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Estimating intervention effects in longitudinal studies.

Longitudinal studies aimed at assessing the impact of interventions on disease risk factors often confront several statistical problems. These problems include 1) dependent variables measured by ordered categories, 2) numerous potentially relevant patterns of transition between outcome levels, 3) mixed units of analysis (e.g., assignment by social unit while theorizing in terms of individuals), 4) incomplete randomization, and 5) correlated estimates for successive occasions of longitudinal measurement. Longitudinal data on use of cigarettes, alcohol, and marijuana among adolescents (n = 1,244, complete data) from the Midwestern Prevention Project are used to demonstrate solutions to each of these problems: 1) a proportional odds regression model, 2) conditional logistic models of transitions with interactions between baseline level and intervention effect, 3) a logistic model estimated with linear regression methods on measures aggregated by social unit, 4) conditional and unconditional models of effect magnitude, and 5) a repeated measures logistic regression technique. Panel data fit to the various models yielded the following conclusions concerning intervention effects in the Midwestern Prevention Project: reduction in the prevalence of cigarette users in treatment schools compared with control schools (8% vs. 18% smoked in the last week at one year follow-up), mixed evidence of an effect on marijuana use, and no evidence of an effect on alcohol use.

Adolescent↗

Earthquake and coronary heart disease risk factors: a longitudinal study.

The longitudinal association between a number of coronary heart disease risk factors and the experience of a natural disaster (earthquake) was analyzed in a group of workers participating in a longitudinal epidemiologic investigation. The 5-year follow-up examination was interrupted by a major earthquake, and examinations were resumed 2 weeks after the quake. Participants screened after the quake had, on average, higher heart rates, serum cholesterol, and triglycerides than participants examined before the quake; these differences were independent from the coronary heart disease risk factor values measured 5 years previously during the baseline examination. The data collected during the 12-year examination indicated that the observed short-term increase in serum lipids and heart rate was not present long-term (7 years after the quake). These longitudinal data indicate that exposure to a natural disaster can be associated with short-term increases in heart rate, serum cholesterol, and triglycerides but that there is no apparent long-term effect on these coronary heart disease risk factors.

Adult↗

Male and female fertility and hatchability in chickens: a longitudinal mixed model approach.

The objective of the current study was to investigate different approaches for handling missing records and to develop and implement a multivariate longitudinal mixed model for the genetic evaluation of male and female fertility and hatchability in chickens. The traits recorded on a weekly basis were eggs set (E), percentage fertility (F), and percentage hatch of fertile eggs (H). Three approaches for handling missing records were investigated: 1) all records with zero weekly laid eggs were removed and remaining records with missing F and H were predicted (M1); 2) missing records, including zero weekly laid eggs, were assumed known and equal to zero (M2); and 3) zero weekly laid eggs were assumed as a valid record and missing F and H were predicted (M3). A longitudinal mixed model was used for the multiple trait analysis of E, F, and H. Fixed effects included week-flock, age of service sire (rooster in the pen at data collection), and age of hen. Unrelated service sire, additive hen, permanent environmental, and the residual term were included as random effects. Heritability estimates ranged from 0.06 to 0.13 for E, F, and H. Heritability estimates of F and H were overestimated using M2. Correlations among the 3 traits were highest using M2 and lowest using M1. Pearson correlations indicated that reranking of birds and service sires could occur when using M1. Therefore, M1 should not be used for the analysis of longitudinal data of fertility and hatchability in chickens. Furthermore, M3 seems to be the most ideal method for handling missing records.

Analysis of Variance↗

What the Cuban context provides health researchers: the feasibility of a longitudinal multi-method study of the impact of housing improvements on health in Havana, Cuba.

