Effect of community-led delivery of HIV self-testing on HIV testing and antiretroviral therapy initiation in Malawi: A cluster-randomised trial

BackgroundUndiagnosed HIV infection remains substantial in key population subgroups including adolescents, older adults, and men, driving ongoing transmission in sub-Saharan Africa. We evaluated the impact, safety, and costs of community-led delivery of HIV self-testing (HIVST), aiming to increase HIV testing in underserved subgroups and stimulate demand for antiretroviral therapy (ART).Methods and findingsThis cluster-randomised trial, conducted between October 2018 and July 2019, used restricted randomisation (1:1) to allocate 30 group village head clusters in Mangochi district, Malawi to the community-led HIVST intervention in addition to the standard of care (SOC) or the SOC alone. The intervention involved mobilising community health groups to lead the design and implementation of 7-day HIVST campaigns, with cluster residents (≥15 years) eligible for HIVST. The primary outcome compared lifetime HIV testing among adolescents (15 to 19 years) between arms. Secondary outcomes compared: recent HIV testing (in the last 3 months) among older adults (≥40 years) and men; cumulative 6-month incidence of ART initiation per 100,000 population; knowledge of the preventive benefits of HIV treatment; and HIV testing stigma. Outcomes were measured through a post-intervention survey and at neighboring health facilities. Analysis used intention-to-treat for cluster-level outcomes.Community health groups delivered 24,316 oral fluid-based HIVST kits. The survey included 90.2% (3,960/4,388) of listed participants in the 15 community-led HIVST clusters and 89.2% (3,920/4,394) of listed participants in the 15 SOC clusters. Overall, the proportion of men was 39.0% (3,072/7,880). Most participants obtained primary-level education or below, were married, and reported a sexual partner. Lifetime HIV testing among adolescents was higher in the community-led HIVST arm (84.6%, 770/910) than the SOC arm (67.1%, 582/867; adjusted risk difference [RD] 15.2%, 95% CI 7.5% to 22.9%; p < 0.001), especially among 15 to 17 year olds and boys. Recent testing among older adults was also higher in the community-led HIVST arm (74.5%, 869/1,166) than the SOC arm (31.5%, 350/1,111; adjusted RD 42.1%, 95% CI 34.9% to 49.4%; p < 0.001). Similarly, the proportions of recently tested men were 74.6% (1,177/1,577) and 33.9% (507/1,495) in the community-led HIVST and SOC arms, respectively (adjusted RD 40.2%, 95% CI 32.9% to 47.4%; p < 0.001). Knowledge of HIV treatment benefits and HIV testing stigma showed no differences between arms. Cumulative incidence of ART initiation was respectively 305.3 and 226.1 per 100,000 population in the community-led HIVST and SOC arms (RD 72.3, 95% CI −36.2 to 180.8; p = 0.18). In post hoc analysis, ART initiations in the 3-month post-intervention period were higher in the community-led HIVST arm than the SOC arm (RD 97.7, 95% CI 33.4 to 162.1; p = 0.004). HIVST uptake was 74.7% (2,956/3,960), with few adverse events (0.6%, 18/2,955) and at US$5.70 per HIVST kit distributed. The main limitations include the use of self-reported HIV testing outcomes and lack of baseline measurement for the primary outcome.ConclusionsIn this study, we found that community-led HIVST was effective, safe, and affordable, with population impact and coverage rapidly realised at low cost. This approach could enable community HIV testing in high HIV prevalence settings and demonstrates potential for economies of scale and scope.Trial registrationClinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT03541382","term_id":"NCT03541382"}}NCT03541382.

Pitchaya Indravudh and colleagues study community-led HIV self-testing in Malawi.     

Clinical characteristics of OGTT-derived hepatic- and muscle insulin resistance in healthy young men

[Purpose]

Insulin inhibits glucose release in the liver but increases glucose absorption in muscles. When insulin cannot properly control glucose, it negatively affects glucose metabolism and, furthermore, contributes to the onset of metabolic syndrome and chronic disease. Therefore, this study''s goal is to understand the clinical characteristics of hepatic insulin resistance and muscle insulin sensitivity in healthy young men.

[Methods]

Twenty-eight healthy young men (age 23.3 ± 0.5; mean ± SE) participated in this study. Liver function and blood lipids were measured by blood sampling from brachial vein after participants fasted the previous day. Hepatic insulin resistance and muscle insulin sensitivity were evaluated using two-hour OGTT along with surrogate index related to insulin sensitivity. The VO_2max was evaluated using cycle ergometer. Systemic insulin sensitivity was evaluated using two-hour euglycemic hyperinsulinemic clamp method.

[Results]

Hepatic insulin resistance showed a significant correlation with body fat (r = 0.609, p < 0.05). Also, hepatic insulin resistance showed a significant correlation with GOT (r = 0.467), GPT (r = 0.434), and γ-GTP (r = 0.375), reflecting liver functions, as well as showing a significant correlation with hs-CRP (r = 0.492, p < 0.05). On the other hand, muscle insulin sensitivity had no correlation with neither body fat nor liver function index (p > 0.05), and among surrogate indexes, it showed a significant correlation with Avignon (r = -0.493) and Matsuda index (r = -0.577). Glucose infusion rate, using the clamp method, showed a significant correlation with muscle insulin sensitivity (r = 0.448, p < 0.05). The VO_2max had a significant correlation with hepatic insulin resistance (r = -0.435, p < 0.05) and muscle insulin sensitivity (r = 0.474, p < 0.05), respectively.

