A study performed in the United States lends support to the recommendations made by the European Working Time Directive regarding "ring fencing" of rest times for surgical trainees. In that study the effect of daytime sleepiness(measured on the Epworth Sleepiness Scale(ESS) was measured in 19 surgical trainees in otolaryngology-head and neck surgery programmes in 2 academic institution. ESS was documented, and surgical skill(in performig septoplasty) was evaluated by attending physicians using a global assessment tool and a skill-based visual analog scale. The attending physicians were unaware of the trainees' report on the ESS. Trainees, themselves, were also required to rate their own performance. The outcome was that , in regression analysis, there was a statistically significant inverse association between ESS scores and attending physician-rated technical skill both for the global assessment tool(p < 0.001), and for the visual analog scale(p=0.03)(1). Using both parameters the self-rated scores obtained by the trainees did not reach statistical significance(1). In other words, the trainees did not recognise the effect that daytime sleepiness was having on their surgical performance.
The wider inference that can be drawn is as follows:-
Daytime sleepiness impairs performance even though the trainee may be unaware of this adverse effect
These observations are generalisable both to trainees and to consultant staff
Consultan...
A study performed in the United States lends support to the recommendations made by the European Working Time Directive regarding "ring fencing" of rest times for surgical trainees. In that study the effect of daytime sleepiness(measured on the Epworth Sleepiness Scale(ESS) was measured in 19 surgical trainees in otolaryngology-head and neck surgery programmes in 2 academic institution. ESS was documented, and surgical skill(in performig septoplasty) was evaluated by attending physicians using a global assessment tool and a skill-based visual analog scale. The attending physicians were unaware of the trainees' report on the ESS. Trainees, themselves, were also required to rate their own performance. The outcome was that , in regression analysis, there was a statistically significant inverse association between ESS scores and attending physician-rated technical skill both for the global assessment tool(p < 0.001), and for the visual analog scale(p=0.03)(1). Using both parameters the self-rated scores obtained by the trainees did not reach statistical significance(1). In other words, the trainees did not recognise the effect that daytime sleepiness was having on their surgical performance.
The wider inference that can be drawn is as follows:-
Daytime sleepiness impairs performance even though the trainee may be unaware of this adverse effect
These observations are generalisable both to trainees and to consultant staff
Consultant surgeons(who are role models for trainees) who combine a gruelling NHS workload with "out of hours" private work are at risk of underperforming if they do not comply with the European Working Time Directive
References
(1)Tseng YW., Vedula S., Malpani A et al
Association between surgical trainee daytime sleepiness and intraoperative technical skill when performing septoplasty
JAMA Facial Plastic Surgery doi10.1001/amafacial.2018.117
The tension between head, heart and checklist is strikingly exemplified by the clinical decision process involved in the diagnosis of pulmonary embolism(PE). Currently, this process is characterised by a proliferation of clinical decision rules which involve mind numbingly long lists of items, and their associated calculations, the latter intended to generate numerical scores(1)(2) which confer a semblance of scientific credibility to the process. By contrast, a school of thought has emerged which posits that clinical acumen, defined as unstructured clinical impression or "gestalt" is, at the very least, as reliable a sole reliance on clinical prediction rules for discriminating among patients who have a low, moderate, or high pretest probability of PE(1). Over time, gestalt, itself, appears progressively to confer increasing diagnostic accuracy, judging by the diagnostic performance of senior physicians(postgraduate year 4 plus) vs interns(postgraduate year 1) working in the emergency department of a large teaching hospital(3). Concurrently, we have seen the emergence of gestalt-based clinical decision strategies such as the PERC rule(4) and the YEARS algorithm(5). as an attempt to resolve the tension between underdiagnosis and overdiagnosis of PE.
Clinical acumen, itself, performs best when it is informed, not only by the numerical score of years since obtaining one's medical qualification, but also by interaction(through the medium of case co...
The tension between head, heart and checklist is strikingly exemplified by the clinical decision process involved in the diagnosis of pulmonary embolism(PE). Currently, this process is characterised by a proliferation of clinical decision rules which involve mind numbingly long lists of items, and their associated calculations, the latter intended to generate numerical scores(1)(2) which confer a semblance of scientific credibility to the process. By contrast, a school of thought has emerged which posits that clinical acumen, defined as unstructured clinical impression or "gestalt" is, at the very least, as reliable a sole reliance on clinical prediction rules for discriminating among patients who have a low, moderate, or high pretest probability of PE(1). Over time, gestalt, itself, appears progressively to confer increasing diagnostic accuracy, judging by the diagnostic performance of senior physicians(postgraduate year 4 plus) vs interns(postgraduate year 1) working in the emergency department of a large teaching hospital(3). Concurrently, we have seen the emergence of gestalt-based clinical decision strategies such as the PERC rule(4) and the YEARS algorithm(5). as an attempt to resolve the tension between underdiagnosis and overdiagnosis of PE.
Clinical acumen, itself, performs best when it is informed, not only by the numerical score of years since obtaining one's medical qualification, but also by interaction(through the medium of case conferences, "grand" rounds, and clinico-pathological discussions) with colleagues who have addressed similar diagnostic challenges in the workplace. Clinical acumen is also enhanced by mining the immensely rich treasure trove of the published literature of typical as well as atypical cases of PE. In that fullest sense unstructured clinical acumen is likely to outrank even the mot ingeniously devised clinical decision rule in its diagnostic performance.
References
(1) Chunilal SD., Eikelboom JW., Attia J et al
Does this patient have pulmonary embolism?
JAMA2003;290;2849-2858. Also see conclusion by Ginsberg that clinical gestalt strategies and clinical prediction rules have similar discriminate pretest probabilities of pulmonary embolism in www.evidence-basedmedicine.com)
(2)Wahsh RA., Agha MA
Clinical probability of pulmonary embolism: Comparison of different scoring systems
Egyptian Journal of Chest Diseases and Tuberculosis 2012;61:419-424
(3) Kabrhel C., Camargo CA., Goldhaber SZ
Clinical gestalt and the diagnosis of pulmonary embolism: does experience matter?
