Can mHealth Technology Help Mitigate the Effects of the COVID-19 Pandemic?

Goal: The aim of the study herein reported was to review mobile health (mHealth) technologies and explore their use to monitor and mitigate the effects of the COVID-19 pandemic. Methods: A Task Force was assembled by recruiting individuals with expertise in electronic Patient-Reported Outcomes (ePRO), wearable sensors, and digital contact tracing technologies. Its members collected and discussed available information and summarized it in a series of reports. Results: The Task Force identified technologies that could be deployed in response to the COVID-19 pandemic and would likely be suitable for future pandemics. Criteria for their evaluation were agreed upon and applied to these systems. Conclusions: mHealth technologies are viable options to monitor COVID-19 patients and be used to predict symptom escalation for earlier intervention. These technologies could also be utilized to monitor individuals who are presumed non-infected and enable prediction of exposure to SARS-CoV-2, thus facilitating the prioritization of diagnostic testing.

Low pyrrolizidine alkaloid levels in perennial ryegrass is associated with the absence of a homospermidine synthase gene.

BACKGROUND: Pyrrolizidine alkaloids (PAs) are a class of secondary metabolites that function as feeding deterrents in a range of different plant species. In perennial ryegrass (Lolium perenne L.) the only PAs that have been identified are the thesinine-rhamnoside group, which displays significant genetic variation. Homospermidine synthase (HSS) has evolved from deoxyhypusine synthase (DHS) and catalyses the first step in the PA pathway, making it a key candidate for the investigation of genes influencing observed PA trait variation. RESULTS: During PCR amplification and sequence analysis of DHS we identified two putative HSS genes in perennial ryegrass. One of the genes (LpHSS1) was absent in some perennial ryegrass plants. Thesinine-rhamnoside levels were measured using liquid chromatography coupled with mass spectrometry in a diverse association mapping population, consisting of 693 plants free of fungal endophytic symbionts. Association tests that accounted for population structure identified a significant association of absence of the LpHSS1 gene with lower levels of thesinine-rhamnoside PAs. HSS-like gene sequences were identified for other grass species of the Poaceae, including tall fescue, wheat, maize and sorghum. CONCLUSION: HSS is situated at the crucial first step in the PA pathway making it an important candidate gene for investigation of involvement in PA phenotypic variation. In this study, PA level in perennial ryegrass was strongly associated with the presence or absence of the LpHSS1 gene. A genetic marker, developed for the presence/absence of LpHSS1, may be used for marker-assisted breeding to either lower or increase PAs in breeding populations of perennial or Italian ryegrass to investigate a potential role in the deterrence of herbivore pests. The presence of HSS-like genes in several other Poaceae species suggests that PA biosynthesis may occur in plant family members beyond perennial ryegrass and tall fescue and identifies a potential route for manipulating PA levels.

Hypertension in treated and untreated patients with HIV: a study from 2011 to 2013 at the Jos University Teaching Hospital, Nigeria.

Background: Individuals with HIV, especially those on antiretroviral therapy (ART), may have increased risk of hypertension. We investigated the prevalence of hypertension at enrolment and 12 months after commencing ART in a Nigerian HIV clinic. Methods: Data from patients enrolled for ART from 2011 to 2013 were analysed, including 2310 patients at enrolment and 1524 re-evaluated after 12 months of ART. The presence of hypertension, demographic, clinical and biochemical data were retrieved from standardized databases. Bivariate and logistic regressions were used to identify baseline risk factors for hypertension. Results: Prevalence of hypertension at enrolment was 19.3% (95% CI 17.6-20.9%), and age (p<0.001), male sex (p=0.004) and body mass index (BMI) (p<0.001) were independent risk factors for hypertension. Twelve months after initiating ART, a further 31% (95% CI 17.6-20.9%) had developed hypertension. Total prevalence at that point was 50.2%. Hypertension among those on ART was associated with age (p=0.009) and BMI (p=0.008), but not with sex. There were no independently significant associations between hypertension and CD4+ counts, viral load or type of ART. Conclusions: Hypertension is common in HIV infected individuals attending the HIV clinic. Patients initiating ART have a high risk of developing hypertension in the first year of ART. Since BMI is modifiable, life-style advice aimed at weight reduction is strongly advisable.

