during activities when applying four conditions of wrist orthoses: dorsal; volar; semicircular; and no orthosis. Thirteen normal subjects (mean age 27.7 years) performed three lifting and two gripping tasks, repeated on three consecutive days under four orthotic conditions. Measured were RMS and maximum voluntary grip strength. Repeated measures ANOVA's indicated a significant decrease of RMS using the semicircular design during lifting (p < .0005). Grip strength decreased significantly using all three orthotic designs, but RMS recorded during gripping did not. It was concluded that application of a wrist orthosis reduces electrical activity of the wrist extensors less than anticipated and only during lifting.

Effect of work glove and type of muscle action on grip fatigue.

Fatigue plays a major role in limiting work performance. The objectives of this study were: (1) to determine the effect of wearing a work glove on handgrip fatigue; (2) to compare the effect of a sustained grip contraction of concentric versus eccentric nature, named in this study isometric and eccentric; and (3) to determine if there is a relationship between physiological muscle performance and subjective perceptional fatigue during isometric and eccentric gripping. The study had 2 x 2 repeated measures design. The two factors were: (1) glove condition (glove, no glove); and (2) type of contraction (eccentric and isometric). The measurements taken were: (1) time to limit of endurance (Tlim); (2) rate of perceived effort (RPE); (3) mean power frequency (MPF) derived from the electromyogram (EMG); and (4) the fatigue objective-subjective relationship (FOSR, which is the correlation coefficient between RPE and MPF). Twenty-one normal subjects maintained a handgrip of 60% of their maximal effort until exhaustion for each of the four conditions. During each trial EMG values were recorded every 5 s and RPE values were recorded every 10 s. The RPE was recorded as a subjective value selected from a 10-point Borg scale. The results showed that Tlim was greater for the no glove condition (p < 0.0005) and for the eccentric muscle action (p < 0.05). The FOSR was greatest for the glove condition (p < 0.03) and for the isometric muscle action (p < 0.013). The MPF decline showed no significant difference for any condition. These data indicate that glove condition and type of handgrip contraction have an effect on physiological fatigue and subjective perception of fatigue.

Diagnostic dilemmas and results of treatment for chronic constipation.

Chronic functional constipation (CFC) may be difficult to recognise and information regarding its long term prognosis is scarce. The records of 244 children with CFC, aged 0-18 years, were analysed for symptoms at presentation and results of treatment, and long term outcome was evaluated by means of a telephone interview in 137 patients discharged for more than one year. The patients presented with a great variety of symptoms, only 22% having infrequent defecation of increased consistency, another 22% having an obviously normal defecation pattern. The mean duration of treatment was 13 months. At the time of discharge, 69% of the patients still used laxatives. At a median of four years after discharge, 66% of the children were free of symptoms and without medication, 39% having experienced a recurrence. It is concluded that CFC may be difficult to recognise and can be alleviated by an intensive laxative regimen. Recurrence of symptoms is common, but the long term prognosis is good in most patients.

Metabolism of intravenously administered high-dose 6-mercaptopurine with and without allopurinol treatment in patients with non-Hodgkin lymphoma.

PURPOSE: We investigated the metabolism of high dose 6 mercaptopurine (HD-6MP) infusions and its influence on the metabolism by allopurinol, an inhibitor of xanthine oxidase, the enzyme that catabolizes 6MP into thioxanthine and thiouric acid. PATIENTS AND METHODS: Nine patients (aged 2-11 years) with non-Hodgkin lymphoma (NHL) were treated with HD-6MP (1300 mg/m(2).24h) within a therapeutic window after diagnosis. Four patients received oral allopurinol (200 mg/m(2).day) to prevent urate nephropathy, and five did not. Plasma and RBC were isolated before and 4, 20, 24, 28, and 48h after the start of the infusion. All measurements were performed with HPLC. RESULTS: Considerable variations were found in the plasma levels of 6MP, thioxanthine, and thiouric acid and of RBC-MeTIN levels. 6MP-riboside was not detectable, and MeMP and MeMPR levels were <1.3 muM in the plasma. In general, 6MP, thioxanthine, and MeMP levels in plasma were higher, and thiouric acid plasma levels and RBC-MeTIN levels were lower in the patients treated with allopurinol compared to those who did not receive allopurinol. CONCLUSIONS: 6MP is extensively metabolized in patients with NHL treated with HD-6MP. Thiopurine methylation, at the levels of nucleotide, nucleoside, and base, is an important metabolic pathway after HD-6MP. Co-administration of allopurinol can result in both a decreased catabolism and anabolism of 6MP compared to treatment with HD-6MP alone. This observation may have consequences for the therapeutic efficacy and toxic effects of 6MP in combination with allopurinol.

