Adam Trickey

Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies

Summary Background Health care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013. Methods We analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART. Findings 88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men. Interpretation Even in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements. Funding UK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.

Global prevalence of injecting drug use and sociodemographic characteristics and prevalence of HIV, HBV, and HCV in people who inject drugs: a multistage systematic review

Summary Background Sharing of equipment used for injecting drug use (IDU) is a substantial cause of disease burden and a contributor to blood-borne virus transmission. We did a global multistage systematic review to identify the prevalence of IDU among people aged 15–64 years; sociodemographic characteristics of and risk factors for people who inject drugs (PWID); and the prevalence of HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) among PWID. Methods Consistent with the GATHER and PRISMA guidelines and without language restrictions, we systematically searched peer-reviewed databases (MEDLINE, Embase, and PsycINFO; articles published since 2008, latest searches in June, 2017), searched the grey literature (websites and databases, searches between April and August, 2016), and disseminated data requests to international experts and agencies (requests sent in October, 2016). We searched for data on IDU prevalence, characteristics of PWID, including gender, age, and sociodemographic and risk characteristics, and the prevalence of HIV, HCV, and HBV among PWID. Eligible data on prevalence of IDU, HIV antibody, HBsAg, and HCV antibody among PWID were selected and, where multiple estimates were available, pooled for each country via random effects meta-analysis. So too were eligible data on percentage of PWID who were female; younger than 25 years; recently homeless; ever arrested; ever incarcerated; who had recently engaged in sex work, sexual risk, or injecting risk; and whose main drugs injected were opioids or stimulants. We generated regional and global estimates in line with previous global reviews. Findings We reviewed 55 671 papers and reports, and extracted data from 1147 eligible records. Evidence of IDU was recorded in 179 of 206 countries or territories, which cover 99% of the population aged 15–64 years, an increase of 31 countries (mostly in sub-Saharan Africa and the Pacific Islands) since a review in 2008. IDU prevalence estimates were identified in 83 countries. We estimate that there are 15·6 million (95% uncertainty interval [UI] 10·2–23·7 million) PWID aged 15–64 years globally, with 3·2 million (1·6–5·1 million) women and 12·5 million (7·5–18·4 million) men. Gender composition varied by location: women were estimated to comprise 30·0% (95% UI 28·5–31·5) of PWID in North America and 33·4% (31·0–35·6) in Australasia, compared with 3·1% (2·1–4·1) in south Asia. Globally, we estimate that 17·8% (10·8–24·8) of PWID are living with HIV, 52·3% (42·4–62·1) are HCV-antibody positive, and 9·0% (5·1–13·2) are HBV surface antigen positive; there is substantial geographic variation in these levels. Globally, we estimate 82·9% (76·6–88·9) of PWID mainly inject opioids and 33·0% (24·3–42·0) mainly inject stimulants. We estimate that 27·9% (20·9–36·8) of PWID globally are younger than 25 years, 21·7% (15·8–27·9) had recently (within the past year) experienced homelessness or unstable housing, and 57·9% (50·5–65·2) had a history of incarceration. Interpretation We identified evidence of IDU in more countries than in 2008, with the new countries largely consisting of low-income and middle-income countries in Africa. Across all countries, a substantial number of PWID are living with HIV and HCV and are exposed to multiple adverse risk environments that increase health harms. Funding Australian National Drug and Alcohol Research Centre, Australian National Health and Medical Research Council, Open Society Foundation, World Health Organization, the Global Fund, and UNAIDS.

Cause-Specific Mortality in HIV-Positive Patients Who Survived Ten Years after Starting Antiretroviral Therapy

Objectives To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996–1999 and survived for more than ten years. Methods We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liver-related disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes.

Mortality According to CD4 Count at Start of Combination Antiretroviral Therapy Among HIV-infected Patients Followed for up to 15 Years After Start of Treatment: Collaborative Cohort Study

The strong association of CD4 count at start of combination therapy with subsequent survival in HIV-infected patients diminished during the first 5 years of treatment. After 5 years, lower baseline CD4 counts were not associated with higher mortality.