Human Immunodeficiency Virus and Risk of Type 2 Diabetes in a Large Adult Cohort in Jos, Nigeria.

BACKGROUND: Human immunodeficiency virus (HIV) infection and the use of antiretroviral therapy (ART) may increase the risk of type 2 diabetes mellitus (T2DM). However, data from regions with a high burden of HIV/AIDS are limited. We determined the prevalence of T2DM at the time of presentation to a large HIV clinic in Nigeria, as well as the incidence of diabetes 12 months following ART initiation. METHODS: Data from patients enrolled for ART from 2011 to 2013 was analyzed, including 2632 patients on enrollment and 2452 reevaluated after 12 months of ART commencement. The presence of diabetes, and demographic, clinical, and biochemical data were retrieved from standardized databases. CD4(+), HIV RNA load, and hepatitis C virus status were noted. Bivariate and logistic regressions were used to identify risk factors for T2DM. RESULTS: Baseline T2DM prevalence was 2.3% (95% confidence interval, 1.8%-2.9%); age, but not body mass index (BMI), was a risk factor for diabetes. After 12 months of ART, an additional 5.3% had developed T2DM. Newly developed diabetes was not associated with age, but was associated with BMI. There were no significant associations between prevalent or incident diabetes and CD4(+), viral load, or type of ART. CONCLUSIONS: Diabetes is not uncommon in HIV-infected individuals at the time of presentation to HIV services. Patients initiating ART have a high risk of developing diabetes in the first year of ART. Excessive weight gain should be avoided, as incident diabetes was associated with a BMI ≥25.0 kg/m(2).

New susceptibility loci associated with kidney disease in type 1 diabetes.

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Prediction of hospital mortality from admission laboratory data and patient age: a simple model.

OBJECTIVE: To devise a simple clinical scoring system, using age of patients and laboratory data available on admission, to predict in-hospital mortality of unselected medical and surgical patients. METHODS: All patients admitted as emergencies to a large teaching hospital in Liverpool in the 5 months July-November 2004 were reviewed retrospectively, identifying all who died in hospital and controls who survived. Laboratory data available on admission were extracted to form a derivation dataset. Factors that predicted mortality were determined using logistic regression analysis and then used to construct models tested using receiver operating characteristic curves. Models were simplified to include only seven data items, with minimal loss of predictive efficiency. The simplified model was tested in a second validation dataset of all patients admitted to the same hospital in October and November 2004. RESULTS: The derivation dataset included 550 patients who died and 1100 controls. After logistic regression comparisons, 22 dummy variables were given weightings in discriminant analysis and used to create a receiver operating characteristic curve with area under the curve (AUC) of 0.884. The model was simplified to include the seven most discriminant variables, which can each be assigned scores of 2, 3 or 4 to form an index predicting outcome; a validation dataset contained 4828 patients (overall mortality 4.7%), showed this simplified scoring system accurately predicted mortality with AUC 0.848, compared with an AUC of 0.861 in a model containing all 23 original variables. CONCLUSION: A simple scoring system accurately predicts in-hospital mortality of unselected hospital patients, using age of patient and a small number of laboratory parameters available very soon after admission.

Association of the adiponectin rs266729 C>G variant and coronary heart disease in the low risk 'Golden Years' type 1 diabetes cohort.

The C-allele of rs266729 is associated with CHD, while the G-allele of rs17300539 is associated with metabolic traits. We examined these in type 1 diabetes. For rs266729, the C-allele was associated with 8-fold increase in CHD. For rs17300539, the G-allele was associated with increases in triglycerides and waist circumference.

