Evaluating the transmission risk of SARS-CoV-2 from sewage pollution.

The presence of SARS-CoV-2 in untreated sewage has been confirmed in many countries but its incidence and infection risk in contaminated waters is poorly understood. The River Thames in the UK receives untreated sewage from 57 Combined Sewer Overflows (CSOs), with many discharging dozens of times per year. This study investigated if such discharges provide a pathway for environmental transmission of SARS-CoV-2. Samples of wastewater, surface water, and sediment collected close to six CSOs on the River Thames were assayed over eight months for SARS-CoV-2 RNA and infectious virus. Bivalves were also sampled as an indicator species of viral bioaccumulation. Sediment and water samples from the Danube and Sava rivers in Serbia, where raw sewage is also discharged in high volumes, were assayed as a positive control. No evidence of SARS-CoV-2 RNA or infectious virus was found in UK samples, in contrast to RNA positive samples from Serbia. Furthermore, this study shows that infectious SARS-CoV-2 inoculum is stable in Thames water and sediment for <3 days, while SARS-CoV-2 RNA is detectable for at least seven days. This indicates that dilution of wastewater likely limits environmental transmission, and that detection of viral RNA alone is not an indication of pathogen spillover.

Activity levels after pulmonary rehabilitation - what really happens?

OBJECTIVES: To assess the changes in physical activity in subjects with chronic obstructive pulmonary disease over 6months after pulmonary rehabilitation. DESIGN: Prospective, observational study. Activity was measured over 2-day periods at the end of rehabilitation, and repeated every 6weeks for 6months using the ActivPAL uni-axial accelerometer. These results were compared with the shuttle walking test (SWT) and the St. George's Respiratory Disease Questionnaire (SGRDQ). SETTING: UK community hospital. PARTICIPANTS: Adults completing a community rehabilitation programme. MAIN OUTCOME MEASURE: Time spent standing and mobilising ('uptime'). RESULTS: Of 34 subjects recruited, 28 completed the 6-month study period (mean age 69years, mean forced expiratory volume in 1second 1.3l). Participants wore the monitor for 13.8 to 14.2hours/day. At baseline (post-rehabilitation), participants spent 1.7 [standard deviation (SD) 1.3]hours/day walking and 3.5 (SD 2.6)hours/day standing. Taking the group as a whole, mean uptime decreased marginally by 13.6minutes after 24weeks compared with baseline, with significant individual variability. In all but one subject who showed decreased activity, this was apparent after 6weeks. There were no significant changes in the mean SWT or SGRDQ. Significant associations between total uptime and the SWT were found, but coefficients were weak. It was not possible to predict individual responses from baseline data. CONCLUSION: The accelerometer provides useful supplementary data in patients completing rehabilitation programmes, and the results reveal wide variation. The weak associations between activity data and the SWT suggest that monitors provide additional information. More work is required to determine the factors associated with early deterioration in activity in order to design appropriate interventions.

Comparison of infrared thermography and laser speckle contrast imaging for the dynamic assessment of digital microvascular function.