Effects on transmethylation by high-dose 6-mercaptopurine and methotrexate infusions during consolidation treatment of acute lymphoblastic leukemia.

6-mercaptopurine (6MP) cytotoxicity is caused by thioguanine and methylthioinosine nucleotides. Thiopurine methylation occurs to a large extent in vivo and in vitro. In this reaction, S-adenosyl-L-methionine (AdoMet), produced from methionine and ATP, is converted into S-adenosyl-L-homocysteine (AdoHcy) which, in turn, is hydrolyzed into homocysteine. Remethylation of homocysteine into methionine is inhibited by methotrexate (MTX). In cultured lymphoblasts, AdoMet: AdoHcy ratio and DNA methylation decrease after incubation with 6MP. The aim of the present study was to investigate the influence of high-dose 6MP on the methylation capacity in children with acute lymphoblastic leukemia. Five patients received 4 courses with high-dose intravenous MTX (5' g.m-2 in 24 hr) immediately followed by high-dose 6MP (1300 mg.m-2 in 24 hr). Five control patients received high-dose MTX and oral 6MP (25 mg.m -2 daily for 8 weeks). Leucovorin rescue was started at 36 hr in both groups. In the intravenous 6MP group, 6-methylmercaptopurine, its riboside, and 6-methylmercapto-8-hydroxypurine were detectable in plasma in concentrations of 0.3-2.6 muM (6MP steady state levels: 11.6 muM). In red blood cells, mean methylthioinosine nucleotide levels were one third of those of ATP (13.1 nmol/10(8)). AdoHcy levels (10 pmol/10(8)) remained constant in both groups and AdoMet was not detectable ( < 20 pmol/10(8)). In both groups, plasma homocysteine increased and methionine decreased following administration of MTX. The delay in the recovery of methionine in the intravenous 6MP group after MTX infusion is probably the result of an increased demand on methyl groups during 6MP infusion.

Thiopurine methyltransferase: a review and a clinical pilot study.

Thiopurine methyltransferase (TPMT) is an important enzyme in the metabolism of 6-mercaptopurine (6MP), which is used in the treatment of acute lymphoblastic leukemia (ALL). TPMT catalyzes the formation of methylthioinosine monophosphate (MetIMP), which is cytotoxic for cultured cell lines, and it plays a role in detoxification of 6MP. Population studies show a genetic polymorphism for TPMT with both high and low activity alleles. About 1 of 300 subjects is homozygous for the low activity. The function TPMT plays in detoxification or therapeutic efficacy of 6MP in vivo is not clear. In this article the genetic polymorphism of TPMT is reviewed and the contribution of TPMT to the cytotoxic action, or detoxification, of 6MP in children with ALL is discussed. Induction of TPMT activity has been described during the treatment for ALL. We performed a pilot study on the influence of high-dose 6MP infusions (1300 mg/m2 in 24 h) on TPMT activity of peripheral blood mononuclear cells (pMNC) of eleven patients with ALL. The TPMT activities were in, or, above the normal range. There was no statistically significant difference between the TPMT activities before and after the 6MP infusions. MetIMP levels in pMNC increased during successive courses. This might be explained by TPMT induction, but other explanations are plausible as well. Twenty five percent of the TPMT assays failed, because less than the necessary 5.10(6) pMNC could be isolated from the blood of leukopenic patients. Red blood cells can not be used for TPMT measurements, since transfusions are frequently required during the treatment with 6MP infusions. Therefore, the influence of high-dose 6MP infusions on TPMT activity can only be investigated further when a TPMT assay which requires less pMNC has been developed.

