Nursing, midwifery, and allied health professions research capacities and cultures: a survey of staff within a university and acute healthcare organisation.

BACKGROUND: There is an increasing focus on the development of research capacity and culture in Nursing, Midwifery and Allied Health Professions (NMAHP). However, better understanding of the existing research success and skills, motivators, barriers, and development needs of NMAHP professionals is required to inform this development. This study sought to identify such factors within a university and an acute healthcare organisation. METHODS: An online survey, incorporating the Research Capacity and Culture tool, was administered to NMAHP professionals and students at a university and an acute healthcare organisation in the United Kingdom. Ratings of success/skill levels of teams and individuals were compared between professional groups using Mann-Whitney U tests. Motivators, barriers, and development needs were reported using descriptive statistics. Descriptive thematic analysis was used for open-ended text responses. RESULTS: A total of 416 responses were received (N&M n = 223, AHP n = 133, Other n = 60). N&M respondents were more positive than their AHP counterparts about the success/skill levels of their teams. There were no significant differences between N&M and AHP in their ratings of individual successes/skills. Finding and critically reviewing relevant literature were identified as specific individual strengths; with weaknesses in securing research funding, submitting ethics applications, writing for publication, and advising less experienced researchers. The main motivators for research were to develop skills, increased job satisfaction, and career advancement; whilst barriers included lack of time for research and other work roles taking priority. Key support needs identified included mentorship (for teams and individuals) and in-service training. Open-ended questions generated main themes of 'Employment & staffing', 'Professional services support', 'Clinical & academic management', 'Training & development', 'Partnerships' and 'Operating principles'. Two cross-cutting themes described issues common to multiple main themes: 'Adequate working time for research' and 'Participating in research as an individual learning journey'. CONCLUSIONS: Rich information was generated to inform the development of strategies to enhance research capacity and culture in NMAHP. Much of this can be generic but some nuances may be required to address some specific differences between professional groups, particularly related to perceived team success/skills and priorities identified for support and development.

Patient and Caregiver Experience of Hospital Discharge from an Acute Medicine Unit via the Discharge Lounge: A Qualitative Case Study.

Discharge lounges enable the swift movement of patients imminently awaiting hospital discharge, to free beds without delay. This Qualitative Yin-Style Case Study describes the patient and caregivers experience of transition from an Acute Medicine Unit (AMU) to a discharge lounge and staff perspectives, as organisers of this process. Audiorecorded, interviews and focus groups were undertaken. Data were analysed using Framework Analysis. Lack of patientcenteredness in moving patients to the discharge lounge emerged with three themes: 'moving the problem'; 'being moved' and 'feeling removed'. Patients were transferred at accelerated speed. Communications between staff, patients and carers were abruptly curtailed. Patient transfer from AMU to a discharge lounge is a transitional stage in the acute discharge process and must be adequately communicated.

Initial Safety and Tumor Control Results From a "First-in-Human" Multicenter Prospective Trial Evaluating a Novel Alpha-Emitting Radionuclide for the Treatment of Locally Advanced Recurrent Squamous Cell Carcinomas of the Skin and Head and Neck.

PURPOSE: Our purpose was to report the feasibility and safety of diffusing alpha-emitter radiation therapy (DaRT), which entails the interstitial implantation of a novel alpha-emitting brachytherapy source, for the treatment of locally advanced and recurrent squamous cancers of the skin and head and neck. METHODS AND MATERIALS: This prospective first-in-human, multicenter clinical study evaluated 31 lesions in 28 patients. The primary objective was to determine the feasibility and safety of this approach, and the secondary objectives were to evaluate the initial tumor response and local progression-free survival. Eligibility criteria included all patients with biopsy-proven squamous cancers of the skin and head and neck with either primary tumors or recurrent/previously treated disease by either surgery or prior external beam radiation therapy; 13 of 31 lesions (42%) had received prior radiation therapy. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events version 4.03. Tumor response was assessed at 30 to 45 days at a follow-up visit using the Response Evaluation Criteria in Solid Tumors, version 1.1. Median follow-up time was 6.7 months. RESULTS: Acute toxicity included mostly local pain and erythema at the implantation site followed by swelling and mild skin ulceration. For pain and grade 2 skin ulcerations, 90% of patients had resolution within 3 to 5 weeks. Complete response to the Ra-224 DaRT treatment was observed in 22 lesions (22/28; 78.6%); 6 lesions (6/28, 21.4%) manifested a partial response (>30% tumor reduction). Among the 22 lesions with a complete response, 5 (22%) developed a subsequent local relapse at the site of DaRT implantation at a median time of 4.9 months (range, 2.43-5.52 months). The 1-year local progression-free survival probability at the implanted site was 44% overall (confidence interval [CI], 20.3%-64.3%) and 60% (95% CI, 28.61%-81.35%) for complete responders. Overall survival rates at 12 months post-DaRT implantation were 75% (95% CI, 46.14%-89.99%) among all patients and 93% (95% CI, 59.08%-98.96%) among complete responders. CONCLUSIONS: Alpha-emitter brachytherapy using DaRT achieved significant tumor responses without grade 3 or higher toxicities observed. Longer follow-up observations and larger studies are underway to validate these findings.