OBJECTIVES: Laser speckle contrast imaging (LSCI) is a novel non-invasive microvascular imaging modality. The present study evaluates the validity and reliability of LSCI by comparison with infrared thermography (IRT) for the dynamic assessment of digital microvascular function in healthy volunteers. METHODS: Subjects attended on 3 occasions. Simultaneous assessment of cutaneous perfusion at 3 distinct regions of interest (ROI) within the hands was undertaken using LSCI and infrared thermography (IRT) at baseline, and at 13s intervals over 15 min following a standardised local cold challenge. Endpoints for evaluation included absolute measurements at baseline and following cold stress, in addition to the characteristics of the re-warming curves (maximum % recovery and maximum gradient). Visits 1 and 2 were undertaken in identical conditions (ambient temperature 23°C) to assess reproducibility, whereas visit 3 was undertaken at a lower ambient room temperature of 18°C to evaluate responsiveness to reduction in ambient room temperature. RESULTS: Fourteen healthy participants completed the study. There was greater variability in the data generated using LSCI compared with the highly damped IRT, reflecting greater sensitivity of LSCI to physiological variation and movement artefact. LSCI and IRT correlated well at baseline and following cold challenge for all endpoints (r(s) for pooled data between 0.5 and 0.65, p<0.00005). Reproducibility of both IRT and LSCI was excellent (ICCs>0.75) for absolute assessments but lower for re-warming curve characteristics. LSCI provides greater spatial resolution than IRT identifying variation in cutaneous perfusion within the hands most likely associated with the presence of arteriovenous anastamoses. Both techniques were responsive to reduction in ambient room temperature. Effect sizes were greatest for IRT than LSCI (e.g. -1.17 vs. -0.85 at ROI 1 at baseline) although this may represent heat transfer rather than altered vascular perfusion. DISCUSSION: In the dynamic assessment of digital vascular perfusion, LSCI correlates well with IRT, is reproducible and responsive to reduction in ambient room temperature. Absolute measurements appear preferable to parameters derived from re-warming curve characteristics when assessing digital perfusion following cold challenge. The greater temporal and spatial resolution of LSCI compared with IRT may facilitate the development of novel assessment tools of autonomic function and digital cutaneous perfusion.

Influence of the cold challenge on the discriminatory capacity of the digital distal-dorsal difference in the thermographic assessment of Raynaud's phenomenon.

OBJECTIVES: To investigate the influence of a standardised cold stress test (CST) on the thermographic 'distal-dorsal difference' (DDD) and its capacity to differentiate between disease states in the assessment of Raynaud's phenomenon (RP), and to compare the discriminatory capacity of the DDD of individual digits with composite indices of multiple digits. METHODS: Thermographic images of 55 patients with primary RP (PRP, n=27) and systemic sclerosis (SSc, n=28) who had undergone assessment of RP were retrospectively reviewed. The DDD for individual digits, and composite scores of multiple digits, were calculated at baseline (23°C), and at 10 min following CST. The discriminatory capacity of the mean DDD, and the proportion of patients with a clinically meaningful DDD of <-1°C, were assessed for individual digits and composite indices, at baseline and following cold challenge. RESULTS: There was a more pronounced decrease of the DDD (indicating reduced distal perfusion) following CST in patients with PRP compared to SSc. The disparity in response to CST between groups narrowed the differences that were present at baseline, reducing the discriminatory capacity of the DDD for all endpoints. Sparing of the thumbs occurs to a greater extent in SSc (P<0.005) compared with PRP (P<0.05) but does not facilitate differentiation between groups. Large variability of the DDD within groups precludes easy differentiation between disease states. Composite indices of multiple digits are preferable to individual digital assessment. CONCLUSIONS: The discriminatory capacity of the DDD is lost following CST. The CST may not be essential in the thermographic assessment of RP, potentially allowing greater use of thermography in clinical practise.

Microvascular responses following digital thermal hyperaemia and iontophoresis measured by laser Doppler imaging in idiopathic inflammatory myopathy.

OBJECTIVE: To measure microvascular function using laser Doppler imaging following digital hyperaemia and iontophoresis of vasoactive substances in patients with idiopathic inflammatory myopathy (IIM). METHODS: Fifteen patients with IIM including eight patients with dermatomyositis (DM) and seven patients with polymyositis (PM) were studied. Fifteen age-matched normal controls were also recruited. Scanning red laser Doppler imaging (LDI) was performed after resting the subject in a temperature controlled room at 23 degrees C for 20 min. An initial LDI scan was performed to assess baseline blood flow. Digital microvascular responses were quantified following a maximum hyperaemic response (MHR) and iontophoresis with endothelial dependent acetylcholine (Ach) and endothelial independent sodium nitroprusside (SNP). Maximum vasodilation following iontophoresis was expressed as a percentage of the MHR. RESULTS: All subjects were age matched, and the duration of disease was similar between the IIM patients. There was no significant difference in baseline blood flow when comparing the three study groups. There was no significant difference in MHR or SNP/MHR when comparing DM or PM with controls. However, Ach/MHR was significantly lower in both the DM and PM group compared with controls (both P < 0.01). There was no significant difference in any of the microvascular responses when comparing patients with DM directly with PM. CONCLUSION: This is the first study to evaluate microvascular responses using LDI in patients with IIM. We have demonstrated that patients with DM have abnormal endothelial dependent mediated vasodilation and the same abnormality is present in patients with PM.

