A cross-sectional survey on the effectiveness of public health campaigns for changing knowledge, attitudes, and practices in Kenyan informal settlements during the COVID-19 pandemic.

We performed two cross-sectional surveys across three informal settlements in Kenya (within Kisii county, Nairobi, and Nakuru county) to study the effectiveness of public health interventions during the COVID-19 pandemic. A total of 720 participants were surveyed from 120 randomly selected geographical locations (240 participants/settlement/survey), and a coordinated health promotion campaign was delivered between the two surveys by trained staff. Information relating to knowledge, attitudes, and practices (KAP) were collected by trained field workers using a validated questionnaire. The main outcomes showed improvements in: (i) mask-wearing (% of participants 'Always' using their mask increased from 71 to 74%, and the percentage using their masks 'Sometimes' decreased from 15% to 6%; p<0.001); (ii) practices related to face mask usage (% of subjects covering the mouth and nose increased from 91 to 95%, and those covering only part of their face decreased from around 2.5% to <1%; p<0.001). Significant improvements were also seen in the attitudes and expectations relating to mask wearing, and in the understanding of government directives. Over 50% of subjects in the post-campaign survey reported that social distancing was not possible in their communities and fears associated with COVID-19 testing were resistant to change (unchanged at 10%). Access to COVID-19 testing facilities was limited, leaving a large proportion of people unable to test. As willingness to take a COVID-19 test did not change between surveys (69 vs 70%; p = 0.57), despite increased availability, we recommend that policy level interventions are needed, aimed at mitigating adverse consequences of a positive test. Improvements of KAPs in the more crowded urban environment (Nairobi) were less than at settlements in rural or semi-urban settings (Nakuru and Kisii). We conclude that coordinated public health campaigns are effective in facilitating the change of KAPs amongst people living amidst challenging socio-economic conditions in informal settlements.

Use of mobile phones for rehabilitative services among prosthetics users in rural Acholi sub-region of northern Uganda: findings from a qualitative study.

BACKGROUND: Digital technologies such as mobile phones have shown potential as vital tools for use in healthcare and related services. However, little has been done to explore its use for prosthetics rehabilitative services, especially in the Acholi sub-region of northern Uganda. We address this gap by exploring ownership of the mobile phone, knowledge of the use of mobile phone applications, use of mobile phones for prosthetics rehabilitative services and challenges faced in using the mobile phones. METHODS: A case study design was used. We conducted semi-structured one-on-one interviews with 16 prosthetics users spread in the four districts of Nwoya, Amuru, Omoro, and Gulu of the Acholi sub-region of northern Uganda. We transcribed the data verbatim and explored the contents thematically to derive themes. RESULTS: More prosthetics users (63%) owned mobile phones compared to those without (37%). Many who owned and use mobile phones are knowledgeable about applications for calls and messaging (47%). Some prosthetics users are knowledgeable in mobile money applications (21%), call applications only (16%) and, others were able to use the internet (16%). Many of the prosthetics users in this study use mobile phones to seek information, mainly relating to the management of prosthetics and treatment of diseases. Many participants were positive about the benefits of the use of mobile phones for prosthetics rehabilitation and related services. Common challenges affecting the use of mobile phones include the expensive price of airtime, few places for charging mobile phones, lack of electricity and inadequate skills to operate a mobile phone. CONCLUSION: The use of mobile phones can break down barriers created by distance and allow effective communication linkages between prosthetics users and rehabilitation services. Our results suggest that some prosthetics users owned mobile phones and used them to seek information relating to prosthetics rehabilitation services. We believe that promoting the use of the mobile phone for prosthetic rehabilitative services among prosthetics users is necessary and should be considered for practical and policy discussion relating to its use for prosthetics rehabilitation in rural areas.

Biophysical characterization of the underappreciated and important relationship between heart rate variability and heart rate.