Ecological aspects of pain in sensory modulation disorder.

BACKGROUND: Sensory Modulation Disorder (SMD) interferes with the daily life participation of otherwise healthy individuals and is characterized by over-, under- or seeking responsiveness to naturally occurring sensory stimuli. Previous laboratory findings indicate pain hyper-sensitivity in SMD individuals suggesting CNS alteration in pain processing and modulation. However, laboratory studies lack ecological validity, and warrant clinical completion in order to elicit a sound understanding of the phenomenon studied. Thus, this study explored the association between sensory modulation and pain in a daily life context in a general population sample. METHODS: Daily life context of pain and sensations were measured in 250 adults (aged 23-40 years; 49.6% males) using 4 self-report questionnaires: Pain Sensitivity Questionnaire (PSQ) and Pain Catastrophizing Scale (PCS) to evaluate the sensory and cognitive aspects of pain; the Sensory Responsiveness Questionnaire (SRQ) to appraise SMD; and the Short Form - 36 Health Survey, version 2 (SF36) to assess health related Quality of Life (QoL). RESULTS: Thirty two individuals (12.8%) were found with over-responsiveness type of SMD, forming the SOR-SMD group. While no group differences (SOR-SMD vs. Non-SMD) were found, low-to-moderate total sample correlations were demonstrated between the SRQ-Aversive sub-scale and i) PSQ total (r=0.31, p<0.01) and sub-scales scores (r=0.27-0.28, p<0.01), as well as ii) PCS total and the sub-scales of Rumination and Helplessness scores (r=0.15, p<0.05). PSQ total and sub-scale scores were more highly correlated with SRQ-Aversive in the SOR-SMD group (r=0.57-0.68, p=0.03-<0.01) compared to Non-SMD group. The Physical Health - Total score (but not the Mental Health - Total) of the SF36 was lower for the SOR-SMD group (p=0.03), mainly due to the difference in the Body pain sub-scale (p=0.04). CONCLUSIONS: Results suggest that SOR-SMD is strongly associated with the sensory aspect of pain but weakly associated with the cognitive aspect. This indicates that SMD co-occurs with daily pain sensitivity, thus reducing QoL, but less with the cognitive-catastrophizing manifestation of pain perception.

Outcomes of prospectively-collected consecutive cases of antenatal-suspected placenta accreta.

BACKGROUND: Accurate diagnosis of placenta accreta is tentative before surgery. This study developed a predictive score for antenatal diagnosis of placenta accreta through mathematical modeling using clinical signs. METHODS: Antenatal cases of suspected placenta accreta were collected prospectively in a single-site tertiary delivery center. Women with clinical signs of placenta accreta (placenta previa, number of previous cesarean deliveries and/or ultrasound suspicion of placenta accreta) were included. The diagnosis of accreta was confirmed surgically. The primary endpoint was the proportion of surgically-diagnosed placenta accreta among all suspected cases. Logistic regression modeling was performed to assess preoperative risk factors for placenta accreta. The risk score was tested on a receiver operator characteristic curve to identify subjects with placenta accreta and the optimum cut-point was chosen. RESULTS: Over nine years, 92 suspected accreta cases were identified from 46623 deliveries (0.2%). The diagnosis was confirmed at surgery in 52/92 cases (56%) and there were no maternal deaths. Blood transfusion requirements were greater in patients with placenta accreta versus patients without placenta accreta (median 7 [range 0-25, interquartile range 3-10] versus 0 [0-6, 0-2] units of blood, P <0.0001). Area under the curve of the receiver operator characteristic curve was 0.846, with contribution from three variables (placenta previa, number of previous cesarean deliveries and ultrasound suspicion), each with a P value <0.05. From the ROC curve a cut-point with 100% sensitivity and specificity 25% (95% CI 12.69%-41.20%) was achieved, compared with 86.6% sensitivity (95% CI 74.21%-94.41%) and 60.0% specificity (95% CI 43.33%-75.14%) using ultrasound alone. CONCLUSIONS: Combining diagnostic features associated with placenta accreta through mathematical modeling has better positive predictive value than ultrasound alone.

