Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial.

BACKGROUND: HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. METHODS AND FINDINGS: HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. CONCLUSIONS: In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01900977.

Community-based health workers implementing universal access to HIV testing and treatment: lessons from South Africa and Zambia-HPTN 071 (PopART).

The global expansion of HIV testing, prevention and treatment services is necessary to achieve HIV epidemic control and promote individual and population health benefits for people living with HIV (PLHIV) in sub-Saharan Africa. Community-based health workers (CHWs) could play a key role in supporting implementation at scale. In the HPTN 071 (PopART) trial in Zambia and South Africa, a cadre of 737 study-specific CHWs, working closely with government-employed CHW, were deployed to deliver a 'universal' door-to-door HIV prevention package, including an annual offer of HIV testing and referral services for all households in 14 study communities. We conducted a process evaluation using qualitative and quantitative data collected during the trial (2013-2018) to document the implementation of the CHW intervention in practice. We focused on the recruitment, retention, training and support of CHWs, as they delivered study-specific services. We then used these descriptions to: (i) analyse the fidelity to design of the delivery of the intervention package, and (ii) suggest key insights for the transferability of the intervention to other settings. The data included baseline quantitative data collected with the study-specific CHWs (2014-2018); and qualitative data from key informant interviews with study management (n = 91), observations of CHW training events (n = 12) and annual observations of and group discussions (GD) with intervention staff (n = 68). We show that it was feasible for newly recruited CHWs to implement the PopART intervention with good fidelity, supporting the interpretation of the trial outcome findings. This was despite some challenges in managing service quality and CHW retention in the early years of the programme. We suggest that by prioritizing the adoption of key elements of the in-home HIV services delivery intervention model-including training, emotional support to workers, monitoring and appropriate remuneration for CHWs-these services could be successfully transferred to new settings.

Intra-Target Microdosing - A Novel Drug Development Approach: Proof of Concept, Safety, and Feasibility Study in Humans.

Intra-Target Microdosing (ITM) is a novel drug development approach aimed at increasing the efficiency of first-in-human (FIH) testing of new molecular entities (NMEs). ITM combines intra-target drug delivery and "microdosing," the subpharmacological systemic exposure. We hypothesized that when the target tissue is small (about 1/100th of total body mass), ITM can lead to target therapeutic-level exposure with minimal (microdose) systemic exposure. Each of five healthy male volunteers received insulin microdose into the radial artery or full therapeutic dose intravenously in separate visits. Insulin and glucose levels were similar between systemic administration and ITM administration in the ipsilateral hand, and glucose levels demonstrated a reduction in the ipsilateral hand but not in the contralateral hand. Positron emission tomography (PET) imaging of 18 F-fluorodeoxyglucose (FDG) uptake demonstrated differences between the ipsilateral and contralateral arms. The procedures were safe and well-tolerated. Results are consistent with ITM proof-of-concept (POC) and demonstrate the ethical, regulatory, and logistical feasibility of the approach.

Effects of transients in LIGO suspensions on searches for gravitational waves.

This paper presents an analysis of the transient behavior of the Advanced LIGO (Laser Interferometer Gravitational-wave Observatory) suspensions used to seismically isolate the optics. We have characterized the transients in the longitudinal motion of the quadruple suspensions during Advanced LIGO's first observing run. Propagation of transients between stages is consistent with modeled transfer functions, such that transient motion originating at the top of the suspension chain is significantly reduced in amplitude at the test mass. We find that there are transients seen by the longitudinal motion monitors of quadruple suspensions, but they are not significantly correlated with transient motion above the noise floor in the gravitational wave strain data, and therefore do not present a dominant source of background noise in the searches for transient gravitational wave signals. Using the suspension transfer functions, we compared the transients in a week of gravitational wave strain data with transients from a quadruple suspension. Of the strain transients between 10 and 60 Hz, 84% are loud enough that they would have appeared above the sensor noise in the top stage quadruple suspension monitors if they had originated at that stage at the same frequencies. We find no significant temporal correlation with the suspension transients in that stage, so we can rule out suspension motion originating at the top stage as the cause of those transients. However, only 3.2% of the gravitational wave strain transients are loud enough that they would have been seen by the second stage suspension sensors, and none of them are above the sensor noise levels of the penultimate stage. Therefore, we cannot eliminate the possibility of transient noise in the detectors originating in the intermediate stages of the suspension below the sensing noise.