CHEST 2005;127:1727-1630
(4)Kline JA., Mitchell AM., Kabrhel C., Richman PB., Courtney DM
Clinical criteria to prevent unnecessary diagnostic testing in emergency department patients with suspected pulmonary embolism
J Thromb Haemost 2004;2:1247-1255
(5)van der Hulle T., Cheung WY., Kaoij S et al
Simplified diagnostic management of suspected pulmonary embolism(the YEARS study): a prospective, multicentre, cohort study
Lancet 2017;390:1890197
Review:clinical gestalt strategies and clinical prediction rules have similar discriminate pretest probabilities of pulmonary embolism
Dear Editor,
We read with interest Thomson et al’s article “ECG in suspected pulmonary embolism” which was published in Postgraduate Medical Journal in January 2019. We would like to bring to your attention another important but little-known cause of S1Q3T3, namely left arm – V2 ECG lead misplacement. This occurs when the yellow ECG cables are misplaced and can easily be misdiagnosed as a pulmonary embolism. A characteristic appearance occurs which we believe is pathognomonic for LA – V2 misplacement. In addition to S1Q3T3, a tall R wave in lead III is seen (1). In a study of 62 patients in whom we recorded both a normal and an LA V2 ECG lead misplacement, we observed that the presence of S1Q3T3R3 is highly statistically significant for left arm -V2 lead misplacement (P=0) (1). It is important to exclude lead misplacement, or the patient may have incorrect treatment administered or the correct treatment withheld because of an error in recording an ECG. Of 230 unrecognised ECG lead misplacements in our hospital, 10.9% were left arm – V2 (2).
After a thorough search of the literature we have identified only 2 brief reports on this topic (3,4). Therefore, it is highly likely that if it does occur then ECG features will inadvertently be attributed to pulmonary embolism and managed inappropriately.
1. Lynch R, Ballesty L, Kuan SC, Ponnambolam Y. Left arm – V2 ECG Lead Misplacement by Colour: a largely unknown entity which can easily be Misdiagnosed as a Pulmo...
Dear Editor,
We read with interest Thomson et al’s article “ECG in suspected pulmonary embolism” which was published in Postgraduate Medical Journal in January 2019. We would like to bring to your attention another important but little-known cause of S1Q3T3, namely left arm – V2 ECG lead misplacement. This occurs when the yellow ECG cables are misplaced and can easily be misdiagnosed as a pulmonary embolism. A characteristic appearance occurs which we believe is pathognomonic for LA – V2 misplacement. In addition to S1Q3T3, a tall R wave in lead III is seen (1). In a study of 62 patients in whom we recorded both a normal and an LA V2 ECG lead misplacement, we observed that the presence of S1Q3T3R3 is highly statistically significant for left arm -V2 lead misplacement (P=0) (1). It is important to exclude lead misplacement, or the patient may have incorrect treatment administered or the correct treatment withheld because of an error in recording an ECG. Of 230 unrecognised ECG lead misplacements in our hospital, 10.9% were left arm – V2 (2).
After a thorough search of the literature we have identified only 2 brief reports on this topic (3,4). Therefore, it is highly likely that if it does occur then ECG features will inadvertently be attributed to pulmonary embolism and managed inappropriately.
1. Lynch R, Ballesty L, Kuan SC, Ponnambolam Y. Left arm – V2 ECG Lead Misplacement by Colour: a largely unknown entity which can easily be Misdiagnosed as a Pulmonary Embolism. J Electrocardiol 2019; 53: e18. DOI: 10.1016/j.jelectrocard.2019.01.064. Presented at the International Conference on Electrocardiology, Chiba, Japan, 2018.
2. Lynch RM. ECG Lead Misplacement: Experience from an Irish District Hospital. Abstract accepted for International Conference in Emergency Medicine, Seoul, South Korea, June 2019.
3. Javier García-Niebla, Pablo Llontop García. An unusual case of electrode misplacement: left arm and V2 electrode reversal. J Electrocardiol 2008; 41:380-381.
4. Lynch RM. ECG lead misplacement by colour: what difference does it make? Sud J Med Sci 2014; 9 (3):145-150.
The judgment that imaging studies were over-utilised (1) should not be based on the degree of compliance with the Wells clinical decision rule (CDR), given the fact that the Wells score is not necessarily the optimal one for PE. In a study which compared 7 CDRs, namely, the Wells score, simplified Wells score, original Geneva score, revised Geneva score, Charlotte score and the Pisa model, diagnostic accuracy amounted to 0.44, 0.61, and 0.76 for simplified Wells score, Wells score, and Pisa model, respectively (2). The Wells score was tested in 598 primary care patients presenting with symptoms including cough, unexpected or sudden dyspnoea, deterioration in existing dyspnoea, and pleuritic pain, singly or in combination. These patients were referred to secondary care with suspected PE, where they were subsequently rigorously evaluated and investigated according to hospital guidelines. The diagnosis of PE was subsequently confirmed in 73 cases. However, in as many as 44 of those cases where PE was ruled out, the presenting Wells score amounted to >4 points (3), a score that is taken to signify "PE likely" in the simplified Wells score. In the evaluation of PE diagnostic confusion is compounded by the fact that PE can be an incidental finding, for example, during CT imaging in the oncological context (4). In the latter study, 25% of 52 patients with incidental PE had no PE-related symptoms (4). In the entire group of 52 patients with incidental PE, eight had m...
The judgment that imaging studies were over-utilised (1) should not be based on the degree of compliance with the Wells clinical decision rule (CDR), given the fact that the Wells score is not necessarily the optimal one for PE. In a study which compared 7 CDRs, namely, the Wells score, simplified Wells score, original Geneva score, revised Geneva score, Charlotte score and the Pisa model, diagnostic accuracy amounted to 0.44, 0.61, and 0.76 for simplified Wells score, Wells score, and Pisa model, respectively (2). The Wells score was tested in 598 primary care patients presenting with symptoms including cough, unexpected or sudden dyspnoea, deterioration in existing dyspnoea, and pleuritic pain, singly or in combination. These patients were referred to secondary care with suspected PE, where they were subsequently rigorously evaluated and investigated according to hospital guidelines. The diagnosis of PE was subsequently confirmed in 73 cases. However, in as many as 44 of those cases where PE was ruled out, the presenting Wells score amounted to >4 points (3), a score that is taken to signify "PE likely" in the simplified Wells score. In the evaluation of PE diagnostic confusion is compounded by the fact that PE can be an incidental finding, for example, during CT imaging in the oncological context (4). In the latter study, 25% of 52 patients with incidental PE had no PE-related symptoms (4). In the entire group of 52 patients with incidental PE, eight had main pulmonary artery thrombi, 19 had lobar thrombi, 11 had segmental thrombi, and 14 had subsegmental thrombi (4).