Schizophrenia and birthplace of paternal and maternal grandfather in the Jerusalem perinatal cohort prospective study.

Some forms of epigenetic abnormalities transmitted to offspring are manifested in differences in disease incidence that depend on parent-of-origin. To explore whether such phenomena might operate in schizophrenia spectrum disorders, we estimated the relative incidence of these conditions in relation to parent-of-origin by considering the two grandfathers' countries of birth. In a prospective cohort of 88,829 offspring, born in Jerusalem in 1964-76 we identified 637 cases through Israel's psychiatric registry. Relative risks (RR) were estimated for paternal and maternal grandfathers' countries of birth using proportional hazards methods, controlling for parents' ages, low social class and duration of marriage. After adjusting for multiple observations, we found no significant differences between descendants of maternal or paternal grandfathers born in Iraq, Iran, Turkey, Syria, Yemen, Morocco, Algeria, Tunisia, Libya/Egypt, Poland, USSR, Czechoslovakia, Germany or the USA. Those with paternal grandfathers from Romania (RR=1.9, 95% CI=1.3-2.8) or Hungary (1.6, 1.0-2.6) showed an increased incidence; however, those with maternal grandfathers from these countries experienced reduced incidence (RR=0.5, 0.3-0.8 and 0.4, 0.2-0.8). In post-hoc analyses we found that results were similar whether the comparison groups were restricted to descendants of other Europeans or included those from Western Asia and North Africa; and effects of paternal grandfathers from Romania/Hungary were more pronounced in females, while effects of maternal grandfathers from these countries were similar in males and females. These post-hoc "hypothesis-generating" findings lead one to question whether some families with ancestors in Romania or Hungary might carry a variant or mutation at a parentally imprinted locus that is altering susceptibility to schizophrenia. Such a locus, if it exists, might involve the X chromosome.

Consanguinity and birth defects in the jerusalem perinatal study cohort.

BACKGROUND: While parental consanguinity is known to increase the risk of birth defects in offspring, it is hard to quantify this risk in populations where consanguinity is prevalent. METHODS: To support ongoing studies of cancer and of psychiatric disease, we studied relationships of consanguinity to 1,053 major birth defects in 29,815 offspring, born in 1964-1976. To adjust for confounding variables (geographic origin, social class and hospital), we constructed logistic regression models, using GEE to take into account correlations between sibs. Odds ratios (ORs) and 95% confidence limits were estimated in comparison to a reference group of offspring with grandfathers born in different countries. RESULTS: With 10.1% of offspring having consanguineous parents, the adjusted OR for major birth defect was 1.41 (1.12-1.74). Offspring of marriages between uncles-nieces, first cousins and more distant relatives showed adjusted ORs of 2.36 (0.98-5.68), 1.59 (1.22-2.07) and 1.20 (0.89-1.59) respectively. For descendents of grandfathers born in the same country, but not known to be related, the OR was 1.05 (0.91-1.21); these showed increased risk associated with ancestries in Western Asia (1.27, 1.04-1.55, p < 0.02) or Europe (1.13, 0.79-1.80). CONCLUSIONS: A strong association of consanguinity with poverty and low education points to the need to avoid exposure to environmental hazards in these families.

Gestational diabetes and the risk of breast cancer among women in the Jerusalem Perinatal Study.

Gestational diabetes is becoming increasingly common; it is important to determine how it relates to future risk of disease. We investigated the relation of gestational diabetes to breast cancer in 37,926 women who had one or more live births in 1964-1976 for whom information had been collected on complications of pregnancy. In this cohort there were 1,626 cases of breast cancer reported to the Israel Cancer Registry before January 1, 2005 and 410 cases of gestational diabetes recorded from birth records. There were 29 cases of breast cancer among women diagnosed with gestational diabetes. Using Cox proportional hazards models to control for age and birth order at the first observed birth and other characteristics, we found that the incidence of breast cancer was increased among women diagnosed with gestational diabetes (relative rate = 1.5, 95% confidence interval 1.0-2.1). This effect was seen only among women 50 years and older (relative rate 1.7, 95% confidence interval 1.1-2.5) but not among women <50 (relative rate = 1.0, 95% confidence interval 0.5-2.1). The findings suggest that gestational diabetes may be an important early marker of breast cancer risk among post-menopausal women, but these results need to be confirmed in future studies.

