Social media as a tool to understand the distribution and ecology of elusive mammals.

Comparatively little is known about the distribution and ecology of Aardvark (Orycteropus afer) and Temminck's Ground Pangolin (Smutsia temminckii). Both are elusive species that are normally nocturnal, solitary, and fossorial. Formally collected records have been used to map the distribution of these species, and social media records provide a tool to gather information on their distribution and ecology. We obtained 680 photographs and videos of aardvarks and 790 of ground pangolins in southern Africa from publicly available posts on Facebook and Instagram (2010-2019). The images provide new insights into the distribution, activity, drinking, and predation-and confirm that aardvarks are more diurnally active when they are in poor body condition. Social media can provide useful supplementary information for understanding of elusive mammals. These "soft" data can be applied to other species.

Temminck pangolins relax the precision of body temperature regulation when resources are scarce in a semi-arid environment.

Climate change is impacting mammals both directly (for example, through increased heat) and indirectly (for example, through altered food resources). Understanding the physiological and behavioural responses of mammals in already hot and dry environments to fluctuations in the climate and food availability allows for a better understanding of how they will cope with a rapidly changing climate. We measured the body temperature of seven Temminck's pangolins (Smutsia temminckii) in the semi-arid Kalahari for periods of between 4 months and 2 years. Pangolins regulated body temperature within a narrow range (34-36°C) over the 24-h cycle when food (and hence water, obtained from their prey) was abundant. When food resources were scarce, body temperature was regulated less precisely, 24-h minimum body temperatures were lower and the pangolins became more diurnally active, particularly during winter when prey was least available. The shift toward diurnal activity exposed pangolins to higher environmental heat loads, resulting in higher 24-h maximum body temperatures. Biologging of body temperature to detect heterothermy, or estimating food abundance (using pitfall trapping to monitor ant and termite availability), therefore provide tools to assess the welfare of this elusive but threatened mammal. Although the physiological and behavioural responses of pangolins buffered them against food scarcity during our study, whether this flexibility will be sufficient to allow them to cope with further reductions in food availability likely with climate change is unknown.

A Systematic Review and Meta-analysis of Non-pharmacological Methods to Manipulate Experimentally Induced Secondary Hypersensitivity.

This systematic review and meta-analysis investigated the effects of non-pharmacological manipulations on experimentally induced secondary hypersensitivity in pain-free humans. We investigated the magnitude (change/difference in follow-up ratings from pre-manipulation ratings) of secondary hypersensitivity (primary outcome), and surface area of secondary hypersensitivity (secondary outcome), in 27 studies representing 847 participants. Risk of bias assessment concluded most studies (23 of 27) had an unclear or high risk of performance and detection bias. Further, 2 (of 27) studies had a high risk of measurement bias. Datasets were pooled by the method of manipulation and outcome. The magnitude of secondary hypersensitivity was decreased by diverting attention, anodal transcranial direct current stimulation, or emotional disclosure; increased by directing attention toward the induction site, nicotine deprivation, or negative suggestion; and unaffected by cathodal transcranial direct current stimulation or thermal change. Area of secondary hypersensitivity was decreased by anodal transcranial direct current stimulation, emotional disclosure, cognitive behavioral therapy, hyperbaric oxygen therapy, placebo analgesia, or spinal manipulation; increased by directing attention to the induction site, nicotine deprivation, or sleep disruption (in males only); and unaffected by cathodal transcranial direct current stimulation, thermal change, acupuncture, or electroacupuncture. Meta-analytical pooling was only appropriate for studies that used transcranial direct current stimulation or hyperbaric oxygen therapy, given the high clinical heterogeneity among the studies and unavailability of data. The evidence base for this question remains small. We discuss opportunities to improve methodological rigor including manipulation checks, structured blinding strategies, control conditions or time points, and public sharing of raw data. PERSPECTIVE: We described the effects of several non-pharmacological manipulations on experimentally induced secondary hypersensitivity in humans. By shedding light on the potential for non-pharmacological therapies to influence secondary hypersensitivity, it provides a foundation for the development and testing of targeted therapies for secondary hypersensitivity.

Chronic pain is no more prevalent in people living with HIV than in their uninfected counterparts in South Africa.

