Publications by authors named "Richard Donovan"

22 Publications

  • Page 1 of 1

Common elective orthopaedic procedures and their clinical effectiveness: umbrella review of level 1 evidence.

BMJ 2021 07 7;374:n1511. Epub 2021 Jul 7.

National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK.

Objective: To determine the clinical effectiveness of common elective orthopaedic procedures compared with no treatment, placebo, or non-operative care and assess the impact on clinical guidelines.

Design: Umbrella review of meta-analyses of randomised controlled trials or other study designs in the absence of meta-analyses of randomised controlled trials.

Data Sources: Ten of the most common elective orthopaedic procedures-arthroscopic anterior cruciate ligament reconstruction, arthroscopic meniscal repair of the knee, arthroscopic partial meniscectomy of the knee, arthroscopic rotator cuff repair, arthroscopic subacromial decompression, carpal tunnel decompression, lumbar spine decompression, lumbar spine fusion, total hip replacement, and total knee replacement-were studied. Medline, Embase, Cochrane Library, and bibliographies were searched until September 2020.

Eligibility Criteria For Selecting Studies: Meta-analyses of randomised controlled trials (or in the absence of meta-analysis other study designs) that compared the clinical effectiveness of any of the 10 orthopaedic procedures with no treatment, placebo, or non-operative care.

Data Extraction And Synthesis: Summary data were extracted by two independent investigators, and a consensus was reached with the involvement of a third. The methodological quality of each meta-analysis was assessed using the Assessment of Multiple Systematic Reviews instrument. The Jadad decision algorithm was used to ascertain which meta-analysis represented the best evidence. The National Institute for Health and Care Excellence Evidence search was used to check whether recommendations for each procedure reflected the body of evidence.

Main Outcome Measures: Quality and quantity of evidence behind common elective orthopaedic interventions and comparisons with the strength of recommendations in relevant national clinical guidelines.

Results: Randomised controlled trial evidence supports the superiority of carpal tunnel decompression and total knee replacement over non-operative care. No randomised controlled trials specifically compared total hip replacement or meniscal repair with non-operative care. Trial evidence for the other six procedures showed no benefit over non-operative care.

Conclusions: Although they may be effective overall or in certain subgroups, no strong, high quality evidence base shows that many commonly performed elective orthopaedic procedures are more effective than non-operative alternatives. Despite the lack of strong evidence, some of these procedures are still recommended by national guidelines in certain situations.

Systematic Review Registration: PROSPERO CRD42018115917.
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http://dx.doi.org/10.1136/bmj.n1511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262448PMC
July 2021

Definitive fixation outcomes of open tibial shaft fractures: Systematic review and network meta-analysis.

J Orthop Trauma 2021 Mar 27. Epub 2021 Mar 27.

Department of Orthopaedic Surgery, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom. Department of Orthopaedic Surgery, Southmead Hospital, Bristol, United Kingdom. Department of Orthopaedic Surgery, The Royal National Orthopaedic Hospital, Stanmore, United Kingdom. Department of Orthopaedic Surgery, McMaster University, Ontario, Canada Department of Orthopaedic Surgery, Boston Medical Center, Boston, USA.

Objectives: To delineate if there were differences in outcomes between definitive fixation strategies in open tibial shaft fractures.

Data Sources: MEDLINE, EMBASE, CENTRAL, OpenGrey.

Study Selection: Randomized and Quasi-randomized studies analyzing adult patients (>18 years) with open tibial shaft fractures (AO-42), undergoing definitive fixation treatment of any type.

Data Extraction: Data regarding patient demographics, definitive bony/soft-tissue management, irrigation, type of antibiotics and follow up. Definitive intervention choices included unreamed intramedullary nailing (UN), reamed intramedullary nailing (RN), plate fixation, multiplanar, and uniplanar external fixation (EF). The primary outcome was unplanned reoperation rate. Cochrane risk of bias tool and GRADE systems were used for quality analysis.

Data Synthesis: A random-effects meta-analysis of head-to-head evidence, followed by a network analysis that modelled direct and indirect data was conducted to provide precise estimates (relative risks (RR) and associated 95% confidence intervals (95% CI)).