BACKGROUND: From extensive participatory research in inner city communities in Central Havana, Cuba, we found housing to be the largest perceived source of health risk. The objective of this study, therefore, was to ascertain the feasibility of conducting a multi-method longitudinal evaluation of the impact of housing improvements on health. METHODS: Meetings with community and governmental stakeholders were held; housing policy documents were reviewed; key informants were interviewed; decisions were made by a collaborative interdisciplinary team regarding measurement instruments for health as well as housing quality; training was conducted for use of new measurement tools; and a 3 month multi-method trial with repeated measures was conducted on individuals in good housing and poor housing in the inner city of Central Havana. Questionnaires were administered at monthly intervals for 3 months to 25 adults living in good housing and 25 in poor housing. RESULTS: Cuba's housing policies made it easy to identify a suitable cohort and control group for possible longitudinal study. Consent to participate was enthusiastically obtained, and no difficulties were encountered in collecting or analysing the data. Housing quality measurements were conducted using validated instruments with minimal difficulties. There was strong community involvement and support for a comprehensive longitudinal study. CONCLUSION: Cuba, although a poor country, has the necessary infrastructural support and capacity to make it an excellent site for health and housing intervention studies.

Adult↗

Longitudinal change in food habits between adolescence (11-12 years) and adulthood (32-33 years): the ASH30 Study.

BACKGROUND: Links between diet in childhood and the prevention of disease in adulthood have been established. This longitudinal dietary survey provided quantitative evidence of dietary change from adolescence to adulthood, in Northumberland, England. OBJECTIVE: To report longitudinal dietary change in 198 respondents between the ages of 12 and 33 years, to explore dietary 'tracking' between the same time points and to describe the effects of gender, socio-economic status and location on dietary change. METHODS: A longitudinal study recorded dietary change from adolescence to adulthood. Two 3-day food diaries were collected in 1980 and 2000 from the same 198 respondents. Foods consumed were assigned to the five categories in the Balance of Good Health (BGH). Demographic and socio-economic information were obtained in 1980 and 2000. RESULTS: Intakes of foods containing fat and/ or sugar and milk and dairy foods decreased (p < 0.01 and p < 0.031, respectively), while intakes of fruits and vegetables increased (p < 0.01). Intakes of bread, other cereals and potatoes (p = 0.002, r = +0.219); fruits and vegetables (p < 0.01, r = +0.256) and meat, fish and alternatives (p = 0.026, r = +0.158) 'tracked' from adolescence to adulthood. Men had increased intake from meat, fish and alternatives and decreased milk and dairy foods more than female respondents (p = 0.003 and p = 0.019). Respondents who had moved away from Northumberland had a greater increase in intake of fruits and vegetables compared with those who remained in the local (p = 0.010). Individuals who had moved to a lower socio-economic group had increased their intake of bread, other cereals and potatoes (p = 0.040). CONCLUSION: Food intake changed considerably in a direction more in the line with current dietary recommendations. Food intake in adolescence was a significant, but not strong, predictor of intake in adulthood. Dietary change is influenced by variables including gender, location and socio-economic status.

Adult↗

A pilot randomized, controlled trial of a longitudinal residents-as-teachers curriculum.

PURPOSE: To determine whether a longitudinal residents-as-teachers curriculum improves generalist residents' teaching skills. METHOD: From May 2001 to February 2002, 23 second-year generalist residents in four residencies affiliated with the University of California, Irvine, College of Medicine, completed a randomized, controlled trial of a longitudinal residents-as-teachers program. Thirteen intervention residents underwent a 13-hour curriculum during one-hour noon conferences twice monthly for six months, practicing teaching skills and receiving checklist-guided feedback. In a 3.5-hour, eight-station objective structured teaching examination (OSTE) enacted and rated by 15 senior medical students before and after the curriculum, two trained, blinded raters independently assessed each station with detailed, case-specific rating scales (rating scale reliability = 0.96, inter-rater reliability = 0.78). RESULTS: The intervention and control groups were similar in academic performance, specialty distribution, and gender (chi(2) = 0.434, p =.81). On a five-point Likert scale (5 = best teaching skills), intervention and control residents showed similar mean pretest OSTE scores (2.83 vs. 2.88, p =.736). The intervention group improved their mean overall OSTE scores 22.3% (more than two standard deviations) from 2.83 (pretest) to 3.46 (post-test; p <.0005; 95% CI 0.53 to 0.72). Intervention residents also improved significantly on six of eight OSTE stations. Within the control group, no pretest-to-post-test change achieved statistical significance. Mann-Whitney and Wilcoxon signed-rank tests confirmed these results. CONCLUSIONS: Generalist residents randomly assigned to receive a 13-hour longitudinal residents-as-teachers curriculum consistently showed improved OSTE scores. Future research should clarify which aspects of residents-as-teachers curricula most effectively improve educational outcomes.