BACKGROUND: There are few studies on chronic pain prevalence in people living with HIV, and there are no studies comparing chronic pain prevalence in an HIV-infected group (HIV+) to that found in an uninfected group (HIV-) in the same population. This study was undertaken to (1) estimate the chronic pain prevalence in HIV+ individuals and (2) compare chronic pain prevalence between HIV+ and HIV- groups in a population. METHODS: Individuals ≥15 years old were recruited using multi-stage probability sampling in the 2016 South African Demographic and Health Survey. In an interview, participants were asked whether they currently had pain or discomfort, and if so, whether that pain or discomfort had persisted for at least 3 months (operational definition of chronic pain). Blood samples were taken from a volunteering sub-sample for HIV testing. RESULTS: A total of 6584 of 12,717 eligible individuals answered the questionnaire and were tested for HIV. Mean age: 39.1 years (95% confidence interval [CI]: 38.3-39.9), per cent female: 55% (95% CI: 52-56) and tested HIV+: 19% (95% CI: 17-20). The prevalence of chronic pain was 19% (95% CI: 16-23) in the HIV+ group, which was similar to that found in the HIV- group (20% [95% CI: 18-22]; odds ratio [adjusted for age, sex, socio-economic status] = 0.93 [95% CI: 0.74-1.17], p-value = 0.549). CONCLUSION: The prevalence of chronic pain in South Africans living with HIV was approximately 20%, and having HIV was not associated with an increased risk of chronic pain. SIGNIFICANCE: Using data from a large, national, population-based study in South Africa, I show for the first time that the prevalence of chronic pain in that population did not differ materially between the part of the population that was living with HIV compared with their uninfected counterparts (both approximately 20%). These findings run counter to the dogma that there is a greater risk of having pain in people living with HIV.

South African men and women living with HIV have similar distributions of pain sites.

BACKGROUND: No studies have investigated sex differences in the location and number of pain sites in people living with human immunodeficiency virus (HIV) (PLWH), despite evidence that women, in general, bear a greater burden of pain than men. AIM: To determine sex differences in the location and number of pain sites, and whether there were demographic or disease-related differences in the number of pain sites. SETTING: South African tertiary hospital HIV clinics and a community healthcare centreMethods: We conducted a retrospective analysis of records from South African PLWH who had pain. RESULTS: Of the 596 participant records, 19% were male (115/596) and the median number of pain sites for both sexes was 2 (interquartile range [IQR]: 1 to 3). Pain was most frequently experienced in the head (men: 12%, women: 38%), feet and ankles (men: 42%, women: 28%), abdomen (men = 19%, women = 28%) and chest (men = 20%, women = 20%). After correcting for multiple comparisons, males were less likely to experience headache than females (Fisher's exact text, odds ratio [OR] = 0.23, 95% confidence interval [CI]: 0.12 - 0.42, p = 0.000). Pain at other body sites was experienced similarly between the sexes. There was no meaningful variation in the number of pain sites between the sexes (logistic regression, p = 0.157). CONCLUSION: A similar location and number of pain sites were experienced by male and female South African PLWH. The locations of pain sites were different from previous reports, however, suggesting that research into pain in PLWH cannot necessarily be generalised across cultures.

Importance of testing the internal consistency and construct validity of the Pittsburgh Sleep Quality Index (PSQI) in study groups of day and night shift workers: Example of a sample of long-haul truck drivers in South Africa.

Irregular work times promote inconsistent completion of the Pittsburgh Sleep Quality Index (PSQI) among shift workers. We aimed to demonstrate the importance of testing the internal consistency and construct validity of the PSQI and of the Epworth Sleepiness Scale (ESS) by presenting the methodology in a sample of long-haul truckers in South Africa. Internal consistency of the questionnaires was assessed by Cronbach's alpha (defined as raw alpha≥0.70), and construct validity by factor analysis. 302 participants (49.3%) reported at least one night shift/week. Overall, the PSQI and ESS's alpha were 0.42 and 0.85, respectively. The factors explained 19.6% of 57.0% of the variance. The PSQI's alpha was 0.46 in night shift workers and 0.38 in non-night shift workers. In this occupational group, the PSQI must be used with caution. Testing the internal consistency and construct validity among the assessed population seems necessary. Sleep questionnaires adapted to shift workers should be preferred.

