Evaluation of the Nutritive Value of Mixture of Fermented Bovine Blood and Rumen Digesta for Broiler Finisher

A 35-day feeding trials involving three hundred (300) 5 week old broilers was carried out in a completely randomized design to evaluate the performance, organ characteristics, nutrient utilization and economic analysis of broiler finishers fed diets containing a mixture of fermented dried bovine blood and rumen digesta (FBBRD) at dietary levels of 0, 5, 10, 15 and 20% respectively. At the end of the feeding trials, two birds were randomly selected from each treatment and transferred to a metabolism cage for faecal collection and determination of nutrient digestibility. Another set of five (5) birds were randomly selected from each treatment for carcass and organ weight evaluation. Birds on the test material performed generally better in all the parameters measured than the control group. There were no significant (P<0.05) difference among the groups in relative organ weight. The groups on the test materials (FBBRD) also recorded better nutrient nutrient utilization values than the control group. The results suggest that up to 20% inclusion level of FBBRD meal could be tolerated by broiler finisher without any adverse effects on performance. Keywords: Fermented Bovine Blood and Rumen Digesta, Performance, Broiler Finisher

Addressing social issues in a universal HIV test and treat intervention trial (ANRS 12249 TasP) in South Africa: methods for appraisal

Background: The Universal HIV Test and Treat (UTT) strategy represents a challenge for science, but is also a challenge for individuals and societies. Are repeated offers of provider-initiated HIV testing and immediate antiretroviral therapy (ART) socially-acceptable and can these become normalized over time? Can UTT be implemented without potentially adding to individual and community stigma, or threatening individual rights? What are the social, cultural and economic implications of UTT for households and communities? And can UTT be implemented within capacity constraints and other threats to the overall provision of HIV services? The answers to these research questions will be critical for routine implementation of UTT strategies. Methods/design: A social science research programme is nested within the ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomised trial in rural South Africa. The programme aims to inform understanding of the (i) social, economic and environmental factors affecting uptake of services at each step of the continuum of HIV prevention, treatment and care and (ii) the causal impacts of the TasP intervention package on social and economic factors at the individual, household, community and health system level. We describe a multidisciplinary, multi-level, mixed-method research protocol that includes individual, household, community and clinic surveys, and combines quantitative and qualitative methods. Discussion: The UTT strategy is changing the overall approach to HIV prevention, treatment and care, and substantial social consequences may be anticipated, such as changes in social representations of HIV transmission, prevention, HIV testing and ART use, as well as changes in individual perceptions and behaviours in terms of uptake and frequency of HIV testing and ART initiation at high CD4. Triangulation of social science studies within the ANRS 12249 TasP trial will provide comprehensive insights into the acceptability and feasibility of the TasP intervention package at individual, community, patient and health system level, to complement the trial's clinical and epidemiological outcomes. It will also increase understanding of the causal impacts of UTT on social and economic outcomes, which will be critical for the long-term sustainability and routine UTT implementation. Trial registration: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974

Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa

Introduction The universal test‐and‐treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa. Methods The TasP cluster‐randomized trial (2012 to 2016) implemented six‐monthly repeat home‐based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 × 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level. Results 8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited. Conclusions PVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART‐initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90‐90‐90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context‐specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH‐27‐0512‐3974 (South African National Clinical Trials Register)

Sorafenib for the treatment of advanced hepatocellular cancer – a UK audit

Aims: Sorafenib is the current standard treatment for advanced hepatocellular carcinoma. We carried out a national audit of UK patients treated with sorafenib as standard-of-care and those treated with systemic therapy in first-line trials. Materials and methods: Sorafenib-treated and trial-treated patients were identified via the Cancer Drugs Fund and local databases. Data were collected retrospectively from medical records according to a standard case report form. The primary outcome measure was overall survival, estimated by the Kaplan–Meier method. Results: Data were obtained for 448 sorafenib-treated patients from 15 hospitals. The median age was 68 years (range 17–89) and 75% had performance status ≤ 1. At baseline, 77% were Child-Pugh A and 16.1% Child-Pugh B; 38% were albumin–bilirubin grade 1 (ALBI-1) and 48% ALBI-2; 23% were Barcelona Clinic Liver Classification B (BCLC-B) and 72% BCLC-C. The median time on sorafenib was 3.6 months, with a mean daily dose of 590 mg. The median overall survival for 448 evaluable sorafenib-treated patients was 8.5 months. There were significant differences in overall survival comparing Child-Pugh A versus Child-Pugh B (9.5 versus 4.6 months), ALBI-1 versus ALBI-2 (12.9 versus 5.9 months) and BCLC-B versus BCLC-C (13.0 versus 8.3 months). For trial-treated patients (n = 109), the median overall survival was 8.1 months and this was not significantly different from the sorafenib-treated patients. Conclusion: For Child-Pugh A patients with good performance status, survival outcomes were similar to those reported in global randomised controlled trials. Patients with ALBI grade &gt; 1, Child-Pugh B or poor performance status seem to derive limited benefit from sorafenib treatment

Results of a single-arm pilot study of 32P microparticles in unresectable locally advanced pancreatic adenocarcinoma with gemcitabine/nab-paclitaxel or FOLFIRINOX chemotherapy.

