Herpes zoster incidence in a multicenter cohort of solid organ transplant recipients

S.A. Pergam, C.W. Forsberg, M.J. Boeckh, C. Maynard, A.P. Limaye, A. Wald, N.L. Smith, B.A. Young. Herpes zoster incidence in a multicenter cohort of solid organ transplant recipients.
Transpl Infect Dis 2011: 13: 15–23. All rights reserved Background. Immunosuppressed patients are at increased risk for herpes zoster (HZ), but incidence in solid organ transplant (SOT) recipients has varied in multiple studies. To assess incidence of HZ, we examined patients who underwent SOT and received follow‐up care within the large multicenter US Department of Veteran's Affairs healthcare system. Methods. Incident cases of HZ were determined using ICD‐9 coding from administrative databases. A multivariable Cox proportional hazards model, adjusted for a priori risk factors, was used to assess demographic factors associated with development of HZ. Results. Among the 1077 eligible SOT recipients, the cohort‐specific incidence rate of HZ was 22.2 per 1000 patient‐years (95% confidence interval [CI], 18.1–27.4). African Americans (37.6 per 1000 [95% CI, 25.0–56.6]) and heart transplants recipients (40.0 per 1000 [95% CI, 23.2–68.9]) had the highest incidence of HZ. Patients transplanted between 2005 and 2007 had the lowest incidence (15.3 per 1000 [95% CI, 8.2–28.3]). In a multivariable model, African Americans (hazard ratio [HR] 1.88; 95% CI: 1.12, 3.17) and older transplant recipients (HR 1.13; 95% CI: 1.01, 1.27 [per 5‐year increment]) had increased relative hazards of HZ. Conclusions. These data demonstrate that HZ is a common infectious complication following SOT. Future studies focused on HZ prevention are needed in this high‐risk population.     

The world‐wide incidence of Kaposi's sarcoma in the HIV/AIDS era

Objectives

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunosuppression or immunodeficiency. Consequently, KS is one of the most common cancers in HIV‐infected individuals and frequently occurs among transplant recipients. Nevertheless, its incidence in different populations is not well understood.

Methods

We searched online databases for publications on KS incidence. A random‐effect meta‐analysis was performed to combine the KS incidences and incidence rate ratios (IRRs) for associated risk factors.

Results

Seventy‐six eligible studies representing 71 time periods were included. For HIV‐infected people, the overall KS incidence was 481.54 per 100 000 person‐years with a 95% confidential interval (CI) of 342.36–677.32 per 100 000 person‐years. HIV‐infected men who have sex with men (MSM) had the highest incidence of KS (1397.11 per 100 000 person‐years; 95% CI 870.55–2242.18 per 100 000 person‐years). The incidence of KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI 1.70–5.62). People receiving highly active antiretroviral therapy (HAART) had a lower incidence compared with people who had never received HAART (IRR 6.57; 95% CI 1.91–24.69). The incidence of KS was 68.59 (95% CI 31.39–149.86) per 100 000 person‐years in transplant recipients, 52.94 (95% CI 39.90–70.20) per 100 000 person‐years in children with HIV infection, and 1.53 (95% CI 0.33–7.08) per 100 000 person‐years in the general population.

Conclusions

Globally, a relatively high incidence of KS was found among HIV‐seropositive people and, in particular, in HIV‐infected MSM. The introduction of HAART has largely prevented the development of KS, but it has not entirely removed the challenge of KS. In Africa, in particular, KS imposes a very heavy disease burden, which can mainly be attributed to the high prevalence of KS‐associated herpesvirus and poor access to HAART.