[Conclusion]

For young men in their 20''s, the OGTT-based hepatic insulin sensitivity was an indicator of hepatic function and body fat but muscle insulin sensitivity was related to peripheral insulin sensitivity. Also, for young men, higher VO_2max indicated lower hepatic insulin resistance and higher muscle insulin sensitivity.     

Clinical Significance of the Edema Index in Incident Peritoneal Dialysis Patients

Background

Proper monitoring for volume overload is important to improve prognosis in peritoneal dialysis (PD) patients. The association between volume status and residual renal function (RRF) remains an unresolved issue. The aim of the present study was to evaluate the association between the edema index and survival or RRF in incident PD patients.

Patients and Methods

We identified all adults who underwent PD. The edema index was defined as the ratio of extracellular fluid to total body fluid. Participants with available data regarding survivorship or non-survivorship during the first year after PD initiation were included in the area under the receiver operating characteristic curve analysis. The cutoff value of the edema index for 1-year mortality was >0.371 in men and >0.372 in women. Participants were divided into two groups according to the cutoff value of their baseline edema indices: High (>cutoff value) and Low (≤cutoff value). Survivors during the first year after PD initiation were divided into two groups according to the initial and 1-year edema index: Non-improvement (maintenance of criteria in the initial Low group during the year) and Other (all participants except those in the Non-improvement group).

Results

In total, 631 patients were enrolled in the present study. The cutoff value of the edema index for 1-year mortality was >0.371 in men and >0.372 in women. The respective mean initial RRF values (mL·min^-1·1.73 m^-2) in the Low and High groups, respectively, were 4.88 ± 4.09 and 4.21 ± 3.28 in men (P = 0.108), and 3.19 ± 2.57 and 2.98 ± 2.70 in women (P = 0.531). There were no significant differences between groups in either sex. The respective mean RRF values at 1 year after PD initiation in the Low and High groups, respectively, were 3.56 ± 4.35 and 2.73 ± 2.53 in men, and 2.80 ± 2.36 and 1.85 ± 1.51 in women. RRF at 1 year after PD initiation was higher in the Low group than in the High group (men: P = 0.027; women: P = 0.001). In men, the cumulative 5-year survival rates were 78.7% and 46.2% in the Low and High groups, respectively, whereas in women, rates were 77.2% and 58.8% in the Low and High groups, respectively. For survivors during the first year after PD initiation, the Non-improvement group was associated with a poor survival rate compared with the Other group for both sexes.

Conclusion

A high edema index was associated with mortality in incident PD patients at baseline and follow-up. The edema index may be used as a new marker for predicting mortality in PD patients.     

Rare coding variation in paraoxonase-1 is associated with ischemic stroke in the NHLBI Exome Sequencing Project

HDL-associated paraoxonase-1 (PON1) is an enzyme whose activity is associated with cerebrovascular disease. Common PON1 genetic variants have not been consistently associated with cerebrovascular disease. Rare coding variation that likely alters PON1 enzyme function may be more strongly associated with stroke. The National Heart, Lung, and Blood Institute Exome Sequencing Project sequenced the coding regions (exomes) of the genome for heart, lung, and blood-related phenotypes (including ischemic stroke). In this sample of 4,204 unrelated participants, 496 had verified, noncardioembolic ischemic stroke. After filtering, 28 nonsynonymous PON1 variants were identified. Analysis with the sequence kernel association test, adjusted for covariates, identified significant associations between PON1 variants and ischemic stroke (P = 3.01 × 10⁻³). Stratified analyses demonstrated a stronger association of PON1 variants with ischemic stroke in African ancestry (AA) participants (P = 5.03 × 10⁻³). Ethnic differences in the association between PON1 variants with stroke could be due to the effects of PON1_Val109Ile (overall P = 7.88 × 10⁻³; AA P = 6.52 × 10⁻⁴), found at higher frequency in AA participants (1.16% vs. 0.02%) and whose protein is less stable than the common allele. In summary, rare genetic variation in PON1 was associated with ischemic stroke, with stronger associations identified in those of AA. Increased focus on PON1 enzyme function and its role in cerebrovascular disease is warranted.     

Peer-led counselling with problem discussion therapy for adolescents living with HIV in Zimbabwe: A cluster-randomised trial