Greater baseline pain inclusion criteria in clinical trials increase regression to the mean effect: a modelling study.

ABSTRACT: We modelled the effects of pain intensity inclusion thresholds (3/10, 4/10, and 5/10 on a 0- to 10-point numerical pain rating scale) on the magnitude of the regression to the mean effect under conditions that were consistent with the sample mean and variance, and intermeasurement correlation observed in clinical trials for the management of chronic pain. All data were modelled on a hypothetical placebo control group. We found a progressive increase in the mean pain intensity as the pain inclusion threshold increased, but this increase was not uniform, having an increasing effect on baseline measurements compared with study endpoint measurements as the threshold was increased. That is, the regression to the mean effect was magnified by increasing inclusion thresholds. Furthermore, the effect increasing pain inclusion thresholds had on the regression to the mean effect was increased by decreasing sample mean values at baseline and intermeasurement correlations, and increasing sample variance. At its smallest, the regression to the mean effect was 0.13/10 (95% confidence interval: 0.03/10-0.24/10; threshold: 3/10, baseline mean pain: 6.5/10, SD: 1.6/10, and correlation: 0.44), and at its greatest, it was 0.78/10 (95% confidence interval: 0.63/10-0.94/10; threshold: 5/10, baseline mean pain: 6/10, SD: 1.8/10, and correlation: 0.19). We have shown that using pain inclusion thresholds in clinical trials drives progressively larger regression to the mean effects. We believe that a threshold of 3/10 offers the best compromise between maintaining assay sensitivity (the goal of thresholds) and the size of the regression to the mean effect.

Use of blood colour for assessment of arterial oxygen saturation in immobilized impala (Aepyceros melampus).

OBJECTIVE: To determine the relationship between arterial blood colour [as defined by the International Commission on Illumination (CIE) L∗a∗b∗ colour space] and haemoglobin oxygen saturation [functional saturation (SaO2) and fractional saturation (FO2Hb)], and if arterial blood colour can be used to predict arterial haemoglobin oxygen saturation. STUDY DESIGN: Descriptive study as an adjunct to two prospective randomized crossover studies. ANIMALS: A group of 10 wild caught adult female impala (Aepyceros melampus) weighing 34.1 ± 5.2 kg (mean ± standard deviation). METHODS: Impala were immobilized with potent opioids (0.09 mg kg-1 of etorphine or thiafentanil). A total of 163 arterial blood samples were collected anaerobically into heparinized syringes from arterial cannulae and analysed immediately using spectrocolourimetry and co-oximetry. Data were analysed by modelling the relationship between predicted arterial blood colour CIE L∗a∗b∗ components and SaO2 and FO2Hb. The models were then used to predict values for L∗, a∗ and b∗ to produce a colour palette for the range of SaO2 and FO2Hb used. The modified version of the Farnsworth-Munsell hue test was used to assess the subjective ordering of the resulting colour palette by 20 observers. RESULTS: The second-order polynomial (quadratic) model produced the best fit for all three arterial blood colour CIE L∗a∗b∗ components for both SaO2 and FO2Hb. The regression models were used to generate predicted arterial blood colour CIE L∗a∗b∗ components for the midpoint of each decile over a range of SaO2 and FO2Hb percentages (15% to 95%). The resulting colour palettes were correctly ordered by all observers in the SaO2 range of 45-95% saturation. CONCLUSIONS AND CLINICAL RELEVANCE: An association between arterial blood colour (as defined by CIE L∗a∗b∗ components) and SaO2 and FO2Hb exists, and arterial blood colour can be used to give a clinically useful estimate of arterial haemoglobin oxygen saturation in impala.

High individual pain variability in people living with HIV: A graphical analysis.

