Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria

Objective Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria. Materials and Methods All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)]. Results 53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria. Conclusions IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.

Small nerve fiber quantification in the diagnosis of diabetic sensorimotor polyneuropathy: Comparing corneal confocal microscopy with intraepidermal nerve fiber density

OBJECTIVE Quantitative assessment of small fiber damage is key to the early diagnosis and assessment of progression or regression of diabetic sensorimotor polyneuropathy (DSPN). Intraepidermal nerve fiber density (IENFD) is the current gold standard, but corneal confocal microscopy (CCM), an in vivo ophthalmic imaging modality, has the potential to be a noninvasive and objective image biomarker for identifying small fiber damage. The purpose of this study was to determine the diagnostic performance of CCM and IENFD by using the current guidelines as the reference standard. RESEARCH DESIGN AND METHODS Eighty-nine subjects (26 control subjects and 63 patients with type 1 diabetes), with and without DSPN, underwent a detailed assessment of neuropathy, including CCM and skin biopsy. RESULTS Manual and automated corneal nerve fiber density (CNFD) (P < 0.0001), branch density (CNBD) (P < 0.0001) and length (CNFL) (P < 0.0001), and IENFD (P < 0.001) were significantly reduced in patients with diabetes with DSPN compared with control subjects. The area under the receiver operating characteristic curve for identifying DSPN was 0.82 for manual CNFD, 0.80 for automated CNFD, and 0.66 for IENFD, which did not differ significantly (P = 0.14). CONCLUSIONS This study shows comparable diagnostic efficiency between CCM and IENFD, providing further support for the clinical utility of CCM as a surrogate end point for DSPN.

The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy

PURPOSE: In vivo corneal confocal microscopy (CCM) is increasingly used as a surrogate endpoint in studies of diabetic polyneuropathy (DPN). However, it is not clear whether imaging the central cornea provides optimal diagnostic utility for DPN. Therefore, we compared nerve morphology in the central cornea and the inferior whorl, a more distal and densely innervated area located inferior and nasal to the central cornea. METHODS: A total of 53 subjects with type 1/type 2 diabetes and 15 age-matched control subjects underwent detailed assessment of neuropathic symptoms (NPS), deficits (neuropathy disability score [NDS]), quantitative sensory testing (vibration perception threshold [VPT], cold and warm threshold [CT/WT], and cold- and heat-induced pain [CIP/HIP]), and electrophysiology (sural and peroneal nerve conduction velocity [SSNCV/PMNCV], and sural and peroneal nerve amplitude [SSNA/PMNA]) to diagnose patients with (DPN+) and without (DPN-) neuropathy. Corneal nerve fiber density (CNFD) and length (CNFL) in the central cornea, and inferior whorl length (IWL) were quantified. RESULTS: Comparing control subjects to DPN- and DPN+ patients, there was a significant increase in NDS (0 vs. 2.6 ± 2.3 vs. 3.3 ± 2.7, P < 0.01), VPT (V; 5.4 ± 3.0 vs. 10.6 ± 10.3 vs. 17.7 ± 11.8, P < 0.01), WT (°C; 37.7 ± 3.5 vs. 39.1 ± 5.1 vs. 41.7 ± 4.7, P < 0.05), and a significant decrease in SSNCV (m/s; 50.2 ± 5.4 vs. 48.4 ± 5.0 vs. 39.5 ± 10.6, P < 0.05), CNFD (fibers/mm2; 37.8 ± 4.9 vs. 29.7 ± 7.7 vs. 27.1 ± 9.9, P < 0.01), CNFL (mm/mm2; 27.5 ± 3.6 vs. 24.4 ± 7.8 vs. 20.7 ± 7.1, P < 0.01), and IWL (mm/mm2; 35.1 ± 6.5 vs. 26.2 ± 10.5 vs. 23.6 ± 11.4, P < 0.05). For the diagnosis of DPN, CNFD, CNFL, and IWL achieved an area under the curve (AUC) of 0.75, 0.74, and 0.70, respectively, and a combination of IWL-CNFD achieved an AUC of 0.76. CONCLUSIONS: The parameters of CNFD, CNFL, and IWL have a comparable ability to diagnose patients with DPN. However, IWL detects an abnormality even in patients without DPN. Combining IWL with CNFD may improve the diagnostic performance of CCM.

