Diverging Maternal and Cord Antibody Functions From SARS-CoV-2 Infection and Vaccination in Pregnancy.

Maternal immunity impacts the infant, but how is unclear. To understand the implications of the immune exposures of vaccination and infection in pregnancy for neonatal immunity, we evaluated antibody functions in paired peripheral maternal and cord blood. We compared those who in pregnancy received mRNA coronavirus disease 2019 (COVID-19) vaccine, were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the combination. We found that vaccination enriched a subset of neutralizing activities and Fc effector functions that was driven by IgG1 and was minimally impacted by antibody glycosylation in maternal blood. In paired cord blood, maternal vaccination also enhanced IgG1. However, Fc effector functions compared to neutralizing activities were preferentially transferred. Moreover, changes in IgG posttranslational glycosylation contributed more to cord than peripheral maternal blood antibody functional potency. These differences were enhanced with the combination of vaccination and infection as compared to either alone. Thus, Fc effector functions and antibody glycosylation highlight underexplored maternal opportunities to safeguard newborns.

Study design and methods: U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER).

INTRODUCTION: The U.S. study to protect brain health through lifestyle intervention to reduce risk (U.S. POINTER) is conducted to confirm and expand the results of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) in Americans. METHODS: U.S. POINTER was planned as a 2-year randomized controlled trial of two lifestyle interventions in 2000 older adults at risk for dementia due to well-established factors. The primary outcome is a global cognition composite that permits harmonization with FINGER. RESULTS: U.S. POINTER is centrally coordinated and conducted at five clinical sites (ClinicalTrials.gov: NCT03688126). Outcomes assessments are completed at baseline and every 6 months. Both interventions focus on exercise, diet, cognitive/social stimulation, and cardiovascular health, but differ in intensity and accountability. The study partners with a worldwide network of similar trials for harmonization of methods and data sharing. DISCUSSION: U.S. POINTER is testing a potentially sustainable intervention to support brain health and Alzheimer's prevention for Americans. Impact is strengthened by the targeted participant diversity and expanded scientific scope through ancillary studies.

A population-based study of KCNH7 p.Arg394His and bipolar spectrum disorder.

We conducted blinded psychiatric assessments of 26 Amish subjects (52 ± 11 years) from four families with prevalent bipolar spectrum disorder, identified 10 potentially pathogenic alleles by exome sequencing, tested association of these alleles with clinical diagnoses in the larger Amish Study of Major Affective Disorder (ASMAD) cohort, and studied mutant potassium channels in neurons. Fourteen of 26 Amish had bipolar spectrum disorder. The only candidate allele shared among them was rs78247304, a non-synonymous variant of KCNH7 (c.1181G>A, p.Arg394His). KCNH7 c.1181G>A and nine other potentially pathogenic variants were subsequently tested within the ASMAD cohort, which consisted of 340 subjects grouped into controls subjects and affected subjects from overlapping clinical categories (bipolar 1 disorder, bipolar spectrum disorder and any major affective disorder). KCNH7 c.1181G>A had the highest enrichment among individuals with bipolar spectrum disorder (χ(2) = 7.3) and the strongest family-based association with bipolar 1 (P = 0.021), bipolar spectrum (P = 0.031) and any major affective disorder (P = 0.016). In vitro, the p.Arg394His substitution allowed normal expression, trafficking, assembly and localization of HERG3/Kv11.3 channels, but altered the steady-state voltage dependence and kinetics of activation in neuronal cells. Although our genome-wide statistical results do not alone prove association, cumulative evidence from multiple independent sources (parallel genome-wide study cohorts, pharmacological studies of HERG-type potassium channels, electrophysiological data) implicates neuronal HERG3/Kv11.3 potassium channels in the pathophysiology of bipolar spectrum disorder. Such a finding, if corroborated by future studies, has implications for mental health services among the Amish, as well as development of drugs that specifically target HERG3/Kv11.3.

Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors.

BACKGROUND: Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country. STUDY DESIGN AND METHODS: An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios. RESULTS: Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population. CONCLUSION: The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety.

Trends in transfusion-transmissible infections among Australian blood donors from 2005 to 2010.