Results: In open tibial shaft fractures, direct comparison UN showed a lower risk of unplanned reoperation versus EF (RR 0.67, 95% CI 0.43 - 1.05, p=0.08, moderate confidence). In Gustilo type III open fractures, the risk reduction with nailing compared to EF was larger (RR 0.61, 95% CI 0.37 - 1.01, p=0.05, moderate confidence). UN had a lower reoperation risk compared to RN (RR 0.91, 95% CI 0.58 - 1.4, p=0.68, low confidence), however this was not significant and did not demonstrate a clear advantage.

Conclusion: Intramedullary nailing reduces the risk of unplanned reoperation by a third compared to EF, with a slightly larger reduction in type III open fractures. Future trials should focus on major complication rates and health-related quality of life in high-grade tibial shaft fractures.

Level Of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
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http://dx.doi.org/10.1097/BOT.0000000000002090DOI Listing
March 2021

Tranexamic acid use to decrease blood loss in primary shoulder and elbow replacement: A systematic review and meta-analysis.

J Orthop 2021 Mar-Apr;24:239-247. Epub 2021 Mar 18.

Musculoskeletal Research Unit, University of Bristol, Level 1 Learning and Research Building, Southmead Hospital, Bristol, BS10 5NB, UK.

Purpose: Tranexamic acid (TXA) is an inexpensive antifibrinolytic agent that significantly reduces peri-operative blood loss and transfusion requirements after total hip and knee replacement. This meta-analysis demonstrates the effects of TXA on blood loss in total shoulder replacement (TSR) and total elbow replacement (TER).

Methods: We systematically searched MEDLINE, EMBASE and CENTRAL from inception to September 03, 2020 for randomised controlled trial (RCTs) and observational studies. Our primary outcome was blood loss. Secondary outcomes included the need for blood transfusion, and post-operative venous thromboembolic (VTE) complications. Mean differences (MD) and relative risks with 95% confidence intervals (CIs) were reported.

Results: Four RCTs and five retrospective cohort studies (RCS) met eligibility criteria for TSRs, but none for TERs. RCT data determined that TXA administration significantly decreased estimated total blood loss (MD -358mL), post-operative blood loss (MD -113mL), change in haemoglobin (Hb) (MD -0.71 g/dL) and total Hb loss (MD -35.3g) when compared to placebo. RCS data demonstrated significant association between TXA administration and decreased in post-operative blood loss, change in Hb, change in Hct and length of stay. There was no significant difference in transfusion requirements or VTE complications.

Conclusion: TXA administration in safe and effective in patients undergoing primary TSR: it significantly decreases blood loss compared with placebo and is associated with shorter length of stay compared with no treatment. No significant increase in VTE complications was found. TXA administration should be routinely considered for patients undergoing TSR. Further research is needed to demonstrate the treatment effect in patients undergoing TER.
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http://dx.doi.org/10.1016/j.jor.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022108PMC
March 2021

Estimation of blood volume and blood loss in primary total hip and knee replacement: An analysis of formulae for perioperative calculations and their ability to predict length of stay and blood transfusion requirements.

J Orthop 2021 Mar-Apr;24:227-232. Epub 2021 Mar 12.

Musculoskeletal Research Unit, University of Bristol, Level 1 Learning and Research Building, Bristol, BS10 5NB, UK.

Introduction: Blood loss continues to be a common surgical risk in total hip (THR) and knee replacements (TKR). Accurate prediction of blood loss permits appropriate counselling of risks to patients, target optimisation and forecasting future transfusion requirements. We compared blood volume formulae of Moore and Nadler, and blood loss formulae of Liu, Mercuriali, Bourke, Ward, Gross, Lisander and Meunier, to assess associations between calculated values with length of stay and transfusion requirements and determine which are useful in contemporary practice.

Methods: We retrospectively studied patients undergoing primary THR and TKR. We collected data on patient demographics, surgical interventions, pre- and postoperative haemoglobin and haematocrit values, length of stay and blood transfusion requirements. Spearman correlation tests and least squares multiple linear regression were performed.

Results: 149 THRs and 90 TKRs in 239 patients were analysed over four months. There was a very strong correlation between blood volume formulae. There were multiple very strong and strong associations between blood loss formulae. Bourke correlated significantly to length of stay, and Liu, Mercuriali, Lisander and Meunier correlated for incidence of transfusion.