References
(1) Dhakal P., Iftikhar MH., Wang L., Atti V., Panthi S., Ling X et al
Overutilisation of imaging studies for diagnosis of pulmonary embolism: are we following the guidelines?
Postgrad Med J Jan 2019 doi;10.1136/postgradmedj-2018-135995
(2)Wahsh RA,, Agha MA Clinical probability of pulmonary embolism: comparison of different scoring systems
Egyptian Journal of Chest Diseases and Tuberculosis 2012;61:4190424
(3)Erkens PMG., Lucassen WAM., Geerding G-J., van Weert HCP., Kuijs-Augustijn M., van Heugten M et al
Alternative diagnoses in patients in whom the GP considered the diagnosis of pulmonary embolism
Family Practice 2014;31:670-677
(4)O'Connell CL., Boswell WD., Duddalwar V., Canton A., Mark LS., Vigen C., Liebman HA
Unsuspected pulmonary emboli in cancer patients: Clinical correlates and relevance
Journal of Clinical Oncology 2006;24:4828-4832
The terminology of the chest x-ray report can, indeed, impact on the timeliness of the eventual validation of the diagnosis of pulmonary tuberculosis, as shown by the case report of a 75 year old man who was originally admitted with fever and backache. Chest x-ray showed "fibronodular infiltration of the left apex of the lung" (1). On the basis of magnetic resonance imaging, backache was attributed to osteomyelitis, and he was treated with antibiotics, and there was no "work-up" of the fibronodular infiltration of the lung apex. Over a period of two weeks fever persisted, and he became pancytopenic. However, it was only after a further 3 weeks, when pancytopenia became more severe, that bone marrow aspiration and bone marrow biopsy was performed. The latter showed epitheloid granulomas and acid fast bacilli. Polymerase chain reaction analysis of the bone marrow specimens was positive for M tuberculosis DNA, and his sputum was culture positive for M tuberculosis. Although antituberculous chemotherapy was initiated immediately after the bone marrow results he died 3 days after commencing treatment (2).
Comment
Arguably, if the term "tuberculosis" had been used to qualify the nodular infiltration seen on chest x-ray, that would have raised the index of suspicion for tuberculosis (TB), and computed tomography might have been utilised to characterise the nodularity as being TB-related (2). Two weeks later, in the light of that heightene...
The terminology of the chest x-ray report can, indeed, impact on the timeliness of the eventual validation of the diagnosis of pulmonary tuberculosis, as shown by the case report of a 75 year old man who was originally admitted with fever and backache. Chest x-ray showed "fibronodular infiltration of the left apex of the lung" (1). On the basis of magnetic resonance imaging, backache was attributed to osteomyelitis, and he was treated with antibiotics, and there was no "work-up" of the fibronodular infiltration of the lung apex. Over a period of two weeks fever persisted, and he became pancytopenic. However, it was only after a further 3 weeks, when pancytopenia became more severe, that bone marrow aspiration and bone marrow biopsy was performed. The latter showed epitheloid granulomas and acid fast bacilli. Polymerase chain reaction analysis of the bone marrow specimens was positive for M tuberculosis DNA, and his sputum was culture positive for M tuberculosis. Although antituberculous chemotherapy was initiated immediately after the bone marrow results he died 3 days after commencing treatment (2).
Comment
Arguably, if the term "tuberculosis" had been used to qualify the nodular infiltration seen on chest x-ray, that would have raised the index of suspicion for tuberculosis (TB), and computed tomography might have been utilised to characterise the nodularity as being TB-related (2). Two weeks later, in the light of that heightened index of suspicion for TB, the subsequent development of pancytopenia might have raised the index of suspicion for disseminated tuberculosis, and bone marrow studies would have been initiated at that stage. Instead there was a further 3 weeks delay before the appropriate work-up for TB "kicked in" (1).
In the United States it is already recognised that delays in diagnosis of pulmonary TB are, in part, responsible for the paradox whereby population subgroups, such as white Americans, those in employment, and the US-born (all of them with background pulmonary TB rates of < 2 per 100,000 of the 2006 population) had higher 13-year increases in prevalence of cavitating tuberculosis than counterparts with higher background pulmonary TB rate (3). Might this phenomenon be attributable to greater prevalence of non-specific characterisation of chest x-ray images antedating cavitation in white, affluent, US-born citizens?
References
(1) Chien C-C., Chiou T-J., Lee M-Y., Hsiao L-T., Kwang W-K
Tuberculosis associated hemopahgocytic syndrome in a hemodialysis patient with protracted fever
International Journal of Hematology 2004;79:334-336
(2) Yoy M., Ellis S
Radiological diagnosis and follow up of pulmonary tuberculosis
Thorax 2010;86;663-674
(3)Wallace RM., Kammerer JS., Iademarco MF. et al
Increasing proportions of advanced pulmonary tuberculosis reported in the United States. Are delays in diagnosis on the rise?
Am J Respir Crit Care Med 2009;180:1016-1022
Given the fact that the risk of heparin-induced thrombocytopenia (HIT) is higher with prolonged therapy, the new oral anticoagulants (NOACs) might have a role in shortening the duration of low molecular weight heparin (LMWH) thromboprophylaxis in cancer patients from its currently recommended minimum of 3 months (1) to a much shorter duration by facilitating a transition to NOACSs( 2). That strategy might mitigate the risk of occurrence of HIT.