     

Pseudomonas aeruginosa bacteremia over a 10-year period: multidrug resistance and outcomes in transplant recipients

Abstract: Aim. Transplant recipients are at risk for hospital‐acquired infections (HAIs), including those caused by Pseudomonas aeruginosa. Of all HAIs, bloodstream infection (BSI) remains one of the most life‐threatening. Methods. Over a 10‐year period, we studied 503 patients, including 149 transplant recipients, with pseudomonal BSI from the University of Pittsburgh Medical Center. Trends in antimicrobial susceptibility, risk factors for multidrug resistance (MDR), and outcomes were compared between transplant and non‐transplant patients. Results. Resistance to all antibiotic classes was significantly greater in pseudomonal blood culture isolates from transplant compared with non‐transplant patients (P<0.001). Of isolates from transplant recipients (n=207), 43% were MDR, compared with 18% of isolates from non‐transplant patients (n=391) (odds ratio [OR] 3.47; 95% confidence interval [CI] 2.34–5.14, P<0.001). Among all patients, independent risk factors for MDR P. aeruginosa BSI included previous transplantation (OR 2.38; 95% CI 1.51–3.76, P<0.001), hospital‐acquired BSI (OR 2.41; 95% CI 1.39–4.18, P=0.002), and prior intensive care unit (ICU) admission (OR 2.04; 95% CI 1.15–3.63, P=0.015). Mortality among transplant recipients was 42%, compared with 32% in non‐transplant patients (OR 1.55; 95% CI 0.87–2.76, P=0.108). For transplant recipients, onset of BSI in the ICU was the only independent predictor of mortality (OR 8.00; 95% CI 1.71–37.42, P=0.008). Conclusions. Transplant recipients are at greater risk of MDR P. aeruginosa BSI, with an appreciable mortality. Future management must concentrate on the implementation of effective preventative strategies.     

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis

M.G.J. de Boer, F.P. Kroon, S. le Cessie, J.W. de Fijter, J.T. van Dissel. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.
Transpl Infect Dis 2011: 13: 559–569. All rights reserved Abstract: Risk stratification‐based duration of trimethoprim‐sulfamethoxazole (TMP‐SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence‐based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time‐matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni‐ and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3–5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1–17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2–7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9–18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients – and during the first year posttransplantation for patients >55 years of age or those treated for rejection – would result in very low PCP incidence and optimal avoidance of TMP‐SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.     

Umbilical cord blood transplantation in adults with advanced hodgkin's disease: high incidence of post‐transplant lymphoproliferative disease

We report the outcome of 30 consecutive patients with Hodgkin disease (HD) who underwent single‐unit UCBT. Most (90%) patients had failed previous autologous hematopoietic stem cell transplantation. The conditioning regimens were based on combinations of thiotepa, busulfan, cyclophosphamide or fludarabine, and antithymocyte globulin. The cumulative incidence (CI) of myeloid engraftment was 90% [95% confidence interval (C.I.), 74–98%] with a median of 18 d (range, 10–48). CI of acute graft‐versus‐host disease (GvHD) grades II–IV was 30% (95% C.I., 17–44%), while the incidence of chronic GVHD was 42% (95% C.I., 23–77%). The non‐relapse mortality (NRM) at 100 d and 4 yr was 30% (95% C.I., 13–46%) and 47% (95% C.I., 29–65%), respectively. EBV‐related post‐transplant lymphoproliferative disease (EBV‐PTLD) accounted for more than one‐third of transplant‐related death, with an estimate incidence of 26% (95% C.I., 9–44). The incidence of relapse at 4 yr was 25% (95% C.I., 9–42%). Four‐year event‐free survival (EFS) and overall survival (OS) were 28% and 30%, respectively. Despite a high NRM and an unexpected high incidence of EBV‐PTLD, UCBT in heavily pretreated HD patients is an option for patients lacking a suitable adult donor, provided the disease is not in refractory relapse.     

Temporal trend and risk determinants of hepatocellular carcinoma in chronic hepatitis B patients on entecavir or tenofovir