Conclusion: Accurate estimation of perioperative blood loss is increasingly important as demand for joint replacement surgery increases in an ageing population. If the primary interest is the association of blood loss and length of stay, Bourke's formula should be preferred. If the primary interest is calculating risk of transfusion, the formulae of Liu or Meunier should be preferred. The formulae of Mercuriali and Lisander are becoming redundant in contemporary practice.
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http://dx.doi.org/10.1016/j.jor.2021.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995348PMC
March 2021

Outcomes of Orthopaedic Trauma Services at a UK Major Trauma Centre During a National Lockdown and Pandemic: The Need for Continuing the Provision of Services.

Cureus 2020 Oct 20;12(10):e11056. Epub 2020 Oct 20.

Trauma and Orthopaedic Surgery, North Bristol National Health Service (NHS) Trust, Bristol, GBR.

Aim To review the trauma operating workload, theatre time and outcomes at a time of national lockdown at the beginning of the coronavirus disease 2019 (COVID-19) pandemic, comparing it with a year prior. Methods A retrospective case-control study was performed in a single Level 1 Major Trauma Centre (MTC) in the UK. Inclusion criteria were all patients undergoing operative intervention for an emergency or urgent trauma admission within our Trauma and Orthopaedics department. Data collected included anatomical area of injury, cause of injury, operative procedure, type of anaesthesia, total theatre time, complications, and mortality at 30 days. Results A total of 159 operations were performed on 142 patients in April 2019, and 110 operations on 106 patients in April 2020 (time of national lockdown). There was a 30% decrease due to reduced numbers of road traffic accidents and sport-related injuries. The number of hip fractures and those injuring themselves from less than 2m height remained the same. Operative total theatre time increased by a mean of 14 minutes, and complications and mortality were not significantly changed. The incidence of COVID in the patients tested was 8.5%, which matched the population incidence at the time.  Conclusions Orthopaedic trauma services need to be provided during a national lockdown. There was no decrease in the volume of patients sustaining falls, which includes hip fractures. Mean operating time only increases by 14 minutes with the wearing of PPE. This should be part of future planning of any pandemics or national lockdowns.
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http://dx.doi.org/10.7759/cureus.11056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676444PMC
October 2020

Flexible nails have a significantly increased risk of complications compared with plating techniques when treating diaphyseal femoral fractures in children aged 5-12: A systematic review.

Injury 2020 Dec 16;51(12):2763-2770. Epub 2020 Sep 16.

North Bristol NHS Trust, Southmead Rd, Bristol, BS10 5NB, UK; Musculoskeletal Research Unit, University of Bristol, Level 1 Learning and Research Building, Bristol, BS10 5NB, UK. Electronic address:

Background: One third of paediatric femoral fractures occur between the ages of 5 and 12. The American Academy of Orthopaedic Surgeons (AAOS) provide evidence-based guidance for treating such fractures that occur in children under 5 and over 12 but not for this age cohort. We aimed to synthesise the available evidence comparing flexible nailing versus plating techniques for diaphyseal femoral fractures in children between the ages of 5 and 12.

Methodology: A systematic review of interventional and observational studies was performed using MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, WHO Global Index Medicus and LILACS. The search strategy combined keywords for: children, diaphyseal femoral fractures, plates and nails. Two independent reviewers screened, selected, assessed quality and extracted data from identified studies. The primary outcome was overall complication rates. Secondary outcomes assessed rates of individual complications, and operative variables (e.g. operative time, blood loss).

Results: Five studies fulfilled the eligibility criteria. No RCTs were identified. The studies included 308 femoral fractures in 306 patients: 174 fractures were treated with flexible nailing and 134 with plating. The post-operative complication rate was 27.0% (n = 47) after flexible nails and 12.7% (n = 17) after plating, relative risk 2.13 (95% CI 1.28, 3.53; p = 0.0035). The relative risk of malunion was 3.59 (95% CI 1.05, 12.25; p = 0.0409) with flexible nails and of prominent metalwork was 5.39 (95% CI 1.25, 23.31; p = 0.0241) with flexible nails.

Conclusions: Data on this topic for this age group is limited despite accounting for one third of paediatric femoral fractures. This review identified a significantly increased relative risk of all complications, and in particular with respect to malunion and prominent metalwork when fractures in this cohort are treated with flexible nails compared to plates. A multi-centre randomised trial to determine if either treatment is superior would be justified.
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http://dx.doi.org/10.1016/j.injury.2020.09.024DOI Listing
December 2020

Time to intravenous antibiotic administration (TIbiA) in severe open tibial fractures: Impact of change to national guidance.