Detection and identification of 6-methylmercapto-8-hydoxypurine, a major metabolite of 6-mercaptopurine, in plasma during intravenous administration.

6-Mercaptopurine, a hypoxanthine antimetabolite, is used in the treatment of acute lymphoblastic leukemia (ALL) in children. Extensively metabolized before it exerts cytotoxic action, it is catabolized into 6-mercapto-2,8-dihydroxypurine (thiouric acid), which is excreted by the kidneys. We describe a metabolite of 6-mercaptopurine, 6-methylmercapto-8-hydroxypurine, whose presence has not been previously reported in plasma. This compound was found in high concentrations in plasma during high-dose 6-mercaptopurine infusions (1300 mg/m2 in 24 h). This previously unknown compound was identified by reversed-phase HPLC with absorbance detection and by gas chromatography-mass spectrometry. The pathways leading to 6-methylmercapto-8-hydroxypurine in vivo are not yet fully understood. In a group of 17 patients treated with four courses of high-dose 6-mercaptopurine infusions according to the ALL-8 treatment protocol of the Dutch Childhood Leukemia Study Group, the steady-state concentrations of 6-methylmercapto-8-hydroxypurine in plasma were one-fifth of the parent drug concentrations, with wide interindividual variation. The formation of high concentrations of 6-methylmercapto-8-hydroxypurine in plasma, especially during the infusion, probably indicates another catabolic pathway of high-dose 6-mercaptopurine, apart from its conversion into thiouric acid.

Determination of extracellular and intracellular thiopurines and methylthiopurines by high-performance liquid chromatography.

The thiopurine antimetabolites 6-thioguanine and 6-mercaptopurine are important chemotherapeutic drugs in the treatment of childhood acute lymphoblastic leukaemia. Measurement of metabolites of these thiopurines is important because correlations exist between levels of these metabolites and the prognosis in childhood acute lymphoblastic leukaemia. The reversed-phase method for the determination of extracellular thiopurine nucleosides and bases was previously developed and has been modified such that methylthiopurine nucleosides, bases, thioxanthine and thiouric acid can be measured also. The anion-exchange method enables the determination of intracellular mono-, di- and triphosphate (methyl)thiopurine nucleotides in one run. Extraction on ice with perchloric acid and dipotassium hydrogenphosphate results in good recoveries for (methyl)thiopurine nucleotides in lymphoblasts and peripheral mononuclear cells and for methylthioinosine nucleotides in red blood cells. Measurement of the low concentrations of mono-, di- and triphosphate thioguanine nucleotides in red blood cells (detection limit 20 pmol/10(9) cells) is possible after extraction with methanol and methylene chloride, followed by oxidation of thioguanine nucleotides with permanganate and fluorimetric detection.

Measurement of range of motion of the finger after flexor tendon repair in zone II of the hand.

The purpose of this study was to compare classification systems of active range of motion of the finger after flexor tendon surgery in zone II of the hand. Active range of motion of 20 fingers (16 subjects) was classified according to five systems. Agreement between the systems was only fair. Strickland's original system and the Louisville system rated the results most strictly, followed by Strickland's adjusted system. Buck-Gramcko's systems (in centimeters and degrees) rated the results least strictly. Strickland's systems conformed most closely to measurement principles. This article concludes that at this time Strickland's original classification system is preferable for scientific and clinical purposes. However, additional research is needed to evaluate reliability of the measurement, the variability of the scaling factor of 175 degrees, the sensitivity of the measurement, and the validity of the measurement with regard to functional use of the finger and gliding of the repaired tendon.