This study aimed to elucidate the temporal change and determinants for the risk of HCC in patients with chronic hepatitis B continuously receiving NUC. Through analysis of the national healthcare database in Taiwan, we screened a total of 65 426 infected patients receiving entecavir or tenofovir for at least 3 months and excluded those with lamivudine, adefovir or telbivudine exposure, malignancy, end‐stage renal failure or a diagnosis of HCC within 3 months of starting treatment. Eligible patients (N = 27 820) were followed until HCC occurrence, completion of the allowed 3‐year regimen or 31 December 2013. During a median follow‐up of 25.1 (12.1‐35.6) months, 802 patients developed HCC, with 1‐, 2‐ and 3‐year cumulative incidence of 1.82% (95% CI, 1.66‐1.99%), 3.05% (95% CI, 2.82‐3.28%) and 4.06% (95% CI, 3.77‐4.36%), respectively. HCC annual incidence decreased with an adjusted IRR of 0.73 (95% CI, 0.66‐0.80) per yearly interval and was associated with cirrhosis (IRR, 10.07; 95% CI, 6.00‐16.90 in age <40 years; 4.69; 95% CI, 3.94‐5.59 in age ≧40 years), age (IRR, 3.38; 95% CI, 2.10‐5.47 for 40‐50 years; 6.92; 95% CI, 4.27‐11.21 for 50‐60 years; 12.50; 95% CI, 7.71‐20.25 for ≧60 years; <40 years as reference), male sex (IRR, 1.71; 95% CI, 1.44‐2.04), HCV coinfection (IRR, 1.27; 95% CI, 1.02‐1.58) and diabetes (IRR, 1.24; 95% CI, 1.05‐1.45). In conclusion, the risk of HCC in patients with chronic hepatitis B receiving entecavir or tenofovir declines over time and is determined by cirrhosis, age, male sex, HCV coinfection and diabetes.     

The nonlinear relationship between gait speed and falls: the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston Study

OBJECTIVES: To examine the relationship between gait speed and falls risk. DESIGN: Longitudinal analysis of the association between gait speed and subsequent falls and analysis of gait speed decline as a predictor of future falls. SETTING: Population‐based cohort study. PARTICIPANTS: Seven hundred sixty‐three community‐dwelling older adults underwent baseline assessments and were followed for falls; 600 completed an 18‐month follow‐up assessment to determine change in gait speed and were followed for subsequent falls. MEASUREMENTS: Gait speed was measured during a 4‐m walk, falls data were collected from monthly post‐card calendars, and covariates were collected from in‐home and clinic visits. RESULTS: There was a U‐shaped relationship between gait speed and falls, with participants with faster (≥1.3 m/s, incident rate ratio (IRR)=2.12, 95% confidence interval (CI)=1.48–3.04) and slower (<0.6 m/s, IRR=1.60, 95% CI=1.06–2.42) gait speeds at higher risk than those with normal gait speeds (1.0–<1.3 m/s). In adjusted analyses, slower gait speeds were associated with greater risk of indoor falls (<0.6 m/s, IRR=2.17, 95% CI=1.33–3.55; 0.6–<1.0 m/s, IRR=1.45, 95% CI=1.08–1.94), and faster gait speed was associated with greater risk of outdoor falls (IRR=2.11, 95% CI=1.40–3.16). A gait speed decline of more than 0.15 m/s per year predicted greater risk of all falls (IRR=1.86, 95% CI=1.15–3.01). CONCLUSION: There is a nonlinear relationship between gait speed and falls, with a greater risk of outdoor falls in fast walkers and a greater risk of indoor falls in slow walkers.     

Trends in invasive disease due to Candida species following heart and lung transplantation

Abstract: Although invasive candidiasis (IC) causes significant morbidity and mortality in patients who undergo heart, lung, or heart–lung transplantation, a systematic study in a large cohort of thoracic organ transplant recipients has not been reported to date. Clinical and microbiological data were reviewed for 1305 patients who underwent thoracic organ transplantation at Stanford University Medical Center between 1980 and 2004. We identified and analyzed 76 episodes of IC in 68 patients (overall incidence 5.2% per patient). The incidence of IC was higher in lung (LTx) and heart–lung transplant (HLTx) recipients as compared with heart transplant (HTx) recipients (risk ratio [RR] 1.7, 95% confidence interval [CI] 1.1–2.7). The incidence of IC decreased over time in all thoracic organ transplant recipients, decreasing from 6.1% in the 1980–1986 time period to 2.1% in the 2001–2004 era in the HTx recipients, and from 20% in the 1980–1986 period to 1.8% in the 2001–2004 period in the LTx and HLTx recipients. The most common site of infection differed between the HTx and LTx cohorts, with bloodstream or disseminated disease in the former and tracheobronchitis in the latter. IC in the first year after transplant was significantly associated with death in both HTx (RR 2.9, 95% CI 1.8–4.6, P=0.001) and LTx and HLTx patients (RR 3.0, 95% CI 1.9–4.6, P<0.001). The attributable mortality from IC decreased during the 25‐year period of observation, from 36% to 20% in the HTx recipients and from 39% to 15% in the LTx and HLTx recipients. There were a significant number of cases caused by non‐albicans Candida species in all patients, with a trend toward higher mortality in the HTx group. In conclusion, the incidence and attributable mortality of IC in thoracic organ transplant recipients has significantly declined over the past 25 years. The use of newer antifungal agents for prophylaxis and treatment, the decrease in the incidence of cytomegalovirus disease, and the use of more selective immunosuppression, among other factors, may have been responsible for this change.     