What is white?

To shed light on the perceptual basis of the color white, we measured settings of unique white in a dark surround. We find that settings reliably show more variability in an oblique (blue-yellow) direction in color space than along the cardinal axes of the cone-opponent mechanisms. This is against the idea that white perception arises at the null point of the cone-opponent mechanisms, but one alternative possibility is that it occurs through calibration to the visual environment. We found that the locus of maximum variability in settings lies close to the locus of natural daylights, suggesting that variability may result from uncertainty about the color of the illuminant. We tested this by manipulating uncertainty. First, we altered the extent to which the task was absolute (requiring knowledge of the illumination) or relative. We found no clear effect of this factor on the reduction in sensitivity in the blue-yellow direction. Second, we provided a white surround as a cue to the illumination or left the surround dark. Sensitivity was selectively worse in the blue-yellow direction when the surround was black than when it was white. Our results can be functionally related to the statistics of natural images, where a greater blue-yellow dispersion is characteristic of both reflectances (where anisotropy is weak) and illuminants (where it is very pronounced). Mechanistically, the results could suggest a neural signal responsive to deviations from the blue-yellow locus or an adaptively matched range of contrast response functions for signals that encode different directions in color space.

Impact of hindcast length on estimates of seasonal climate predictability.

It has recently been argued that single-model seasonal forecast ensembles are overdispersive, implying that the real world is more predictable than indicated by estimates of so-called perfect model predictability, particularly over the North Atlantic. However, such estimates are based on relatively short forecast data sets comprising just 20 years of seasonal predictions. Here we study longer 40 year seasonal forecast data sets from multimodel seasonal forecast ensemble projects and show that sampling uncertainty due to the length of the hindcast periods is large. The skill of forecasting the North Atlantic Oscillation during winter varies within the 40 year data sets with high levels of skill found for some subperiods. It is demonstrated that while 20 year estimates of seasonal reliability can show evidence of overdispersive behavior, the 40 year estimates are more stable and show no evidence of overdispersion. Instead, the predominant feature on these longer time scales is underdispersion, particularly in the tropics. KEY POINTS: Predictions can appear overdispersive due to hindcast length sampling errorLonger hindcasts are more robust and underdispersive, especially in the tropicsTwenty hindcasts are an inadequate sample size to assess seasonal forecast skill.

Using multi-country household surveys to understand who provides reproductive and maternal health services in low- and middle-income countries: a critical appraisal of the Demographic and Health Surveys.

OBJECTIVE: The Demographic and Health Surveys (DHS) are a vital data resource for cross-country comparative analyses. This study is part of a set of analyses assessing the types of providers being used for reproductive and maternal health care across 57 countries. Here, we examine some of the challenges encountered using DHS data for this purpose, present the provider classification we used, and provide recommendations to enable more detailed and accurate cross-country comparisons of healthcare provision. METHODS: We used the most recent DHS surveys between 2000 and 2012; 57 countries had data on family planning and delivery care providers and 47 countries had data on antenatal care. Every possible response option across the 57 countries was listed and categorised. We then developed a classification to group provider response options according to two key dimensions: clinical nature and profit motive. RESULTS: We classified the different types of maternal and reproductive healthcare providers, and the individuals providing care. Documented challenges encountered during this process were limitations inherent in household survey data based on respondents' self-report; conflation of response options in the questionnaire or at the data processing stage; category errors of the place vs. professional for delivery; inability to determine whether care received at home is from the public or private sector; a large number of negligible response options; inconsistencies in coding and analysis of data sets; and the use of inconsistent headings. CONCLUSIONS: To improve clarity, we recommend addressing issues such as conflation of response options, data on public vs. private provider, inconsistent coding and obtaining metadata. More systematic and standardised collection of data would aid international comparisons of progress towards improved financial protection, and allow us to better characterise the incentives and commercial nature of different providers.

Visualizing the uncertainty in the relationship between seasonal average climate and malaria risk.