BackgroundAdolescents living with HIV have poor virological suppression and high prevalence of common mental disorders (CMDs). In Zimbabwe, the Zvandiri adolescent peer support programme is effective at improving virological suppression. We assessed the effect of training Zvandiri peer counsellors known as Community Adolescent Treatment Supporters (CATS) in problem-solving therapy (PST) on virological suppression and mental health outcomes.Methods and findingsSixty clinics were randomised 1:1 to either normal Zvandiri peer counselling or a peer counsellor trained in PST. In January to March 2019, 842 adolescents aged 10 to 19 years and living with HIV who screened positive for CMDs were enrolled (375 (44.5%) male and 418 (49.6%) orphaned of at least one parent). The primary outcome was virological nonsuppression (viral load ≥1,000 copies/mL). Secondary outcomes were symptoms of CMDs measured with the Shona Symptom Questionnaire (SSQ ≥8) and depression measured with the Patient Health Questionnaire (PHQ-9 ≥10) and health utility score using the EQ-5D. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were estimated using logistic regression adjusting for clinic-level clustering. Case reviews and focus group discussions were used to determine feasibility of intervention delivery.At baseline, 35.1% of participants had virological nonsuppression and 70.3% had SSQ≥8. After 48 weeks, follow-up was 89.5% for viral load data and 90.9% for other outcomes. Virological nonsuppression decreased in both arms, but there was no evidence of an intervention effect (prevalence of nonsuppression 14.7% in the Zvandiri-PST arm versus 11.9% in the Zvandiri arm; AOR = 1.29; 95% CI 0.68, 2.48; p = 0.44). There was strong evidence of an apparent effect on common mental health outcomes (SSQ ≥8: 2.4% versus 10.3% [AOR = 0.19; 95% CI 0.08, 0.46; p < 0.001]; PHQ-9 ≥10: 2.9% versus 8.8% [AOR = 0.32; 95% CI 0.14, 0.78; p = 0.01]). Prevalence of EQ-5D index score <1 was 27.6% versus 38.9% (AOR = 0.56; 95% CI 0.31, 1.03; p = 0.06). Qualitative analyses found that CATS-observed participants had limited autonomy or ability to solve problems. In response, the CATS adapted the intervention to focus on empathic problem discussion to fit adolescents’ age, capacity, and circumstances, which was beneficial. Limitations include that cost data were not available and that the mental health tools were validated in adult populations, not adolescents.ConclusionsPST training for CATS did not add to the benefit of peer support in reducing virological nonsuppression but led to improved symptoms of CMD and depression compared to standard Zvandiri care among adolescents living with HIV in Zimbabwe. Active involvement of caregivers and strengthened referral structures could increase feasibility and effectiveness.Trial registrationPan African Clinical Trials Registry PACTR201810756862405.

Victoria Simms and co-workers report on a trial of problem discussion therapy for adolescents with HIV infection and common mental disorders in Zimbabwe.     

The Relationship between Poverty and Healthcare Seeking among Patients Hospitalized with Acute Febrile Illnesses in Chittagong,Bangladesh

Delays in seeking appropriate healthcare can increase the case fatality of acute febrile illnesses, and circuitous routes of care-seeking can have a catastrophic financial impact upon patients in low-income settings. To investigate the relationship between poverty and pre-hospital delays for patients with acute febrile illnesses, we recruited a cross-sectional, convenience sample of 527 acutely ill adults and children aged over 6 months, with a documented fever ≥38.0°C and symptoms of up to 14 days’ duration, presenting to a tertiary referral hospital in Chittagong, Bangladesh, over the course of one year from September 2011 to September 2012. Participants were classified according to the socioeconomic status of their households, defined by the Oxford Poverty and Human Development Initiative’s multidimensional poverty index (MPI). 51% of participants were classified as multidimensionally poor (MPI>0.33). Median time from onset of any symptoms to arrival at hospital was 22 hours longer for MPI poor adults compared to non-poor adults (123 vs. 101 hours) rising to a difference of 26 hours with adjustment in a multivariate regression model (95% confidence interval 7 to 46 hours; P = 0.009). There was no difference in delays for children from poor and non-poor households (97 vs. 119 hours; P = 0.394). Case fatality was 5.9% vs. 0.8% in poor and non-poor individuals respectively (P = 0.001)—5.1% vs. 0.0% for poor and non-poor adults (P = 0.010) and 6.4% vs. 1.8% for poor and non-poor children (P = 0.083). Deaths were attributed to central nervous system infection (11), malaria (3), urinary tract infection (2), gastrointestinal infection (1) and undifferentiated sepsis (1). Both poor and non-poor households relied predominantly upon the (often informal) private sector for medical advice before reaching the referral hospital, but MPI poor participants were less likely to have consulted a qualified doctor. Poor participants were more likely to attribute delays in decision-making and travel to a lack of money (P<0.001), and more likely to face catastrophic expenditure of more than 25% of monthly household income (P<0.001). We conclude that multidimensional poverty is associated with greater pre-hospital delays and expenditure in this setting. Closer links between health and development agendas could address these consequences of poverty and streamline access to adequate healthcare.     

The Support to Rural India's Public Education System (STRIPES) Trial: A Cluster Randomised Controlled Trial of Supplementary Teaching,Learning Material and Material Support

Background

The aim of the STRIPES trial was to assess the effectiveness of providing supplementary, remedial teaching and learning materials (and an additional ‘kit’ of materials for girls) on a composite of language and mathematics test scores for children in classes two, three and four in public primary schools in villages in the Nagarkurnool division of Andhra Pradesh, India.

Methods

STRIPES was a cluster randomised trial in which 214 villages were allocated either to the supplementary teaching intervention (n = 107) or to serve as controls (n = 107). 54 of the intervention villages were further randomly allocated to receive additional kit for girls. The study was not blinded. Analysis was conducted on the intention to treat principle, allowing for clustering.