Injury 2020 Apr 2;51(4):1086-1090. Epub 2020 Mar 2.

Department of Plastic Surgery, Southmead Hospital, North Bristol NHS Trust, UK.

Introduction: Severe open tibial fractures are limb-threatening injuries. Outcomes depend on a complex interplay of patient, injury and treatment factors. 2009 guidelines from the British Orthopaedic Association (BOA) and British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS) recommend prophylactic intravenous antibiotic administration within three hours of injury. More recent National Institute for Health and Care Excellence (NICE) 2016 guidelines recommend pre-hospital antibiotic administration where possible. This study aimed to analyse the impact of time to antibiotics on development of deep infection.

Methods: Adult acute Gustilo-Anderson 3B open tibial fractures managed at a single UK Major Trauma Centre were reviewed retrospectively over a three-year period, including a period before and after the regional ambulance service introduced a policy of administering pre-hospital intravenous antibiotics to open fractures in 2016. Development of deep infection was recorded as the primary outcome measure. Complete case regression analysis was performed. Time was assessed as a continuous variable and as thresholds with antibiotics received within one or three hours of injury.

Results: 156 patients with 159 fractures were included. Following introduction of new guidance in 2016, median time to antibiotics decreased from 180 to 160 min and more patients received pre-hospital antibiotics (2% vs. 33%). Overall, 7.5% developed deep infection (n = 12) within a median follow-up of 26 months. Logistic regression found no relationship between any independent variable, including time to antibiotic administration, and development of deep infection.

Conclusions: There are a variety of factors identified in the literature and in national policies and treatment guidelines as potentially modifiable to reduce the risk of deep infection following open fractures. In this study, time to antibiotic administration was not associated with the risk of developing deep infection. The results of this study demonstrate a low infection rate, which may be due to expedient expert care delivered by a dedicated orthoplastic service in line with national guidance where achievable.
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http://dx.doi.org/10.1016/j.injury.2020.03.005DOI Listing
April 2020

The "FCR" Approach to the Knee for the Management of Posterior Tibial Plateau Fractures.

J Orthop Trauma 2020 Jun;34(6):e221-e224

Department of Trauma & Orthopaedic Surgery, Southmead Hospital, North Bristol Trust, Bristol, United Kingdom.

Three-column fixation of tibial plateau fractures is now an established philosophy. A direct posterior approach with the patient prone affords enhanced exposure of the posterior column and ease of access for fixation using a buttress plate and posterior-to-anterior screws. A "direct posterior" approach through a reverse L-shaped incision to back of the knee is popular, yet complications associated with raising a fascial flap can occur. We present a simple method of conceptualizing a direct posterior approach through a single longitudinal incision, by likening it to a commonly performed orthopedic approach, the flexor carpi radialis approach to the wrist.
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http://dx.doi.org/10.1097/BOT.0000000000001716DOI Listing
June 2020

Outcome of total knee arthroplasty in patients with poliomyelitis: A systematic review.

EFORT Open Rev 2018 Jun 6;3(6):358-362. Epub 2018 Jun 6.

Trauma and Orthopaedic Surgery Department, Royal London Hospital, UK.

Total knee arthroplasty (TKA) in patients affected by poliomyelitis is technically challenging owing to abnormal anatomical features including articular and metaphyseal angular deformities, external rotation of the tibia, excessive valgus alignment, bone loss, narrowness of the femoral and tibial canals, impaired quadriceps strength, flexion contractures, genu recurvatum and ligamentous laxity. Little information is available regarding the results and complications of TKA in this challenging group of patients.We carried out a systematic review of the literature to determine the functional outcome, complications and revision rates of TKA in patients with poliomyelitis-affected knees. Six studies including 82 knees met the inclusion criteria and were reviewed. The mean patient age was 63 years (45 to 85) and follow-up was 5.5 years (0.5 to 13).All studies reported significant improvement in knee function following TKA. There were six failures requiring revision surgery in 82 cases (7%) occurring at a mean of 6.2 years (0.4 to 12). The reasons for revision surgery were aseptic loosening (17%, n=1), infection (33%, n=2), periprosthetic fracture (17%, n=1) and instability (33%, n=2). Thirty-six knees had a degree of recurvatum pre-operatively (44%), which was in the range of 5° to 30°. Ten of these knees (28%) developed recurrent recurvatum post-operatively.The findings support the use of TKA in patients with poliomyelitis-affected knees. The post-operative functional outcome is similar to other patients; however, the revision rate is higher. Quadriceps muscle power appears to be an important prognostic factor for functional outcome and the use of constrained implant designs is recommended in the presence of less than antigravity quadriceps strength. Cite this article: 2018;3:358-362. DOI: 10.1302/2058-5241.3.170028.
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http://dx.doi.org/10.1302/2058-5241.3.170028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6026880PMC
June 2018

The analysis of illicit 25X-NBOMe seizures in Western Australia.