Gestational diabetes as a risk factor for pancreatic cancer: a prospective cohort study.

BACKGROUND: Diabetes is known to be associated with cancer of the pancreas, though there is some debate as to whether it is a cause or a consequence of the disease. We investigated the incidence of pancreatic cancer in a cohort of 37926 Israeli women followed for 28-40 years for whom information on diabetes had been collected at the time they gave birth, in 1964-1976, in Jerusalem. There were 54 cases of pancreatic cancer ascertained from the Israel Cancer Registry during follow-up. METHODS: We used Cox proportional hazards models to adjust for age at baseline and explore effects of other risk factors, including ethnic groups, preeclampsia, birth order and birth weight of offspring. RESULTS: We observed no cases of pancreatic cancer in the women with insulin dependent diabetes; however, there were five cases in the women with gestational diabetes. The interval between the record of diabetes in pregnancy and the diagnosis of pancreatic cancer ranged from 14-35 years. Women with a history of gestational diabetes showed a relative risk of pancreatic cancer of 7.1 (95% confidence interval, 2.8-18.0). CONCLUSION: We conclude that gestational diabetes is strongly related to the risk of cancer of the pancreas in women in this population, and that gestational diabetes can precede cancer diagnosis by many years.

Late fetal death in offspring and subsequent incidence of prostate cancer in fathers: the Jerusalem Perinatal Study cohort.

BACKGROUND: Little is known of the causes of prostate cancer and few previous studies have investigated men's reproductive histories in relation to this disease. We sought to determine whether risk of prostate cancer was altered in men who had fathered stillborn offspring. METHODS: We studied the incidence of prostate cancer (N = 252) in a cohort of 15,268 fathers followed for 28-41 years from the birth of a live offspring, whose wives participated in one of two separate surveys of outcomes of previous births. Proportional hazards models were used to estimate relative risks (RR) associated with previous stillbirths, controlling for changes in incidence over time, social and occupational factors. RESULTS: The 543 men with one or more stillborn offspring experienced an increased risk of prostate cancer (adjusted RR = 1.87, 95% confidence interval = 1.17-3.00, P = 0.0095), compared to men without stillbirths. With one reported stillbirth, the RR was 1.68 (0.99-2.84); with two or more, the RR was 3.29 (1.22-8.88). Results were consistent in men whose wives were interviewed in 1965-1968 and 1974-1976. In 100 fathers with no male offspring and at least one stillbirth the RR was 4.04 (1.87-8.71, P = 0.0004). CONCLUSIONS: These findings should be considered hypothesis-generating and require confirmation in other studies. They suggest that stillbirth and prostate cancer may have shared environmental causes; alternatively, genetic susceptibility to prostate cancer might increase the risk of a stillbirth in offspring.

Risk factors for pre-eclampsia in nulliparous and parous women: the Jerusalem perinatal study.

Pre-eclampsia has been described as a 'disease of first pregnancies' and many believe that its occurrence in a later pregnancy signals a fundamentally different entity. We sought to compare risk factors in first and subsequent pregnancies. We studied 1319 cases of pre-eclampsia recorded in a historical cohort of 82,436 deliveries in Jerusalem in 1964-76. Logistic regression was used to control for covariates. The adjusted odds ratio (OR) for pre-eclampsia in first births was 2.58 (95% confidence interval[CI] 2.23, 2.97), compared with all later birth order groups, between which there were no detectable differences in risk. Other risk factors included increasing maternal age, diabetes (OR 5.64, 95% CI 4.33, 7.35), multiple gestations (OR 3.38, 95% CI 2.54, 4.49), fetal haemolytic disease (OR 2.24, 95% CI 1.43, 3.50) and lower maternal education. The risk of pre-eclampsia was not associated with the mother's employment outside the home and did not differ between immigrants vs. Israeli-born mothers or between groups of women whose fathers had been born in Western Asia, North Africa or Europe. Effects of each risk factor were similar within first and subsequent births. These results lend no support to the hypothesis that there is a fundamental difference between pre-eclampsia in a first pregnancy compared with that occurring in a later pregnancy; conclusions may be moderated, however, by the knowledge that the incidence of pre-eclampsia was low in this historical cohort.

Birthweight and relationship with infant, child and adult mortality in the Jerusalem perinatal study.