Around $1.6 billion per year is spent financing anti-malaria initiatives, and though malaria morbidity is falling, the impact of annual epidemics remains significant. Whilst malaria risk may increase with climate change, projections are highly uncertain and to sidestep this intractable uncertainty, adaptation efforts should improve societal ability to anticipate and mitigate individual events. Anticipation of climate-related events is made possible by seasonal climate forecasting, from which warnings of anomalous seasonal average temperature and rainfall, months in advance are possible. Seasonal climate hindcasts have been used to drive climate-based models for malaria, showing significant skill for observed malaria incidence. However, the relationship between seasonal average climate and malaria risk remains unquantified. Here we explore this relationship, using a dynamic weather-driven malaria model. We also quantify key uncertainty in the malaria model, by introducing variability in one of the first order uncertainties in model formulation. Results are visualized as location-specific impact surfaces: easily integrated with ensemble seasonal climate forecasts, and intuitively communicating quantified uncertainty. Methods are demonstrated for two epidemic regions, and are not limited to malaria modeling; the visualization method could be applied to any climate impact.

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery.

We examined the hypotheses that: (1) during incremental exercise and recovery following 4-6 days at high altitude (HA) global cerebral blood flow (gCBF) increases to preserve cerebral oxygen delivery (CDO2) in excess of that required by an increasing cerebral metabolic rate of oxygen ( CM RO2); (2) the trans-cerebral exchange of oxygen vs. carbohydrates (OCI; carbohydrates = glucose + ½lactate) would be similar during exercise and recovery at HA and sea level (SL). Global CBF, intra-cranial arterial blood velocities, extra-cranial blood flows, and arterial-jugular venous substrate differences were measured during progressive steady-state exercise (20, 40, 60, 80, 100% maximum workload (Wmax)) and through 30 min of recovery. Measurements (n = 8) were made at SL and following partial acclimatization to 5050 m. At HA, absolute Wmax was reduced by ∼50%. During submaximal exercise workloads (20-60% Wmax), despite an elevated absolute gCBF (∼20%, P < 0.05) the relative increases in gCBF were not different at HA and SL. In contrast, gCBF was elevated at HA compared with SL during 80 and 100% Wmax and recovery. Notwithstanding a maintained CDO2 and elevated absolute CM RO2 at HA compared with SL, the relative increase in CM RO2 was similar during 20-80% Wmax but half that of the SL response (i.e. 17 vs. 27%; P < 0.05 vs. SL) at 100% Wmax. The OCI was reduced at HA compared with SL during 20, 40, and 60% Wmax but comparable at 80 and 100% Wmax. At HA, OCI returned almost immediately to baseline values during recovery, whereas at SL it remained below baseline. In conclusion, the elevations in gCBF during exercise and recovery at HA serve to maintain CDO2. Despite adequate CDO2 at HA the brain appears to increase non-oxidative metabolism during exercise and recovery.

Compensation for red-green contrast loss in anomalous trichromats.

For anomalous trichromats, threshold contrasts for color differences captured by the L and M cones and their anomalous analogs are much higher than for normal trichromats. The greater spectral overlap of the cone sensitivities reduces chromatic contrast both at and above threshold. But above threshold, adaptively nonlinear processing might compensate for the chromatically impoverished photoreceptor inputs. Ratios of sensitivity for threshold variations and for color appearance along the two cardinal axes of MacLeod-Boynton chromaticity space were calculated for three groups: normals (N = 15), deuteranomals (N = 9), and protanomals (N = 5). Using a four-alternative forced choice (4AFC) task, threshold sensitivity was measured in four color-directions along the two cardinal axes. For the same participants, we reconstructed perceptual color spaces for the positions of 25 hues using multidimensional scaling (MDS). From the reconstructed color spaces we extracted "color difference ratios," defined as ratios for the size of perceived color differences along the L/(L + M) axis relative to those along the S/(L + M) axis, analogous to "sensitivity ratios" extracted from the 4AFC task. In the 4AFC task, sensitivity ratios were 38% of normal for deuteranomals and 19% of normal for protanomals. Yet, in the MDS results, color difference ratios were 86% of normal for deuteranomals and 67% of normal for protanomals. Thus, the contraction along the L/(L + M) axis shown in the perceptual color spaces of anomalous trichromats is far smaller than predicted by their reduced sensitivity, suggesting that an adaptive adjustment of postreceptoral gain may magnify the cone signals of anomalous trichromats to exploit the range of available postreceptoral neural signals.

Regional cerebral blood flow in humans at high altitude: gradual ascent and 2 wk at 5,050 m.