Leukocytosis as an alarming sign for mortality in patients hospitalized in general wards.

There is some evidence that leukocytosis without infection is associated with increased hospital mortality, but data in this regard are very incomplete. This study was designed to investigate the relationship between leukocytosis at the time of admission and mortality among patients hospitalized in general wards. During July to Nov 2004, all deceased patients who had a white blood cell (WBC) count record for the first 24 hours of admission were selected as cases. Among survivors, twice the number of cases was selected as controls. Different levels of WBC counts were compared between cases and controls. Totally 1650 patients, including 550 deceased (cases) and 1100 survivors (controls) were analyzed. Of these, 876 (53%) were males and 774 (47%) females, and 42 (3%) were admitted to ICU, 1426 (86%) to medical and 182 (11%) to surgical wards. There was a significant difference between the mean age of deceased patients (78.0 years) and survivors (53.0 years) (P<0.0001). The median WBC for deceased and surviving patients was 9.4 and 11.4×10(9)/l, respectively. Patients with a WBC >10×10(9)/l accounted for 804, among which 335 (42%) were deceased. Leukocytosis and leukopoenia were more frequent among the deceased patients compared to the survivors. The likelihood ratio for leukocytosis and leukopenia among the cases and controls was 1.4 and 2.3, respectively. Leukocytosis was identified as an alarming sign for mortality among patients admitted to general hospital wards at early stages of admission. A quick medical intervention for amendment of the causes related to leukocytosis should consequently reduce hospital mortality.

Comparison between surrogate indices of insulin sensitivity and resistance, and the hyperinsulinaemic euglycaemic glucose clamp in urban South African blacks with and without coronary artery disease.

Coronary artery disease (CAD) and diabetes mellitus (DM) are increasing in urban black South Africans during their transition from a rural to a western lifestyle. Insulin resistance is associated with CAD and DM. Fasting-based indices [homeostasis model assessment of insulin resistance (HOMA IR), log HOMA IR, and quantitative insulin sensitivity check index (QUICKI)] were calculated and their correlations with the glucose disposal rate (M) obtained from the hyperinsulinaemic euglycaemic glucose clamp were compared in 40 patients with CAD and 20 patients without CAD. Normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM were categorised using the oral glucose tolerance test. M and QUICKI were lower in patients with CAD (p<0.0001 and p<0.02); HOMA IR and log HOMA IR were higher (p<0.02). M and QUICKI decreased and HOMA IR and log HOMA IR increased progressively across the NGT, IGT and DM categories in patients with and without CAD. Glucose concentrations increased across the glucose tolerance categories in patients with CAD (p<0.001) and without CAD (p<0.01). Linear regression analysis revealed significant correlations between M and log HOMA IR (r=-0.3412; p<0.02) and QUICKI (r=0.4078; p<0.003), and between waist circumference (WC) and log HOMA IR (r=0.4637) and QUICKI (r=-0.4680) both p<0.001. We concluded that patients with CAD were more insulin resistant than patients without CAD. As glucose tolerance declined, insulin resistance worsened. Log HOMA IR and QUICKI were comparable to the hyperinsulinaemic euglycaemic glucose clamp and these surrogate indices provided a valid method to estimate insulin sensitivity/resistance in our patients.

Carotid intima-media thickness is a predictor of coronary artery disease in South African black patients.