Drug Test Anal 2018 Apr 27;10(4):786-790. Epub 2017 Oct 27.

ChemCentre, Perth, Western Australia.

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http://dx.doi.org/10.1002/dta.2260DOI Listing
April 2018

A Review of Environmental Life Cycle Assessments of Liquid Transportation Biofuels in the Pan American Region.

Environ Manage 2015 Dec 4;56(6):1356-76. Epub 2015 Jun 4.

University of California, Irvine, CA, USA.

Life-cycle assessment (LCA) has been applied to many biofuel and bioenergy systems to determine potential environmental impacts, but the conclusions have varied. Different methodologies and processes for conducting LCA of biofuels make the results difficult to compare, in-turn making it difficult to make the best possible and informed decision. Of particular importance are the wide variability in country-specific conditions, modeling assumptions, data quality, chosen impact categories and indicators, scale of production, system boundaries, and co-product allocation. This study has a double purpose: conducting a critical evaluation comparing environmental LCA of biofuels from several conversion pathways and in several countries in the Pan American region using both qualitative and quantitative analyses, and making recommendations for harmonization with respect to biofuel LCA study features, such as study assumptions, inventory data, impact indicators, and reporting practices. The environmental management implications are discussed within the context of different national and international regulatory environments using a case study. The results from this study highlight LCA methodology choices that cause high variability in results and limit comparability among different studies, even among the same biofuel pathway, and recommendations are provided for improvement.
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http://dx.doi.org/10.1007/s00267-015-0543-8DOI Listing
December 2015

The gut mucosal viral reservoir in HIV-infected patients is not the major source of rebound plasma viremia following interruption of highly active antiretroviral therapy.

J Virol 2011 May 23;85(10):4772-82. Epub 2011 Feb 23.

Dept. of Medical Microbiology and Immunology, GBSF, Room 5511, University of California, Davis, California 95616, USA.

Interruption of suppressive highly active antiretroviral therapy (HAART) in HIV-infected patients leads to increased HIV replication and viral rebound in peripheral blood. Effects of therapy interruption on gut-associated lymphoid tissue (GALT) have not been well investigated. We evaluated longitudinal changes in viral replication and emergence of viral variants in the context of T cell homeostasis and gene expression in GALT of three HIV-positive patients who initiated HAART during primary HIV infection but opted to interrupt therapy thereafter. Longitudinal viral sequence analysis revealed that a stable proviral reservoir was established in GALT during primary HIV infection that persisted through early HAART and post-therapy interruption. Proviral variants in GALT and peripheral blood mononuclear cells (PBMCs) displayed low levels of genomic diversity at all times. A rapid increase in viral loads with a modest decline of CD4(+) T cells in peripheral blood was observed, while gut mucosal CD4(+) T cell loss was severe following HAART interruption. This was accompanied by increased mucosal gene expression regulating interferon (IFN)-mediated antiviral responses and immune activation, a profile similar to those found in HAART-naive HIV-infected patients. Sequence analysis of rebound virus suggested that GALT was not the major contributor to the postinterruption plasma viremia nor were GALT HIV reservoirs rapidly replaced by HIV rebound variants. Our data suggest an early establishment and persistence of viral reservoirs in GALT with minimal diversity. Early detection of and therapy for HIV infection may be beneficial in controlling viral evolution and limiting establishment of diverse viral reservoirs in the mucosal compartment.
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http://dx.doi.org/10.1128/JVI.02409-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3126205PMC
May 2011

Creating a model program for influenza surveillance in California: results from the 2005-2006 influenza season.

Am J Prev Med 2007 Oct;33(4):353-7

Department of Health Services, Viral and Ricksettial Disease Laboratory, California Department of Public Health, 850 Marina Bay Parkway, Richmond, CA 94804, USA.