INCIDENCE AND RISK FACTORS OF TRANSPLANT RENAL ARTERY STENOSIS IN LIVING UNRELATED DONOR RENAL TRANSPLANTATION

Background : This study was designed to evaluate the incidence and risk factors of transplant renal artery stenosis (TRAS) among living donor unrelated kidney recipients. Patients and methods: Three hundred and sixty kidney consecutive transplant recipients were included in this retrospective cohort study. Informed written consent was obtained, only TRAS occurring three months after transplantation were considered. After five‐year follow up, TRAS was established in 6.6% (24 patients) of patients. Results: Mean ± SD age of recipients was 39.8 ± 14.9 years old (range 16–77). Upon multivariate analysis recipient age >50 (RR = 2.9, CI 95%: 1.33–2.93, p = 0.008), recipient BMI >30 (kg/m²) (RR: 7.97, CI 95%: 3.44–18.46, p < 0.001), retransplantation (RR = 4.88, CI 95%: 2.21–10.77, p < 0.001), cytomegalovirus (CMV) infection and delayed graft function (DGF) (RR: 4.29, CI 95%: 3.12–13.79, p = 0.01) appeared to be independently associated with TRAS. Positive CMV‐antibody was more frequent in recipients with TRAS (95.83% vs. 70.8%, p = 0.04) but all of them were HCV‐antibody negative. Other variables as discussed were similar between two groups. Conclusion: High recipient age, BMI > 30, hyper trigelyceridaemia, previous transplantation, CMV infection and DGF are shown to be risk factors for TRAS.     

Relapse after non-T-cell-depleted allogeneic bone marrow transplantation for chronic myelogenous leukemia: early transplantation, use of an unrelated donor, and chronic graft-versus- host disease are protective

We analyzed the incidence of posttransplant chronic myelogenous leukemia (CML) relapse in 283 consecutive related-donor (n = 177) and unrelated-donor (n = 106) allogeneic transplant recipients. Twenty-two of 165 related-donor recipients with stable or advanced disease at the time of transplant had hematologic relapse of CML following transplant (5-year Kaplan-Meier estimate of relapse, 20%; 95% confidence interval [CI], 11 to 30%). One of 12 patients transplanted in second stable phase following blast crisis also relapsed. Fifteen related-donor transplant recipients relapsed within 5 years of transplant; however, seven relapsed between 5 and 9 years after transplant. Factors independently associated with an increased risk of posttransplant relapse for related-donor recipients included prolonged interval between diagnosis and transplant (relative risk, [RR], 3.81; P = .009) and bone marrow basophilia (RR, 5.62; P = .01). Related-donor recipients with posttransplant chronic graft-versus-host disease (CGVHD) had a decreased risk of relapse (RR, 0.24; P = .005). Only two of 106 unrelated-donor transplant recipients relapsed following transplant (5-year Kaplan-Meier estimate of relapse, 3%; 95% CI, 0% to 7%). When both related- and unrelated-donor recipients were considered, the use of an unrelated donor was independently associated with a decreased risk of relapse (RR, 0.24; P = .07). Twelve of 16 relapsing patients who received further therapy (nine of 13 who underwent second transplant and three of three who received donor leukocyte infusions) remain alive. This analysis shows that relapse, sometimes occurring long after transplant, is an important adverse outcome in allogeneic transplantation for CML. Early transplant, posttransplant CGVHD, and use of an unrelated donor are associated with a reduced incidence of relapse, perhaps due to allogeneic disparities enhancing the graft- versus-leukemia effect.     