Currently, international guidelines recommend LMWH instead of warfarin for management of cancer-related venous thromboembolism (1), but the duration of that management strategy puts patients at risk of HIT, with all its attendant consequences. In an open-label, noninferiority trial, patients with cancer-associated venous thromboembolism were randomly assigned to LMWH for at least 5 days followed by oral edoxaban (60 mg/day) (edoxaban group) or subcutaneous dalteparin at an appropriate dose. Treatment duration in both cases was at least 6 months. In that study, recurrent venous thromboembolism occurred in 7.9% of the edoxaban group vs. 11.3% of the dalteparin group (P=0.09). Major bleeding occurred in 6.9% of the edoxaban group vs. 4% of the dalteparin group (P=0.04). The increase in major bleeding was principally attributable to upper gastrointestinal bleeding in patients who had gastric cancer (2). A criticism of that study is that the 60 mg/day of edoxaban is inherently associated with significantly (P=0.03) greater risk of...
Given the fact that the risk of heparin-induced thrombocytopenia (HIT) is higher with prolonged therapy, the new oral anticoagulants (NOACs) might have a role in shortening the duration of low molecular weight heparin (LMWH) thromboprophylaxis in cancer patients from its currently recommended minimum of 3 months (1) to a much shorter duration by facilitating a transition to NOACSs( 2). That strategy might mitigate the risk of occurrence of HIT.
Currently, international guidelines recommend LMWH instead of warfarin for management of cancer-related venous thromboembolism (1), but the duration of that management strategy puts patients at risk of HIT, with all its attendant consequences. In an open-label, noninferiority trial, patients with cancer-associated venous thromboembolism were randomly assigned to LMWH for at least 5 days followed by oral edoxaban (60 mg/day) (edoxaban group) or subcutaneous dalteparin at an appropriate dose. Treatment duration in both cases was at least 6 months. In that study, recurrent venous thromboembolism occurred in 7.9% of the edoxaban group vs. 11.3% of the dalteparin group (P=0.09). Major bleeding occurred in 6.9% of the edoxaban group vs. 4% of the dalteparin group (P=0.04). The increase in major bleeding was principally attributable to upper gastrointestinal bleeding in patients who had gastric cancer (2). A criticism of that study is that the 60 mg/day of edoxaban is inherently associated with significantly (P=0.03) greater risk of gastrointestinal bleeding (GIB) than vitamin K antagonists (VKA) therapy, but apixaban does not incur greater risk in that respect (3). For those patients who are eligible for the 30 mg/day dose of edoxaban, that preparation is an even better choice because it is associated with a significantly (p<0.001) lower risk of GIB than VKAs (3). Arguably, a NOAC with lower risk of GIB than VKAs might have a correspondingly lower risk of GIB than LWMH, but that hypothesis needs validating. Nevertheless, arguably with that hypothesis in mind, Al-Samkari et al. proposed a strategy for use of NOACs in cancer-related venous thromboembolism, whereby the most eligible patients would be those with no gastrointestinal malignancy, low risk of major bleeding, and no strong drug-drug interactions, especially if ease of treatment was a priority for that patient (4). I would add "especially if avoidance of HIT was also a priority".
References
(1)Farge D., Debourdeau P., Beckers P et al
International clinical practice guidelines for treatment and prophylaxis of venous thromboembolism in patients with cancer
J Thromb. Haemostat 2013;11:56-70
(2)Raskob GE., van Es N., Verhamme P et al
Edoxaban for the treatment of cancer-associated venous thromboembolism
N Engl J Med 2018;378:615-624
(3)Eikelboom J., Merli G
Bleeding with direct oral anticoagulants vs warfarin: Clinical experience
Am J Med 2016;129:S33-S40
(4)Al-Samkari H., Connors JM
The role of direct oral anticoagulants in treatment of cancer-associated thrombosis
Cancers 2018;10:271;doi:10.3390/cancers10080271
In their excellent review the authors drew attention to alternative oral anticoagulants to manage heparin-induced thrombocytopenia(HIT)(1). The American College of Chest Physicians guideline for HIT and HIT-associated thrombosis(HITT) cautions against premature transition to vitamin K antagonist therapy due to significant risk of warfarin-induced skin necrosis or development of venous limb gangrene(2). According to a recent review, the new oral anticoagulants(NOACs) are not burdened with that disadvantage, and their rapid onset of action generates a smooth transition to forward anticoagulation in patients with HIT/HITT. Furthermore, NOACs do not cross-react with HIT antibodies(3). That review encompassed data from 56 HIT/HITT patients subsequently treated with NOACs. Data were derived from 3 studies and 8 case reports. Mean age of the 56 patients was 70, twenty four had HIT, and thirty two had HITT. At the time of HIT/HITT diagnosis a nonheparin parenteral agent was initiated in 42, and the remaining 14 transitioned to NOACs straightaway. The NOACS used in the 56 patients were rivaroxaban, apixaban, and dabigatran in 54%, 29%, and 18% of cases, respectively. There were only 2 instances of recurrent thrombosis with NOAC therapy. Major bleeding occurred in 3 patients who did not appear to be on NOAC therapy at the time of the bleed.
References
(1) Prince M., Wenham T
Heparin-induced thrombocytopemia
Postgrad Med J 2018;94:453-547
(2)Linkins L-A....
In their excellent review the authors drew attention to alternative oral anticoagulants to manage heparin-induced thrombocytopenia(HIT)(1). The American College of Chest Physicians guideline for HIT and HIT-associated thrombosis(HITT) cautions against premature transition to vitamin K antagonist therapy due to significant risk of warfarin-induced skin necrosis or development of venous limb gangrene(2). According to a recent review, the new oral anticoagulants(NOACs) are not burdened with that disadvantage, and their rapid onset of action generates a smooth transition to forward anticoagulation in patients with HIT/HITT. Furthermore, NOACs do not cross-react with HIT antibodies(3). That review encompassed data from 56 HIT/HITT patients subsequently treated with NOACs. Data were derived from 3 studies and 8 case reports. Mean age of the 56 patients was 70, twenty four had HIT, and thirty two had HITT. At the time of HIT/HITT diagnosis a nonheparin parenteral agent was initiated in 42, and the remaining 14 transitioned to NOACs straightaway. The NOACS used in the 56 patients were rivaroxaban, apixaban, and dabigatran in 54%, 29%, and 18% of cases, respectively. There were only 2 instances of recurrent thrombosis with NOAC therapy. Major bleeding occurred in 3 patients who did not appear to be on NOAC therapy at the time of the bleed.