Background: Influenza surveillance is valuable for monitoring trends in influenza-related morbidity and mortality. Using the 2005-2006 influenza season as an example, this paper describes a comprehensive influenza surveillance program used by the California Department of Public Health (CDPH).

Methods: Data collected from patients evaluated for acute respiratory illness in a given week were reported and summarized the following week, including (1) electronic hospital pneumonia and influenza admission and antiviral usage records from Kaiser Permanente, (2) sentinel provider influenza-like illness (ILI) reports, (3) severe pediatric influenza case reports (e.g., children either hospitalized in intensive care or expired), (4) school clinic ILI evaluations, and (5) positive influenza test results from a network of academic, hospital, commercial, and public health laboratories and the state CDPH Viral and Rickettsial Disease Laboratory.

Results: Influenza activity in California in the 2005-2006 season was moderate in severity; all clinical and laboratory markers rose and fell consistently. Extensive laboratory characterization identified the predominant circulating virus strain as A/California/7/2004(H3N2), which was a component of the 2005-2006 influenza vaccine; 96% of samples tested showed adamantane resistance.

Conclusions: By using multiple, complementary surveillance methods coupled with a strong laboratory component, the CDPH has developed a simple, flexible, stable, and widely accepted influenza surveillance system that can monitor trends in statewide influenza activity, ascertain the correlation between circulating strains with vaccine strains, and assist with detection of new strain variants. The methods described can serve as a model for influenza surveillance in other states.
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http://dx.doi.org/10.1016/j.amepre.2007.05.008DOI Listing
October 2007

Flash-heat inactivation of HIV-1 in human milk: a potential method to reduce postnatal transmission in developing countries.

J Acquir Immune Defic Syndr 2007 Jul;45(3):318-23

Division of Epidemiology, School of Public Health, University of California, Berkeley, CA 94720-7360, USA.

Background: Up to 40% of all mother-to-child transmission of HIV occurs by means of breast-feeding; yet, in developing countries, infant formula may not be a safe option. The World Health Organization recommends heat-treated breast milk as an infant-feeding alternative. We investigated the ability of a simple method, flash-heat, to inactivate HIV in breast milk from HIV-positive mothers.

Methods: Ninety-eight breast milk samples, collected from 84 HIV-positive mothers in a periurban settlement in South Africa, were aliquoted to unheated control and flash-heating. Reverse transcriptase (RT) assays (lower detection limit of 400 HIV copies/mL) were performed to differentiate active versus inactivated cell-free HIV in unheated and flash-heated samples.

Results: We found detectable HIV in breast milk samples from 31% (26 of 84) of mothers. After adjusting for covariates, multivariate logistic regression showed a statistically significant negative association between detectable virus in breast milk and maternal CD4+ T-lymphocyte count (P=0.045) and volume of breast milk expressed (P=0.01) and a positive association with use of multivitamins (P=0.03). All flash-heated samples showed undetectable levels of cell-free HIV-1 as detected by the RT assay (P<0.00001).

Conclusions: Flash-heat can inactivate HIV in naturally infected breast milk from HIV-positive women. Field studies are urgently needed to determine the feasibility of in-home flash-heating breast milk to improve infant health while reducing postnatal transmission of HIV in developing countries.
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http://dx.doi.org/10.1097/QAI.0b013e318074eecaDOI Listing
July 2007

HIV type 1 subtype C gag and nef diversity in Southern Africa.

AIDS Res Hum Retroviruses 2007 Mar;23(3):477-81

Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Observatory, Cape Town, South Africa.

Several HIV-1 subtype C-specific gag- and/or nef-based vaccines are currently intended for clinical trial in southern Africa. Here we provide sequences of 64 gag and 45 nef genes sampled in Malawi, Zambia, Zimbabwe, and South Africa and assess the degree of southern African HIV-1 diversity that will confront these vaccines. Whereas reasonable phylogenetic evidence exists for geographical clustering of subtype C gag and nef sequences from various other parts of the world, there is little evidence of similar population founder effects in the southern African epidemic. The entire breadth of subtype C diversity is represented in the southern African genes suggesting there may be no advantage in producing region- or country-specific subtype C vaccines. We do not, however, find much evidence of intersubtype recombination in the Southern African genes, implying that the likelihood of vaccine failure due to the emergence of intersubtype recombinants is probably low.
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http://dx.doi.org/10.1089/aid.2006.0232DOI Listing
March 2007

Viral, nutritional, and bacterial safety of flash-heated and pretoria-pasteurized breast milk to prevent mother-to-child transmission of HIV in resource-poor countries: a pilot study.