Diffuse lymphoproliferative disease after renal transplantation and its relation with Epstein-Barr virus. Experience at one center

Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous lymphoid proliferations in chronic immunosuppressed recipients which appear to be related to Epstein Barr Virus (EBV). Receptor EBV seronegativity, use of antilymphocyte antibodies and CMV disease have been identified as risk factors that may tigger development of PTLD. We have studied the incidence of PTLD and its relationship with EBV in 588 adult renal transplant recipients who were transplanted in our hospital from 1988 to 2001. We have also evaluated the diagnostic and therapeutic methods used, the risk factors and outcome of the patients who developed PTLD. We identified 8 recipients (4 males and 4 females), range from 18 to 67 years (mean age 45.6 years) with a median time between grafting and PTLD of 4.1 years (0.1-7 years), who developed PTLD (1.3%). Only 1 patient received OKT3 and had CMV disease, two of them (25%) had been treated with hight doses of prednisolone, another was EBV seronegative, but the rest of them (50%) had no risk factors. Two patients were diagnosed at autopsy, the diagnosis of 5 was based on the histology of biopsy and the last one by CT scans of chest-abdomen and cytology. The presence of EBV in the lymphoproliferative cells was assessed in 5 out of the 7 studied patients (71.4%). The outcome of our recipients was poor. Five out of 8 patients died shortly after diagnosis as a direct consecuence of PTLD and another of an infectious complication of the treatment (75%). The 2 patients alive started dialysis and 1 of them died 2 years later of a non-related cause. In conclusion, PTLD is a relatively frequent disease with a poor prognosis in renal transplant patients. It seems to have a close relationship with EBV and can develop in the absence of the classical risk factors.     

Results of a prospective multicentre myeloablative double‐unit cord blood transplantation trial in adult patients with acute leukaemia and myelodysplasia

Double‐unit cord blood (CB) grafts may improve engraftment and relapse risk in adults with haematological malignancies. We performed a prospective high‐dose myeloablative double‐unit CB transplantation (CBT) trial in adults with high‐risk acute leukaemia or myelodysplasia (MDS) between 2007 and 2011. The primary aim was to establish the 1‐year overall survival in a multi‐centre setting. Fifty‐six patients (31 acute myeloid leukaemia, 19 acute lymphoblastic leukaemia, 4 other acute leukaemias, 2 myelodysplastic syndrome [MDS]) were transplanted at 10 centres. The median infused total nucleated cell doses were 2·62 (larger unit) and 2·02 (smaller unit) x 10⁷/kg. The cumulative incidence of day 100 neutrophil engraftment was 89% (95% confidence interval [CI]: 80–96). Day 180 grade II‐IV acute graft‐versus‐host disease (GVHD) incidence was 64% (95%CI: 51–76) and 36% (95%CI: 24–49) of patients had chronic GVHD by 3‐years. At 3‐years post‐transplant, the transplant‐related mortality (TRM) was 39% (95%CI: 26–52), and the 3‐year relapse incidence was 11% (95%CI: 4–21). With a median 37‐month (range 23–71) follow‐up of survivors, the 3‐year disease‐free survival was 50% (95%CI: 37–63). Double‐unit CBT is a viable alternative therapy for high‐risk acute leukaemia/ MDS in patients lacking a matched unrelated donor. This is especially important for minority patients. The relapse incidence was low but strategies to ameliorate TRM are needed.     

Prevalence, incidence and correlates of HHV-8/KSHV infection and Kaposi's sarcoma in renal and liver transplant recipients.