Heart rate (HR) variability (HRV; beat-to-beat changes in the R-wave to R-wave interval) has attracted considerable attention during the past 30+ years (PubMed currently lists >17 000 publications). Clinically, a decrease in HRV is correlated to higher morbidity and mortality in diverse conditions, from heart disease to fetal distress. It is usually attributed to fluctuation in cardiac autonomic nerve activity. We calculated HRV parameters from a variety of cardiac preparations (including humans, living animals, Langendorff-perfused heart, and single sinoatrial nodal cell) in diverse species, combining this with data from previously published articles. We show that regardless of conditions, there is a universal exponential decay-like relationship between HRV and HR. Using 2 biophysical models, we develop a theory for this and confirm that HRV is primarily dependent on HR and cannot be used in any simple way to assess autonomic nerve activity to the heart. We suggest that the correlation between a change in HRV and altered morbidity and mortality is substantially attributable to the concurrent change in HR. This calls for re-evaluation of the findings from many articles that have not adjusted properly or at all for HR differences when comparing HRV in multiple circumstances.

The effects of tumor necrosis factor-alpha on systolic and diastolic function in rat ventricular myocytes.

The proinflammatory cytokine tumor necrosis factor-alpha (TNF-α) is associated with myocardial dysfunction observed in sepsis and septic shock. There are two fundamental components to this dysfunction. (1) systolic dysfunction; and (2) diastolic dysfunction. The aim of these experiments was to determine if any aspect of whole-heart dysfunction could be explained by alterations to global intracellular calcium ([Ca(2+)]i), contractility, and [Ca(2+)]i handling, by TNF-α, at the level of the individual rat myocyte. We took an integrative approach to simultaneously measure [Ca(2+)]i, contractility and sarcolemmal Ca fluxes using the Ca indicator fluo-3, video edge detection, and the perforated patch technique, respectively. All experiments were performed at 37°C. The effects of 50 ng/mL TNF-α were immediate and sustained. The amplitude of systolic [Ca(2+)]i was reduced by 31% and systolic shortening by 19%. Diastolic [Ca(2+)]i, myocyte length and relaxation rate were not affected, nor were the activity of the [Ca(2+)]i removal mechanisms. The reduction in systolic [Ca(2+)]i was associated with a 14% reduction in sarcoplasmic reticulum (SR) content and a 11% decrease in peak L-type Ca current (IC a-L). Ca influx was decreased by 7% associated with a more rapid IC a-L inactivation. These data show that at the level of the myocyte, TNF-α reduces SR Ca which underlies a reduction in systolic [Ca(2+)]i and thence shortening. Although these findings correlate well with aspects of systolic myocardial dysfunction seen in sepsis, in this model, acutely, TNF-α does not appear to provide a cellular mechanism for sepsis-related diastolic myocardial dysfunction.

Administration of human recombinant activated protein C is not associated with pancreatic parenchymal haemorrhage in L-arginine-induced experimental acute pancreatitis.

CONTEXT: Microvascular thrombosis is a critical event in severe acute pancreatitis. Human recombinant activated protein C (Xigris®, Eli Lilly, Indianapolis, IN, USA) modulates the interplay between pro-inflammatory and pro-coagulant pathways and maintains microvascular patency. However, the anticoagulant properties of Xigris® may precipitate bleeding from the inflamed pancreas. OBJECTIVE: This study tests the hypothesis that Xigris® can ameliorate experimental acute pancreatitis without causing pancreatic haemorrhage. METHODS: Sprague Dawley rats were allocated as follows: Group 1: control (n=7); Group 2: acute pancreatitis (n=6); Group 3: administration of Xigris® 500 µg/kg body weight before induction of acute pancreatitis (n=6); and Group 4: Administration of Xigris® 500 µg/kg body weight 30 minutes after induction of acute pancreatitis (n=6). Acute pancreatitis was induced by intraperitoneal administration of L-arginine 300 mg/100 g body weight. Animals were sacrificed at 48 hours and biochemical, haematological, and histological markers of pancreatic haemorrhage and inflammation assessed. RESULTS: Median lipase in animals with acute pancreatitis was 10 U/mL (range: 7-16 U/mL) compared to 5.5 (range: 3-8 U/mL) in controls (P=0.028). Lipase was also elevated in animals given Xigris® both before (12 U/mL, range: 8-22 U/mL; P=0.031 vs. control group) and after (46 U/mL, range: 9-71 U/mL; P=0.015 vs. control group) induction of acute pancreatitis). Haemoglobin levels were similar among all groups (P=0.323). There was no histological evidence of pancreatic haemorrhage in animals treated with Xigris®. Pre-treatment with Xigris® was associated with a significant reduction in pancreatic injury. This effect was absent when Xigris® was administered after induction of acute pancreatitis. CONCLUSION: Xigris® did not lead to pancreatic haemorrhage in experimental acute pancreatitis. Administration of Xigris® prior to induction of acute pancreatitis was associated with amelioration of injury. This effect was not seen with administration of Xigris® after induction of acute pancreatitis.

