Does prophylactic decompression of distal nerves following nerve repair improve functional recovery? A systematic review.

BACKGROUND: Peripheral nerve injuries are burdensome on healthcare systems, individuals and society as a whole. The current standard of treatment for neurotmesis is primary neurorrhaphy or nerve grafting. However, several patients do not recover their full function. There has been a suggestion that primary distal neurolysis at common entrapment sites maximises surgical outcomes; however, no guidelines exist on this practice. This scoping review aims to ascertain the existing evidence on prophylactic distal decompression of peripheral nerves following repair. METHODS: A literature search was performed using Ovid Medline, PubMed, Embase and Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews for studies published in the past 50 years. Studies were screened using a selection criteria and study quality was assessed using standardised tools. Furthermore, thematic content analysis was performed. RESULTS: Six studies were eligible for inclusion after screening; all studies were retrospective and at most level 3 evidence. No studies were designed specifically to assess the efficacy of distal neurolysis following proximal repair, thus no comparative data with control cohorts are available. All studies that recommended distal decompression of proximally repaired nerves based their conclusions on cases observed by the authors in practice or from theories on nerve regeneration. CONCLUSIONS: This systematic review suggests that the evidence on the role of immediate distal neurolysis in primary neurorrhaphy is inadequate. Recommendations are limited by the lack of large-scale and generalisable data. Further research is needed with definitive objective outcomes and patient-related outcome measures.

Relationship between rate of glucose or propionate infusion and milk protein yield and concentration in dairy cows: A meta-regression.

Although postruminal glucose infusion into dairy cows has increased milk protein yield in some past experiments, the same trend has not been observed in others. A meta-regression of 64 sets of observations from 29 previously published glucose and propionate infusion studies in dairy cattle, treating study and experiment (study) as random effects, was performed to establish the general effects of glucose equivalent (GlcE) infusion rate on milk true protein (MTP) yield and content, if any, and to identify independent, fixed-effect variables that accounted for the changes in MTP yield and content that were observed. Candidate explanatory variables included rate and site of infusion, diet composition and intake, body weight and lactation stage of the cows, and the change in nutrient intake between GlcE and control treatments. Across all studies, according to a model containing only the random effects of study and experiment, GlcE infusion at an average of 954 g/d increased MTP yield by 26 g/d, on average, whereas mean MTP content was not affected. Backward stepwise elimination of potential explanatory variables from a full mixed model produced a final, reduced model for MTP yield that retained a positive, second-order quadratic effect of infusion rate of GlcE and a positive, linear effect of the change in crude protein intake (CPI) between GlcE treatment and control. This change in CPI due to GlcE infusion ranged from -0.546 to 0.173 kg/d in the dataset. The model fit indicated that when CPI was allowed to drop during GlcE infusion, the effect of GlcE on MTP yield was smaller than when CPI was maintained or increased, in a manifestation of the classic protein:energy interaction. The final reduced model for MTP content contained the same explanatory variables as for MTP yield, plus a negative effect of intravenous compared with gastrointestinal infusion. Overall, the meta-analysis revealed that both MTP yield, and content were positively related to GlcE infusion rate and to the change in CPI between glucose treatment and control.

Quantitative Assessment of Systematic Bias: A Guide for Researchers.

Observational research provides valuable opportunities to advance oral health science but is limited by vulnerabilities to systematic bias, including unmeasured confounding, errors in variable measurement, or bias in the creation of study populations and/or analytic samples. The potential influence of systematic biases on observed results is often only briefly mentioned among the discussion of limitations of a given study, despite existing methods that support detailed assessments of their potential effects. Quantitative bias analysis is a set of methodological techniques that, when applied to observational data, can provide important context to aid in the interpretation and integration of observational research findings into the broader body of oral health research. Specifically, these methods were developed to provide quantitative estimates of the potential magnitude and direction of the influence of systematic biases on observed results. We aim to encourage and facilitate the broad adoption of quantitative bias analyses into observational oral health research. To this end, we provide an overview of quantitative bias analysis techniques, including a step-by-step implementation guide. We also provide a detailed appendix that guides readers through an applied example using real data obtained from a prospective observational cohort study of preconception periodontitis in relation to time to pregnancy. Quantitative bias analysis methods are available to all investigators. When appropriately applied to observational studies, findings from such studies can have a greater impact in the broader research context.