Maximum blood flow and microvascular regulatory responses in systemic sclerosis.

Objectives. To investigate microvascular function using laser Doppler imaging (LDI) following response to hyperaemia, neurovascular reflex and iontophoresis in systemic sclerosis (SSc) in comparison with primary Raynaud's phenomenon (PRP) and age-matched controls. A secondary aim was to evaluate if SSc patients with a higher Medsger vascular score have lower endothelial responses. Methods. Twenty patients with SSc, 10 PRP and 17 controls were studied. Patients with SSc were scored using the vascular component of the Medsger severity scale. A baseline LDI scan was performed on the dorsal aspect of both hands. Digital responses were quantified following maximum hyperaemic response (MHR), contralateral vasoconstrictor response (CLVc) and iontophoresis with acetylcholine (Ach)-endothelial dependent and sodium nitroprusside (SNP)-endothelial independent. Mean blood flow was quantified over a standard region of interest. Results. MHR was lower in SSc patients compared with controls (P < 0.001). A similar trend was seen when comparing SSc with PRP although this did not reach significance (P = 0.07). CLVc and Ach/MHR were lower in SSc vs PRP (P < 0.05) and controls (P < 0.001). No difference was observed in MHR, CLVc and Ach/MHR between PRP and controls. Overall, SNP/MHR was similar in all the three groups. SSc patients with a higher Medsger vascular score had lower endothelial-dependent (P < 0.01) and independent (P < 0.05) responses. Conclusion. SSc patients have abnormal microvascular regulatory responses compared with PRP and controls. This study also suggests that the degree of endothelial dysfunction may be related to the degree of peripheral vascular involvement.

Position-sensing technologies for movement analysis in stroke rehabilitation.

Research has focused on improvement of the quality of life of stroke patients. Gait detection, kinematics and kinetics analysis, home-based rehabilitation and telerehabilitation are the areas where there has been increasing research interest. The paper reviews position-sensing technologies and their application for human movement tracking and stroke rehabilitation. The review suggests that it is feasible to build a home-based telerehabilitation system for sensing and tracking the motion of stroke patients.

Effect of atenolol on QTc interval lengthening during hypoglycaemia in type 1 diabetes.

AIMS/HYPOTHESIS: Hypoglycaemia is associated with heart rate-corrected QT (QTc) interval lengthening on the ECG; this may be important in the pathogenesis of sudden overnight death in young people with diabetes. Since hypoglycaemic QTc lengthening appears to be mediated through the sympathoadrenal response, we tested the hypothesis that beta1-blockade will prevent these changes in type 1 diabetic patients and so provide a potential therapeutic intervention. METHODS: We studied eight type 1 diabetic adults without cardiovascular or renal complications. Similar hypoglycaemic clamp studies were performed on two occasions, at least 4 weeks apart, but immediately before one visit subjects received atenolol 100 mg daily for 7 days. Following a 60-min euglycaemic (5 mmol/l) period, blood glucose was lowered over 30 min to 2.5 mmol/l, and held for 60 min. High-resolution ECG was recorded at baseline and at 0, 30 and 60 min during each glycaemic plateau. QT interval was measured using a semiautomated tangent method and QTc was derived from QT using the Fridericia formula. RESULTS: Mean (SD) baseline QTc was similar at both visits: control 391 (30) ms, post-atenolol 386 (34) ms; (p=0.33). Without atenolol pretreatment, QTc lengthened during hypoglycaemia to a maximum of 448 (34) ms (p<0.001). On atenolol, QTc lengthening was significantly reduced (peak QTc 413 (27) ms; p=0.004 vs control visit). CONCLUSIONS/INTERPRETATION: Hypoglycaemic QTc lengthening is blunted by atenolol in patients with type 1 diabetes. Selective beta1-blockade may help prevent sudden death, if we can identify those at high risk.

Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes.

AIMS/HYPOTHESIS: It has been postulated that hypoglycaemia-related cardiac dysrhythmia and, in particular, prolonged cardiac repolarisation, may contribute to increased mortality rates in children and adolescents with type 1 diabetes. METHODS: We examined the prevalence of prolonged QT interval on ECG during spontaneous hypoglycaemia in 44 type 1 diabetic subjects (aged 7-18 years), and explored the relationships between serial overnight measurements of QT interval corrected for heart rate (QTc) and serum glucose, potassium and epinephrine levels. Each subject underwent two overnight profiles; blood was sampled every 15 min for glucose measurements and hourly for potassium and epinephrine. Serial ECGs recorded half-hourly between 23.00 and 07.00 hours were available on 74 nights: 29 with spontaneous hypoglycaemia (defined as blood glucose <3.5 mmol/l) and 45 without hypoglycaemia. RESULTS: Mean overnight QTc was longer in females than in males (412 vs 400 ms, p=0.02), but was not related to age, diabetes duration or HbA(1)c. Prolonged QTc (>440 ms) occurred on 20 out of 74 (27%) nights, with no significant differences between male and female subjects, and was more prevalent on nights with hypoglycaemia (13/29, 44%) than on nights without (7/45, 15%, p=0.0008). Potassium levels were lower on nights when hypoglycaemia occurred (minimum potassium 3.4 vs 3.7 mmol/l, p=0.0003) and were inversely correlated with maximum QTc (r=-0.40, p=0.03). In contrast, epinephrine levels were not higher on nights with hypoglycaemia and were not related to QTc. CONCLUSIONS/INTERPRETATION: In young type 1 diabetic subjects, prolonged QTc occurred frequently with spontaneous overnight hypoglycaemia and may be related to insulin-induced hypokalaemia.

Changes in cardiac repolarization during clinical episodes of nocturnal hypoglycaemia in adults with Type 1 diabetes.

AIMS/HYPOTHESIS: Experimental hypoglycaemia leads to abnormal cardiac repolarization manifest by a lengthened QT interval and caused by adrenergic stimulation. However it is less clear whether spontaneous clinical episodes lead to similar changes. We have therefore measured cardiac ventricular repolarization and counterregulatory responses in patients with Type 1 diabetes during hypoglycaemic and euglycaemic nights. METHODS: We studied 22 patients with Type 1 diabetes (mean age 40.4+/-17.2 years, duration of diabetes 17.2+/-9.3 years, HbA1c 8.2+/-1.2% overnight). Measurements were taken hourly of blood glucose, plasma potassium, catecholamines and high resolution electrocardiograms. RESULTS: Hypoglycaemia (blood glucose level <2.5 mmol/l) occurred on 7 of the 22 nights. During overnight hypoglycaemia, QTc interval increased by 27 ms (+/-15) above baseline, compared with 9 ms (+/-19) during nights with no nocturnal hypoglycaemia (p=0.034, 95%CI 2, 35). Adrenaline increased by 0.33 nmol/l (+/-0.21) above baseline during hypoglycaemia, compared with -0.05 nmol/l (+/-0.08) during euglycaemia (p=0.001, 95%CI 0.19, 0.56 nmol/l). There was no significant difference between potassium, and noradrenaline concentrations between the two groups. CONCLUSION/INTERPRETATION: QTc interval lengthens significantly during spontaneous nocturnal hypoglycaemia. Increases are generally less than those observed during experimental hypoglycaemia and could reflect attenuated sympathoadrenal responses during clinical episodes. The clinical relevance of these changes is uncertain but is consistent with the hypothesis that clinical hypoglycaemia can cause abnormal cardiac repolarization and an attendant risk of cardiac arrhythmia.

Increased sural nerve epineurial blood flow in human subjects with painful diabetic neuropathy.