Small fibre neuropathy in patients with latent autoimmune diabetes in adults

The prevalence of latent autoimmune diabetes in adults (LADA) in patients diagnosed with type 2 diabetes mellitus (T2DM) ranges from 7 to 10% (1). They present at a younger age and have a lower BMI but poorer glycemic control, which may increase the risk of complications (2). However, a recent analysis of the Collaborative Atorvastatin Diabetes Study (CARDS) has demonstrated no difference in macrovascular or microvascular events between patients with LADA and T2DM, but neuropathy was not assessed (3). Previous studies quantifying neuropathy in patients with LADA are limited. In this study, we aimed to accurately quantify neuropathy in subjects with LADA compared with matched patients with T2DM.

‘I really needed help’: What mothers say about their post-birth care in Queensland, Australia

Background Australian mothers consistently rate postnatal care as the poorest aspect of their maternity care, and researchers and policymakers have widely acknowledged the need for improvement in how postnatal care is provided. Aim To identify and analyse mothers’ comments about postnatal care in their free text responses to an open ended question in the Having a Baby in Queensland Survey, 2010, and reflect on their implications for midwifery practice and maternity service policies. Methods The survey assessed mothers’ experiences of maternity care four months after birth. We analysed free-text data from an open-ended question inviting respondents to write ‘anything else you would like to tell us’. Of the final survey sample (N = 7193), 60% (N = 4310) provided comments, 26% (N = 1100) of which pertained to postnatal care. Analysis included the coding and enumeration of issues to identify the most common problems commented on by mothers. Comments were categorised according to whether they related to in-hospital or post-discharge care, and whether they were reported by women birthing in public or private birthing facilities. Results The analysis revealed important differences in maternal experiences according to birthing sector: mothers birthing in public facilities were more likely to raise concerns about the quality and/or duration of their in-hospital stay than those in private facilities. Conversely, mothers who gave birth in private facilities were more likely to raise concerns about inadequate post-discharge care. Regardless of birthing sector, however, a substantial proportion of all mothers spontaneously raised concerns about their experiences of inadequate and/or inconsistent breastfeeding support. Conclusion Women who birth in private facilities were more likely to spontaneously report concerns about their level of post-discharge care than women from public facilities in Queensland, and publically provided community based care is not sufficient to meet women's needs. Inadequate or inconsistent professional breastfeeding support remains a major issue for early parenting women regardless of birthing sector.

The cost-effectiveness of the MobileMums intervention to increase physical activity among mothers with young children: A Markov model informed by a randomised controlled trial

Objectives: To determine the cost-effectiveness of the MobileMums intervention. MobileMums is a 12-week programme which assists mothers with young children to be more physically active, primarily through the use of personalised SMS text-messages. Design: A cost-effectiveness analysis using a Markov model to estimate and compare the costs and consequences of MobileMums and usual care. Setting: This study considers the cost-effectiveness of MobileMums in Queensland, Australia. Participants: A hypothetical cohort of over 36 000 women with a child under 1 year old is considered. These women are expected to be eligible and willing to participate in the intervention in Queensland, Australia. Data sources: The model was informed by the effectiveness results from a 9-month two-arm community-based randomised controlled trial undertaken in 2011 and registered retrospectively with the Australian Clinical Trials Registry (ACTRN12611000481976). Baseline characteristics for the model cohort, treatment effects and resource utilisation were all informed by this trial. Main outcome measures: The incremental cost per quality-adjusted life year (QALY) of MobileMums compared with usual care. Results: The intervention is estimated to lead to an increase of 131 QALYs for an additional cost to the health system of 1.1 million Australian dollars (AUD). The expected incremental cost-effectiveness ratio for MobileMums is 8608 AUD per QALY gained. MobileMums has a 98% probability of being cost-effective at a cost-effectiveness threshold of 64 000 AUD. Varying modelling assumptions has little effect on this result. Conclusions: At a cost-effectiveness threshold of 64 000 AUD, MobileMums would likely be a cost-effective use of healthcare resources in Queensland, Australia. Trial registration number: Australian Clinical Trials Registry; ACTRN12611000481976.