Results

Composite test scores were significantly higher in the intervention group (107 villages; 2364 children) than in the control group (106 villages; 2014 children) at the end of the trial (mean difference on a percentage scale 15.8; 95% CI 13.1 to 18.6; p<0.001; 0.75 Standard Deviation (SD) difference). Composite test scores were not significantly different in the 54 villages (614 girls) with the additional kits for girls compared to the 53 villages (636 girls) without these kits at the end of the trial (mean difference on a percentage scale 0.5; 95% CI -4.34 to 5.4; p = 0.84). The cost per 0.1 SD increase in composite test score for intervention without kits is Rs. 382.97 (£4.45, $7.13), and Rs.480.59 (£5.58, $8.94) for the intervention with kits.

Conclusions

A 18 month programme of supplementary remedial teaching and learning materials had a substantial impact on language and mathematics scores of primary school students in rural Andhra Pradesh, yet providing a ‘kit’ of materials to girls in these villages did not lead to any measured additional benefit.

Trial Registration

Controlled-Trials.com ISRCTN69951502     

Interactive Video Game Cycling Leads to Higher Energy Expenditure and Is More Enjoyable than Conventional Exercise in Adults

Background

Despite the widely accepted health benefits of regular physical activity, only a small percentage of the population meets the current recommendations. The reasons include a wide use of technology and a lack of enjoyment while exercising. The purpose of this study was to compare the physiological, perceptual and enjoyment responses between a single bout of (I) conventional cycling and (II) interactive cycling video game at a matched workload.

Methods

A cross-sectional study in 34 healthy participants was performed. Initially, participants completed an incremental maximal cycling test to measure peak oxygen uptake and to determine ventilatory threshold. In random order, participants carried out a 30 min interactive cycling trial and a 30 min conventional cycling trial at 55% of peak power output. During the trials, oxygen uptake and energy expenditure were measured by open-circuit spirometry and heart rate was measured by radiotelemetry. RPE and enjoyment were measured every 10 minutes with Borg scale and a modified PACES scale.

Results

Interactive cycling resulted in a significantly greater %V̇O₂Reserve (68.2% ± 9.2% vs 64.7% ± 8.1%), rate of energy expenditure (505.8±75.2 vs 487.4±81.2 j·kg^-1·min^-1), and enjoyment (63.4% ± 17 vs 42% ± 13.6), P&lt;0.05. Participants were working at a higher intensity in relation to the individual’s ventilatory threshold during the interactive cycling video game trial (M = 11.86, SE = 3.08) than during the Conventional cycling trial (M = 7.55, SE = 3.16, t(33) = -2.69, P&lt;0.05, r = .42). No significant differences were found for heart rate reserve (72.5 ± 10.4 vs 71.4±10.1%) and RPE (13.1 ± 1.8 vs 13.2 ± 1.7).

Conclusion

Interactive cycling games can be a valid alternative to conventional exercise as they result in a higher exercise intensity than conventional cycling and a distraction from aversive cognitive and physiological states at and above the ventilatory threshold.     

The Role of Explicit and Implicit Self-Esteem in Peer Modeling of Palatable Food Intake: A Study on Social Media Interaction among Youngsters

Objective

This experimental study investigated the impact of peers on palatable food intake of youngsters within a social media setting. To determine whether this effect was moderated by self-esteem, the present study examined the roles of global explicit self-esteem (ESE), body esteem (BE) and implicit self-esteem (ISE).

Methods

Participants (N = 118; 38.1% boys; M age 11.14±.79) were asked to play a computer game while they believed to interact online with a same-sex normal-weight remote confederate (i.e., instructed peer) who ate either nothing, a small or large amount of candy.

Results

Participants modeled the candy intake of peers via a social media interaction, but this was qualified by their self-esteem. Participants with higher ISE adjusted their candy intake to that of a peer more closely than those with lower ISE when the confederate ate nothing compared to when eating a modest (β = .26, p = .05) or considerable amount of candy (kcal) (β = .32, p = .001). In contrast, participants with lower BE modeled peer intake more than those with higher BE when eating nothing compared to a considerable amount of candy (kcal) (β = .21, p = .02); ESE did not moderate social modeling behavior. In addition, participants with higher discrepant or “damaged” self-esteem (i.e., high ISE and low ESE) modeled peer intake more when the peer ate nothing or a modest amount compared to a substantial amount of candy (kcal) (β = −.24, p = .004; β = −.26, p<.0001, respectively).

Conclusion

Youngsters conform to the amount of palatable food eaten by peers through social media interaction. Those with lower body esteem or damaged self-esteem may be more at risk to peer influences on food intake.     