AIMS/HYPOTHESIS: The pathogenesis of painful diabetic neuropathy remains unknown. As a consequence we still do not have any effective, rational treatments and a greater understanding of the mechanisms is urgently required. Previous studies have shown no consistent morphological differences in the nerves of patients with and without painful neuropathy. The aim of this study was to compare epineurial haemodynamics in patients with chronic painful and painless neuropathy. METHODS: The techniques of microlightguide spectrophotometry and fluorescein angiography were used to measure epineurial intravascular oxygen saturation and blood flow respectively. Eleven patients with painful and eight with painless neuropathy were studied, with the groups matched carefully in terms of severity of neuropathy and diabetes control. RESULTS: Intravascular oxygen saturation was higher in the painful neuropathy group compared to those without pain (median 73.8% vs 67.7%, respectively; p=0.021). Fluorescein rise time was also faster in those with painful symptoms (median 18.3 s vs 53.6 s; p=0.046) indicating higher epineurial blood flow in these subjects. CONCLUSION/INTERPRETATION: These results indicate that there are distinct differences in haemodynamics within the epineurium of the sural nerve in subjects with painful and painless neuropathy. Haemodynamic factors could therefore have an important role in the pathogenesis of neuropathic pain and might offer further insight into potential treatments for this distressing condition.

Effects of adrenaline and potassium on QTc interval and QT dispersion in man.

BACKGROUND: Hypoglycaemia alters cardiac repolarization acutely, with increases in rate-corrected QT (QTc) interval and QT dispersion (QTd) on the electrocardiogram (ECG); such changes are related to the counterregulatory sympatho-adrenal response. Adrenaline produces both QTc lengthening and a fall in plasma potassium (K+) when infused into healthy volunteers. Hypokalaemia prolongs cardiac repolarization independently however, and therefore our aim was to determine whether adrenaline-induced repolarization changes are mediated directly or through lowered plasma K+. MATERIALS AND METHODS: Ten healthy males were studied on two occasions. At both visits they received similar l-adrenaline infusions but on one occasion potassium was also administered; infusion rates were adjusted to maintain circulating K+ at baseline. The QTc interval, QTd, peripheral physiological responses and plasma adrenaline and potassium concentrations were measured during both visits. RESULTS: The QTc interval and QTd increased both with and without potassium clamping. Without K+ replacement, mean (SE) QTc lengthened from 378 (5) ms to a final maximum value of 433 (10) ms, and QTd increased from 36 (5) ms to 69 (8) ms (both P < 0.001). During K+ replacement, QTc duration at baseline and study end was 385 (7) ms and 423 (11) ms, respectively (P < 0.001), and QTd 38 was (4) ms and 63 (5) ms (P = 0.001). CONCLUSIONS: These data suggest that disturbed cardiac repolarization as a result of increases in circulating adrenaline occurs independently of extracellular potassium. A direct effect of adrenaline upon the myocardium appears the most likely mechanism.

Spinal-cord involvement in diabetic peripheral neuropathy.

The pathogenesis of diabetic distal symmetrical polyneuropathy (DSP) is poorly understood but there is some evidence that the disease process might extend beyond peripheral nerves. We used magnetic-resonance imaging to measure spinal-cord cross-sectional area in diabetic patients with and without DSP and in healthy controls. There were significant differences in cord area between the groups at C4/5 and T3/4 (p=0.004 and p=0.033, respectively), with a smaller cord area in those with DSP compared with controls (p=0.001 and p=0.016 for C4/5 and T3/4, respectively). These results indicate that DSP is not simply a disease of the peripheral nerve and that there is substantial involvement of the spinal cord.

Measurement of high resolution ECG QT interval during controlled euglycaemia and hypoglycaemia.