Mortality according to CD4 count at start of combination antiretroviral therapy among HIV positive patients followed for up to 15 years after start of treatment: collaborative cohort study

The strong association of CD4 count at start of combination therapy with subsequent survival in HIV-infected patients diminished during the first 5 years of treatment. After 5 years, lower baseline CD4 counts were not associated with higher mortality.

The Relationship Between Left Ventricular Wall Thickness, Myocardial Shortening, and Ejection Fraction in Hypertensive Heart Disease: Insights From Cardiac Magnetic Resonance Imaging

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age‐ and sex‐matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T. Long‐axis shortening (R=0.62), midwall fractional shortening (R=0.68), and radial strain (R=0.48) all decreased (P<.001) as end‐diastolic wall thickness increased. However, absolute wall thickening (defined as end‐systolic minus end‐diastolic wall thickness) was maintained, despite the reduced myocardial shortening. Absolute wall thickening correlated with ejection fraction (R=0.70, P<.0001). In multiple linear regression analysis, increasing wall thickness by 1 mm independently increased ejection fraction by 3.43 percentage points (adjusted β‐coefficient: 3.43 [2.60–4.26], P<.0001). Increasing end‐diastolic wall thickness augments ejection fraction through preservation of absolute wall thickening. Left ventricular ejection fraction should not be used in patients with hypertensive heart disease without correction for degree of hypertrophy.

CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC)

Summary Associations of CD4:CD8 ratio or CD8 count with all-cause and cause-specific mortality were too small for them to be useful as independent prognostic markers in addition to CD4 count in virally suppressed patients on antiretroviral therapy with high CD4 count.

Evaluation of an intervention to reduce tidal volumes in ventilated ICU patients

BACKGROUND There is considerable evidence that the use of tidal volumes <6 ml kg(-1) predicted body weight (PBW) reduces mortality in mechanically ventilated patients. We evaluated the effectiveness of using a large screen displaying delivered tidal volume in ml kg(-1) (PBW) for reducing tidal volumes. METHODS We assessed the intervention in two 6-month periods. A qualitative study was undertaken after the intervention period to examine staff interaction with the intervention. The study was conducted in a mixed medical and surgical intensive care unit at University Hospitals Bristol, UK. Consecutive patients requiring controlled mechanical ventilation for more than 1 h were included. Alerts were triggered when tidal volume breached predetermined targets and these alerts were visible to ICU clinicians in real time. RESULTS A total of 199 patients with 7640 h of data were observed during the control time period and 249 patients with 10 656 h of data were observed in the intervention period. Time spent with tidal volumes <6 ml kg(-1) PBW increased from 17.5 to 28.6% of the period of controlled mechanical ventilation. Time spent with a tidal volume <8 ml kg(-1) PBW increased from 60.6 to 73.9%. The screens were acceptable to staff and stimulated an increase in attendance of clinicians at the bedside to adjust ventilators. CONCLUSIONS Changing the format of data and displaying it with real-time alerts reduced delivered tidal volumes. Configuring information in a format more likely to result in desired outcomes has the potential to improve the translation of evidence into practice.

The TeaM (Therapeutic Mammaplasty) study: Protocol for a prospective multi-centre cohort study to evaluate the practice and outcomes of therapeutic mammaplasty

Highlights • Multicentre prospective study involving breast and plastic surgical units across the UK.• Will produce valuable data regarding the practice and outcomes of therapeutic mammaplasty.• Will inform decision-making and lead to future definitive study.• Will strengthen the collaborative network to facilitate the delivery of future projects.• Will increase awareness of the techniques among trainees such that participation is educational.

Multicentre observational study of adherence to Sepsis Six guidelines in emergency general surgery

Evidence‐based interventions may reduce mortality in surgical patients. This study documented the prevalence of sepsis, adherence to guidelines in its management, and timing of source control in general surgical patients presenting as an emergency.