Expanding syphilis test uptake using rapid dual self-testing for syphilis and HIV among men who have sex with men in China: A multiarm randomized controlled trial

BackgroundLow syphilis testing uptake is a major public health issue among men who have sex with men (MSM) in many low- and middle-income countries. Syphilis self-testing (SST) may complement and extend facility-based testing. We aimed to evaluate the effectiveness and costs of providing SST on increasing syphilis testing uptake among MSM in China.Methods and findingsAn open-label, parallel 3-arm randomized controlled trial (RCT) was conducted between January 7, 2020 and July 17, 2020. Men who were at least 18 years of age, had condomless anal sex with men in the past year, reported not testing for syphilis in the last 6 months, and had a stable residence with mailing addresses were recruited from 124 cities in 26 Chinese provinces. Using block randomization with blocks of size 12, enrolled participants were randomly assigned (1:1:1) into 3 arms: standard of care arm, standard SST arm, and lottery incentivized SST arm (1 in 10 chance to win US$15 if they had a syphilis test). The primary outcome was the proportion of participants who tested for syphilis during the trial period and confirmed with photo verification and between arm comparisons were estimated with risk differences (RDs). Analyses were performed on a modified intention-to-treat basis: Participants were included in the complete case analysis if they had initiated at least 1 follow-up survey. The Syphilis/HIV Duo rapid test kit was used. A total of 451 men were enrolled. In total, 136 (90·7%, 136/150) in the standard of care arm, 142 (94·0%, 142/151) in the standard of SST arm, and 137 (91·3%, 137/150) in the lottery incentivized SST arm were included in the final analysis. The proportion of men who had at least 1 syphilis test during the trial period was 63.4% (95% confidence interval [CI]: 55.5% to 71.3%, p = 0.001) in the standard SST arm, 65.7% (95% CI: 57.7% to 73.6%, p = 0.0002) in the lottery incentivized SST arm, and 14.7% (95% CI: 8.8% to 20.7%, p < 0.001) in the standard of care arm. The estimated RD between the standard SST and standard of care arm was 48.7% (95% CI: 37.8% to 58.4%, p < 0.001). The majority (78.5%, 95% CI: 72.7% to 84.4%, p < 0.001) of syphilis self-testers reported never testing for syphilis. The cost per person tested was US$26.55 for standard SST, US$28.09 for the lottery incentivized SST, and US$66.19 for the standard of care. No study-related adverse events were reported during the study duration. Limitation was that the impact of the Coronavirus Disease 2019 (COVID-19) restrictions may have accentuated demand for decentralized testing.ConclusionsCompared to standard of care, providing SST significantly increased the proportion of MSM testing for syphilis in China and was cheaper (per person tested).Trial registrationChinese Clinical Trial Registry: ChiCTR1900022409.

In a multi-arm randomized controlled trial, Cheng Wang and colleagues determine the effectiveness and cost of expanding syphilis self testing among men who have sex with men in China.     

Effect of timing of protein and carbohydrate intake after resistance exercise on nitrogen balance in trained and untrained young men

Background

Resistance exercise alters the post-exercise response of anabolic and catabolic hormones. A previous study indicated that the turnover of muscle protein in trained individuals is reduced due to alterations in endocrine factors caused by resistance training, and that muscle protein accumulation varies between trained and untrained individuals due to differences in the timing of protein and carbohydrate intake. We investigated the effect of the timing of protein and carbohydrate intake after resistance exercise on nitrogen balance in trained and untrained young men.

Methods

Subjects were 10 trained healthy men (mean age, 23 ± 4 years; height, 173.8 ± 3.1 cm; weight, 72.3 ± 4.3 kg) and 10 untrained healthy men (mean age, 23 ± 1 years; height, 171.8 ± 5.0 cm; weight, 64.5 ± 5.0 kg). All subjects performed four sets of 8 to 10 repetitions of a resistance exercise (comprising bench press, shoulder press, triceps pushdown, leg extension, leg press, leg curl, lat pulldown, rowing, and biceps curl) at 80% one-repetition maximum. After each resistance exercise session, subjects were randomly divided into two groups with respect to intake of protein (0.3 g/kg body weight) and carbohydrate (0.8 g/kg body weight) immediately after (P0) or 6 h (P6) after the session. All subjects were on an experimental diet that met their individual total energy requirement. We assessed whole-body protein metabolism by measuring nitrogen balance at P0 and P6 on the last 3 days of exercise training.

Results

The nitrogen balance was significantly lower in the trained men than in the untrained men at both P0 (P <0.05) and P6 (P <0.01). The nitrogen balance in trained men was significantly higher at P0 than at P6 (P <0.01), whereas that in the untrained men was not significantly different between the two periods.

Conclusion

The timing of protein and carbohydrate intake after resistance exercise influences nitrogen balance differently in trained and untrained young men.     

Risk Stratification of Patients with Peripheral Arterial Disease and Abdominal Aortic Aneurysm Using Aortic Augmentation Index

BackgroundCentral augmentation index (cAIx) is an indicator for vascular stiffness. Obstructive and aneurysmatic vascular disease can affect pulse wave propagation and reflection, causing changes in central aortic pressures.AimTo assess and compare cAIx in patients with peripheral arterial disease (PAD) and / or abdominal aortic aneurysm (AAA).MethodscAIx was assessed by radial applanation tonometry (Sphygmocor) in a total of 184 patients at a tertiary referral centre. Patients were grouped as having PAD only, AAA only, or both AAA and PAD. Differences in cAIx measurements between the three patient groups were tested by non-parametric tests and stepwise multivariate linear regression analysis to investigate associations with obstructive or aneurysmatic patterns of vascular disease.ResultsIn the study sample of 184 patients, 130 had PAD only, 20 had AAA only, and 34 patients had both AAA and PAD. Mean cAIx (%) was 30.5 ± 8.2 across all patients. It was significantly higher in females (35.2 ± 6.1, n = 55) than males (28.4 ± 8.2, n = 129), and significantly higher in patients over 80 years of age (34.4 ± 6.9, n = 22) than in those under 80 years (30.0 ± 8.2, n = 162). Intergroup comparison revealed a significant difference in cAIx between the three patient groups (AAA: 27.3 ± 9.5; PAD: 31.4 ± 7.8; AAA & PAD: 28.8 ± 8.5). cAIx was significantly lower in patients with AAA, higher in patients with both AAA and PAD, and highest in patients with PAD only (beta = 0.21, p = 0.006).ConclusionNon-invasive assessment of arterial stiffness in high-risk patients indicates that cAIx differs according to the pattern of vascular disease. Measurements revealed significantly higher cAIx values for patients with obstructive peripheral arterial disease than for patients with aneurysmatic disease.     