The interindividual variation in ventilatory acclimatization to high altitude is likely reflected in variability in the cerebrovascular responses to high altitude, particularly between brain regions displaying disparate hypoxic sensitivity. We assessed regional differences in cerebral blood flow (CBF) measured with Duplex ultrasound of the left internal carotid and vertebral arteries. End-tidal Pco2, oxyhemoglobin saturation (SpO2), blood pressure, and heart rate were measured during a trekking ascent to, and during the first 2 wk at, 5,050 m. Transcranial color-coded Duplex ultrasound (TCCD) was employed to measure flow and diameter of the middle cerebral artery (MCA). Measures were collected at 344 m (TCCD-baseline), 1,338 m (CBF-baseline), 3,440 m, and 4,371 m. Following arrival to 5,050 m, regional CBF was measured every 12 h during the first 3 days, once at 5-9 days, and once at 12-16 days. Total CBF was calculated as twice the sum of internal carotid and vertebral flow and increased steadily with ascent, reaching a maximum of 842 ± 110 ml/min (+53 ± 7.6% vs. 1,338 m; mean ± SE) at ∼ 60 h after arrival at 5,050 m. These changes returned to +15 ± 12% after 12-16 days at 5,050 m and were related to changes in SpO2 (R(2) = 0.36; P < 0.0001). TCCD-measured MCA flow paralleled the temporal changes in total CBF. Dilation of the MCA was sustained on days 2 (+12.6 ± 4.6%) and 8 (+12.9 ± 2.9%) after arrival at 5,050 m. We observed no significant differences in regional CBF at any time point. In conclusion, the variability in CBF during ascent and acclimatization is related to ventilatory acclimatization, as reflected in changes in SpO2.

Accuracy of the Lifebox pulse oximeter during hypoxia in healthy volunteers.

Pulse oximetry is a standard of care during anaesthesia in high-income countries. However, 70% of operating environments in low- and middle-income countries have no pulse oximeter. The 'Lifebox' oximetry project set out to bridge this gap with an inexpensive oximeter meeting CE (European Conformity) and ISO (International Organization for Standardization) standards. To date, there are no performance-specific accuracy data on this instrument. The aim of this study was to establish whether the Lifebox pulse oximeter provides clinically reliable haemoglobin oxygen saturation (Sp O2 ) readings meeting USA Food and Drug Administration 510(k) standards. Using healthy volunteers, inspired oxygen fraction was adjusted to produce arterial haemoglobin oxygen saturation (Sa O2 ) readings between 71% and 100% measured with a multi-wavelength oximeter. Lifebox accuracy was expressed using bias (Sp O2 - Sa O2 ), precision (SD of the bias) and the root mean square error (Arms). Simultaneous readings of Sa O2 and Sp O2 in 57 subjects showed a mean (SD) bias of -0.41% (2.28%) and Arms 2.31%. The Lifebox pulse oximeter meets current USA Food and Drug Administration standards for accuracy, thus representing an inexpensive solution for patient monitoring without compromising standards.

Regional brain blood flow in man during acute changes in arterial blood gases.

Despite the importance of blood flow on brainstem control of respiratory and autonomic function, little is known about regional cerebral blood flow (CBF) during changes in arterial blood gases.We quantified: (1) anterior and posterior CBF and reactivity through a wide range of steady-state changes in the partial pressures of CO2 (PaCO2) and O2 (PaO2) in arterial blood, and (2) determined if the internal carotid artery (ICA) and vertebral artery (VA) change diameter through the same range.We used near-concurrent vascular ultrasound measures of flow through the ICA and VA, and blood velocity in their downstream arteries (the middle (MCA) and posterior (PCA) cerebral arteries). Part A (n =16) examined iso-oxic changes in PaCO2, consisting of three hypocapnic stages (PaCO2 =∼15, ∼20 and ∼30 mmHg) and four hypercapnic stages (PaCO2 =∼50, ∼55, ∼60 and ∼65 mmHg). In Part B (n =10), during isocapnia, PaO2 was decreased to ∼60, ∼44, and ∼35 mmHg and increased to ∼320 mmHg and ∼430 mmHg. Stages lasted ∼15 min. Intra-arterial pressure was measured continuously; arterial blood gases were sampled at the end of each stage. There were three principal findings. (1) Regional reactivity: the VA reactivity to hypocapnia was larger than the ICA, MCA and PCA; hypercapnic reactivity was similar.With profound hypoxia (35 mmHg) the relative increase in VA flow was 50% greater than the other vessels. (2) Neck vessel diameters: changes in diameter (∼25%) of the ICA was positively related to changes in PaCO2 (R2, 0.63±0.26; P<0.05); VA diameter was unaltered in response to changed PaCO2 but yielded a diameter increase of +9% with severe hypoxia. (3) Intra- vs. extra-cerebral measures: MCA and PCA blood velocities yielded smaller reactivities and estimates of flow than VA and ICA flow. The findings respectively indicate: (1) disparate blood flow regulation to the brainstem and cortex; (2) cerebrovascular resistance is not solely modulated at the level of the arteriolar pial vessels; and (3) transcranial Doppler ultrasound may underestimate measurements of CBF during extreme hypoxia and/or hypercapnia.