References
(1) Prince M., Wenham T
Heparin-induced thrombocytopemia
Postgrad Med J 2018;94:453-547
(2)Linkins L-A., Dans AL., Moores LK et al
American College of Chest Physicians. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis: American College of Chest Physicians evidence-based clinical practice guidelines
CHEST 2012;141(2 suppl) e4958-5308
(3) Trands PN., Trans M-H
Emerging role of direct oral anticoagulants in the management of heparin-induced thrombocytopenia
Clinical and Applied Thrombosis/Hemostasis 2018;24:201-209
A point of view:
Diuretics and many dietary components significantly increase the risk of uric acid stone formation--Our major concern.
We read with interest and applauded the authors of the review article that mentions adjustment of potential pathophysiologic defects by pharmacotherapy and strongly recommends dietary modification for the prevention of uric stone recurrence (1).
Two thirds of urate excretion occurs at the kidney, the remainder being excreted by the gut. Earlier studies have suggested that the urate is almost fully reabsorbed and that the urate excreted by the kidney is the result of tubular secretion. But more recent data suggests that secretion plays little part, and that excreted urate largely represents the filtered urate which escapes reabsorption. (2)
Different diuretics are likely to have different effects on the renal handling of urate, but this has not been critically ascertained; patients receiving more powerful loop diuretics have a higher risk of developing gout than those receiving the weaker thiazides (3)
Conceptually, a visit to a beer garden is dangerous for two reasons, the intake of purine rich food and drinks (beer) and the intake of fructose-rich soft drinks that blocks certain urate transporters that facilitate urate excretion (4).
These are also associated with a number of common situations, such as the metabolic syndrome, which is correctable by changing to a low caloric diet, essential hypertensio...
A point of view:
Diuretics and many dietary components significantly increase the risk of uric acid stone formation--Our major concern.
We read with interest and applauded the authors of the review article that mentions adjustment of potential pathophysiologic defects by pharmacotherapy and strongly recommends dietary modification for the prevention of uric stone recurrence (1).
Two thirds of urate excretion occurs at the kidney, the remainder being excreted by the gut. Earlier studies have suggested that the urate is almost fully reabsorbed and that the urate excreted by the kidney is the result of tubular secretion. But more recent data suggests that secretion plays little part, and that excreted urate largely represents the filtered urate which escapes reabsorption. (2)
Different diuretics are likely to have different effects on the renal handling of urate, but this has not been critically ascertained; patients receiving more powerful loop diuretics have a higher risk of developing gout than those receiving the weaker thiazides (3)
Conceptually, a visit to a beer garden is dangerous for two reasons, the intake of purine rich food and drinks (beer) and the intake of fructose-rich soft drinks that blocks certain urate transporters that facilitate urate excretion (4).
These are also associated with a number of common situations, such as the metabolic syndrome, which is correctable by changing to a low caloric diet, essential hypertension, decompensated heart failure, saturnine gout, which is correctable by lead chelation, and alcohol consumption (3).
Conclusion:
Recently gained insight into the mechanisms of urate transport through tubular cells is the identification of four proteins which act as urate transporters at that level. These are UAT (urate transporter/channel), two members of the of the family of organic anion transporters (OAT1 and OAT3) related to the tubular secretion of urate, and the main protein responsible for tubular reabsorption of urate (URAT1), located at the apical membrane of the proximal tubular cells (5, 6).
However, as we learn to what extent hyperuricaemia associated with diuretics is due to a direct and specific action of these drugs on the tubular wall or whether they act more generally by reducing the vascular volumes, this will undoubtedly increase our understanding of the association (3). Meanwhile, we need to be careful about dietary components which may also be responsible for the menace.
References:
1. Qi Ma,Li Fang,Rui Su et al, Review: Uric acid stones, clinical manifestations and therapeutic considerations. https://pmj.bmj.com/content/early/2018/07/12/postgradmedj-2017-135332
2. Roch-Ramel F, Guisan B. Renal transport of urate in humans. News Physiol Sci1999; 14:80–4.
3. E Pascual, M Perdiguero. Editorial: Gout, diuretics and the kidney. Annals of the Rheumatic diseases. Volume 65, Issue 8
4. H.-J. Anders. Crystal arthritis: SP0125 Renal Handling of Urate and Gout. Annals of Reumatic diseases. Volume 75, Issue Suppl 2
5. Hediger MA, Johnson RJ, Miyazaki H, Endou H. Molecular physiology of urate transport. Physiology (Bethesda) 2005; 20:125–33.
6. Enomoto A, Endou H. Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease. Clin Exp Nephrol2005; 9:195–205.
The secondary syphilis we see today is potentially different from the secondary syphilis which belongs to the era antedating the presently high incidence and prevalence of human immunodeficiency virus (HIV) infection. Sexually active subjects who harbour the coexistence of HIV infection (with attendant immune suppression) and syphilis are also at risk of opportunistic infections such as tuberculosis and cryptococcosis (1)(2)(3). In one HIV-positive patient aged 43, neurosyphilis coexisted with both cryptococcal meningitis and tuberculous meningitis. The cerebrospinal fluid (CSF) was characterised by lymphocyte predominance low glucose and high protein. Furthermore, in the CSF, cryptococcal antigen amounted to 1;640, and the VDRL from the CSF was also reactive. CSF culture grew M. tuberculosis, and this was confirmed by the polymerase chain reaction (1). In another instance, a 37 year old man with past medical history of HIV infection had neurosyphilis coexisting with cryptococcal meningitis. The CSF was characterised by lymphocyte predominance, positive fluorescent treponemal antibody test and cryptococcal antigen titre of 1:640 (2). Another report involved a 40 year old man with coexisting neurosyphilis and cryptococcal meningitis. The CSF showed lymphocyte predominance and high protein concentration. Cryptococcus was cultured from the CSF and both serum serology and CSF were positive for syphilis (3). These anecdotal reports might underestimate the true prevalence of coe...