Biology, ecology and conservation of the Mobulidae

The Mobulidae are zooplanktivorous elasmobranchs comprising two recognized species of manta rays (Manta spp.) and nine recognized species of devil rays (Mobula spp.). They are found circumglobally in tropical, subtropical and temperate coastal waters. Although mobulids have been recorded for over 400 years, critical knowledge gaps still compromise the ability to assess the status of these species. On the basis of a review of 263 publications, a comparative synthesis of the biology and ecology of mobulids was conducted to examine their evolution, taxonomy, distribution, population trends, movements and aggregation, reproduction, growth and longevity, feeding, natural mortality and direct and indirect anthropogenic threats. There has been a marked increase in the number of published studies on mobulids since c. 1990, particularly for the genus Manta, although the genus Mobula remains poorly understood. Mobulid species have many common biological characteristics although their ecologies appear to be species-specific, and sometimes region-specific. Movement studies suggest that mobulids are highly mobile and have the potential to rapidly travel large distances. Fishing pressure is the major threat to many mobulid populations, with current levels of exploitation in target fisheries unlikely to be sustainable. Advances in the fields of population genetics, acoustic and satellite tracking, and stable-isotope and fatty-acid analyses will provide new insights into the biology and ecology of these species. Future research should focus on the uncertain taxonomy of mobulid species, the degree of overlap between their large-scale movement and human activities such as fisheries and pollution, and the need for management of inter-jurisdictional fisheries in developing nations to ensure their long-term sustainability. Closer collaboration among researchers worldwide is necessary to ensure standardized sampling and modelling methodologies to underpin global population estimates and status.

Chronic disease risks and use of a smartphone application during a physical activity and dietary intervention in Australian truck drivers

- Objective This study examined chronic disease risks and the use of a smartphone activity tracking application during an intervention in Australian truck drivers (April-October 2014). - Methods Forty-four men (mean age=47.5 [SD 9.8] years) completed baseline health measures, and were subsequently offered access to a free wrist-worn activity tracker and smartphone application (Jawbone UP) to monitor step counts and dietary choices during a 20-week intervention. Chronic disease risks were evaluated against guidelines; weekly step count and dietary logs registered by drivers in the application were analysed to evaluate use of the Jawbone UP. - Results Chronic disease risks were high (e.g. 97% high waist circumference [≥94 cm]). Eighteen drivers (41%) did not start the intervention; smartphone technical barriers were the main reason for drop out. Across 20-weeks, drivers who used the Jawbone UP logged step counts for an average of 6 [SD 1] days/week; mean step counts remained consistent across the intervention (weeks 1–4=8,743[SD 2,867] steps/day; weeks 17–20=8,994[SD 3,478] steps/day). The median number of dietary logs significantly decreased from start (17 [IQR 38] logs/weeks) to end of the intervention (0 [IQR 23] logs/week; p<0.01); the median proportion of healthy diet choices relative to total diet choices logged increased across the intervention (weeks 1–4=38[IQR 21]%; weeks 17–20=58[IQR 18]%). - Conclusions Step counts were more successfully monitored than dietary choices in those drivers who used the Jawbone UP. - Implications Smartphone technology facilitated active living and healthy dietary choices, but also prohibited intervention engagement in a number of these high-risk Australian truck drivers.

Sitting-time and 9-year all-cause mortality in older women

Background Studies of mid-aged adults provide evidence of a relationship between sitting-time and all-cause mortality, but evidence in older adults is limited. The aim is to examine the relationship between total sitting-time and all-cause mortality in older women. Methods The prospective cohort design involved 6656 participants in the Australian Longitudinal Study on Women's Health who were followed for up to 9 years (2002, age 76–81, to 2011, age 85–90). Self-reported total sitting-time was linked to all-cause mortality data from the National Death Index from 2002 to 2011. Cox proportional hazard models were used to examine the relationship between sitting-time and all-cause mortality, with adjustment for potential sociodemographic, behavioural and health confounders. Results There were 2003 (30.1%) deaths during a median follow-up of 6 years. Compared with participants who sat <4 h/day, those who sat 8–11 h/day had a 1.45 times higher risk of death and those who sat ≥11 h/day had a 1.65 times higher risk of death. These risks remained after adding sociodemographic and behavioural covariates, but were attenuated after adjustment for health covariates. A significant interaction (p=0.02) was found between sitting-time and physical activity (PA), with increased mortality risk for prolonged sitting only among participants not meeting PA guidelines (HR for sitting ≥8 h/day: 1.31, 95% CI 1.07 to 1.61); HR for sitting ≥11 h/day: 1.47, CI 1.15 to 1.93). Conclusions Prolonged sitting-time was positively associated with all-cause mortality. Women who reported sitting for more than 8 h/day and did not meet PA guidelines had an increased risk of dying within the next 9 years.