BACKGROUND: To determine whether the incidence of HHV-8/KSHV infection and the risk of developing KS among organ transplant recipients differ by type of organ transplanted, we calculated the rate of HHV-8/KSHV seroconversion and the risk of developing KS among renal and liver transplant recipients. METHODS: The study population consisted of renal and liver transplant recipients recruited in two transplant centres in Rome, Italy. Both pre-transplant and post-transplant serum samples were available for all participants. The prevalence of HHV-8/KSHV infection before transplantation was calculated. To determine risk factors for infection, we calculated ORs and 95% CI. Seroconversion rates (i.e. attack rates) after transplantation were also calculated. Differences in attack rates were calculated using a binomial test for proportions. RESULTS: Of the 130 participants, 21 (16.1%) were HHV-8/KSHV-positive before transplantation. Women were more likely to be infected than men, whereas no difference was observed by type of organ transplanted. Of the 109 initially negative individuals, 13 (11.9%) developed anti-HHV-8/KSHV antibodies after transplantation. The incidence of HHV-8/KSHV infection tended to be higher among liver transplant recipients. Four renal transplant recipients and none of the liver transplant recipients developed KS after transplantation. The risk of KS was higher among recipients who were already HHV-8/KSHV-positive before transplantation. CONCLUSIONS: HHV-8/KSHV seroconversion rates appear to be higher among liver transplant recipients, compared to renal transplant recipients. However, renal transplant recipients tend to have a higher risk of KS. HHV-8/KSHV reactivation appears to play a greater role on the risk of KS than incident infections.     

Smoking,alcohol consumption,and risk of systemic lupus erythematosus in the Black Women's Health Study

OBJECTIVE: Several case-control studies, mostly of prevalent disease, have suggested that systemic lupus erythematosus (SLE) is positively associated with cigarette smoking and inversely associated with alcohol consumption. We prospectively investigated the associations of smoking and alcohol consumption with incident SLE in the Black Women's Health Study (BWHS). METHODS: In 1995, 64,500 African-American women provided information on demographic characteristics, reproductive and medical histories, smoking, and alcohol consumption. Followup questionnaires in 1997 and 1999 ascertained incident cases of SLE. Cox proportional hazards regression was used to estimate incidence rate ratios (IRR) and 95% confidence intervals (CI). RESULTS: Sixty-seven women reported a new diagnosis of SLE and use of appropriate medication for that illness. In multivariate analyses, the IRR for current and past smoking were 1.6 (both 95% CI 0.8-3.3). The risk was greater for women who began smoking before age 19 years (IRR 1.9, 95% CI 1.0-3.6). Neither current alcohol consumption (IRR 1.0, 95% CI 0.4-2.4) nor past alcohol consumption (IRR 0.9, 95% CI 0.3-2.7) was associated with SLE. CONCLUSION: Our results suggest an increased risk of SLE among smokers, but no effect of alcohol consumption on risk. The inverse association of alcohol consumption with SLE found in studies of prevalent disease may have resulted from women with SLE giving up drinking.     

Association of widespread body pain with an increased risk of cancer and reduced cancer survival: A prospective,population‐based study

Objective

To determine whether reported widespread body pain is related to an increased incidence of cancer and/or reduced survival from cancer, since our previous population surveys have demonstrated a relationship between widespread body pain and a subsequent 2‐fold increase in mortality from cancer over an 8‐year period.

Methods

A total of 6,565 subjects in Northwest England participated in 2 health surveys during 1991–1992. The subjects were classified according to their reported pain status (no pain, regional pain, and widespread pain), and were subsequently followed up prospectively until December 31, 1999. During followup, information was collected on incidence of cancer and survival rates among those developing cancer. Associations between the original pain status and development of cancer and cancer survival were expressed as the incidence rate ratio (IRR) and mortality rate ratio (MRR), respectively. All analyses were adjusted for age, sex, and study location, the latter being a proxy measure of socioeconomic status.