Symptomatic benefit of momelotinib in patients with myelofibrosis: Results from the SIMPLIFY phase III studies.

BACKGROUND: Myelofibrosis (MF)-associated constitutional symptoms can severely impact health-related quality of life. Clinical trials in MF traditionally measure symptom response to treatment as a landmark endpoint of total symptom score (TSS) reduction ≥50% from baseline. However, this dichotomous assessment provides a limited view of clinically relevant symptomatic changes. Herein we evaluated longitudinal change from baseline in TSS over the continuous 24-week period and individual symptom scores to obtain a more comprehensive understanding of symptom benefits experienced by patients with MF receiving therapy. METHODS: Longitudinal symptom change was evaluated using mixed-effect model repeated measure (MMRM) methodology with individual item-level analyses to complement the interpretation of the landmark symptom results in the completed phase III SIMPLIFY studies of momelotinib in MF. MMRM compared mean change in TSS from baseline with Week 24 using data from all patient visits. Generalized estimating equations were used to estimate item-level odds ratios using multiple predictive imputations for missing data. RESULTS: Momelotinib and ruxolitinib groups reported similar overall symptom improvements, with a TSS difference of <1.5 points between groups for each post-baseline visit in SIMPLIFY-1. In SIMPLIFY-2, the improvement in TSS observed in momelotinib-treated patients was consistent with that observed in SIMPLIFY-1, whereas progressive TSS deterioration was observed with control. Item-level scores were heterogeneous in both studies. A similar and greater proportion of momelotinib-treated patients were categorized as "improved" or "stable" compared with control in SIMPLIFY-1 and SIMPLIFY-2, respectively. Odds ratios for between-group comparison ranged from 0.75 to 1.21 in SIMPLIFY-1, demonstrating similarity in likelihood of symptom improvement. In SIMPLIFY-2, the likelihood of symptom improvement in each item was higher in the momelotinib arm. CONCLUSIONS: These findings suggest that momelotinib provides clinically relevant symptom benefits in the JAK inhibitor-naïve and JAK inhibitor-exposed settings.

Characterization of striatal dopamine projections across striatal subregions in behavioral flexibility.

Behavioural flexibility is key to survival in a dynamic environmentWhile flexible, goal-directed behaviours are initially dependent on dorsomedial striatum, they become dependent on lateral striatum as behaviours become inflexible. Similarly, lesions of dopamine terminals in lateral striatum disrupt the development of inflexible habits. This work suggests that dopamine release in lateral striatum may drive inflexible behaviours, though few studies have investigated a causative role of subpopulations of striatal dopamine terminals in reversal learning, a measure of flexibility. Here, we performed two optogenetic experiments to activate dopamine terminals in dorsomedial (DMS), dorsolateral (DLS) or ventral (nucleus accumbens [NAc]) striatum in DAT-Cre mice that expressed channelrhodopsin-2 via viral injection (Experiment I) or through transgenic breeding with an Ai32 reporter line (Experiment II) to determine how specific dopamine subpopulations impact reversal learning. Mice performed a reversal task in which they self-stimulated DMS, DLS, or NAc dopamine terminals by pressing one of two levers before action-outcome lever contingencies were reversed. Largely consistent with presumed ventromedial/lateral striatal function, we found that mice self-stimulating medial dopamine terminals reversed lever preference following contingency reversal, while mice self-stimulating NAc showed parial flexibility, and DLS self-stimulation resulted in impaired reversal. Impairments in DLS mice were characterized by more regressive errors and reliance on lose-stay strategies following reversal, as well as reduced within-session learning, suggesting reward insensitivity and overreliance on previously learned actions. This study supports a model of striatal function in which DMS and ventral dopamine facilitate goal-directed responding, and DLS dopamine supports more inflexible responding.