Comparing population attributable risks for heart disease across the adult lifespan in women

Background Recent estimates suggest that high body mass index (BMI), smoking, high blood pressure (BP) and physical inactivity are leading risk factors for the overall burden of disease in Australia. The aim was to examine the population attributable risk (PAR) of heart disease for each of these risk factors, across the adult lifespan in Australian women. Methods PARs were estimated using relative risks (RRs) for each of the four risk factors, as used in the Global Burden of Disease Study, and prevalence estimates from the Australian Longitudinal Study on Women's Health, in 15 age groups from 22–27 (N=9608) to 85–90 (N=3901). Results RRs and prevalence estimates varied across the lifespan. RRs ranged from 6.15 for smoking in the younger women to 1.20 for high BMI and high BP in the older women. Prevalence of risk exposure ranged from 2% for high BP in the younger women to 79% for high BMI in mid-age women. In young adult women up to age 30, the highest population risk was attributed to smoking. From age 31 to 90, PARs were highest for physical inactivity. Conclusions From about age 30, the population risk of heart disease attributable to inactivity outweighs that of other risk factors, including high BMI. Programmes for the promotion and maintenance of physical activity deserve to be a much higher public health priority for women than they are now, across the adult lifespan.

Does vigorous physical activity provide additional benefits beyond those of moderate?

Background Although guidelines suggest that vigorous physical activity (PA) confers “extra” benefits compared with those from moderate-intensity activity alone, the magnitude of this additional benefit is unclear. The aim was to compare the reduction in risk of hypertension (HT) and depressive symptoms (DS) for 12 yr in middle-age women who reported (a) only moderate-intensity PA (MOPA) and (b) a combination of moderate and vigorous PA (MVPA), after controlling for overall volume of activity. Methods The study involved 11,285 participants in the Australian Longitudinal Study on Women’s Health, who completed surveys in 1998 (age = 46–52 yr), 2001, 2004, 2007, and 2010. Generalized estimating equation models (with 3-yr time lag) were used to examine the relationship between PA in seven categories from 0 to >2000 MET·min·wk−1 and occurrence of HT and DS for women who reported MOPA or MVPA. Results For HT, risk was slightly lower for MVPA than for MOPA across the entire range of PA levels, but this difference was only significant at the highest PA level (>2000; odds ratio [OR] = 0.80 MOPA and 0.56 MVPA). For DS, OR values were similar in both groups up to 500 MET·min·wk−1, then slightly lower for MVPA than for MOPA at higher PA levels. Again, this difference was only significant at the highest PA level (>2000; OR = 0.57 MOPA and 0.42 MVPA). OR values were slightly attenuated in adjusted models. Conclusions Doing both vigorous and moderate activity does not have significant additional benefits in terms of HT and DS, above those from moderate-intensity activity alone, except at very high levels of PA.

Assessing the effectiveness of High Intensity Interval Training (HIIT) for smoking cessation in women: HIIT to quit study protocol