BACKGROUND: People living with HIV (PLWH) frequently experience pain. Following calls to analyse individual-level data in addition to group-level data in pain studies, we compared individual and group-level changes in pain prevalence, intensity and number of pain sites over 48 weeks in a large cohort of PLWH. This is the largest ever cohort study of pain in PLWH, and is the first to report pain at the level of the individual. METHODS: Participants included all participants with complete pain records from a randomized clinical trial (RCT) for the treatment of HIV (n = 787/1053). At weeks 0, 12, 24, 36 and 48 we assessed participants' pain in the last week; presence of pain, and if present, the intensity and locations of the pain. We used standard averaging methods to describe data at the group level, and unique graphical reporting methods to analyse data at the level of the individual. RESULTS: Group-level data demonstrated a trend for pain prevalence to decline over time (19% week 0, 12% week 48). Worst pain intensity remained stable (median between 4/10 and 5/10), as did the number (median = 1) and common sites of pain across the 48 weeks. In contrast, individual-level data demonstrated high intra-individual variability with regards to the presence of pain, and the intensity and location of the pain. CONCLUSIONS: While our group-level data were similar to previous longitudinal studies, an apparent reduction in pain over 48 weeks, the individual-level data showed large variability within individuals in that same time frame. SIGNIFICANCE: This graphical analysis highlights the high variability in pain (pain prevalence, intensity and body sites) across time in people living with HIV, and how presenting averaged data hides this important variability. Our data support the reporting of individual-level data in human experimental and observational studies.

Almost 1 in 5 South African adults have chronic pain: a prevalence study conducted in a large nationally representative sample.

Limited information on the prevalence and risk factors for chronic pain is available for developing countries. Therefore, we investigated the prevalence of chronic pain and the association between this pain and various personal and sociodemographic factors by including questions in the South Africa Demographic and Household Survey 2016. The survey was conducted by face-to-face interviews with a nationally representative sample of the adult population (ages 15 and older, n = 10,336). Chronic pain was defined as pain or discomfort that had been experienced all the time or on and off for 3 months or more. The prevalence of chronic pain was 18.3% (95% confidence interval [CI]: 17.0-19.7). Women were more likely than were men to have chronic pain (men = 15.8% [95% CI: 13.9-17.8]; woman = 20.1% [95% CI: 18.4-21.8]), and the prevalence of chronic pain increased from 11.3% (95% CI: 9.6-13.3) for the age range 15 to 24 years to 34.4% (95% CI: 30.6-38.4) for the age range over 65 years. The body sites affected most frequently were the limbs (43.6% [95% CI: 40.4-46.9]), followed by the back (30.5% [95% CI: 27.7-33.6]). This article presents the prevalence of chronic pain in the general population of a middle-income African country. These data give much needed insights into the burden of, and risk factors for, chronic pain in low-resource settings, and identify priority groups for intervention.

Pain in Clients Attending a South African Voluntary Counseling and Testing Center Was Frequent and Extensive But Did Not Depend on HIV Status.

BACKGROUND: The frequency of pain is reported to be high in people living with HIV, but valid comparisons between people living with HIV and HIV-negative cohorts are rare. We investigated whether HIV infection influenced frequency and characteristics of pain in adults undergoing voluntary testing for HIV. SETTING: Participants were recruited from an HIV voluntary counseling and testing center at the Chris Hani Baragwanath Academic Hospital, Soweto, South Africa. METHODS: Pain was assessed using the Wisconsin Brief Pain Questionnaire. Depressive and anxiety symptomatology was determined using the Hopkins Symptom checklist-25. We then stratified by HIV status. RESULTS: Data from 535 black South Africans were analyzed: HIV-infected n = 70, HIV-uninfected n = 465. Overall, frequency of any current pain was high with 59% [95% confidence interval (CI): 55 to 63, n: 316/535] of participants reporting pain, with no difference related to HIV status: HIV-infected 50% (95% CI: 37 to 61, n: 35/70), HIV-uninfected 60% (95% CI: 56 to 65, n: 281/465). Pain intensity and number of pain sites were similar between the groups as were symptoms of anxiety and depression: mean Hopkins Symptom Checklist-25 1.72 (95% CI: 1.57 to 1.87) HIV-infected participants and 1.68 (95% CI: 1.63 to 1.73) HIV-uninfected participants. Univariate analysis showed female sex and greater depressive and anxiety symptomatology associated with pain. In a multivariable modeling, only depressive and anxiety symptomatology was retained in the model. CONCLUSION: The high frequency of pain found in both HIV-infected and HIV-uninfected individuals presenting at a voluntary counseling and testing center was more likely to be associated with depression and anxiety, than with the presence or absence of HIV.