Leveraging routine data in impact evaluation: Understanding data systems in primary healthcare prior to a matched cluster-randomised evaluation of adherence guidelines in South Africa.

BACKGROUND: An essential part of providing high-quality patient care and a means of efficiently conducting research studies relies upon high-quality routinely collected medical information. OBJECTIVES: To describe the registers, paper records and databases used in a sample of primary healthcare clinics in South Africa (SA) with the view to conduct an impact evaluation using routine data. METHODS: Between October 2015 and December 2015, we collected information on the presence, quality and completeness of registers, clinical stationery and databases at 24 public health facilities in SA. We describe each register and type of clinical stationery we encountered, their primary uses, and the quality of completion. We also mapped the ideal flow of data through a site to better understand how its data collection works. RESULTS: We identified 13 registers (9 standard, 4 non-standard), 5 types of stationery and 4 databases as sources of medical information within a site. Not all clinics used all the standardised registers, and in those that did, registers were kept in various degrees of completeness: a common problem was inconsistent recording of folder numbers. The quality of patient stationery was generally high, with only the chronic patient record being considered of varied quality. The TIER.Net database had high-quality information on key variables, but national identification (ID) number was incompletely captured (42% complete). Very few evaluation sites used electronic data collection systems for conditions other than HIV/AIDS. CONCLUSION: Registers, databases and clinical stationery were not implemented or completed consistently across the 24 evaluation sites. For those considering using routinely collected data for research and evaluation purposes, we would recommend a thorough review of clinic data collection systems for both quality and completeness before considering them to be a reliable data source.

Optogenetic stimulation of striatal patches modifies habit formation and inhibits dopamine release.

Habits are inflexible behaviors that develop after extensive repetition, and overreliance on habits is a hallmark of many pathological states. The striatum is involved in the transition from flexible to inflexible responding, and interspersed throughout the striatum are patches, or striosomes, which make up ~15% of the volume of the striatum relative to the surrounding matrix compartment. Previous studies have suggested that patches are necessary for normal habit formation, but it remains unknown exactly how patches contribute to habit formation and expression. Here, using optogenetics, we stimulated striatal patches in Sepw1-NP67 mice during variable interval training (VI60), which is used to establish habitual responding. We found that activation of patches at reward retrieval resulted in elevated responding during VI60 training by modifying the pattern of head entry and pressing. Further, this optogenetic manipulation reduced subsequent responding following reinforcer devaluation, suggesting modified habit formation. However, patch stimulation did not generally increase extinction rates during a subsequent extinction probe, but did result in a small 'extinction burst', further suggesting goal-directed behavior. On the other hand, this manipulation had no effect in omission trials, where mice had to withhold responses to obtain rewards. Finally, we utilized fast-scan cyclic voltammetry to investigate how patch activation modifies evoked striatal dopamine release and found that optogenetic activation of patch projections to the substantia nigra pars compacta (SNc) is sufficient to suppress dopamine release in the dorsal striatum. Overall, this work provides novel insight into the role of the patch compartment in habit formation, and provides a potential mechanism for how patches modify habitual behavior by exerting control over dopamine signaling.

Offshore pelagic subsidies dominate carbon inputs to coral reef predators.

Coral reefs were traditionally perceived as productive hot spots in oligotrophic waters. While modern evidence indicates that many coral reef food webs are heavily subsidized by planktonic production, the pathways through which this occurs remain unresolved. We used the analytical power of carbon isotope analysis of essential amino acids to distinguish between alternative carbon pathways supporting four key reef predators across an oceanic atoll. This technique separates benthic versus planktonic inputs, further identifying two distinct planktonic pathways (nearshore reef-associated plankton and offshore pelagic plankton), and revealing that these reef predators are overwhelmingly sustained by offshore pelagic sources rather than by reef sources (including reef-associated plankton). Notably, pelagic reliance did not vary between species or reef habitats, emphasizing that allochthonous energetic subsidies may have system-wide importance. These results help explain how coral reefs maintain exceptional productivity in apparently nutrient-poor tropical settings, but also emphasize their susceptibility to future ocean productivity fluctuations.