BACKGROUND: Routine monitoring of trends in transfusion-transmissible infections (TTIs) is essential to maintaining and improving transfusion safety. Although periodic studies have been published there is no comprehensive trend analysis for TTIs in Australian donors. This study determined recent trends in TTIs for which testing is conducted in Australia and described key attributes of infected blood donors. STUDY DESIGN AND METHODS: This is a retrospective analysis using data on donation testing for TTIs (2005-2010) from the national blood service donor database and data on postdonation interviews with TTI-positive donors (2008-2010) from a risk factor database incorporating responses to standardized interview questions. The study measured the prevalence and incidence of TTIs in Australia and assessed their time trends. Multivariate analysis of time trends was conducted using Poisson regression models. RESULTS: Overall, the prevalence and incidence of TTIs in 2005 to 2010 remained low and steady. The prevalence of hepatitis C virus decreased (rate ratio [RR], 0.93; 95% confidence interval [CI], 0.89-0.97) and the prevalence of active syphilis increased (RR, 1.51; 95% CI, 1.15-1.99) significantly during the study period. Prevalence of TTIs among Australian blood donors was substantially lower than that in the general population and no unique risk factors were identified in test-positive blood donors when compared with the general population. CONCLUSION: Both the prevalence and the incidence of TTIs in Australian blood donors remained low, with a steady or declining trend for most infections except active syphilis. The lower prevalence of TTIs in blood donors compared with the general population reflects the effectiveness of donor education and donor selection measures in Australia.

Paediatric health-care professionals: relationships between psychological distress, resilience and coping skills.

AIM: To investigate the impact of regular exposure to paediatric medical trauma on multidisciplinary teams in a paediatric hospital and the relationships between psychological distress, resilience and coping skills. METHOD: Symptoms of post-traumatic stress disorder, secondary traumatic stress, depression, anxiety, stress, burnout, compassion satisfaction, resilience and coping skills were measured in 54 health professionals and compared with published norms. RESULTS: Participants experienced more symptoms of secondary traumatic stress (P < 0.01), showed less resilience (P = 0.05) and compassion satisfaction (≥ 0.01), more use of optimism and sharing as coping strategies, and less use of dealing with the problem and non-productive coping strategies than comparative groups. Non-productive coping was associated with more secondary traumatic stress (r = 0.50, P = 0.05), burnout (r = 0.45, P = 0.01), post-traumatic stress disorder (r = 0.41, P = 0.05), anxiety (r = 0.42, P = 0.05), depression (r = 0.54, P = 0.01), and stress (r = 0.52, P = 0.01) and resilience was positively associated with optimism (r = 0.48, P = 0.01). Health professionals <25 years old used more non-productive coping strategies (P = 0.05), less 'sharing as a coping strategy' (P = 0.05) and tended to have more symptoms of depression (P = 0.06). CONCLUSION: Paediatric medical trauma can adversely affect a health professional's well-being, particularly those <25 years of age who make less use of positive coping strategies and more use of non-productive coping. These findings will assist the development of effective and meaningful interventions for health professionals working in paediatric hospitals.

Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy.

Immunization in pregnancy is a critical tool that can be leveraged to protect the infant with an immature immune system but how vaccine-induced antibodies transfer to the placenta and protect the maternal-fetal dyad remains unclear. Here, we compare matched maternal-infant cord blood from individuals who in pregnancy received mRNA COVID-19 vaccine, were infected by SARS-CoV-2, or had the combination of these two immune exposures. We find that some but not all antibody neutralizing activities and Fc effector functions are enriched with vaccination compared to infection. Preferential transport to the fetus of Fc functions and not neutralization is observed. Immunization compared to infection enriches IgG1-mediated antibody functions with changes in antibody post-translational sialylation and fucosylation that impact fetal more than maternal antibody functional potency. Thus, vaccine enhanced antibody functional magnitude, potency and breadth in the fetus are driven more by antibody glycosylation and Fc effector functions compared to maternal responses, highlighting prenatal opportunities to safeguard newborns as SARS-CoV-2 becomes endemic.

No excess risk of follicular lymphoma in kidney transplant and HIV-related immunodeficiency.