Clinical diagnosis of sensory neuropathy in HIV patients treated with tenofovir: A 6-month follow-up study.

BACKGROUND: Sensory neuropathy (SN) is a common and often painful neurological condition associated with HIV-infection and its treatment. However, data on the incidence of SN in neuropathy-free individuals initiating combination antiretroviral therapies (cART) that do not contain the neurotoxic agent stavudine are lacking. AIMS: We investigated the 6-month incidence of SN in ART naïve individuals initiating tenofovir (TDF)-based cART, and the clinical factors associated with the development of SN. METHODS: 120 neuropathy-free and ART naïve individuals initiating cART at a single center in Johannesburg, South Africa were enrolled. Participants were screened for SN using clinical signs and symptoms at study enrolment and approximately every 2-months for a period of ~6-months. Diagnostic criteria for symptomatic SN was defined by the presence of at least one symptom (pain/burning, numbness, paraesthesias) and at least two clinical signs (reduced vibration sense, absent ankle reflexes or pin-prick hypoaesthesia). Diagnostic criteria for asymptomatic SN required at least two clinical signs only (as above). RESULTS: A total of 88% of the cohort completed three visits within the 6-month period. The 6-month cumulative incidence of neuropathy was 140 cases per 1000 patients (95% CI: 80-210) at an incidence rate of 0.37 (95% CI: 0.2-0.5) per person year. Height and active tuberculosis (TB) disease were independently associated with the risk of developing SN (P < .05). INTERPRETATION: We found that within the first 6 months of starting cART, incident SN persists in the post-stavudine era, with 11 (9%) of individuals developing asymptomatic SN, and 9 (8%) developing symptomatic SN.

A systematic review of experimental methods to manipulate secondary hyperalgesia in humans: protocol.

BACKGROUND: Neuropathic pain affects 7-10% of people, but responds poorly to pharmacotherapy, indicating a need for better treatments. Mechanistic research on neuropathic pain frequently uses human surrogate models of the secondary hyperalgesia that is a common feature of neuropathic pain. Experimentally induced secondary hyperalgesia has been manipulated with pharmacological and non-pharmacological methods to clarify the relative contributions of different mechanisms to secondary hyperalgesia. However, this literature has not been systematically synthesised. The aim of this systematic review is to identify, describe, and compare methods that have been used to manipulate experimentally induced secondary hyperalgesia in healthy humans. METHODS: A systematic search strategy will be supplemented by reference list checks and direct contact with identified laboratories to maximise the identification of data reporting the experimental manipulation of experimentally induced secondary hyperalgesia in healthy humans. Duplicated screening, risk of bias assessment, and data extraction procedures will be used. Authors will be asked to provide data as necessary. Data will be pooled and meta-analyses conducted where possible, with subgrouping according to manipulation method. Manipulation methods will be ranked for potency and risk. DISCUSSION: The results of this review will provide a useful reference for researchers interested in using experimental methods to manipulate secondary hyperalgesia in humans and will help to clarify the relative contributions of different mechanisms to secondary hyperalgesia. SYSTEMATIC REVIEW REGISTRATION: This protocol will be registered on PROSPERO before the review begins. Review records will be updated on PROSPERO once the review is complete. This review is intended for publication in a peer-reviewed journal. Analyses and scripts will be made publicly available.

Colocalization of pain and reduced intraepidermal nerve fiber density in individuals with HIV-associated sensory neuropathy.