California↗

Anterior floating method for cervical myelopathy caused by ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament lessens the sagittal diameter of the cervical canal and compresses the spinal cord anteriorly, and may produce severe disabling myelopathy. The anterior floating method is one of the anterior decompression and reconstructions used in the treatment of cervical myelopathy caused by ossification of the posterior longitudinal ligament. This procedure consists of subtotal resection of vertebral bodies and discs, with slight thinning and release of the ossified ligament using air instrumentation. This is followed by reconstruction of the cervical spine using autogenous strut bone graft accompanied by postoperative application of a halo vest. This method is indicated for patients who present with moderate or severe myelopathies, and especially in those where the canal narrowing ratio exceeds 60%. This radical procedure causes decompression of the spinal cord and restores its function by enlarging the neural canal with anterior migration of the ossified ligament. The procedure minimizes the extent of surgical invasions and avoids damage to the neural tissue, because it does not require the removal of the ossification of the posterior longitudinal ligament. It also stops postoperative regrowth of the ossification. The operative results with long term followup indicate a 71% average recovery rate based on the criteria established by the Japan Orthopedic Association.

Adult↗

Hearing levels of firefighters: risk of occupational noise-induced hearing loss assessed by cross-sectional and longitudinal data.

OBJECTIVE: It is well known that firefighters face serious risk to their health and safety in the performance of their duties. To determine whether individuals who work as firefighters sustain occupational noise-induced hearing losses, we evaluated results of hearing tests completed by firefighters and compared them with age-matched, non-occupationally exposed groups of individuals. DESIGN: The results of annual audiometric testing and a related questionnaire collected as part of a company-wide hearing conservation program were obtained from two large urban fire departments. The records from 12,609 tests conducted over an 11-year period were evaluated. Hearing levels obtained from the tests were compared with age-matched control populations from an American national standard, and a longitudinal study comparing the rate of hearing loss to that expected due to presbycusis alone was conducted. RESULTS: Comparisons of the data to the national standard indicated that firefighters do not exhibit excessive loss of hearing compared with age-matched, non-occupationally exposed control subjects. The longitudinal study that examined the regression of firefighters' hearing with age compared with the expected presbycasic regression function indicated that the hearing of firefighters in the study declined over the 7-year period at a rate that was less than that expected due to age alone. CONCLUSIONS: The results of this large-scale, cross-sectional, and longitudinal study indicate that firefighters are not at risk for occupational noise-induced hearing loss, even though they work nonstandard shifts and are occasionally exposed to high levels of noise. The results are consistent with the findings but not the conclusions of several other studies of firefighters' hearing.

Adult↗

Influence of prenatal cocaine exposure on early language development: longitudinal findings from four months to three years of age.

The influence of prenatal cocaine exposure on children's language functioning was evaluated longitudinally at six time points from 4 months to 3 years of age. The Miami Prenatal Cocaine Study prospectively enrolled 476 full-term African-American infants at birth, categorized as cocaine-exposed (n = 253) or non-cocaine-exposed (n = 223) by maternal self-report and bioassays (maternal/infant urine, meconium). The Bayley Scales of Infant Development, scored using the Kent Scoring Adaptation for language, was administered at 4, 8, 12, 18, and 24 months. The Clinical Evaluation of Language Fundamentals-Preschool was administered at 3 years. In longitudinal analyses using Generalized Estimating Equations, cocaine-exposed children had lower overall language skills than non-cocaine-exposed children (D = -0.151; 95% CI = -0.269, -0.033; p =.012). Longitudinal findings remained stable after evaluation of potential confounding influences including other prenatal substance exposures and sociodemographic factors. Preliminary evidence also indicated possible mediation through an intermediary effect involving cocaine-associated deficits in fetal growth.