Relative importance of prenatal and postnatal androgen action in determining growth of the penis and anogenital distance in the rat before, during and after puberty.

Experimental animal studies show that measurement of anogenital distance (AGD) and/or penis length may provide lifelong 'read-outs' of foetal androgen exposure during the masculinization programming window (MPW). However, variation in postnatal androgen exposure may complicate interpretation of such measurements. This is important to clarify if such measurements are to be applied to humans. The present aim was to evaluate effects of prenatal and/or postnatal manipulation of androgen production/action on growth of AGD and the penis in rats. Pregnant rats were treated daily before (e13.5-e21.5) and after birth (postnatal days 1-15) with either vehicle, 500 mg/kg di(n-butyl) phthalate (DBP) or 100 mg/kg flutamide (postnatal only) in prenatal + postnatal treatment combinations (N = 6 treatment combinations); DBP impairs androgen production whereas flutamide impairs androgen action. Male offspring were killed on postnatal day 8 (prepuberty), 25 (early puberty) or 90 (adulthood) when AGD was measured, the penis dissected out and its weight and length measured; plasma testosterone and ventral prostate weight were measured at day 90 to assess endogenous androgen exposure. In controls, penis length, girth and AGD increased 2.2-, 5.3-and 5.9-fold respectively from day 8 to day 90. Significant inhibition of penis growth and final length and girth was induced by treatments that inhibited postnatal androgen action. Conversely, growth and ultimate (adult) AGD was inhibited by prenatal inhibition of androgen production whereas postnatal androgen inhibition had negligible effect. Nevertheless, AGD and penis length were highly correlated at every age (R(2) > 0.33; p < 0.0001). However, altered endogenous androgen exposure may confound interpretation of changes in adults exposed prenatally/postnatally to DBP/flutamide. We conclude that AGD provides a lifelong guide to prenatal androgen exposure (in the MPW) whereas penis size reflects both prenatal + postnatal androgen exposure. At the group treatment level, prepubertal measurement of either AGD or penis size accurately predicts their size in adulthood.

Androgen action in the masculinization programming window and development of male reproductive organs.

We have shown previously that deficient androgen action within a masculinization programming window (MPW; e15.5-e18.5 in rats) is important in the origin of male reproductive disorders and in programming male reproductive organ size, but that androgen action postnatally may be important to achieve this size. To further investigate importance of the MPW, we used two rat models, in which foetal androgen production or action was impaired during the MPW by exposing in utero to either di(n-butyl) phthalate (DBP) or to flutamide. Reduced anogenital distance (AGD) was used as a monitor of androgen production/action during the MPW. Offspring were evaluated in early puberty (Pnd25) to establish if reproductive organ size was altered. The testes, penis, ventral prostate (VP) and seminal vesicles (SV) were weighed and penis length measured. Both DBP and flutamide exposure in the MPW significantly reduced penis, VP and SV size along with AGD at Pnd25; AGD and organ size were highly correlated. In DBP-, but not flutamide-, exposed animals, testis weight was also reduced and correlated with AGD. Intratesticular testosterone was also measured in control and DBP-exposed males during (e17.5) or after (e21.5) the MPW and related to AGD at e21.5. To evaluate the importance of postnatal androgen action in reproductive organ growth, the effect of combinations of prenatal and postnatal maternal treatments on AGD and penis size at Pnd25 was evaluated. In prenatally DBP-exposed animals, further postnatal exposure to either DBP or flutamide significantly reduced AGD and penis size in comparison with prenatal DBP exposure alone. In comparison, rats exposed postnatally to testosterone propionate after prenatal vehicle-exposure showed considerable increase in these parameters vs. controls. In conclusion, we show that the size of all male reproductive organs is programmed by androgen exposure in the MPW, but that growth towards this size is dependent on androgen action postnatally.