Subtype-specific incidence patterns in populations at high risk of lymphoma offer insight into lymphomagenesis. The incidence profiles for the 2 most common non-Hodgkin lymphoma subtypes were compared for 2 immunodeficient populations, adults receiving a kidney transplant 1982-2003 (n = 7,730) or diagnosed with human immunodeficiency virus (HIV) infection 1982-2004 (n = 17,175). National, population-based registries were linked and standardized incidence ratios (SIRs) were computed for each cohort and lymphoma subtype. Risk of diffuse large B-cell lymphoma was significantly increased after transplantation (SIR 17.83, 95% CI: 13.61-22.95) and after HIV infection (SIR 58.81, 95% CI: 52.59-65.56). Rates of follicular lymphoma (FL) were neither significantly increased nor decreased in transplant recipients (SIR 0.82, 95% CI: 0.10-2.96) and in people with HIV (SIR 1.25, 95% CI: 0.41-2.91). The findings argue against an infectious or other immunodeficiency-related etiology for FL and clearly differentiate it from diffuse large B-cell lymphoma.

Identifying missed clinical opportunities for the earlier diagnosis of HIV in Australia, a retrospective cohort data linkage study.

BACKGROUND: Treatment as prevention approaches for HIV require optimal HIV testing strategies to reduce undiagnosed HIV infections. In most settings, HIV testing strategies still result in unacceptably high rates of missed and late diagnoses. This study aimed to identify clinical opportunities for targeted HIV testing in persons at risk to facilitate earlier HIV diagnosis in New South Wales, Australia; and to assess the duration between the diagnosis of specific conditions and HIV diagnosis. METHODS: The Australian National HIV registry was linked to cancer diagnoses, notifiable condition diagnoses, emergency department presentations and hospital admissions for all HIV diagnoses between 1993 and 2012 in NSW. Date of HIV acquisition was estimated from back-projection models and people with a likely duration from infection to diagnosis of less than 180 days were excluded. Risk factors associated with clinical opportunities for the earlier diagnosis of HIV were identified. RESULTS: Sexually transmitted infection diagnoses (particularly gonorrhoea and syphilis) and some hospital admissions (mental health and drug-related diagnoses, and non-infective digestive disorder diagnoses) were prominent among people estimated to be living with undiagnosed HIV. The length of time between a clinical opportunity for the earlier HIV diagnosis and actual HIV diagnosis was 13.3 months for notifiable conditions, and 15.2 months for hospital admissions. People with lower CD4+ cell count at diagnosis, and older people were significantly less likely to have a missed opportunity for earlier HIV diagnosis. CONCLUSIONS: Additional targeted clinical HIV testing strategies are warranted for people with gonorrhoea and syphilis; and hospital presentations or admissions for mental health, drug-related and gastrointestinal diagnoses.

HIV incidence in Indigenous and non-Indigenous populations in Australia: a population-level observational study.

BACKGROUND: Australia has set a national target of ending HIV by 2020, achieving this will require the inclusion of priority populations (eg, Indigenous Australians) in strategies to reach elimination. To assist in evaluating the target of elimination, we analysed HIV notification data for Indigenous and non-Indigenous Australians. METHODS: Using the National HIV Registry at The Kirby Institute at UNSW, Sydney, NSW, Australia, we collated and analysed annual HIV notification data for 1996-2015. Patients who were not born in Australia were excluded. We calculated the rates of HIV diagnoses with annual trends in notification rates for Indigenous versus non-Indigenous Australians by demographic characteristics, exposure categories, and stage of HIV at diagnosis. For missing data, assumptions were made and verified through sensitivity analyses. Annual rate ratio (RR) and 4 year summary rate ratio (SRR) trends were calculated to determine patterns of HIV diagnosis in the two populations. FINDINGS: Between Jan 1, 1996, and Dec 31, 2015, 11 492 people born in Australia were reported with a diagnosis of HIV, of whom 461 (4%) were recorded as Indigenous Australians and we classified the remaining 11 031 (96%) as non-Indigenous Australians. For exposure to HIV, among Indigenous Australians a higher proportion of diagnoses occurred among women, and through injecting drug use and heterosexual sex than among non-Indigenous Australians (p<0·0001). Among Indigenous Australians, we found a significantly higher SRR of HIV diagnoses among men in the period 2012-15 than in previous periods (SRR 1·53, 95% CI 1·28-1·83; p<0·0001), and significantly higher diagnosis among Indigenous women (4·92, 4·02-6·02; p<0·0001) for the entire study period than among non-Indigenous women. Concurrently, a decrease in HIV diagnoses of 1% per annum (RR 0·99, 95% CI 0·98-0·99; p<0·0001) across the study period was seen among non-Indigenous people. Indigenous Australians were more likely to be diagnosed at an advanced stage of HIV infection than non-Indigenous Australians (20·8% vs 15·1%; p=0·0088). INTERPRETATION: Greater efforts should be made to include Indigenous people in prevention strategies, particularly newer biomedical interventions, such as scale up of pre-exposure prophylaxis and treatment as prevention initiatives in Australia. More involvement of Indigenous Australians in these approaches is also required to prevent widening of the gap in HIV diagnosis rates between non-Indigenous and Indigenous Australians. FUNDING: None.