TGF-ß1-mediated fibrosis and ion channel remodeling are key mechanisms in producing the sinus node dysfunction associated with SCN5A deficiency and aging.

BACKGROUND: Mutations in the cardiac Na(+) channel gene (SCN5A) can adversely affect electric function in the heart, but effects can be age dependent. We explored the interacting effects of Scn5a disruption and aging on the pathogenesis of sinus node dysfunction in a heterozygous Scn5a knockout (Scn5a(+/-)) mouse model. METHODS AND RESULTS: We compared functional, histological, and molecular features in young (3 to 4 month) and old (1 year) wild type and Scn5a(+/-) mice. Both Scn5a disruption and aging were associated with decreased heart rate variability, reduced sinoatrial node automaticity, and slowed sinoatrial conduction. They also led to increased collagen and fibroblast levels and upregulated transforming growth factor-ß(1) (TGF-ß(1)) and vimentin transcripts, providing measures of fibrosis and reduced Nav1.5 expression. All these effects were most noticeable in old Scn5a(+/-) mice. Na(+) channel inhibition by Nav1.5-E3 antibody directly increased TGF-ß(1) production in both cultured human cardiac myocytes and fibroblasts. Finally, aging was associated with downregulation of a wide range of ion channel and related transcripts and, again, was greatest in old Scn5a(+/-) mice. The quantitative results from these studies permitted computer simulations that successfully replicated the observed sinoatrial node phenotypes shown by the different experimental groups. CONCLUSIONS: These results implicate a tissue degeneration triggered by Nav1.5 deficiency manifesting as a TGF-ß(1)-mediated fibrosis accompanied by electric remodeling in the sinus node dysfunction associated with Scn5a disruption or aging. The latter effects interact to produce the most severe phenotype in old Scn5a(+/-) mice. In demonstrating this, our findings suggest a novel regulatory role for Nav1.5 in cellular biological processes in addition to its electrophysiologic function.

The effects of hydrogen peroxide on intracellular calcium handling and contractility in the rat ventricular myocyte.

Elevations in reactive oxygen species are implicated in many disease states and cause systolic and diastolic myocardial dysfunction. To understand the underlying cellular dysfunction, we characterised the effects of H2O2 on [Ca(2+)](i) handling and contractility in the rat ventricular myocyte. This was achieved using patch clamping, [Ca(2+)](i) measurement using Fluo-3, video edge detection and confocal microscopy. All experiments were performed at 37°C. 200 µM H2O2 resulted in a 44% decrease in the [Ca(2+)](i) transient amplitude, a 30% increase in diastolic [Ca(2+)](i) and an 18% decrease in the rate of systolic Ca(2+) removal. This was associated with a 61% reduction in systolic shortening, a contracture of 3 µm and a 42% increase in relaxation time respectively. The decrease in the [Ca(2+)](i) transient amplitude could be explained by a 27% decrease in SR Ca(2+) content. This, in turn results from a 22% decrease of SERCA activity. The decreased SR Ca(2+) content also provides a mechanism for a reduction in [Ca(2+)](i) spark frequency with no evidence for a Ca(2+) independent modification of ryanodine receptor open probability. We conclude that decreased SERCA activity is the major factor responsible for the changes of the systolic [Ca(2+)](i) transient.

Clinical trials in ventilator treatment: current perspectives and future challenges.