A case report of gastroparesis secondary to acute renal failure.

A 45-year-old female with a background of poorly differentiated ovarian adenocarcinoma treated with bilateral salpingo-oophorectomy presented with one week history of nausea, vomiting and decreased urine output. On examination, she was mildly dehydrated but haemodynamically stable. Abdominal examination revealed tender swelling in upper abdomen. Biochemistry revealed that she had acute renal failure and interestingly the acute renal failure was out of proportion to the degree of dehydration. Abdominal ultrasound showed marked distension of the stomach without any evidence of renal tract obstruction. She was aggressively treated with volume replacement and careful monitoring of input and output. She responded very well to fluid replacement and her renal failure resolved within four days of treatment. This case illustrates a case of acute renal failure secondary to gastroparesis which resolved after treatment of renal failure. Patients with chronic renal failure are prone to develop gastroparesis but it is extremely rare to have gastric stasis following acute renal failure. This case also illustrates the importance of aggressive treatment of a reversible but potentially fatal medical condition which could have been easily overlooked in view of patient's poorly differentiated ovarian cancer.

Patient adherence with emergency department referral to a cardiovascular evaluation and risk assessment clinic.

OBJECTIVE: Patient adherence with emergency department (ED) referral has not been well studied in Canada, and there are no Canadian studies assessing patient follow-up for evaluation of cardiovascular disease. Our primary objective was to determine the proportion of patients who adhered with an ED referral to a cardiac evaluation and risk assessment (CERA) clinic in Calgary, Alta. Secondary objectives included determining the final diagnoses and outcomes for patients attending CERA appointments. We also assessed the association between adherence and various system and patient factors. METHODS: A retrospective review of 385 patients who were referred to CERA from EDs in the study region between June 1, 2004, and Apr. 7, 2005, was performed. Hospital charts and the database at the medical examiner's office were reviewed for patients who did not attend their CERA appointment. RESULTS: The majority of patients (345/385, 89.6%) followed through with their referral to CERA. No deaths were identified from hospital records or from the medical examiner's office for nonadherent patients. Of the 315 patients who completed their follow-up, 225 (71.4%) were diagnosed with noncardiac or low-risk cardiac disease, whereas 90 (28.6%) were diagnosed with cardiovascular disease. The referring hospital was the only variable significantly associated with adherence with the referral (p=0.004). CONCLUSION: The great majority of patients referred to CERA from Calgary EDs were adherent with the referral. Future studies may identify factors impairing adherence that are amenable to intervention. Implementation of a referral model similar to the one used by CERA may improve adherence with attendance at other outpatient clinics.

Physiological determinants of climbing-specific finger endurance and sport rock climbing performance.

The aim of the study was to examine several physiological responses to a climbing-specific task to identify determinants of endurance in sport rock climbing. Finger strength and endurance of intermediate rock climbers (n = 11) and non-climbers (n = 9) were compared using climbing-specific apparatus. After maximum voluntary contraction (MVC) trials, two isometric endurance tests were performed at 40% (s = 2.5%) MVC until volitional exhaustion (continuous contractions and intermittent contractions of 10 s, with 3 s rest between contractions). Changes in muscle blood oxygenation and muscle blood volume were recorded in the flexor digitorum superficialis using near infra-red spectroscopy. Statistical significance was set at P < 0.05. Climbers had a higher mean MVC (climbers: 485 N, s = 65; non-climbers 375 N, s = 91) (P = 0.009). The group mean endurance test times were similar. The force-time integral, used as a measure of climbing-specific endurance, was greater for climbers in the intermittent test (climbers: 51,769 N x s, s = 12,229; non-climbers: 35,325 N x s, s = 9724) but not in the continuous test (climbers: 21,043 N x s, s = 4474; non-climbers: 15,816 N x s, s = 6263). Recovery of forearm oxygenation during rest phases (intermittent test) explained 41.1% of the variability in the force-time integral. Change in total haemoglobin was significantly greater in non-climbers (continuous test) than climbers (P = 0.023--40% test timepoint, P = 0.014--60% test timepoint). Pressor responses were similar between groups and not related to the force-time integral for either test. We conclude that muscle re-oxygenation during rest phases is a predictor of endurance performance.