INTRODUCTION: There is poor correlation between decreases in intraepidermal nerve fiber density (IENFD) and the presence of pain in HIV-associated sensory neuropathy (HIV-SN) and other painful distal symmetrical polyneuropathies. OBJECTIVES: We investigated whether in individuals with HIV-SN, having pain at the ankle skin biopsy site was associated with lower IENFD compared to when there was no pain at the ankle biopsy site. METHODS: We recruited 15 individuals with symptomatic HIV-SN. Nine had pain at the site where the ankle biopsy was taken, whereas 6 did not. Skin punch biopsies for IENFD quantification were taken from the ankle and the thigh. Contrasts between the 2 groups were made using the overlap of confidence interval (CI) method. RESULTS: Intraepidermal nerve fiber density was substantially lower in the group that had pain at the site of the ankle biopsy compared with the other group (6.6 [CI: 5.3-7.2] vs 3.3 [CI: 10.0-15.0] fibers/mm). However, there was no group differences at the thigh biopsy site (15.6 [CI: 15.0-15.9] vs 16.2 [CI: 14.5-17.8] fibers/mm). When taking the ratio of ankle IENFD:thigh IENFD, the point estimate for the pain at the ankle group (0.43 [CI: 0.36-0.48]) was about half that of the other group (0.81 [CI: 0.68-0.87]). CONCLUSION: Thus, colocalization of pain to the ankle is associated with meaningful decreases in ankle IENFD.

Was That Painful or Nonpainful? The Sensation and Pain Rating Scale Performs Well in the Experimental Context.

In experiments on pain, participants are frequently exposed to nonpainful and painful stimuli; however, the conventional pain-rating scales lack a nonpainful range and a clear point of transition from nonpainful to painful events. The Sensation and Pain Rating Scale (SPARS) assesses the full stimulus intensity range, extending from no sensation (rating: -50) to worst pain imaginable (rating: +50), and it explicitly identifies pain threshold (rating: 0). Here, we tested the SPARS in 2 experiments by using laser heat stimuli to establish its stimulus-response characteristics (Experiment 1, N = 19, 13 stimulus intensities applied 26 times each across a 1-4 J range), and compared it to 0 to 100 scales that assess nonpainful (0: no sensation, 100: pain) and painful (0: no pain, 100: worst pain imaginable) events (Experiment 2, N = 7, 9 stimulus intensities applied 36 times each across a 1.5-4.5 J range). Despite high inter- and intraindividual variations, we found a reasonably consistent curvilinear stimulus-response relationship (the curve flattens around pain threshold), with stable response characteristics across the range of the scale. The SPARS ratings transformed to a 0 to 100 range tended to be lower than the 0 to 100 pain rating scale in the noxious stimulus intensity range and greater than the 0 to 100 nonpainful sensation scale in the non-noxious stimulus range, likely reflecting differences in scale dimensionality. The SPARS overcomes limitations in scale range inherent to conventional pain rating scales. As such, it is well suited to experimental studies that must quantify a wider range of perceptual intensity or distinguish between painful and nonpainful events. PERSPECTIVE: This article presents the stimulus-response characteristics of a new scale designed to allow participants to rate a range of nonpainful and painful stimuli. The scale could be useful for research that involves exposing participants to a range of stimulation intensities or requires a clear distinction between nonpainful and painful events.

Neuropathic pain clinical trials: factors associated with decreases in estimated drug efficacy.

Multiple recent pharmacological clinical trials in neuropathic pain have failed to show beneficial effect of drugs with previously demonstrated efficacy, and estimates of drug efficacy seems to have decreased with accumulation of newer trials. However, this has not been systematically assessed. Here, we analyze time-dependent changes in estimated treatment effect size in pharmacological trials together with factors that may contribute to decreases in estimated effect size. This study is a secondary analysis of data from a previous published NeuPSIG systematic review and meta-analysis, updated to include studies published up till March 2017. We included double-blind, randomized, placebo-controlled trials examining the effect of drugs for which we had made strong or weak recommendations for use in neuropathic pain in the previously published review. As the primary outcome, we used an aggregated number needed to treat for 50% pain reduction (alternatively 30% pain reduction or moderate pain relief). Analyses involved 128 trials. Number needed to treat values increased from around 2 to 4 in trials published between 1982 and 1999 to much higher (less effective) values in studies published from 2010 onwards. Several factors that changed over time, such as larger study size, longer study duration, and more studies reporting 50% or 30% pain reduction, correlated with the decrease in estimated drug effect sizes. This suggests that issues related to the design, outcomes, and reporting have contributed to changes in the estimation of treatment effects. These factors are important to consider in design and interpretation of individual study data and in systematic reviews and meta-analyses.