Case-Control Studies↗

The PedsQL in pediatric cancer pain: a prospective longitudinal analysis of pain and emotional distress.

The objective of this prospective study was to investigate the cross-sectional and longitudinal associations between pain and emotional distress in children and adolescents with cancer as measured by the Pediatric Quality of Life Inventory (PedsQL) Emotional Functioning and Pain Scales. The PedsQL 1.0 Generic Core Scales are multidimensional scales developed as the generic core measure to be integrated with the PedsQL Disease-Specific Modules. The PedsQL 1.0 Cancer Module was designed to measure pediatric cancer-specific health-related quality of life. The PedsQL Generic Core Scales, Emotional Functioning Scale and Cancer Module Pain Scale, were administered to 69 children and 59 adolescents and their parents at Time 1 and Time 2, which was 6 months on average after Time 1. Prospective hierarchical multiple regression analyses supported a longitudinal predictive model with Time 1 pain predicting Time 2 pain and Time 1 emotional distress predicting Time 2 emotional distress, respectively. Time 1 emotional distress did not predict Time 2 pain, and Time 1 pain did not predict Time 2 emotional distress. The results demonstrate that pediatric cancer pain and emotional distress, although associated cross-sectionally, are differentially predictive in prospective longitudinal analyses. These results suggest that both pain and emotional distress should be targeted for treatment interventions concurrently to enhance long-term health-related quality of life of the pediatric patient with cancer.

Adolescent↗

Interaction between the C(-344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study.

OBJECTIVE: To study the interaction between the C(-344)T polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. DESIGN: Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy. SETTING: Medical centre of the Olivetti factories. PARTICIPANTS: In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. MAIN OUTCOME MEASURES: Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. RESULTS: In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic ( P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P<0.001 and TC, P= 0.005), but not in CC homozygotes ( P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 +/- 0.6, versus CC: -0.4 +/- 1.5 mmHg, P= 0.04). CONCLUSION: Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.

Aging↗

Longitudinal assessment of quality of life in acute psychiatric inpatients: reliability and validity.

This study examined the reliability, validity, and responsiveness of Lehman's Quality of Life Interview (QOLI) as an outcome measure on 981 acutely ill psychiatric inpatients assessed longitudinally at admission and discharge. Patients were stratified into five diagnostic (DX) (depressed bipolar, depressed unipolar, schizophrenia, mania, and other diagnoses) and two substance use disorder (SA) strata (with and without concurrent substance abuse/dependence) based on DSM-III-R criteria. There was good replication of the factor structure, excellent internal consistency, overall and within DX and SA groups. Intercorrelations showed that the functional and satisfaction indices measure unique aspects of the quality of life. The construct consistency of the QOLI was dependent upon psychiatric diagnosis and life domain. Intercorrelations of functional and satisfaction indices for patients with depression were greater than for manic patients. We demonstrated strong consistency of construct validity for family and social relation domains, but not safety or leisure activities. Construct validity was shown to hold longitudinally. Analyses of DX and SA group differences on satisfaction and functional indices of the 8 life domains supported discriminative validity: Depressed patients reported the most dissatisfaction, followed by schizophrenic patients, and manic patients reported the greatest satisfaction in most life domains. Patients with concurrent substance abuse generally reported less satisfaction and lower quality of life than patients without a dual diagnosis. Examination of longitudinal changes in satisfaction indicated the QOLI is responsive to changes in global life, leisure activities, living situation, and social relations from hospital admission to discharge (an average of 2 weeks). This study supports the use of the QOLI as an outcome measure to assess quality of life in acutely ill hospitalized psychiatric patients.