PURPOSE OF REVIEW: Mortality/morbidity-based end points have been useful in evaluating treatments that modulate 'mediator variables' with a large effect size. Ventilation is usually a supportive measure, and hence is best seen as a 'moderator variable'. It can, therefore, have only a modest impact on disease-specific mortality. In this context, over reliance on final outcome-based end points (mortality, length of stay, etc.) risks the abandonment of several potentially useful developments. These concepts are important in considering how future developments should be evaluated. MAIN FINDINGS: A modest effect size implies that large sample sizes will be necessary to demonstrate mortality/morbidity benefits. Recruiting large numbers over geographically/culturally/economically heterogeneous areas over long periods (during which clinical practice is unlikely to remain constant) has several limitations. Furthermore, manifestations of critical illness are based on nonlinear interactions between insult, host responses and other moderator variables. In such nonlinear systems the final outcome is unpredictable and does not follow simple linear assumptions. Such 'unexpected' events occurring in clinical trials involving moderator variables, may potentially lead to erroneous conclusions. SUMMARY: It is crucial that a more dynamic approach, not based on final outcome alone, is considered in designing new clinical trials involving new ventilation strategies.

Emerging trends in minimally invasive haemodynamic monitoring and optimization of fluid therapy.

BACKGROUND: For decades the pulmonary artery catheter has been the mainstay of cardiac output monitoring in critically ill patients, and pressure-based indices of ventricular filling have been used to gauge fluid requirements with acknowledged limitations. In recent years, alternative technologies have become available which are minimally invasive, allow beat-to-beat cardiac output monitoring and permit assessment of fluid requirements by volumetric means and by allowing assessment of heart-lung interaction in mechanically ventilated patients. METHODS: A qualitative review of the basic science behind the transpulmonary dilution technique used in the measurement of cardiac output, global end-diastolic volume and extravascular lung water; the basic science and validation of pulse contour analysis methods of real-time cardiac output monitoring; the application and limitations of these technologies to guide rational fluid therapy in surgical and critically ill patients. RESULTS: Transpulmonary dilution techniques correlate well with pulmonary artery catheter-derived measurement of cardiac output. Volumetric measures of preload appear to be superior to central venous and pulmonary artery occlusion pressures. Dynamic indices of preload responsiveness such as stroke volume variation are more useful than static measures in mechanically ventilated patients. CONCLUSION: In fully mechanically ventilated patients, dynamic measurements of heart-lung interaction such as stroke volume variation are superior to static measures of preload in assessing whether a patient is volume-responsive (i.e. will increase stroke volume in response to a fluid challenge). For patients who are not fully mechanically ventilated, pulse contour analysis allows real-time assessment of increases in cardiac output in response to passive leg-raising.

Does a higher positive end expiratory pressure decrease mortality in acute respiratory distress syndrome? A systematic review and meta-analysis.

BACKGROUND: Positive end expiratory pressure (PEEP) is an important component of therapy in patients with acute lung injury or acute respiratory distress syndrome. The independent effect of PEEP on mortality is currently unknown. METHODS: A systematic review and meta-analysis of randomized controlled clinical trials comparing the use of higher and lower levels of PEEP. RESULTS: Six trials with a total of 2,484 patients from 102 intensive care units and 9 countries met the eligibility criteria. In three trials, the effect of different levels of PEEP was compared in groups receiving comparable tidal volumes. Three trials accounted for more than 85% of total weighting in the meta-analyses. The pooled relative risk obtained from these three trials showed a trend towards improved mortality with high PEEP, even though the difference did not reach statistical significance: Pooled cumulative risk of 0.90 (95% CI 0.72-1.02, P = 0.077). The reduction in absolute risk of death was approximately 4%. There was no evidence of a significant increase in baro-trauma in patients receiving high PEEP, with a pooled risk of 0.95 (95% CI 0.62-1.45, P = 0.81). CONCLUSION: High PEEP strategy may have a clinically relevant independent mortality benefit. Despite a possible increase in baro-trauma, the benefits far outweigh potential risks. Current evidence therefore favors the use of high PEEP as the preferred option when ventilating patients with severe acute respiratory distress syndrome. As the reduction in absolute risk of death is less than 5%, a future clinical trial aimed at demonstrating statistical significance is likely to pose considerable financial and ethical burdens.