The secondary syphilis we see today is potentially different from the secondary syphilis which belongs to the era antedating the presently high incidence and prevalence of human immunodeficiency virus (HIV) infection. Sexually active subjects who harbour the coexistence of HIV infection (with attendant immune suppression) and syphilis are also at risk of opportunistic infections such as tuberculosis and cryptococcosis (1)(2)(3). In one HIV-positive patient aged 43, neurosyphilis coexisted with both cryptococcal meningitis and tuberculous meningitis. The cerebrospinal fluid (CSF) was characterised by lymphocyte predominance low glucose and high protein. Furthermore, in the CSF, cryptococcal antigen amounted to 1;640, and the VDRL from the CSF was also reactive. CSF culture grew M. tuberculosis, and this was confirmed by the polymerase chain reaction (1). In another instance, a 37 year old man with past medical history of HIV infection had neurosyphilis coexisting with cryptococcal meningitis. The CSF was characterised by lymphocyte predominance, positive fluorescent treponemal antibody test and cryptococcal antigen titre of 1:640 (2). Another report involved a 40 year old man with coexisting neurosyphilis and cryptococcal meningitis. The CSF showed lymphocyte predominance and high protein concentration. Cryptococcus was cultured from the CSF and both serum serology and CSF were positive for syphilis (3). These anecdotal reports might underestimate the true prevalence of coexistence of neurosyphilis and other meningeal infections in HIV-positive patients. In order to obtain a true measure of this subtype of mixed meningitis, the recommendation to test for cryptococcal meningitis in all cases of suspected tuberculous meningitis evaluated in HIV-positive patients (4) should be extended to include testing for neurosyphilis in all HIV-positive patients with suspected tuberculous meningitis or suspected cryptococcal meningitis.
References
(1) Zamora JA., Espinoza LA., Nwanyanwu RN
Neurosyphilis with concomitant cryptococcal and tuberculous meningitis in a patient with AIDS: report of a unique case
Case reports in Infectious diseases 2017;doi.org/10.1155/2017/410.3558
(2)Swe T., Laurent BP., Shah NN
Concurrent central nervous system infective pathology in a severely immunocompromised patient
Journal of Family Medicine and Primary Care 2016;5:685-687
(3) Silber E., Sonnenberg P., Koornof HJ., Morris L., Saffer D
Dual infective pathology in patients with cryptococcal meningitis
Neurology 1998;51:1213-1215
(4)Thwaites G., Fisher M., Hemingway C., Scott G., Solomon T., Innes J
british Infection society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children
Journal of Infection 2009;59;167-187
While it is true, as the authors assert, that there is limited data on exercise-induced reversal of cardiac remodeling, a recent study suggests that the cardiac effects of sedentary aging(in middle age) can be reversed by exercise training(1). In that study sixty one(48% male) healthy sedentary participants of mean age 53 were randomly assigned to either 2 years of exercise training(n=34) or attention control(control=27). In each subject measurements were taken to evaluate left ventricular stiffness. Maximal oxygen uptake was measured to quantify changes in fitness. Fifty three participants completed the study. Adherence to prescribed exercise sessions was 88% on average. As a result of exercise training left ventricular stiffness was significantly(p=0.0018)reduced(right/ downward shift in the end-diastolic pressure-volume relationships) in comparison with its pre-exercise value. This parameter did not change in the control group. Exercise significantly(p<0.001)increased the left ventricular end diastolic volume , whereas pulmonary capillary wedge pressure was unchanged, thereby generating significantly(p=0.007) greater stroke volume for any given filling pressure. The authors concluded that regular exercise training could provide protection against the future risk of heart failure with preserved ejection fraction by mitigating the risk of increase in cardiac stiffness attributable to a sedentary lifestyle(1). Accordingly, although we cannot influence the natu...
While it is true, as the authors assert, that there is limited data on exercise-induced reversal of cardiac remodeling, a recent study suggests that the cardiac effects of sedentary aging(in middle age) can be reversed by exercise training(1). In that study sixty one(48% male) healthy sedentary participants of mean age 53 were randomly assigned to either 2 years of exercise training(n=34) or attention control(control=27). In each subject measurements were taken to evaluate left ventricular stiffness. Maximal oxygen uptake was measured to quantify changes in fitness. Fifty three participants completed the study. Adherence to prescribed exercise sessions was 88% on average. As a result of exercise training left ventricular stiffness was significantly(p=0.0018)reduced(right/ downward shift in the end-diastolic pressure-volume relationships) in comparison with its pre-exercise value. This parameter did not change in the control group. Exercise significantly(p<0.001)increased the left ventricular end diastolic volume , whereas pulmonary capillary wedge pressure was unchanged, thereby generating significantly(p=0.007) greater stroke volume for any given filling pressure. The authors concluded that regular exercise training could provide protection against the future risk of heart failure with preserved ejection fraction by mitigating the risk of increase in cardiac stiffness attributable to a sedentary lifestyle(1). Accordingly, although we cannot influence the natural history of diastolic heart failure we can mitigate the risk of its occurence.
References
Howden EJ., Sarma S., Lawley JS., Opondo M., Cornwell W., Stoller D et al
Reversing the cardiac effects of sedentary aging in middle age-A randomised controlled trial
Circulation 2018;137:DOI 10.1161/CIRCULATIONAHA.117.030617
A study performed in the United States lends support to the recommendations made by the European Working Time Directive regarding "ring fencing" of rest times for surgical trainees. In that study the effect of daytime sleepiness(measured on the Epworth Sleepiness Scale(ESS) was measured in 19 surgical trainees in otolaryngology-head and neck surgery programmes in 2 academic institution. ESS was documented, and surgical skill(in performig septoplasty) was evaluated by attending physicians using a global assessment tool and a skill-based visual analog scale. The attending physicians were unaware of the trainees' report on the ESS. Trainees, themselves, were also required to rate their own performance. The outcome was that , in regression analysis, there was a statistically significant inverse association between ESS scores and attending physician-rated technical skill both for the global assessment tool(p < 0.001), and for the visual analog scale(p=0.03)(1). Using both parameters the self-rated scores obtained by the trainees did not reach statistical significance(1). In other words, the trainees did not recognise the effect that daytime sleepiness was having on their surgical performance.