A feasible method for linkage studies avoiding clerical review: linkage of the national HIV/AIDS surveillance databases with the National Death Index in Australia.

OBJECTIVE: To assess the sensitivity and specificity of linkage of HIV/AIDS diagnoses in Australia to the National Death Index (NDI). METHODS: An aggregated file containing 19,772 matched HIV/AIDS diagnoses reported to the national HIV/AIDS databases from 1980 to 30 June 2004 was linked to the NDI using probabilistic linkage methods based on the namecode, date of birth, and sex as identifiers. Based on the 6,900 HIV/AIDS known deaths reported by 1 January 2003 and 1,455 known non-deaths with an active follow-up beyond 1 January 2003, the different combinations of weights assigned to matched pairs were examined to obtain maximum sensitivity and specificity. RESULTS: The trade-off between sensitivity and specificity was used to obtain an optimal linkage. The optimal linkage was found to link 5,658 of the 6,900 HIV/AIDS known deaths (a sensitivity of 82%), and 116 false positives of the 1,455 known not deaths (specificity of 92%). Causes of deaths were recorded for 86.5% of deaths that were linked to the NDI. CONCLUSION: This is a feasible method for conducting linkage studies if both the identifying deaths and non-deaths are available. The relatively poor sensitivity could be due to limited identifiers available for linkage on the HIV/AIDS databases.

Concept Inventory Development Reveals Common Student Misconceptions about Microbiology.

Misconceptions, or alternative conceptions, are incorrect understandings that students have incorporated into their prior knowledge. The goal of this study was the identification of misconceptions in microbiology held by undergraduate students upon entry into an introductory, general microbiology course. This work was the first step in developing a microbiology concept inventory based on the American Society for Microbiology's Recommended Curriculum Guidelines for Undergraduate Microbiology. Responses to true/false (T/F) questions accompanied by written explanations by undergraduate students at a diverse set of institutions were used to reveal misconceptions for fundamental microbiology concepts. These data were analyzed to identify the most difficult core concepts, misalignment between explanations and answer choices, and the most common misconceptions for each core concept. From across the core concepts, nineteen misconception themes found in at least 5% of the coded answers for a given question were identified. The top five misconceptions, with coded responses ranging from 19% to 43% of the explanations, are described, along with suggested classroom interventions. Identification of student misconceptions in microbiology provides a foundation upon which to understand students' prior knowledge and to design appropriate tools for improving instruction in microbiology.

Development, Validation, and Application of the Microbiology Concept Inventory.

If we are to teach effectively, tools are needed to measure student learning. A widely used method for quickly measuring student understanding of core concepts in a discipline is the concept inventory (CI). Using the American Society for Microbiology Curriculum Guidelines (ASMCG) for microbiology, faculty from 11 academic institutions created and validated a new microbiology concept inventory (MCI). The MCI was developed in three phases. In phase one, learning outcomes and fundamental statements from the ASMCG were used to create T/F questions coupled with open responses. In phase two, the 743 responses to MCI 1.0 were examined to find the most common misconceptions, which were used to create distractors for multiple-choice questions. MCI 2.0 was then administered to 1,043 students. The responses of these students were used to create MCI 3.0, a 23-question CI that measures students' understanding of all 27 fundamental statements. MCI 3.0 was found to be reliable, with a Cronbach's alpha score of 0.705 and Ferguson's delta of 0.97. Test item analysis demonstrated good validity and discriminatory power as judged by item difficulty, item discrimination, and point-biserial correlation coefficient. Comparison of pre- and posttest scores showed that microbiology students at 10 institutions showed an increase in understanding of concepts after instruction, except for questions probing metabolism (average normalized learning gain was 0.15). The MCI will enable quantitative analysis of student learning gains in understanding microbiology, help to identify misconceptions, and point toward areas where efforts should be made to develop teaching approaches to overcome them.