Systemic arterial pressure wave reflections during acute hemorrhage.

OBJECTIVE: To determine the effects of hemorrhage on wave-reflection-induced systolic pressure augmentation in the aorta. DESIGN: Randomized, controlled laboratory experiment. SETTING: University research laboratory. SUBJECTS: Twenty-five anesthetized pigs randomized to surgical controls (n = 7), hemorrhage (n = 9, H), and hemorrhage with reinfusion (n = 9, HR). INTERVENTIONS: Hemorrhage of 1 mL/kg/min over 20 mins followed by observation (H) or reinfusion (HR) of shed blood. MEASUREMENTS AND MAIN RESULTS: High-fidelity systemic arterial pressure waveforms, from ascending aorta to femoral artery, were transduced and archived digitally using intravascular semiconductor catheter-tipped pressure transducers. Wave-reflection-induced systolic pressure augmentation was determined using the augmentation index in the ascending aorta (AIaa) and distal descending aorta (AIda). Pulse wave velocity, wave travel times, and lumped pressure wave reflection sites were also calculated. AI values were positive at baseline with greater decreases in AIda compared with AIaa observed following hemorrhage, with negative values achieved for AIda alone. AI returned to control values following reinfusion. Lumped reflection site positions and pressure contour maps suggested that a single lumped reflection site (lower abdomen/pelvis) at baseline was replaced by two discrete sites (upper abdomen and pelvis) following hemorrhage, which only recovered following reinfusion. Hemorrhage was associated with hemodynamic conditions that favored late return of wave reflection from the trunk and with the absence of significant changes in systemic vascular resistance. CONCLUSIONS: Hemorrhage-induced early return of pressure wave reflection from the abdominal vasculature is associated with systolic pressure augmentation in the ascending aorta and has the potential to worsen afterload conditions and decrease coronary artery perfusion and cardiac performance. Hemorrhage-induced splanchnic vasoconstriction causing pressure wave reflection may explain these loading conditions in the ascending aorta, and systolic pressure augmentation may be a more useful guide to left ventricular afterload than systemic vascular resistance.

Estimation of errors in determining intrathoracic blood volume using the single transpulmonary thermal dilution technique in hypovolemic shock.

BACKGROUND: The transpulmonary thermal dilution technique has been widely adopted for monitoring cardiac preload and extravascular lung water in critically ill patients. This method assumes intrathoracic blood volume (ITBV) to be a fixed proportion of global end-diastolic volume (GEDV). This study determines the relation between GEDV and ITBV under normovolemic and hypovolemic conditions and quantifies the errors in estimating ITBV. METHODS: Nineteen pigs allocated to control (n = 9) and shock (n = 10) groups were studied. Shock was maintained for 60 min followed by volume resuscitation. The dual dye-thermal dilution technique was used to measure GEDV and ITBV (ITBVm) at baseline (time 0), shock phase (30 and 90 min), and after resuscitation (150 min). The regression equations estimated from paired GEDV and ITBVm measurements under normovolemic and hypovolemic conditions were used to estimate ITBV from the corresponding GEDV, and the estimation errors were quantified. A more simplified equation, used in a commercially available clinical monitor (ITBV = 1.25 x GEDV), was then used to estimate ITBV. RESULTS: The regression equation in the control group was ITBVm = 1.21 x GEDV + 99 (r = 0.89, P < 0.0001) and in the shock group at 30 and 90 min was ITBVm = 1.45 x GEDV + 0.6 (r = 0.95, P < 0.0001). The 95% confidence interval for the y-intercept was relatively wide, ranging from 31 to 168 and -47 to 49, respectively, for the two equations. The equation estimated in the control group led to overestimation of ITBV and a significant (P < 0.05) increase in errors in the shock group at 30 and 90 min. Errors in estimating ITBV using the simplified commercial algorithm were less than 15% under normovolemic and hypovolemic conditions. CONCLUSIONS: The linear relation between GEDV and ITBV is maintained in hypovolemic shock. Even though the relation between GEDV and ITBV is influenced by circulatory volume and cardiac output, the mean errors in predicting ITBV were small and within clinically tolerable limits.