During hypoglycaemia, typically there is a change in the surface ECG characterized by a flattened and prolonged T wave, often accompanied by a fused U wave. The QT interval is a useful parameter for quantifying the ECG morphology. However, reliable measurement of QT is not straightforward, particularly for hypoglycaemic ECG morphology. The objective of this study was to compare the ability of two methods of QT measurement to distinguish between ECGs recorded during euglycaemia and hypoglycaemia. The first method involves manually setting the intersection of the isoelectric line and the T wave or, where this is not possible, the nadir between the T and U wave. The second method is semi-automatic and fits a tangent to the point of maximum gradient on the downward slope of the T wave. Two independent observers used both methods to measure the QT for high resolution ECG data recorded during a study of 17 non-diabetic subjects undergoing controlled euglycaemia and hypoglycaemia. Using the mean results of the two observers, the mean +/- SD increase in heart rate corrected QT, QTc, for ECGs recorded during euglycaemia and hypoglycaemia was 32 +/- 25 ms for the non-tangent method and 60 +/- 24 ms for the tangent method. Therefore, the tangent method provides greater distinction between ECGs recorded during euglycaemia and hypoglycaemia than the non-tangent method. A potential clinical application could be the non-invasive detection of impending hypoglycaemia at night, which would be of significant benefit to adults and young children with diabetes.

Diuretic induced change in lung water assessed by electrical impedance tomography.

Monitoring patients with left ventricular failure can be difficult. Electrical impedance tomography (EIT) produces cross-sectional images of changes in the impedance of the thorax. We measured changes in the electrical impedance of the lung in nine volunteers following a diuretic challenge. The hypothesis was that lung impedance would increase with diuretic induced fluid loss. Heart rate, blood pressure and urine output were also recorded. After diuretic the mean urine output was 1220 ml compared with 187 ml after placebo. Following diuretic administration, mean thoracic impedance increased by 13.6% (p < 0.01) and lung impedance increased by 7.8% (p < 0.05). Taken as a group there was a correlation between overall impedance change and total urine output. However, for each individual, the time course of change in impedance and urine output did not correlate significantly. Our findings show that EIT may offer a better guide to the response of the lung to diuretic treatment than simply measuring urine output. The urine output is neither specific nor sensitive in the assessment of lung water. Mean lung impedance, however, is largely determined by lung water. The study showed that lung impedance can be recorded at supra-normal values. EIT may help in the management of patients with excess lung water.

The Black Sea Tele-Diab System: development-implementation-clinical evaluation.

This paper describes the application of the GEHR (Good European Health Record) architecture to develop a system to enable the storage and exchange of EHCRs (Electronic Health Care Record) of patients with diabetes, in the Black Sea area. The objectives of the Black Sea Tele Diab System (BSTD) were to develop and evaluate the use of a fully-computerised healthcare record system in a clinical setting, to promote the use of electronic data exchange of healthcare information and to provide a framework for the epidemiological study and monitoring of diabetes care.

Early identification of diabetic foot ulcers that may require intervention using the micro lightguide spectrophotometer.

OBJECTIVE: Adequate tissue oxygenation is known to be essential for the healing of diabetic foot ulcers, but hypoxia has also been shown to be a potent stimulus for growth. There are no studies looking specifically at ulcer oxygen levels during the healing process. We measured the serial microvascular oxygen saturation (SaO2) of the foot ulcer, the ulcer margin, and a control site using the Erlangen micro lightguide spectrophotometer (EMPHO II; Bodenseewerk Geratetechnik, Erlangen, Germany) to study serial changes during healing. RESEARCH AND DESIGN METHODS: Studied over 9 months were 14 patients with neuropathy with a total of 24 foot ulcer sites. Of these patients, four (seven ulcers) had significant ischemia as determined by the ankle-brachial pressure index (ABPI) and transcutaneous oxygen tension. RESULTS: Of 21 ulcer sites with serial measurements, only 13 ulcers healed. In those ulcers, a significant reduction (P<0.05) in SaO2 occurred with healing. SaO2 dropped from 58% at initial presentation (mean area 2.6 cm2) to 47% at midsize (mean area 1.2 cm2 at 5.2 weeks) and finally reduced to 45% just before it healed. Similar trends were also seen around the margin of the ulcers (initial 49%, midsize 45%, and final 41%; P = 0.1). However, there were no such changes on the control sites (43, 40, and 40%; P = 0.5) or within the eight ulcers that did not heal (46, 42, and 53%; P = 0.2). CONCLUSIONS: Serial microvascular oxygen measurements may be used to identify at an early stage those ulcers that are unlikely to heal and, therefore, need surgical intervention.