BACKGROUND: Unresectable locally advanced pancreatic cancer (LAPC) is generally managed with chemotherapy or chemoradiotherapy, but prognosis is poor with a median survival of ∼13 months (or up to 19 months in some studies). We assessed a novel brachytherapy device, using phosphorous-32 (32P) microparticles, combined with standard-of-care chemotherapy. PATIENTS AND METHODS: In this international, multicentre, single-arm, open-label pilot study, adult patients with histologically or cytologically proven unresectable LAPC received 32P microparticles, via endoscopic ultrasound-guided fine-needle implantation, planned for week 4 of 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) or gemcitabine/nab-paclitaxel chemotherapy, per investigator's choice. The primary endpoint was safety and tolerability measured using Common Terminology Criteria for Adverse Events version 4.0. The lead efficacy endpoint was local disease control rate at 16 weeks. RESULTS: Fifty patients were enrolled and received chemotherapy [intention-to-treat (ITT) population]. Forty-two patients received 32P microparticle implantation [per protocol (PP) population]. A total of 1102 treatment-emergent adverse events (TEAEs) were reported in the ITT/safety population (956 PP), of which 167 (139 PP) were grade ≥3. In the PP population, 41 TEAEs in 16 (38.1%) patients were possibly or probably related to 32P microparticles or implantation procedure, including 8 grade ≥3 in 3 (7.1%) patients, compared with 609 TEAEs in 42 (100%) patients attributed to chemotherapy, including 67 grade ≥3 in 28 patients (66.7%). The local disease control rate at 16 weeks was 82.0% (95% confidence interval: 68.6% to 90.9%) (ITT) and 90.5% (95% confidence interval: 77.4% to 97.3%) (PP). Tumour volume, carbohydrate antigen 19-9 levels, and metabolic tumour response at week 12 improved significantly. Ten patients (20.0% ITT; 23.8% PP) had surgical resection and median overall survival was 15.2 and 15.5 months for ITT and PP populations, respectively. CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC

CD4+ T-cell count at antiretroviral therapy initiation in the "treat all" era in rural South Africa: an interrupted time series analysis

BACKGROUND: South Africa implemented universal test and treat (UTT) in September 2016 in an effort to encourage earlier initiation of antiretroviral therapy (ART). METHODS: We therefore conducted an interrupted time series (ITS) analysis to assess the impact of UTT on mean CD4 count at ART initiation among adults ≥16 years old attending 17 public sector primary care services in rural South Africa between July 2014 and March 2019. RESULTS: Among 20,599 individuals (69% women), CD4 counts were available for 74%. Mean CD4 at ART initiation increased from 317.1 cells/μL (95% confidence interval, CI, 308.6 to 325.6)-one to eight months prior to UTT-to 421.0 cells/μL (95% CI 413.0 to 429.0) one to twelve months after UTT, including an immediate increase of 124.2 cells/μL (95% CI 102.2 to 146.1). However, mean CD4 count subsequently fell to 389.5 cells/μL (95% CI 381.8 to 397.1) 13 to 30 months after UTT, but remained above pre-UTT levels. Men initiated ART at lower CD4 counts than women (-118.2 cells/μL, 95% CI -125.5 to -111.0) throughout the study. CONCLUSIONS: Although UTT led to an immediate increase in CD4 count at ART initiation in this rural community, the long-term effects were modest. More efforts are needed to increase initiation of ART early in HIV infection, particularly among men

Findings from home-based HIV testing and facilitated linkage after scale-up of test and treat in rural South Africa: young people still missing

Objectives The aim of the study was to estimate rates of linkage to HIV care and antiretroviral treatment (ART) initiation after the introduction of home‐based HIV counselling and testing (HBHCT) and telephone‐facilitated support for linkage in rural South Africa. Methods A population‐based prospective cohort study was carried out in KwaZulu Natal, South Africa. All residents aged ≥ 15 years were eligible for HBHCT. Those who tested positive and were not in care were referred for ART at one of 11 public‐sector clinics. Individuals who did not attend the clinic within 2 weeks were sent a short message service (SMS) reminder; those who had not attended after a further 2 weeks were telephoned by a nurse counsellor, to discuss concerns and encourage linkage. Kaplan–Meier methods were used to estimate the proportion of newly diagnosed individuals linking to care and initiating ART. Results Among 38 827 individuals visited, 26% accepted HBHCT. Uptake was higher in women than in men (30% versus 20%, respectively), but similar in people aged < 30 years and ≥ 30 years (28% versus 26%, respectively). A total of 784 (8%) tested HIV positive, of whom 427 (54%) were newly diagnosed. Within 6 months, 31% of women and 18% of men < 30 years old had linked to care, and 29% and 16%, respectively, had started ART. Among those ≥ 30 years, 41% of women and 38% of men had linked to care within 6 months, and 41% and 35%, respectively, had started ART. Conclusions Despite facilitated linkage, rates of timely linkage to care and ART initiation after HBHCT were very low, particularly among young men. Innovations are needed to provide effective HIV care and prevention interventions to young people, and thus maximize the benefits of universal test and treat