Activities of Daily Living↗

Longitudinal evaluation of professional nursing practice redesign.

OBJECTIVES: The authors describe a 5-year study at a western university teaching hospital that evaluated the effect of organizational redesign on nurse job satisfaction, autonomy, and patient satisfaction. BACKGROUND: Change in institutional status from public to private authority stimulated this hospital to map a new direction for professional nursing practice, to strengthen autonomy and job satisfaction while improving quality care outcomes. Evaluating redesign changes systematically provided significant longitudinal trended data to guide nurse executive actions. METHODS: Phase-I evaluation, from 1992 to 1995, was a quasi-experimental design comparing pre- and poststudy outcomes of facilitator-led activities on units receiving interventions compared with control units. Of 12 outcome variables measured, 3 were sustained longitudinally into Phase II: nursing job satisfaction using the McCloskey Mueller Satisfaction Scale (MMSS), autonomy using Schutzenhofer's Scale, and patient satisfaction using the Picker Institute survey. Data were trended across units and departments over a 5-year period. RESULTS: Phase-I results reported that control units held higher nursing documentation scores than the experimental units. There were no significant differences in aggregate nurse job satisfaction scores. Nurse autonomy scores significantly improved. Other results are reported descriptively. Phase II continued the evaluation, reporting no differences in nurse job satisfaction aggregate scores a decline in autonomy, and decreased patient satisfaction scores. There were significant differences by units and across departments. CONCLUSIONS: Longitudinal evaluation provides significant data to guide nurse executives in an uncertain healthcare environment. Of theoretical interest is the absence of congruence in nurse job satisfaction and autonomy scores, suggesting more independence between these variables than previously reported.

Colorado↗

Longitudinal follow-up of exocrine pancreatic function in pancreatic sufficient cystic fibrosis patients using the fecal elastase-1 test.

BACKGROUND: A progressive decline in pancreatic function is possible in cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. The secretin-cholecystokinin test is invasive and not acceptable as a repeatable procedure for children. Steatorrhea, conversely, has low sensitivity. Therefore, the aim of the present study was to evaluate the usefulness of the noninvasive fecal elastase-1 (E1) test for the longitudinal assessment of exocrine pancreatic function (EPF) in pancreatic-sufficient (PS) CF patients. METHODS: One hundred eighty-four CF patients were included in the study. In all subjects, E1 concentrations and fecal fat excretion were measured. PS patients were followed for 5 years. RESULTS: At the beginning of the study, 35 (19.0%) CF patients were PS, and 32 (17.4%) had normal E1 concentrations. Longitudinal measurements of E1 concentrations in PS patients with CF demonstrated stable enzyme output in 27 and gradual decrease in 8. The decrease was rapid in five infant patients and gradual in three older patients. The decrease of E1 concentrations preceded the appearance of steatorrhea in all eight subjects. CONCLUSIONS: The decline of EPF in patients with CF appears more frequently during the first months and years of life. However, late PS to pancreatic-insufficient (PI) conversion is also possible. The appearance of maldigestion is preceded by the decrease of fecal E1 concentration. Thus, the fecal E1 test is a helpful screening tool for the longitudinal assessment of declining EPF in PS patients with CF to demonstrate pancreatic deterioration. In suspected patients, fecal fat excretion should be assessed.

Adolescent↗

Factors differentiating dropouts from completers in a longitudinal, multicenter clinical trial.

BACKGROUND: Subject dropout from a prospective, longitudinal trial can produce biases in the remaining sample that affect study findings and their interpretation, yet little is known about factors contributing to dropout. OBJECTIVE: To determine characteristics differentiating those who complete from those who drop out of a longitudinal multicenter clinical trial. METHODS: In this study, 578 parents and other caretakers of infants at risk for cardiopulmonary arrest enrolled in a longitudinal trial investigating the psychosocial impact of cardiopulmonary resuscitation training. In this secondary analysis, the baseline sociodemographic, emotional, psychosocial, and infant characteristics of those who dropped from the trial were compared with those who completed the study. RESULTS: The study was completed by 60% (n = 347) of the participants. Those most likely to drop out were fathers or other caretakers (vs. mothers) employed outside the home who spoke English (vs. Spanish); were assigned to an experimental group (vs. a control group); had higher levels of depression, hostility, and overall psychosocial distress; and held negative views about health care. CONCLUSION: Although a few sociodemographic characteristics differentiated dropouts from completers, personal, emotional and psychosocial factors were the predominant predictors of dropouts. Other reputed sources of retention difficulties (e.g., income, education, minority status, lack of social support, or problems with family functioning) did not predict dropout.