There is growing evidence that several chronic adult diseases, such as coronary heart disease and stroke, can result from events occurring in fetal life. The aim of this study was to examine the relation between birthweight and all-cause mortality in young adults. We studied total mortality in a population-based cohort of 80 936 offspring born in Jerusalem in 1964-76. During an average follow-up of 28.8 years 2 324 984 person-years were contributed and 2092 deaths occurred. Overall, in both genders, the univariable and the multivariable Cox-proportional hazard models indicated a strong negative relationship between birthweight and total mortality, mostly because of infant deaths. At ages 1-14 birthweight seemed unrelated to all-cause mortality. In males aged 15+, birthweight was again a significant predictor of death (Hazard ratio (HR) = 0.88, 95% confidence interval (CI) [0.78, 0.99], for 1 standard deviation (SD) increase in birthweight). The analysis by categories suggested a general decreasing of the risk of mortality with increasing birthweight (HRs = 1.0, 1.02, 0.85, 0.77, 0.57 for those belonging to birthweight groups of < 2500 g, 2500-2999 g, 3000-3499 g, 3500-3999 g and > or = 4000 g, respectively). In females aged 15+ there was a J-shaped relation between birthweight and mortality but these associations were not statistically significant. These findings add to a growing body of evidence that events during intrauterine life have remote consequences for adult health and underline the need to consider gender differences.

Seminal fluid analysis in chronic prostatitis/chronic pelvic pain syndrome.

Prostatitis is a common cause of morbidity among adult men. There are more than 2,000,000 doctor visits per year in the United States, approximately half to urologists (Collins et al., 1998, J Urol 159:1224; Roberts et al., 1998, Urology 51:578; Krieger et al., 2003, Urology). The problem is that very few patients have obvious infections, or functional or structural abnormalities. The aim of this study is to examine our experience with seminal fluid analysis in this patient population, and to outline the potential utility of this examination in patient evaluation.

Factors associated with survival in patients with progressive disease following autologous transplant for lymphoma.

Our objectives were to assess survival and predictors for survival among lymphoma patients whose disease had progressed after autologous bone marrow (ABMT) or stem cell transplantation (ASCT). Patients transplanted at Hadassah University Hospital between October 1983 and February 1999 were included. We compared survival of patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) after relapse or progression. Predictors for survival were assessed in a multivariate model. Of 88 transplanted patients with HD and 152 with NHL, relapse/progression occurred in 27 (31%) and 75 (49%), respectively. Median survival postrelapse was 25 months for HD and 7.5 months for NHL (P=0.12). Seven relapsed patients with HD (26%) and 10 (13%) with NHL survived >4 years. In NHL, longer postrelapse survival was associated with indolent histologies (P=0.007). On multivariate analysis, factors associated with survival included attainment of remission postrelapse (for both diseases), use of prophylactic immunotherapy (for HD), LDH level and time from transplant to relapse (for NHL). The short-term prognosis for patients with disease progression postautologous transplant may be somewhat better for HD compared to NHL. Long-term survival is poor in both diseases. However, the survival times in the current study are twice as long as those previously reported. Treatment regimens with the potential for achieving remission may have an impact on survival.

Identifying bipolar disorders in individuals with intellectual disability.

OBJECTIVE: The aim of the present study was to characterize adults with intellectual disability (ID) and concomitant clinical diagnoses of bipolar disorder (BPD), and determine whether DSM-IV criteria would distinguish individuals with BPD from patients with other psychiatric diagnoses. METHODS: A retrospective chart review was done of a convenience sample of adult patients seen over a 3-year period in a specialty clinic for adults with ID and psychiatric disorders. The DSM-IV criteria were used to differentiate individuals with clinical symptoms of BPD from groups of patients with other mood or thought disorders with behavioural symptoms which frequently overlap those of BPD. Behavioural symptoms were also catalogued and used to distinguish the diagnostic groups. RESULTS: Subjects with clinical symptoms of BPD had significantly more DSM-IV mood-related and non-mood-related symptoms, as well as functional impairments, compared to individuals with major depression, depression with psychosis or schizophrenia/psychosis NOS (not otherwise specified). Likewise, behavioural profiles of the BPD group of patients differed significantly from patients in the other three groups. CONCLUSIONS: Bipolar disorder can be readily recognized and distinguished from other behavioural and psychiatric diagnoses in individuals with ID, and DSM-IV criteria can be useful in the diagnosis of BPD.

Bioavailability of omega-3 essential fatty acids from perilla seed oil.