Influence of the ABCG2 gout risk 141?K allele on urate metabolism during a fructose challenge

Introduction

Both genetic variation in ATP-binding cassette sub-family G member 2 (ABCG2) and intake of fructose-containing beverages are major risk factors for hyperuricemia and gout. This study aimed to test the hypothesis that the ABCG2 gout risk allele 141 K promotes the hyperuricaemic response to fructose loading.

Methods

Healthy volunteers (n = 74) provided serum and urine samples immediately before and 30, 60, 120 and 180 minutes after ingesting a 64 g fructose solution. Data were analyzed based on the presence or absence of the ABCG2 141 K gout risk allele.

Results

The 141 K risk allele was present in 23 participants (31%). Overall, serum urate (SU) concentrations during the fructose load were similar in those with and without the 141 K allele (P_SNP = 0.15). However, the 141 K allele was associated with a smaller increase in SU following fructose intake (P_SNP <0.0001). Those with the 141 K allele also had a smaller increase in serum glucose following the fructose load (P_SNP = 0.002). Higher fractional excretion of uric acid (FEUA) at baseline and throughout the fructose load was observed in those with the 141 K risk allele (P_SNP <0.0001). However, the change in FEUA in response to fructose was not different in those with and without the 141 K risk allele (P_SNP = 0.39). The 141 K allele effects on serum urate and glucose were more pronounced in Polynesian participants and in those with a body mass index ≥25 kg/m².

Conclusions

In contrast to the predicted responses for a hyperuricemia/gout risk allele, the 141 K allele is associated with smaller increases in SU and higher FEUA following a fructose load. The results suggest that ABCG2 interacts with extra-renal metabolic pathways in a complex manner to regulate SU and gout risk.

Clinical Trials Registration

The study was registered by the Australian Clinical Trials Registry (ACTRN12610001036000).     

Sterol metabolism and protein metabolism are differentially correlated with sarcopenia in Asian Chinese men and women

ObjectivesOur aim was to investigate the prevalence and predictive variables of sarcopenia.MethodsWe recruited participants from the Peking Union Medical College Hospital Multicenter Prospective Longitudinal Sarcopenia Study (PPLSS). Muscle mass was quantified using bioimpedance, and muscle function was quantified using grip strength and gait speed. Logistic regression revealed the relationships between sarcopenia and nutritional, lifestyle, disease, psychosocial and physical variables.ResultsThe prevalence of sarcopenia and sarcopenic obesity was 9.2%‐16.2% and 0.26%‐9.1%, respectively. Old age, single status, undernourishment, higher income, smoking, low physical activity, poor appetite and low protein diets were significantly associated with sarcopenia. Multiple logistic regression analysis showed that age was a risk factor for all stages of sarcopenia, and participants above 80 years were greater than fivefold more susceptible to sarcopenia, while lower physical activity was an independent risk factor. The optimal cut‐off value for age was 71 years, which departs from the commonly accepted cut‐off of 60 years. Female participants were greater than twofold less susceptible to sarcopenia than male participants. The sterol derivative 25‐hydroxyvitamin D was associated with fourfold lower odds of sarcopenia in male participants. Several protein intake variables were also correlated with sarcopenia. Based on these parameters, we defined a highly predictive index for sarcopenia.ConclusionsOur findings support a predictive index of sarcopenia, which agglomerates the complex influences that sterol metabolism and nutrition exert on male vs female participants.     

The impact of removing financial incentives and/or audit and feedback on chlamydia testing in general practice: A cluster randomised controlled trial (ACCEPt-able)