G-POEM in patients with gastroparesis - gambling for healing or bigger armamentarium ? A case series and review of the literature.

Approximately 30% of all affected patients suffering from gastroparesis do not respond to any available treatment modality. Gastric peroral endoscopic myotomiy (G-POEM, antropyloromyotomy) represents a new principle of therapy. In this single center study, G-POEM showed a high technical success rate with a very low procedural complication rate. However, the clinical response beyond a short-term post-interventional improvement did not succeed in a single patient. The heterogeneity of the clinical picture, which represents a spectrum of different pathophysiological, etiological and clinical characteristics, still requires a therapy tailored to the individual patient. G-POEM should be considered especially in patients with pylorus-dominant gastroparesis.

Incidence and predictors of sexually transmitted infections among adult HIV-positive patients receiving antiretroviral therapy at Themba Lethu HIV clinic in Johannesburg, South Africa.

BACKGROUND: Sexually transmitted infections (STIs) among people living with HIV/AIDS can facilitate the spread of HIV. OBJECTIVES: To estimate STI incidence and identify predictors of STI acquisition among HIV-positive patients during their first 24 months of antiretroviral therapy (ART) in Johannesburg, South Africa. METHODS: We conducted a cohort study using prospectively collected routine data on patients who initiated ART between January 2004 and January 2015 at the Themba Lethu HIV clinic in Johannesburg. Kaplan-Meier analysis was used to estimate STI incidence rates (based on evidence of laboratory diagnosis and STI syndromic treatment prescription records). STI predictors were identified using Cox regression analysis. RESULTS: Among 26 762 adult patients on ART, there were 1 906 (7.1%) cases of STI (incidence 4.8/100 person-years; 95% confidence interval (CI) 4.7 - 5.1). Non-pregnant women were 60% more likely than men to be diagnosed with an STI (adjusted hazard ratio (aHR) 1.6; 95% CI 1.4 - 1.8). The risk of STI decreased with increasing baseline CD4 count (aHR 0.8, 0.5 and 0.4 for CD4 counts 101 - 200, 201 - 350 and >350 cells/µL, respectively, compared with CD4 count <100 cells/µL). Patients with advanced baseline World Health Organization (WHO) clinical stages had a higher risk (aHR 1.6 for WHO stage 4; 95% CI 1.3 - 1.9) compared with those with WHO stage 1. However, there was a 20% increase in the risk of STI among obese patients compared with underweight patients (aHR 1.3; 95% CI 1.0 - 1.7). Over 80% of obese patients diagnosed with an STI had a CD4 count <200 cells/µL. CONCLUSIONS: STIs are common in HIV-infected patients who are receiving ART. While both ART and the syndromic management of STIs are high-impact interventions for controlling the spread of HIV, closer monitoring of STI occurrences is warranted, particularly among immunologically vulnerable patients.

Treatment outcomes among HIV-positive orphaned and non-orphaned children on antiretroviral therapy in Johannesburg, South Africa.