Results

Among the study population, 6,331 had never been diagnosed with cancer at the time of participation in the survey. Of these subjects, 956 (15%) were classified as having widespread pain, 3,061 (48%) as having regional pain, and 2,314 (37%) as having no pain. There were a total of 395 first malignancies recorded during followup. In comparison with subjects reporting no pain, those with regional pain (IRR 1.19, 95% confidence interval [95% CI] 0.94–1.50) and widespread pain (IRR 1.61, 95% CI 1.21–2.13) experienced an excess incidence of cancer during the followup period. The increased incidence among subjects previously reporting widespread pain was related, most strongly, to breast cancer (IRR 3.67, 95% CI 1.39–9.68), but there were also cancers of the prostate (IRR 3.46, 95% CI 1.25–9.59), large bowel (IRR 2.35, 95% CI 0.96–5.77), and lung (IRR 2.04, 95% CI 0.96–4.34). Subjects reporting widespread pain who subsequently developed cancer, in comparison with those previously reporting no pain, had an increased risk of death (MRR 1.82, 95% CI 1.18–2.80). This decreased survival was highest among subjects with cancers of the breast and prostate, although the effects on site‐specific survival were nonsignificant.

Conclusion

This study has demonstrated that widespread pain reported in population surveys is associated with a substantial subsequent increased incidence of cancer and reduced cancer survival. At present there are no satisfactory biologic explanations for this observation, although several possible leads have been identified.

     

The STEP into Action study: a peer-based, personal risk network-focused HIV prevention intervention with injection drug users in Baltimore, Maryland

Aims To assess the effectiveness of a peer‐based, personal risk network‐focused HIV prevention intervention to (i) train injection drug users (IDUs) to reduce injection and sex risk behaviors, (ii) conduct outreach to behaviorally risky individuals in their personal social networks [called risk network members (RNM)], and (iii) reduce RNM HIV risk behaviors. Design Randomized controlled trial with prospective data collection at 6, 12 and 18 months. Intervention condition consisted of five group sessions, one individual session and one session with Index and the RNM. Setting This study was conducted in Baltimore, Maryland from March 2004 to March 2006. Participants (i) Index participants were aged ≥18 years and self‐reported injection drug use in the prior 6 months and (ii) their RNM who were aged ≥18 years and drug users or sex partners of Index. Measurements Outcomes included: (i) injection risk based on sharing needles, cookers and cotton for injection and drug splitting, (ii) sex risk based on number of sex partners, condom use and exchanging sex and (iii) Index HIV outreach behaviors. Findings A total of 227 Index participants recruited 336 RNM. Retention of Index at 18‐month follow‐up exceeded 85%. Findings suggest that the experimental condition was efficacious at 18 months in reducing Index participant injection risk [odds ratio (OR) = 0.38; 95% confidence interval (CI) = 0.18–0.77), drug‐splitting risk (OR = 0.46; 95% CI = 0.25–0.88) and sex risk among Index (OR = 0.53; 95% CI = 0.34–0.86). Significant intervention effect on increased condom use among female RNM was observed (OR = 0.34; 95% CI = 0.18–0.62). Conclusions Training active IDU to promote HIV prevention with behaviorally risky individuals in their networks is feasible, efficacious and sustainable.     

Risk factors for early-onset and late-onset post-transplant lymphoproliferative disorder in kidney recipients in the United States

Solid-organ transplant recipients have an elevated risk for some malignancies because of the requirement for immunosuppression [1]. In particular, non-Hodgkin's lymphoma (NHL) is common and comprises one end of a spectrum of post-transplant lymphoproliferative disorder (PTLD) ranging from benign hyperplasia to lymphoid malignancy [2]. PTLD risk is influenced by the type of organ transplanted, the age and Epstein-Barr virus (EBV) serostatus of the transplant recipient, and the intensity of immunosuppression [3-9]. PTLD incidence is high immediately after transplantation, decreases subsequently, and then rises again 4-5 years from transplantation [10,11]. This incidence pattern suggests the presence of separate early-onset and late-onset PTLD subtypes. Early-onset PTLDs tend to be EBV-positive and, when extranodal, are more likely than late-onset PTLDs to be localized to the transplanted organ [12,13]. Late-onset PTLD is less likely to be associated with EBV and, overall, is more likely than early-onset PTLD to be extranodal [13,14]. The Scientific Registry of Transplant Recipients (SRTR) includes data on a large number of solid-organ transplant recipients in the United States and information on malignancies diagnosed post-transplantation. We used these data to conduct a retrospective cohort study among kidney transplant recipients to examine differences in risk factors between early-onset PTLD and late-onset PTLD.