Drill down with root cause analysis.

Review the structure of an effective critical event analysis and suggestions for completing documentation and maximizing knowledge while protecting your organization from litigation.

"This is not just a little accident": a qualitative understanding of paediatric burns from the perspective of parents.

PURPOSE: To describe the experiences of parents of children admitted to hospital for a burn. METHODS: In-depth interviews were conducted with 21 parents (14 mothers and seven fathers) of children who had sustained a burn requiring hospitalisation. Face-to-face interviews were conducted six months post-burn, in rural, remote and metropolitan areas. The interview guide explored the overall experience of parents and included probing questions exploring the perceptions, thoughts and feelings of participants. Interviews were digitally recorded and transcribed verbatim. Transcripts were analysed according to the seven-step Coliazzi method. Relationships between themes were explored to identify core concepts. RESULTS: Analysis of interview transcripts revealed three phases that describe the parents' journey: experiencing the accident, the in-patient phase and the return to community. Within these phases, themes were identified. Themes represented subthemes of stressors, behavioural and emotional responses and coping factors. CONCLUSION: Findings from this research will allow health professionals to optimise a holistic clinical service from a consumer's perspective at all stages of the burn journey. These research conclusions could be used for the development of protocols to underpin a comprehensive information and social support management plan for families that would complement and support the surgical, medical and therapeutic treatment plan, providing direction for comprehensive service delivery. Implications for Rehabilitation Health professionals should optimise a holistic clinical service from a consumer's perspective taking into consideration all stages of the burn journey. Therapeutic supports are required to target each phase of the burn journey and address changes in coping strategies and behavioural responses. There is a need for the development of protocols to underpin a comprehensive information and social support management plan for families that will complement and support the surgical and medical treatment plan.

Temporal trends of time to antiretroviral treatment initiation, interruption and modification: examination of patients diagnosed with advanced HIV in Australia.

INTRODUCTION: HIV prevention strategies are moving towards reducing plasma HIV RNA viral load in all HIV-positive persons, including those undiagnosed, treatment naïve, on or off antiretroviral therapy. A proxy population for those undiagnosed are patients that present late to care with advanced HIV. The objectives of this analysis are to examine factors associated with patients presenting with advanced HIV, and establish rates of treatment interruption and modification after initiating ART. METHODS: We deterministically linked records from the Australian HIV Observational Database to the Australian National HIV Registry to obtain information related to HIV diagnosis. Logistic regression was used to identify factors associated with advanced HIV diagnosis. We used survival methods to evaluate rates of ART initiation by diagnosis CD4 count strata and by calendar year of HIV diagnosis. Cox models were used to determine hazard of first ART treatment interruption (duration >30 days) and time to first major ART modification. RESULTS: Factors associated (p<0.05) with increased odds of advanced HIV diagnosis were sex, older age, heterosexual mode of HIV exposure, born overseas and rural-regional care setting. Earlier initiation of ART occurred at higher rates in later periods (2007-2012) in all diagnosis CD4 count groups. We found an 83% (69, 91%) reduction in the hazard of first treatment interruption comparing 2007-2012 versus 1996-2001 (p<0.001), and no difference in ART modification for patients diagnosed with advanced HIV. CONCLUSIONS: Recent HIV diagnoses are initiating therapy earlier in all diagnosis CD4 cell count groups, potentially lowering community viral load compared to earlier time periods. We found a marked reduction in the hazard of first treatment interruption, and found no difference in rates of major modification to ART by HIV presentation status in recent periods.

Root cause analysis of prescription opioid overdoses.