BACKGROUND: Limited research investigating treatment outcomes for HIV-positive orphans compared with non-orphans has shown mixed results, with several studies indicating that HIV-positive orphans are at greater risk of delayed access to HIV care and poor antiretroviral therapy (ART) adherence, while other data suggest that ART outcomes of orphans can be similar to those of non-orphans. Understanding the impact of orphan status on short-term ART outcomes could improve targeted intervention strategies, and subsequent long-term treatment and developmental outcomes, for HIV-positive infants, children and adolescents. OBJECTIVES: To evaluate the relationship between orphan status and ART outcomes among HIV-positive infants, children and adolescents initiating ART at two large public sector HIV clinics in Johannesburg, South Africa. METHODS: This was a retrospective cohort study of HIV-positive children aged <18 years initiating standard first-line ART between June 2004 and May 2013. Using propensity scores, orphans and non-orphans were matched for age, sex, World Health Organization stage and ART regimen. The effect of orphanhood on attrition from care (all-cause mortality and loss to follow-up) was evaluated using Cox proportional hazards regression analysis, and its effect on having a detectable viral load (≥400 copies/mL) at 12 months on ART using binomial regression analysis with modified Poisson distribution. RESULTS: A total of 251 (29.4%) orphans (maternal, paternal or both) and 603 (70.6%) non-orphans were included at ART initiation. Following multiple imputation for missing data and propensity score matching, 222 orphans and 222 non-orphans were included. Orphans had a median age of 8.0 years (interquartile range (IQR) 4.9 - 10.7) and non-orphans 7.4 years (IQR 4.2 - 10.2). A total of 12 (5.4%) orphans and 33 (14.9%) non-orphans experienced attrition from care during the first 12 months on ART (adjusted hazard ratio 0.32, 95% confidence interval (CI) 0.17 - 0.63). Among those alive and in care, with a viral load at 12 months on ART, 18.0% of orphans (33/183) and 14.8% of non-orphans (24/162) had a detectable viral load (adjusted risk ratio 1.15, 95% CI 1.04 - 1.28). CONCLUSIONS: Orphans were less likely than non-orphans to experience attrition, but among those in care at 12 months, orphans were more likely to have detectable viral loads. Lower attrition among orphans may be due to their being in institutional or foster care, ensuring that they make their visits; however, their higher rates of non-suppression may result from lack of psychosocial support or stigma resulting in struggles to adhere. Additional research investigating age-specific outcomes will be important to elucidate these effects further.

"Even if you're HIV-positive there's life after if you take your medication": experiences of people on long-term ART in South Africa: a short report.

South Africa's national antiretroviral treatment (ART) programme, initiated in 2004, is the largest HIV treatment programme in the world with an estimated 4.2 million people on ART. Today, an HIV diagnosis is no longer associated with certain death, but is rather a manageable chronic disease, with all HIV-positive patients now eligible to receive treatment. In this study, we explore patient experiences at the onset of the ART programme, including facilitators and barriers around decision-making along the HIV care cascade (HIV testing, ART initiation, retention, and adherence). We conducted twenty-four in-depth interviews among adults (≥18 years old) who initiated ART between April 2004 and March 2005 and were alive, on treatment at enrolment (October 2015-March 2016) at a large public-sector clinic in Johannesburg, South Africa. Data were analysed using a thematic analysis approach. Patients cited physical wellbeing, responsibility for raising children, supportive clinic staff and noticeable improvements in health on ART as key facilitators to continued care. In contrast, changing clinic conditions, fear of side-effects and stigma were mentioned as barriers. This study provides a unique lens through which to evaluate factors associated with long-term retention and adherence to ART at a crucial time in ART programming when more people will be initiating life-long treatment. We must continue to focus on supportive and empathetic clinic environments, more convenient ways to access medication for patients, and developing tools or interventions that continue to address the issues of stigma and discrimination and build the support networks for all those on treatment.

Study on inactivation of porcine epidemic diarrhoea virus, porcine sapelovirus 1 and adenovirus in the production and storage of laboratory spray-dried porcine plasma.