Show MoreThe wider inference that can be drawn is as follows:-
Daytime sleepiness impairs performance even though the trainee may be unaware of this adverse effect
These observations are generalisable both to trainees and to consultant staff
Consultan...
The tension between head, heart and checklist is strikingly exemplified by the clinical decision process involved in the diagnosis of pulmonary embolism(PE). Currently, this process is characterised by a proliferation of clinical decision rules which involve mind numbingly long lists of items, and their associated calculations, the latter intended to generate numerical scores(1)(2) which confer a semblance of scientific credibility to the process. By contrast, a school of thought has emerged which posits that clinical acumen, defined as unstructured clinical impression or "gestalt" is, at the very least, as reliable a sole reliance on clinical prediction rules for discriminating among patients who have a low, moderate, or high pretest probability of PE(1). Over time, gestalt, itself, appears progressively to confer increasing diagnostic accuracy, judging by the diagnostic performance of senior physicians(postgraduate year 4 plus) vs interns(postgraduate year 1) working in the emergency department of a large teaching hospital(3). Concurrently, we have seen the emergence of gestalt-based clinical decision strategies such as the PERC rule(4) and the YEARS algorithm(5). as an attempt to resolve the tension between underdiagnosis and overdiagnosis of PE.
Show MoreClinical acumen, itself, performs best when it is informed, not only by the numerical score of years since obtaining one's medical qualification, but also by interaction(through the medium of case co...
Dear Editor,
We read with interest Thomson et al’s article “ECG in suspected pulmonary embolism” which was published in Postgraduate Medical Journal in January 2019. We would like to bring to your attention another important but little-known cause of S1Q3T3, namely left arm – V2 ECG lead misplacement. This occurs when the yellow ECG cables are misplaced and can easily be misdiagnosed as a pulmonary embolism. A characteristic appearance occurs which we believe is pathognomonic for LA – V2 misplacement. In addition to S1Q3T3, a tall R wave in lead III is seen (1). In a study of 62 patients in whom we recorded both a normal and an LA V2 ECG lead misplacement, we observed that the presence of S1Q3T3R3 is highly statistically significant for left arm -V2 lead misplacement (P=0) (1). It is important to exclude lead misplacement, or the patient may have incorrect treatment administered or the correct treatment withheld because of an error in recording an ECG. Of 230 unrecognised ECG lead misplacements in our hospital, 10.9% were left arm – V2 (2).
After a thorough search of the literature we have identified only 2 brief reports on this topic (3,4). Therefore, it is highly likely that if it does occur then ECG features will inadvertently be attributed to pulmonary embolism and managed inappropriately.
1. Lynch R, Ballesty L, Kuan SC, Ponnambolam Y. Left arm – V2 ECG Lead Misplacement by Colour: a largely unknown entity which can easily be Misdiagnosed as a Pulmo...
Show MoreThe judgment that imaging studies were over-utilised (1) should not be based on the degree of compliance with the Wells clinical decision rule (CDR), given the fact that the Wells score is not necessarily the optimal one for PE. In a study which compared 7 CDRs, namely, the Wells score, simplified Wells score, original Geneva score, revised Geneva score, Charlotte score and the Pisa model, diagnostic accuracy amounted to 0.44, 0.61, and 0.76 for simplified Wells score, Wells score, and Pisa model, respectively (2). The Wells score was tested in 598 primary care patients presenting with symptoms including cough, unexpected or sudden dyspnoea, deterioration in existing dyspnoea, and pleuritic pain, singly or in combination. These patients were referred to secondary care with suspected PE, where they were subsequently rigorously evaluated and investigated according to hospital guidelines. The diagnosis of PE was subsequently confirmed in 73 cases. However, in as many as 44 of those cases where PE was ruled out, the presenting Wells score amounted to >4 points (3), a score that is taken to signify "PE likely" in the simplified Wells score. In the evaluation of PE diagnostic confusion is compounded by the fact that PE can be an incidental finding, for example, during CT imaging in the oncological context (4). In the latter study, 25% of 52 patients with incidental PE had no PE-related symptoms (4). In the entire group of 52 patients with incidental PE, eight had m...
Show MoreThe terminology of the chest x-ray report can, indeed, impact on the timeliness of the eventual validation of the diagnosis of pulmonary tuberculosis, as shown by the case report of a 75 year old man who was originally admitted with fever and backache. Chest x-ray showed "fibronodular infiltration of the left apex of the lung" (1). On the basis of magnetic resonance imaging, backache was attributed to osteomyelitis, and he was treated with antibiotics, and there was no "work-up" of the fibronodular infiltration of the lung apex. Over a period of two weeks fever persisted, and he became pancytopenic. However, it was only after a further 3 weeks, when pancytopenia became more severe, that bone marrow aspiration and bone marrow biopsy was performed. The latter showed epitheloid granulomas and acid fast bacilli. Polymerase chain reaction analysis of the bone marrow specimens was positive for M tuberculosis DNA, and his sputum was culture positive for M tuberculosis. Although antituberculous chemotherapy was initiated immediately after the bone marrow results he died 3 days after commencing treatment (2).
Show MoreComment
Arguably, if the term "tuberculosis" had been used to qualify the nodular infiltration seen on chest x-ray, that would have raised the index of suspicion for tuberculosis (TB), and computed tomography might have been utilised to characterise the nodularity as being TB-related (2). Two weeks later, in the light of that heightene...
Given the fact that the risk of heparin-induced thrombocytopenia (HIT) is higher with prolonged therapy, the new oral anticoagulants (NOACs) might have a role in shortening the duration of low molecular weight heparin (LMWH) thromboprophylaxis in cancer patients from its currently recommended minimum of 3 months (1) to a much shorter duration by facilitating a transition to NOACSs( 2). That strategy might mitigate the risk of occurrence of HIT.