Increased dietary intake of fish oil omega-3 fatty acids, eicosapentanoic acid and docosohexanoic acid, and their precursor, alpha-linolenic acid (ALA), is associated with various health benefits. Enteric-coating (Entrox), which improves stability of omega-3 capsules, has been shown to facilitate fish oil absorption after chronic treatment. To assess the effect of Entrox coating on the short-term bioavailability of ALA administered in the form of ALA-rich Perilla seed oil, 12 healthy subjects (6 males and 6 females) received in a random order Entrox-coated and non-coated ALA formulations, each as a single 6g dose separated by a 3-week washout period. Measurements of plasma ALA concentrations from 0 to 24h showed no difference in ALA pharmacokinetics between the two formulations. However, significantly greater increases in plasma ALA levels from baseline to 24h were observed after ingestion of Entrox vs. non-coated product, suggesting a possible benefit of Entrox with long-term treatment.

Simultaneous anterior-posterior thoracolumbar spine surgery.

The purpose of this article is to report our experience with simultaneous anterior and posterior approach spine surgery. The patient is placed in the decubitus position. Two teams of spine surgeons simultaneously perform surgical approaches, decompression, arthrodesis, and instrumentation. No repositioning, repreparing, or redraping is necessary. Twelve patients with varying lesions underwent this procedure. This technique is presented as an alternative to the sequential single-staged anterior and posterior procedure and the two-staged procedures performed under separate anesthetics. Although no statistical significance can be concluded, we believe a larger series will demonstrate that operative time is decreased, potential risks of repositioning are avoided, and superior exposure and mobilization of spinal elements are afforded. Exposure, decompression, and stabilization posteriorly is feasible in the decubitus position.

Prophylactic perioperative hypogastric artery balloon occlusion in abnormal placentation.

OBJECTIVE: The aim of this paper is to describe and evaluate the technique of prophylactic balloon occlusion of hypogastric arteries in abnormal placentation. Five patients with suspected placenta accreta, placenta percreta, or placenta increta underwent perioperative balloon occlusion of hypogastric arteries after classic cesarean delivery and before hysterectomy with hypogastric artery ligation. Two patients did not require transfusions; of the three who did, the estimated blood loss ranged from 1100 to 4000 mL. CONCLUSION: We conclude that balloon occlusion of the hypogastric arteries is a safe and effective adjunct to cesarean hysterectomy in an attempt to minimize blood loss in patients with abnormal placentation.

A polymorphism in the regulatory region of the CC-chemokine receptor 5 gene influences perinatal transmission of human immunodeficiency virus type 1 to African-American infants.

There are natural mutations in the coding and noncoding regions of the human immunodeficiency virus type 1 (HIV-1) CC-chemokine coreceptor 5 (CCR5) and in the related CCR2 protein (the CCR2-64I mutation). Individuals homozygous for the CCR5-Delta32 allele, which prevents CCR5 expression, strongly resist HIV-1 infection. Several genetic polymorphisms have been identified within the CCR5 5' regulatory region, some of which influence the rate of disease progression in adult AIDS study cohorts. We genotyped 1,442 infants (1,235 uninfected and 207 HIV-1 infected) for five CCR5 and CCR2 polymorphisms: CCR5-59353-T/C, CCR5-59356-C/T CCR5-59402-A/G, CCR5-Delta32, and CCR2-64I. The clinical significance of each genotype was assessed by measuring whether it influenced the rate of perinatal HIV-1 transmission among 667 AZT-untreated mother-infant pairs (554 uninfected and 113 HIV-1 infected). We found that the mutant CCR5-59356-T allele is relatively common in African-Americans (20.6% allele frequency among 552 infants) and rare in Caucasians and Hispanics (3.4 and 5.6% of 174 and 458 infants, respectively; P < 0.001). There were 38 infants homozygous for CCR5-59356-T, of whom 35 were African-Americans. Among the African-American infants in the AZT-untreated group, there was a highly significant increase in HIV-1 transmission to infants with two mutant CCR5-59356-T alleles (47.6% of 21), compared to those with no or one mutant allele (13.4 to 14.1% of 187 and 71, respectively; P < 0.001). The increased relative risk was 5.9 (95% confidence interval, 2.3 to 15.3; P < 0.001). The frequency of the CCR5-59356-T mutation varies between population groups in the United States, a low frequency occurring in Caucasians and a higher frequency occurring in African-Americans. Homozygosity for CCR5-59356-T is strongly associated with an increased rate of perinatal HIV-1 transmission.