AIM: Evaluation of the thermal and physical conditions for inactivation of adenovirus (AdV), porcine sapelovirus 1 (PSV1) and the economically important viruses porcine epidemic diarrhoea virus (PEDV) and porcine circovirus 2 (PCV2) in the production of spray-dried porcine plasma (SDPP). METHODS AND RESULTS: Citrate-treated porcine plasma of pH 7·5, 9·8 and 10·2 (8·5% dry-matter) was spiked with PEDV, PSV1, PCV2 and AdV and incubated at 3°C for maximum 24 h, and at 44 or 48°C for maximum 10 min (Experiment 1). Spiked citrate-treated concentrated plasma of pH 7·5 and 9·8 (24% dry-matter) was spray dried in a laboratory scale apparatus (Experiment 2). Aliquots of SDPP were stored over a period of 0-10 weeks at 11 and 20°C (Experiment 3). Reverse transcription(RT)-quantitative PCR detected no notable reduction in viral genomes in treated plasma and SDPP samples. No infectious PSV1 was re-isolated from plasma and SDPP samples in cell culture. At pH 10·2 and 3°C, infectivity of PEDV in plasma was reduced with a reduction factor of 4·2 log 10 (LRF) at 10 h contact time, whereas heating to 44°C for at least 1 min at alkali pH was needed to achieve a LRF of 4·2 for AdV. Spray drying at an outlet temperature of 80°C reduced AdV infectivity effectively (LRF = 5·2) and PEDV infectivity for 95% (LRF = 1·4). After storage at 20°C for 2 weeks no infectious PEDV was re-isolated from SDPP anymore (LRF ≥4·0). Due to growth of antibiotic-resistant bacteria from plasma in cell cultures used for PCV2 isolation, no data regarding inactivation of PCV2 were obtained. CONCLUSIONS: Five percent of PEDV stayed infectious after our spray drying conditions. Spray drying in combination with storage for ≥2 weeks at 20°C eliminated infectivity of PEDV effectively. SIGNIFICANCE AND IMPACT OF THE STUDY: The conditions for inactivation of virus in plasma and SDPP determined are important for producers to inactivate PEDV during production of SDPP.

Treatment outcomes among HIV-positive orphaned and non-orphaned children on antiretroviral therapy in Johannesburg, South Africa

Background. Limited research investigating treatment outcomes for HIV-positive orphans compared with non-orphans has shown mixed results, with several studies indicating that HIV-positive orphans are at greater risk of delayed access to HIV care and poor antiretroviral therapy (ART) adherence, while other data suggest that ART outcomes of orphans can be similar to those of non-orphans. Understanding the impact of orphan status on short-term ART outcomes could improve targeted intervention strategies, and subsequent long-term treatment and developmental outcomes, for HIV-positive infants, children and adolescents.Objectives. To evaluate the relationship between orphan status and ART outcomes among HIV-positive infants, children and adolescents initiating ART at two large public sector HIV clinics in Johannesburg, South Africa.Methods. This was a retrospective cohort study of HIV-positive children aged <18 years initiating standard first-line ART between June 2004 and May 2013. Using propensity scores, orphans and non-orphans were matched for age, sex, World Health Organization stage and ART regimen. The effect of orphanhood on attrition from care (all-cause mortality and loss to follow-up) was evaluated using Cox proportional hazards regression analysis, and its effect on having a detectable viral load (≥400 copies/mL) at 12 months on ART using binomial regression analysis with modified Poisson distribution.Results. A total of 251 (29.4%) orphans (maternal, paternal or both) and 603 (70.6%) non-orphans were included at ART initiation. Following multiple imputation for missing data and propensity score matching, 222 orphans and 222 non-orphans were included. Orphans had a median age of 8.0 years (interquartile range (IQR) 4.9 - 10.7) and non-orphans 7.4 years (IQR 4.2 - 10.2). A total of 12 (5.4%) orphans and 33 (14.9%) non-orphans experienced attrition from care during the first 12 months on ART (adjusted hazard ratio 0.32, 95% confidence interval (CI) 0.17 - 0.63). Among those alive and in care, with a viral load at 12 months on ART, 18.0% of orphans (33/183) and 14.8% of non-orphans (24/162) had a detectable viral load (adjusted risk ratio 1.15, 95% CI 1.04 - 1.28).Conclusions. Orphans were less likely than non-orphans to experience attrition, but among those in care at 12 months, orphans were more likely to have detectable viral loads. Lower attrition among orphans may be due to their being in institutional or foster care, ensuring that they make their visits; however, their higher rates of non-suppression may result from lack of psychosocial support or stigma resulting in struggles to adhere. Additional research investigating age-specific outcomes will be important to elucidate these effects further

Can routine inpatient mortality data improve HIV mortality estimates? Inpatient mortality at an urban hospital in South Africa.