BACKGROUND: Several studies have shown that increased carotid intima-media thickness (CIMT) confers risk of future coronary artery disease (CAD) and stroke. The present study aimed at investigating whether CIMT is a predictor of CAD in South African black patients. METHODS AND RESULTS: This was a prospective study of 53 patients, 41 men and 12 women, with ages ranging from 30 to 70 years. All patients had undergone coronary angiography for suspected CAD. B-mode ultrasound measurement of the carotid intima-media thickness was carried out in all patients, the operator being blinded to the coronary angiography findings. Twenty-nine of the 38 (76%) subjects with established CAD had increased CIMT, with an average mean CIMT of 1.13 mm. Single-vessel disease was present in 12 people, double-vessel disease in 11 and triple-vessel disease in 12. There was a significant positive linear trend between CIMT and the number of involved coronary vessels (p < 0.0001, r = 0.44). CONCLUSIONS: Increased CIMT correlated with evidence of angiographically proven CAD. The median percentile scores showed a progressive increase as the number of vessels involved increased. CIMT could be useful as a screening tool for the presence of CAD in the South African black population.

Leptin, adiponectin, and high-sensitivity C-reactive protein in relation to the metabolic syndrome in urban South African blacks with and without coronary artery disease.

BACKGROUND: Metabolic syndrome and coronary artery disease (CAD) are increasing in urban black South Africans during their transition from a rural to a western lifestyle. Inflammation is frequently associated with metabolic syndrome and CAD. This study evaluated markers of inflammation in black CAD patients, some of whom had metabolic syndrome. METHODS: Metabolic syndrome was defined according to International Diabetes Federation criteria. Inflammatory markers leptin, adiponectin, and high-sensitivity C-reactive protein (hs-CRP) were measured in 40 patients and 20 control subjects. RESULTS: Metabolic syndrome was present in 23 patients and absent in 17 patients. Leptin was the only significantly higher marker in patients with metabolic syndrome compared to patients without metabolic syndrome (P < 0.01). Leptin was higher in women than men (P < 0.01) and higher in both genders with metabolic syndrome (P < 0.03 and P < 0.04, respectively). Leptin levels rose significantly with increasing metabolic syndrome criteria (P < 0.05). hs-CRP concentrations were elevated in both patient groups. Positive correlations were found between leptin and body mass index (BMI) (r = 0.7107; P < 0.0001), waist circumference (WC) (r = 0.4981; P <0.002), and hs-CRP (r = 0.3886; P < 0.02). CONCLUSIONS: Leptin differentiated between CAD patients with and without metabolic syndrome and determined metabolic syndrome status in women and men. Leptin was the only marker that increased with additional metabolic syndrome criteria. Elevated hs-CRP concentrations may indicate a low-grade inflammatory state in CAD patients. Association of leptin with BMI, WC, and hs-CRP revealed a close link with metabolic syndrome, obesity, and inflammation in urban black South African CAD patients.

A gene-rich linkage map in the dioecious species Actinidia chinensis (kiwifruit) reveals putative X/Y sex-determining chromosomes.

BACKGROUND: The genus Actinidia (kiwifruit) consists of woody, scrambling vines, native to China, and only recently propagated as a commercial crop. All species described are dioecious, but the genetic mechanism for sex-determination is unknown, as is the genetic basis for many of the cluster of characteristics making up the unique fruit. It is, however, an important crop in the New Zealand economy, and a classical breeding program would benefit greatly by knowledge of the trait alleles carried by both female and male parents. The application of marker assisted selection (MAS) in seedling populations would also aid the accurate and efficient development of novel fruit types for the market. RESULTS: Gene-rich female, male and consensus linkage maps of the diploid species A. chinensis have been constructed with 644 microsatellite markers. The maps consist of twenty-nine linkage groups corresponding to the haploid number n = 29. We found that sex-linked sequence characterized amplified region (SCAR) markers and the 'Flower-sex' phenotype consistently mapped to a single linkage group, in a subtelomeric region, in a section of inconsistent marker order. The region also contained markers of expressed genes, some of unknown function. Recombination, assessed by allelic distribution and marker order stability, was, in the remainder of the linkage group, in accordance with other linkage groups. Fully informative markers to other genes in this linkage group identified the comparative linkage group in the female map, where recombination ratios determining marker order were similar to the autosomes. CONCLUSION: We have created genetic linkage maps that define the 29 linkage groups of the haploid genome, and have revealed the position and extent of the sex-determining locus in A. chinensis. As all Actinidia species are dioecious, we suggest that the sex-determining loci of other Actinidia species will be similar to that region defined in our maps. As the extent of the non-recombining region is limited, our result supports the suggestion that the subtelomeric region of an autosome is in the early stages of developing the characteristics of a sex chromosome. The maps provide a reference of genetic information in Actinidia for use in genetic analysis and breeding programs.