Show MoreCurrently, international guidelines recommend LMWH instead of warfarin for management of cancer-related venous thromboembolism (1), but the duration of that management strategy puts patients at risk of HIT, with all its attendant consequences. In an open-label, noninferiority trial, patients with cancer-associated venous thromboembolism were randomly assigned to LMWH for at least 5 days followed by oral edoxaban (60 mg/day) (edoxaban group) or subcutaneous dalteparin at an appropriate dose. Treatment duration in both cases was at least 6 months. In that study, recurrent venous thromboembolism occurred in 7.9% of the edoxaban group vs. 11.3% of the dalteparin group (P=0.09). Major bleeding occurred in 6.9% of the edoxaban group vs. 4% of the dalteparin group (P=0.04). The increase in major bleeding was principally attributable to upper gastrointestinal bleeding in patients who had gastric cancer (2). A criticism of that study is that the 60 mg/day of edoxaban is inherently associated with significantly (P=0.03) greater risk of...
In their excellent review the authors drew attention to alternative oral anticoagulants to manage heparin-induced thrombocytopenia(HIT)(1). The American College of Chest Physicians guideline for HIT and HIT-associated thrombosis(HITT) cautions against premature transition to vitamin K antagonist therapy due to significant risk of warfarin-induced skin necrosis or development of venous limb gangrene(2). According to a recent review, the new oral anticoagulants(NOACs) are not burdened with that disadvantage, and their rapid onset of action generates a smooth transition to forward anticoagulation in patients with HIT/HITT. Furthermore, NOACs do not cross-react with HIT antibodies(3). That review encompassed data from 56 HIT/HITT patients subsequently treated with NOACs. Data were derived from 3 studies and 8 case reports. Mean age of the 56 patients was 70, twenty four had HIT, and thirty two had HITT. At the time of HIT/HITT diagnosis a nonheparin parenteral agent was initiated in 42, and the remaining 14 transitioned to NOACs straightaway. The NOACS used in the 56 patients were rivaroxaban, apixaban, and dabigatran in 54%, 29%, and 18% of cases, respectively. There were only 2 instances of recurrent thrombosis with NOAC therapy. Major bleeding occurred in 3 patients who did not appear to be on NOAC therapy at the time of the bleed.
Show MoreReferences
(1) Prince M., Wenham T
Heparin-induced thrombocytopemia
Postgrad Med J 2018;94:453-547
(2)Linkins L-A....
A point of view:
Show MoreDiuretics and many dietary components significantly increase the risk of uric acid stone formation--Our major concern.
We read with interest and applauded the authors of the review article that mentions adjustment of potential pathophysiologic defects by pharmacotherapy and strongly recommends dietary modification for the prevention of uric stone recurrence (1).
Two thirds of urate excretion occurs at the kidney, the remainder being excreted by the gut. Earlier studies have suggested that the urate is almost fully reabsorbed and that the urate excreted by the kidney is the result of tubular secretion. But more recent data suggests that secretion plays little part, and that excreted urate largely represents the filtered urate which escapes reabsorption. (2)
Different diuretics are likely to have different effects on the renal handling of urate, but this has not been critically ascertained; patients receiving more powerful loop diuretics have a higher risk of developing gout than those receiving the weaker thiazides (3)
Conceptually, a visit to a beer garden is dangerous for two reasons, the intake of purine rich food and drinks (beer) and the intake of fructose-rich soft drinks that blocks certain urate transporters that facilitate urate excretion (4).
These are also associated with a number of common situations, such as the metabolic syndrome, which is correctable by changing to a low caloric diet, essential hypertensio...
The secondary syphilis we see today is potentially different from the secondary syphilis which belongs to the era antedating the presently high incidence and prevalence of human immunodeficiency virus (HIV) infection. Sexually active subjects who harbour the coexistence of HIV infection (with attendant immune suppression) and syphilis are also at risk of opportunistic infections such as tuberculosis and cryptococcosis (1)(2)(3). In one HIV-positive patient aged 43, neurosyphilis coexisted with both cryptococcal meningitis and tuberculous meningitis. The cerebrospinal fluid (CSF) was characterised by lymphocyte predominance low glucose and high protein. Furthermore, in the CSF, cryptococcal antigen amounted to 1;640, and the VDRL from the CSF was also reactive. CSF culture grew M. tuberculosis, and this was confirmed by the polymerase chain reaction (1). In another instance, a 37 year old man with past medical history of HIV infection had neurosyphilis coexisting with cryptococcal meningitis. The CSF was characterised by lymphocyte predominance, positive fluorescent treponemal antibody test and cryptococcal antigen titre of 1:640 (2). Another report involved a 40 year old man with coexisting neurosyphilis and cryptococcal meningitis. The CSF showed lymphocyte predominance and high protein concentration. Cryptococcus was cultured from the CSF and both serum serology and CSF were positive for syphilis (3). These anecdotal reports might underestimate the true prevalence of coe...
Show MoreWhile it is true, as the authors assert, that there is limited data on exercise-induced reversal of cardiac remodeling, a recent study suggests that the cardiac effects of sedentary aging(in middle age) can be reversed by exercise training(1). In that study sixty one(48% male) healthy sedentary participants of mean age 53 were randomly assigned to either 2 years of exercise training(n=34) or attention control(control=27). In each subject measurements were taken to evaluate left ventricular stiffness. Maximal oxygen uptake was measured to quantify changes in fitness. Fifty three participants completed the study. Adherence to prescribed exercise sessions was 88% on average. As a result of exercise training left ventricular stiffness was significantly(p=0.0018)reduced(right/ downward shift in the end-diastolic pressure-volume relationships) in comparison with its pre-exercise value. This parameter did not change in the control group. Exercise significantly(p<0.001)increased the left ventricular end diastolic volume , whereas pulmonary capillary wedge pressure was unchanged, thereby generating significantly(p=0.007) greater stroke volume for any given filling pressure. The authors concluded that regular exercise training could provide protection against the future risk of heart failure with preserved ejection fraction by mitigating the risk of increase in cardiac stiffness attributable to a sedentary lifestyle(1). Accordingly, although we cannot influence the natu...
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