BACKGROUND: South Africa (SA) has one of the world's largest HIV treatment programmes, to which a dramatic increase in life expectancy has been attributed. However, there continue to be concerns regarding the reporting of HIV-related mortality in SA, which varies by source. As accurate HIV mortality estimates are key to measuring the success of the national programme as well as identifying areas for improvement, we propose a complementary approach to monitoring changes in HIV-related mortality using routine inpatient records to examine trends in causes of death and HIV status over time. OBJECTIVES: To investigate the feasibility of this approach by calculating mortality due to natural causes in the medical ward of a hospital during 2010 by HIV status. METHODS: We conducted a cross-sectional study of inpatient mortality at a regional hospital in Johannesburg, SA, analysing all deaths due to natural causes among adult medical ward inpatients. Cause of death was recorded from the mortuary register. HIV status was ascertained directly from the mortuary register or from laboratory tests specific for HIV diagnosis or monitoring. RESULTS: Of 1 167 inpatients who died, the majority were HIV-positive (58%). HIV positivity among males (55%) was slightly lower than that among females (61%), and HIV-positive patients were younger (median 40 years) than those who were HIV-negative (56 years) and of unknown HIV status (68 years). 'Infections and parasites' was the most common cause of natural death (29%). On average, HIV-positive patients were admitted for slightly longer (mean 10.5 days) than HIV-negative patients (9.6 days) and those of unknown HIV status (8.9 days), yet HIV-positive inpatient deaths accounted for the majority (62%) of the total bed days. CONCLUSIONS: Even with widespread access to antiretroviral therapy, the majority of inpatient natural deaths at a large public sector hospital in 2010 were of HIV-positive patients and were probably related to HIV. In view of the importance of accurate data on causes of death, both for the HIV programme and to track other diseases, large-scale expansion of this approach over a longer period should be considered.

Fluoroscopically Guided Facet Injections: Comparison of Intra-Articular and Periarticular Steroid and Anesthetic Injection on Immediate and Short-Term Pain Relief.

BACKGROUND AND PURPOSE: The effectiveness of facet injections is unclear in the literature. Our objective was to determine the immediate and short-term efficacy of intra-articular and periarticular steroid/anesthetic injections for facet-mediated lumbar pain. MATERIALS AND METHODS: All outpatient fluoroscopically guided facet injections at a single institution during a 54-month period were retrospectively and independently reviewed by 2 musculoskeletal (MSK) trained radiologists. All intra-articular, all periarticular, and partial intra-/periarticular injection locations were determined. Periarticular and partial peri-/intra-articular injections were combined for analysis. Preinjection, immediate, and 1-week postinjection numeric pain scores, patient age, sex, anesthetic/steroid mixture, fluoroscopic time, and physician performing the procedure were recorded. RESULTS: Seventy-seven patients (mean age, 51.1 years) had 100 procedures with 205 total facet joints injected. All intra-articular, all periarticular, and partial peri-/intra-articular injections constituted 54%, 20%, and 26% of the cases, respectively. The immediate and 1-week postprocedural change in pain was -3.7 (95% CI, -4.5 to -2.8; P < .001) and -1.4 (95% CI, -2.2 to -0.6; P = .001) for the all intra-articular and -3.6 (95% CI, -4.4 to -2.9; P < .001) and -1.2 (95% CI, -1.9 to -0.4; P = .002) for the combined group. Changes in immediate pain were significantly associated with the prepain level (P < .001) and patient age (P = .024) but not with the anesthetic used. Analyses revealed no significant difference in pain reduction between the groups either immediately or 1 week postinjection. Intra-articular injections required less fluoroscopic time (geometric mean, 39 versus 52 seconds) (P = .005). CONCLUSIONS: Intra-articular and periarticular fluoroscopically guided facet injections provide statistically significant and similar pain relief both immediately and 1 week postinjection.