BackgroundFinancial incentives and audit/feedback are widely used in primary care to influence clinician behaviour and increase quality of care. While observational data suggest a decline in quality when these interventions are stopped, their removal has not been evaluated in a randomised controlled trial (RCT), to our knowledge. This trial aimed to determine whether chlamydia testing in general practice is sustained when financial incentives and/or audit/feedback are removed.Methods and findingsWe undertook a 2 × 2 factorial cluster RCT in 60 general practices in 4 Australian states targeting 49,525 patients aged 16–29 years for annual chlamydia testing. Clinics were recruited between July 2014 and September 2015 and were followed for up to 2 years or until 31 December 2016. Clinics were eligible if they were in the intervention group of a previous cluster RCT where general practitioners (GPs) received financial incentives (AU$5–AU$8) for each chlamydia test and quarterly audit/feedback reports of their chlamydia testing rates. Clinics were randomised into 1 of 4 groups: incentives removed but audit/feedback retained (group A), audit/feedback removed but incentives retained (group B), both removed (group C), or both retained (group D). The primary outcome was the annual chlamydia testing rate among 16- to 29-year-old patients, where the numerator was the number who had at least 1 chlamydia test within 12 months and the denominator was the number who had at least 1 consultation during the same 12 months. We undertook a factorial analysis in which we investigated the effects of removal versus retention of incentives (groups A + C versus groups B + D) and the effects of removal versus retention of audit/feedback (group B + C versus groups A + D) separately. Of 60 clinics, 59 were randomised and 55 (91.7%) provided data (group A: 15 clinics, 11,196 patients; group B: 14, 11,944; group C: 13, 11,566; group D: 13, 14,819). Annual testing decreased from 20.2% to 11.7% (difference −8.8%; 95% CI −10.5% to −7.0%) in clinics with incentives removed and decreased from 20.6% to 14.3% (difference −7.1%; 95% CI −9.6% to −4.7%) where incentives were retained. The adjusted absolute difference in treatment effect was −0.9% (95% CI −3.5% to 1.7%; p = 0.2267). Annual testing decreased from 21.0% to 11.6% (difference −9.5%; 95% CI −11.7% to −7.4%) in clinics where audit/feedback was removed and decreased from 19.9% to 14.5% (difference −6.4%; 95% CI −8.6% to −4.2%) where audit/feedback was retained. The adjusted absolute difference in treatment effect was −2.6% (95% CI −5.4% to −0.1%; p = 0.0336). Study limitations included an unexpected reduction in testing across all groups impacting statistical power, loss of 4 clinics after randomisation, and inclusion of rural clinics only.ConclusionsAudit/feedback is more effective than financial incentives of AU$5–AU$8 per chlamydia test at sustaining GP chlamydia testing practices over time in Australian general practice.Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12614000595617

In a cluster randomized trial, Jane S Hocking and colleagues investigate the impact of removing financial incentives and/or audit and feedback on chlamydia testing in general practice in Australia.     

A genome‐wide association study of the frailty index highlights brain pathways in ageing

Frailty is a common geriatric syndrome and strongly associated with disability, mortality and hospitalization. Frailty is commonly measured using the frailty index (FI), based on the accumulation of a number of health deficits during the life course. The mechanisms underlying FI are multifactorial and not well understood, but a genetic basis has been suggested with heritability estimates between 30 and 45%. Understanding the genetic determinants and biological mechanisms underpinning FI may help to delay or even prevent frailty. We performed a genome‐wide association study (GWAS) meta‐analysis of a frailty index in European descent UK Biobank participants (n = 164,610, 60–70 years) and Swedish TwinGene participants (n = 10,616, 41–87 years). FI calculation was based on 49 or 44 self‐reported items on symptoms, disabilities and diagnosed diseases for UK Biobank and TwinGene, respectively. 14 loci were associated with the FI (p < 5*10⁻⁸). Many FI‐associated loci have established associations with traits such as body mass index, cardiovascular disease, smoking, HLA proteins, depression and neuroticism; however, one appears to be novel. The estimated single nucleotide polymorphism (SNP) heritability of the FI was 11% (0.11, SE 0.005). In enrichment analysis, genes expressed in the frontal cortex and hippocampus were significantly downregulated (adjusted p < 0.05). We also used Mendelian randomization to identify modifiable traits and exposures that may affect frailty risk, with a higher educational attainment genetic risk score being associated with a lower degree of frailty. Risk of frailty is influenced by many genetic factors, including well‐known disease risk factors and mental health, with particular emphasis on pathways in the brain.     

The Effects of Vibration and Muscle Fatigue on Trunk Sensorimotor Control in Low Back Pain Patients

Introduction

Changes in sensorimotor function and increased trunk muscle fatigability have been identified in patients with chronic low back pain (cLBP). This study assessed the control of trunk force production in conditions with and without local erector spinae muscle vibration and evaluated the influence of muscle fatigue on trunk sensorimotor control.

Methods

Twenty non-specific cLBP patients and 20 healthy participants were asked to perform submaximal isometric trunk extension torque with and without local vibration stimulation, before and after a trunk extensor muscle fatigue protocol. Constant error (CE), variable error (VE) as well as absolute error (AE) in peak torque were computed and compared across conditions. Trunk extensor muscle activation during isometric contractions and during the fatigue protocol was measured using surface electromyography (sEMG).

Results

Force reproduction accuracy of the trunk was significantly lower in the patient group (CE = 9.81 ± 2.23 Nm; AE = 18.16 ± 3.97 Nm) than in healthy participants (CE = 4.44 ± 1.68 Nm; AE = 12.23 ± 2.44 Nm). Local erector spinae vibration induced a significant reduction in CE (4.33 ± 2.14 Nm) and AE (13.71 ± 3.45 Nm) mean scores in the patient group. Healthy participants conversely showed a significant increase in CE (8.17 ± 2.10 Nm) and AE (16.29 ± 2.82 Nm) mean scores under vibration conditions. The fatigue protocol induced erector spinae muscle fatigue as illustrated by a significant decrease in sEMG median time-frequency slopes. Following the fatigue protocol, patients with cLBP showed significant decrease in sEMG root mean square activity at L4-5 level and responded in similar manner with and without vibration stimulation in regard to CE mean scores.