Improving glycaemic control in African diabetic patients on insulin: a resource-free approach.

In the resource-poor areas of the tropics, diabetic patients requiring insulin are often treated with once-daily injections of intermediate-acting insulin. Glycaemic control on this regime is usually poor. We trialled a simple change to twice-daily insulin (same total daily dose, two-thirds given in morning, and one-third in evening) in a group of 20 Ethiopian diabetic patients treated in this way. Nurse support and contact, and self-glucose monitoring were not available. After three months, the haemoglobin Alc (HbAlc) had improved from 10.5 +/- 1.8 to 8.0 +/- 1.5% (P < 0.001). No improvement occurred in the 20 control patients who remained on once-daily insulin. Among the twice-daily insulin group there was a small increase in weight and mild hypoglycaemic episodes. However, all patients were very satisfied and wished to continue the new system. We conclude that a simple change from once- to twice-daily insulin, without monitoring or support, can lead to a significant improvement in the overall glycaemic control, and is suitable for resource-limited tropical countries.

Postprandial hyperglycemia in urban South African blacks with and without coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is increasing in urban black South Africans during their transition from a rural to a western lifestyle. This study assessed postprandial hyperglycemia, which a risk factor for CAD, in blacks with and without CAD. METHODS: Fasting lipid levels and postprandial glucometabolic profiles were measured in 40 patients and 20 controls. Normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM) were categorized according to American Diabetes Association criteria. Postprandial hyperglycemia was assessed by the oral glucose tolerance test (OGTT) and area under curve (AUC) analysis. Insulin resistance was evaluated by hyperinsulinemic euglycemic clamp (insulin-mediated glucose disposal, M-value). RESULTS: Glucose AUC was higher in patients than controls (p < 0.0001). Highest correlations were between AUC and 0-minute glucose (r = 0.7847; p < 0.0001), and 120-minute glucose (r = 0.9187; p < 0.0001). Patients had higher fasting and postprandial glucose responses (p < 0.05). Glucose concentrations increased among NGT, IGT, and DM categories in patients (p < 0.001) and controls (p < 0.01). Abnormal glucose tolerance was more prevalent in patients (50%) than controls (40%). M-values were lower in patients (p < 0.0001) and decreased between categories, significantly in DM patients (p < 0.02). More patients (70%) than controls (13%) had low M-values (p < 0.001). CONCLUSIONS: Postprandial hyperglycemia was common in black CAD patients and glucose concentrations at 0 minute and 120 minutes were the strongest determinants. As glucose tolerance declined, glycemic control deteriorated and insulin resistance worsened. Abnormal glucose tolerance and insulin resistance were more prevalent in patients with CAD.

Hyperglycaemia and mortality.

Several studies over the last decade have linked hyperglycaemia on hospital admission with subsequent mortality risk. The evidence is strongest for patients with myocardial infarction or acute coronary syndromes, but evidence also links hyperglycaemia with mortality from stroke and other medical illnesses. The effect seems independent of a previous diagnosis of diabetes mellitus; indeed, some studies suggest that mortality may be higher in patients with hyperglycaemia and no previous diabetes diagnosis compared with known diabetic patients. The effect on outcome of therapeutically lowering blood glucose levels has been considered in a small number of studies, but so far the results are conflicting. Further work is needed, focusing on more standardized surveys--previous studies vary in their use of blood or plasma, as well as cut-off levels for hyperglycaemia--and larger intervention studies.