Improved simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE II): protocol for a randomized evaluation.

BACKGROUND: The World Health Organization recommends rapid (≤ 7 days) or same-day initiation of antiretroviral treatment (ART) for HIV-positive patients. South Africa adopted this recommendation in 2017, but multiple clinic visits, long waiting times, and delays for laboratory tests remain common. Streamlined approaches to same-day initiation that allow the majority of patients to start ART immediately, while ensuring that patients who do require additional services receive them, are needed to achieve national and international treatment program goals. METHODS/DESIGN: The SLATE II (Simplified Algorithm for Treatment Eligibility) study is an individually randomized evaluation of a clinical algorithm to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. It differs from the earlier SLATE I study in management of patients with symptoms of tuberculosis (under SLATE II these patients may be started on ART immediately) and other criteria for immediate initiation. SLATE II will randomize (1:1) 600 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa. Patients randomized to the standard arm will receive standard-of-care ART initiation from clinic staff. Patients randomized to the intervention arm will be administered a symptom report, medical history, brief physical exam, and readiness assessment. Symptomatic patients will also have a tuberculosis (TB) module with lipoarabinomannan antigen of mycobacteria test. Patients who have satisfactory results for all four components will be dispensed antiretrovirals (ARVs) immediately, at the same clinic visit. Patients who have any negative results will be referred for further investigation, care, counseling, tests, or other services prior to being dispensed ARVs. Follow-up will be by passive medical record review. The primary outcomes will be ART initiation in  ≤ 7 days and retention in care 8 months after study enrollment. DISCUSSION: SLATE II improves upon the SLATE I study by reducing the number of reasons for delaying ART initiation and allowing more patients with TB symptoms to start ART on the day of diagnosis. If successful, SLATE II will provide a simple and streamlined approach that can readily be adopted in other settings without investment in additional technology. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03315013 . Registered on 19 October 2017.

Guidelines for the investigation of chronic diarrhoea in adults: British Society of Gastroenterology, 3rd edition

Chronic diarrhoea is a common problem, hence clear guidance on investigations is required. This is an updated guideline from 2003 for the investigations of chronic diarrhoea commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology (BSG). This document has undergone significant revision in content through input by 13 members of the Guideline Development Group (GDG) representing various institutions. The GRADE system was used to appraise the quality of evidence and grading of recommendations.

The molecular characterisation of Cryptosporidium species in relinquished dogs in Great Britain: a novel zoonotic risk?

Surveillance was conducted to investigate the occurrence of protozoan parasites of the genus Cryptosporidium in dogs newly admitted to a dog rehoming charity in London, Great Britain. Voided faecal samples were collected from all new admissions between 2011 and 2012 during six separate 4-week sampling periods. Information on host signalment, including age, breed and reason for submission and faecal consistency, was collected. Polymerase Chain Reaction (PCR) targeting the 18S ribosomal RNA gene, confirmed by sequencing, was conducted on the faecal samples to detect Cryptosporidium genomic DNA and determine Cryptosporidium identity. In total, 677 dogs were included in the study. The prevalence of Cryptosporidium-positive faecal samples was 4.6% (31/676). There were positive samples in all of the six sampling periods. Cryptosporidium canis (n = 28), C. parvum (n = 2) and C. andersoni (n = 1) were identified. Sixty KDa glycoprotein (gp60) gene amplicon sequencing of the C. parvum samples identified genotypes IIaA17G1R1 and IIaA15G2R1 for the first time from a dog. There were no significant associations between signalment data and Cryptosporidium status. While this was a study of one rehoming shelter, the presence of the potentially zoonotic C. parvum and C. canis in dogs highlights a public health concern. Further research is needed to better understand the epidemiology and potential impacts of Cryptosporidium infection in dogs.