Overdoses (ODs) of prescription opioids (RxOs) have become a major public health issue in the United States. OBJECTIVE: To determine the root causes of accidental prescription opioid overdoses (RxO-OD). DESIGN/SETTING/PARTICIPANTS/INTERVENTION: The authors conducted a root cause analysis using the Antecedent Target-Measurement method, interviewing three types of key informants: survivors of RxO-ODs, family members, and clinical experts. RESULTS: Ten survivors, five family members, and three experts were interviewed. Proximal causes of RxO-ODs described by survivors and family members were recent RxO dose escalation (n = 9), polysubstance use (n = 5), and polypharmacy use (n = 3). Proximal causes were elicited by the following six antecedent causes: wanting to feel good/high (n = 9), perceived tolerance to RxO (n = 6), didn't know/believe it was dangerous (n = 5), wanting to reduce psychosocial pain (n = 5), wanting to reduce physical pain (n = 4), and wanting to avoid discomfort due to withdrawal symptoms (n = 4). RxOs involved in the OD were either prescribed by a doctor (n = 7), purchased from a dealer (n = 6), given/purchased from family/friends (n = 3), or stolen from family (n = 1). Psychosocial stressors (n = 9), chronic recurrent depression (n = 3), and chronic substance abuse/addiction (n = 4) were also distal and proximal causes of OD. Experts cited similar causes but added prescriberrelated causes (eg, inadequate training) and healthcare system and culture. CONCLUSIONS: Patients at risk for OD can be identified and ODs potentially prevented. Opportunities for intervention include routine screening of patients using RxOs for psychosocial distress and coping, flagging of high-risk patients, care pathways for high-risk patients, clinician and patient training on OD prevention, and developing abuse-deterrent formulations of RxOs.

Marked improvement in survival following AIDS dementia complex in the era of highly active antiretroviral therapy.

OBJECTIVE: To determine the effect of introduction of highly active antiretroviral therapy (HAART) on survival following AIDS dementia complex (ADC). METHODS: Australian AIDS notification data in the period 1993-2000 were examined. In order to examine the impact of HAART, two periods of AIDS diagnoses were chosen: pre-HAART (1993-1995) and HAART (1996-2000). Median survival was based on Kaplan-Meier estimates, with examination of factors influencing survival in a Cox proportional hazards model. RESULTS: In the period 1993-2000 in Australia, 5017 initial AIDS illnesses were diagnosed among 4351 AIDS patients. The proportion of AIDS cases with ADC increased from 5.2% in 1993-1995 to 6.8% in 1996-2000 (P = 0.029). Median survival following AIDS increased from 19.6 months for those diagnosed with AIDS in 1993-1995 to 39.6 months for those diagnosed in 1996-2000 (P < 0.0005). Median survival following ADC increased to a greater extent than that for all other AIDS illnesses, from 11.9 months in 1993-1995 to 48.2 in 1996-2000 (P < 0.0005). Most striking was the increase in survival among those with ADC and a CD4 cell count < 100 x 10(6) cells/l at diagnosis; 5.1 months in 1993-1995 to 38.5 months in 1996-2000 (P < 0.0005). CONCLUSION: Although there has been a proportional increase in ADC at AIDS diagnosis, survival following ADC has improved markedly in the era of HAART.

Rates of non-AIDS-defining cancers in people with HIV infection before and after AIDS diagnosis.

OBJECTIVE: To describe the incidence of non-AIDS-defining cancers in people with HIV infection before and after the occurrence of AIDS, and to examine the association of cancer risk with immune deficiency. DESIGN: Cohort study involving nation-wide linkage of HIV, AIDS and cancer registry data. METHODS: Association of cancer risk with immune deficiency was examined by analysing cancer risks in four periods between HIV diagnosis, AIDS and death. RESULTS: Linkage identified 196 cases of non-AIDS-defining cancer in 8351 people notified with HIV infection and 8118 registered with AIDS (total of 13 067 individuals). Overall, we found significantly increased rates of cancer of the lip, anus, Hodgkin's disease, myeloma and leukaemia. Of these cancers, in people with HIV infection who did not develop AIDS, or were more than 5 years prior to development of AIDS, only cancer of the anus occurred at increased rates. A significant trend of increasing relative risk of cancer with increasing time since HIV diagnosis was found for Hodgkin's disease and multiple myeloma. CONCLUSIONS: People with HIV with mild immune deficiency prior to AIDS were at increased risk of anal cancer, but this may reflect other risk factors. Other cancers occurred only later in the course of HIV infection. This is reassuring evidence that people with HIV who are only mildly immune deficient may not be at increased risk of non-AIDS-defining cancers, but larger studies with longer periods of follow-up are needed to confirm this.