Conclusions

Patients with cLBP have a less accurate force reproduction sense than healthy participants. Local muscle vibration led to significant trunk neuromuscular control improvements in the cLBP patients before and after a muscle fatigue protocol. Muscle vibration stimulation during motor control exercises is likely to influence motor adaptation and could be considered in the treatment of cLBP. Further work is needed to clearly identify at what levels of the sensorimotor system these gains are achievable.     

Intestinal helminths as predictors of some malaria clinical outcomes and IL-1β levels in outpatients attending two public hospitals in Bamenda,North West Cameroon

This study aimed at determining the impact of intestinal helminths on malaria parasitaemia, anaemia and pyrexia considering the levels of IL-1β among outpatients in Bamenda. A cohort of 358 consented participants aged three (3) years and above, both males and females on malaria consultation were recruited in the study. At enrolment, patients’ axillary body temperatures were measured and recorded. Venous blood was collected for haemoglobin concentration and malaria parasitaemia determination. Blood plasma was used to measure human IL-1β levels using Human ELISA Kit. The Kato-Katz technique was used to process stool samples. Five species of intestinal helminths Ascaris lumbricoides (6.4%), Enterobius vermicularis (5.0%), Taenia species (4.2%), Trichuris trichiura (1.1%) and hookworms (0.8%) were identified. The overall prevalence of Plasmodium falciparum and intestinal helminths was 30.4% (109/358) and 17.6% (63/358) respectively. The prevalence of intestinal helminths in malaria patients was 17.4% (19/109). Higher Geometric mean parasite density (GMPD ±SD) (malaria parasitaemia) was significantly observed in patients co-infected with Enterobius vermicularis (5548 ± 2829/μL, p = 0.041) and with Taenia species (6799 ± 4584/μL, p = 0.020) than in Plasmodium falciparum infected patients alone (651 ± 6076/ μL). Higher parasitaemia of (1393 ± 3031/μL) and (3464 ± 2828/μL) were recorded in patients co-infected with Ascaris lumbricoides and with hookworms respectively but the differences were not significant (p > 0.05). Anaemia and pyrexia prevalence was 27.1% (97/358) and 33.5% (120/358) respectively. Malaria patients co-infected with Enterobius vermicularis and Ascaris lumbricoides had increased risk of anaemia (OR = 13.712, p = 0.002 and OR = 16.969, p = 0.014) respectively and pyrexia (OR = 18.07, p = 0.001 and OR = 22.560, p = 0.007) respectively than their counterparts. Increased levels of IL-1β were significantly observed in anaemic (148.884 ± 36.073 pg/mL, t = 7.411, p = 0.000) and pyretic (127.737 ± 50.322 pg/mL, t = 5.028, p = 0.000) patients than in non-anaemic (64.335 ± 38.995pg/mL) and apyretic patients (58.479 ± 36.194pg/mL). Malaria patients co-infected with each species of intestinal helminths recorded higher IL-1β levels (IL-1β > 121.68 ± 58.86 pg/mL) and the overall mean (139.63 ± 38.33pg/mL) was higher compared with levels in malaria (121.68 ± 58.86 pg/mL) and helminth (61.78 ± 31.69pg/mL) infected patients alone. Intestinal helminths exacerbated the clinical outcomes of malaria in the patients and increased levels of IL-1β were observed in co-infected patients with anaemia, pyrexia and higher parasitaemia.     

Clinical Assessment of Lamina Cribrosa Curvature in Eyes with Primary Open-Angle Glaucoma

Purpose

Quantitative evaluation of lamina cribrosa (LC) posterior bowing in primary open-angle glaucoma (POAG) eyes using swept-source optical coherence tomography.

Methods

Patients with POAG (n = 123 eyes) and healthy individuals of a similar age (n = 92 eyes) were prospectively recruited. Anterior laminar insertion depth (ALID) was defined as the vertical distance between the anterior laminar insertion and a reference plane connecting the Bruch’s membrane openings (BMO). The mean LC depth (mLCD) was approximated by dividing the area enclosed by the anterior LC, the BMO reference plane, and the two vertical lines for ALID measurement by the length between those two vertical lines. The LC curvature index was defined as the difference between the mLCD and the ALID. The factors influencing the LC curvature index were evaluated.

Results

The ALID and mLCD were significantly larger in POAG eyes than in healthy controls (P < 0.05). The LC curvature index was significantly larger in POAG eyes than in healthy controls on both the horizontal (85.8 ± 34.1 vs. 68.2 ± 32.3 μm) and vertical meridians (49.8 ± 38.5 vs. 32.2 ± 31.1 μm, all P < 0.001). Multivariate regression showed significant associations of greater disc area (P < 0.001), vertical C/D ratio (P < 0.001) and mLCD (P < 0.001), smaller rim area (P = 0.001), thinner average RNFLT (P < 0.001), and myopic refraction (P = 0.049) with increased LC curvature index. There was no difference in the LC curvature index between mild (MD > –6 dB) and moderate-to-advanced glaucoma (MD < –6 dB, P = 0.95).

Conclusions

LC posterior bowing was increased in POAG eyes, and was significantly associated with structural optic nerve head (ONH) changes but not with functional glaucoma severity. Quantitative evaluation of LC curvature can facilitate assessment of glaucomatous ONH change.