Adult↗

Longitudinal changes in trunkal balance after selective fusion of King II curves in adolescent idiopathic scoliosis.

STUDY DESIGN: A retrospective study was performed on the longitudinal changes of the trunkal balance in King II curves treated with selective posterior fusion of the thoracic curve. OBJECTIVES: To determine the effect of selective fusion on the coronal and sagittal plane balance in King II adolescent idiopathic scoliosis by analyzing the changes in shoulder level, pelvic tilt, trunk shift, centering of fusion mass, changes in the T11-L1 sagittal angle, and behavior of the unfused lumbar curve and its correlation with the end level of fusion. SUMMARY OF BACKGROUND DATA: It has been shown that selective fusion of the thoracic curve in a King II curve is associated with good results and arrest of lumbar curve progression in selected cases. Detailed quantitative analysis of the longitudinal changes and correlation between various clinical and radiologic parameters was not readily available in the literature. METHODS: This study investigated 24 patients with King II adolescent idiopathic scoliosis treated with Harrington rod and segmental spinous processes wiring in a 10-year period with follow-up periods of 3 to 8 years. Clinical and radiologic parameters were analyzed longitudinally during the preoperative and immediate postoperative period, then at 6 months, 1 year, 3 years, and final follow-up assessment. RESULTS: Progressive improvement in the trunk shift to within 2 cm of the center sacral line together with progressive leveling and stabilization of the shoulder and pelvic tilt was noted during the first year after surgery. Gradual movement of the Harrington rod toward the center sacral line assuming a "straight rod sign" with a rod to center line distance of less than 1 cm was found in 90% of the cases. Improvement of the sagittal alignment with no significant residual junctional kyphosis also was found. The unfused lumbar curve improved in both the coronal and sagittal plane and did not show any further progression. Patients whose lower end level of fusion was at T12 had a better percentage of lumbar curve correction than those that ended at L1. CONCLUSIONS: Selective thoracic fusion for King II idiopathic scoliosis curve can achieve acceptable coronal and sagittal plane balance of the spine. The rod to centersacral line distance is a helpful parameter in assessing the results and prognosis of surgically treated patients.

Adolescent↗

Longitudinal changes in lung function associated with aspects of swine-confinement exposure.

Several aspects of swine-confinement farming appear to be leading to adverse respiratory effects. This study was set up in a longitudinal design to study the association between certain characteristics of farms or the way they are run and a decline in lung function. A cohort of 171 pig farmers was observed for 3 years. Lung function was measured. Exposure to farm characteristics was determined at the start of the observation period, using data from standardized farm surveys and from diaries kept by the participants. Mean decline in lung function was 73 mL/year for forced expiratory volume in 1 second (FEV1) and 55 mL/year for forced vital capacity (FVC). A longitudinal decline in FEV1 was significantly associated with the use of quaternary ammonium compounds as disinfectants (an additional 43 mL/year) and also with the use of an automated dry feeding system (an additional 28 mL/year). The association with the use of wood shavings as bedding material was not statistically significant. The impact of these characteristics in a longitudinal study provides stronger evidence for causal inference than that shown in previous cross-sectional designs. This may be useful in promoting preventive measures.

Adult↗

Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. BACKGROUND: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. DESIGN: Systematic review and meta-analysis of longitudinal studies. METHODS: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. RESULTS: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. CONCLUSIONS: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.

Female↗