Background: Smoking and physical inactivity are major risk factors for heart disease. Linking strategies that promote improvements in fitness and assist quitting smoking has potential to address both these risk factors simultaneously. The objective of this study is to compare the effects of two exercise interventions (high intensity interval training (HIIT) and lifestyle physical activity) on smoking cessation in female smokers. Method/design: This study will use a randomised controlled trial design. Participants: Women aged 18–55 years who smoke ≥ 5 cigarettes/day, and want to quit smoking. Intervention: all participants will receive usual care for quitting smoking. Group 1 - will complete two gym-based supervised HIIT sessions/week and one home-based HIIT session/week. At each training session participants will be asked to complete four 4-min (4 × 4 min) intervals at approximately 90 % of maximum heart rate interspersed with 3- min recovery periods. Group 2 - participants will receive a resource pack and pedometer, and will be asked to use the 10,000 steps log book to record steps and other physical activities. The aim will be to increase daily steps to 10,000 steps/day. Analysis will be intention to treat and measures will include smoking cessation, withdrawal and cravings, fitness, physical activity, and well-being. Discussion: The study builds on previous research suggesting that exercise intensity may influence the efficacy of exercise as a smoking cessation intervention. The hypothesis is that HIIT will improve fitness and assist women to quit smoking.

Validity of a self-report recall tool for estimating sedentary behaviour in adults

BACKGROUND Sedentary behavior is continuing to emerge as an important target for health promotion. The purpose of this study was to determine the validity of a self-report use of time recall tool, the Multimedia Activity Recall for Children and Adults (MARCA) in estimating time spent sitting/lying, compared with a device-based measure. METHODS Fifty-eight participants (48% female, [mean±standard deviation] 28±7.4 years of age, 23.9±3.05 kg/m2) wore an activPAL device for 24-h and the following day completed the MARCA. Pearson correlation coefficients (r) were used to analyse convergent validity of the adult MARCA compared with activPAL estimates of total sitting/lying time. Agreement was examined using Bland-Altman plots. RESULTS According to activPAL estimates, participants spent 10.4 hr/day [standard deviation (SD)=2.06] sitting or lying down while awake. The correlation between MARCA and activPAL estimates of total sit/lie time was r=0.77 (95% confidence interval = 0.64-0.86; p<0.001). Bland-Altman analyses revealed a mean bias of +0.59 hr/day with moderately wide limits of agreement (-2.35 hours to +3.53 hr/day). CONCLUSIONS This study found a moderate to strong agreement between the adult MARCA and the activPAL, suggesting that the MARCA is an appropriate tool for the measurement of time spent sitting or lying down in an adult population.

The validity of the GENEActiv wrist-worn accelerometer for measuring adult sedentary time in free living

OBJECTIVES Based on self-reported measures, sedentary time has been associated with chronic disease and mortality. This study examined the validity of the wrist-worn GENEactiv accelerometer for measuring sedentary time (i.e. sitting and lying) by posture classification, during waking hours in free living adults. DESIGN Fifty-seven participants (age=18-55 years 52% male) were recruited using convenience sampling from a large metropolitan Australian university. METHODS Participants wore a GENEActiv accelerometer on their non-dominant wrist and an activPAL device attached to their right thigh for 24-h (00:00 to 23:59:59). Pearson's Correlation Coefficient was used to examine the convergent validity of the GENEActiv and the activPAL for estimating total sedentary time during waking hours. Agreement was illustrated using Bland and Altman plots, and intra-individual agreement for posture was assessed with the Kappa statistic. RESULTS Estimates of average total sedentary time over 24-h were 623 (SD 103) min/day from the GENEActiv, and 626 (SD 123) min/day from the activPAL, with an Intraclass Correlation Coefficient of 0.80 (95% confidence intervals 0.68-0.88). Bland and Altman plots showed slight underestimation of mean total sedentary time for GENEActiv relative to activPAL (mean difference: -3.44min/day), with moderate limits of agreement (-144 to 137min/day). Mean Kappa for posture was 0.53 (SD 0.12), indicating moderate agreement for this sample at the individual level. CONCLUSIONS The estimation of sedentary time by posture classification of the wrist-worn GENEActiv accelerometer was comparable to the activPAL. The GENEActiv may provide an alternative, easy to wear device based measure for descriptive estimates of sedentary time in population samples

Response: Special communication: Letters to the Editor-in-Chief [Vigorous exercise in clinical practice: balancing risks and benefits]

The effects of different exercise intensities on health have been investigated in several studies in recent years, in which some authors showed greater benefits for vigorous exercise (6) while others did not find any differences (8). An important issue regarding these conflicting results could be the fact that only a few of the studies controlled the effects of different exercise intensities for the overall volume of physical activity, making the evaluation of the available data difficult.