J Acquir Immune Defic Syndr 2005 Oct;40(2):175-81

Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA.

Background: Heat-treated breast milk of HIV-positive mothers has potential to reduce vertical transmission. This study compared the impact of flash-heating (FH) and Pretoria pasteurization (PP) on HIV, nutrients, and antimicrobial properties in human milk.

Methods: Milk samples were spiked with 1 x 10 (8) copies/mL of clade C HIV-1 and treated with FH and PP. We measured HIV reverse transcriptase (RT) activity before and after heating (n = 5). Heat impact on vitamins A, B6, B12, and C; folate, riboflavin, thiamin, and antimicrobial proteins (lactoferrin and lysozyme) was assessed. Storage safety was evaluated by spiking with Escherichia coli or Staphylococcus aureus.

Results: Both methods inactivated > or = 3 logs of HIV-1. FH resulted in undetectable RT activity. Neither method caused significant decrease in any vitamin, although reductions in vitamins C and E were noted. Heat decreased immunoreactive lactoferrin (P < 0.05) but not the proportions of lactoferrin and lysozyme surviving digestion. FH seems to retain more antibacterial activity. Both treatments eliminated spiked bacteria.

Conclusions: FH may be superior to PP in eliminating all viral activity; both methods retained nutrients and destroyed bacterial contamination. Heat-treated breast milk merits further study as a safe and practical infant feeding option for HIV-positive mothers in developing countries.
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http://dx.doi.org/10.1097/01.qai.0000178929.15904.95DOI Listing
October 2005

Human immunodeficiency virus-specific responses in adult Ugandans: patterns of cross-clade recognition.

J Virol 2005 Apr;79(7):4132-9

Joint Clinical Research Centre, Kampala, Uganda.

Human immunodeficiency virus (HIV) or AIDS is currently the leading cause of death in Uganda, with at least three HIV clades (subtypes) accounting for most new infections. Whether an effective vaccine formulated on viruses from a single clade will be able to protect against infection from other local clades remains unresolved. We examined the T-cell immune responses from a cohort of HIV-seropositive individuals in Uganda with predominantly clade A and D infections. Surprisingly, we observed similar frequencies of cross-clade T-cell responses to the gag, env, and nef regions. Our data suggest that the level of viral sequence variability between distinct HIV strains does not predict the degree of cross-clade responses. High sequence homologies were also observed between consensus peptides and sequences from viral isolates, supporting the use of consensus amino acid sequences to identify immunogenic regions in studies of large populations.
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http://dx.doi.org/10.1128/JVI.79.7.4132-4139.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1061582PMC
April 2005

Intersubtype BF recombinants of HIV-1 in a population of injecting drug users in Argentina.

J Acquir Immune Defic Syndr 2004 May;36(1):630-6

Viral and Rickettsial Disease Laboratory, California Department of Health Services, Richmond, CA, USA.

The presence of recombinant intersubtypes of HIV-1 in Argentina has been reported since the mid-1990s. In this study, sequences of a region of the gag, pol, and vpu genes of HIV-1 were analyzed in samples of 21 injection drug users (IDUs) residing in the suburbs of the city of Buenos Aires. Genomic characterization and identification of recombination sites were made comparing the 3 regions with reference isolation sequences of subtypes B, F, C, A, and B/F recombinants: CRF12_BF and non-CRF12_BF sequences. Subtype assignment of the analyzed segments was phylogenetically confirmed. All the samples turned out to be BF recombinants in at least 1 of the 3 studied genes. Twelve samples (57%) had the same pattern as the Argentinean CRF12_BF, whereas in the rest, the pattern differed in at least 1 of the 3 genes. The relation of these fragments to the CRF12_BF was phylogenetically verified. These results indicate the predominance of BF recombinants and the presence of a high percentage of sequences closely related to the CRF12_BF in the IDU population in Argentina and suggest a possible association between viral variants and the transmission route.
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http://dx.doi.org/10.1097/00126334-200405010-00012DOI Listing
May 2004

The right to die: medico-legal implications of In re Quinlan.

Rutgers Law Rev 1977 ;30(2):267-303

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April 1979
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