Occupations and the risk of buccal mucosa cancer in Indian men: A multi-centre case-control study.

OBJECTIVE: This study aimed to investigate the association between lifetime occupational history and risk of buccal mucosa cancer (BMC). METHODS: We utilized a multi-centric, hospital-based case-control study across five centres of Tata Memorial Centre, Mumbai, India. Cases included men aged 20-75-years with histological confirmed primary cancer of the buccal mucosa. Visitor controls were frequency matched to cases for age (10 years interval) and current residential zone. Study participants were interviewed face-to-face. Logistic regression was performed to estimate odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: Among ever employed males, we identified 1969 BMC cases and 2145 controls. We observed an increased risk of BMC in 'Craft and Related Trades Workers' (OR 1.37; 95 % CI 1.13-1.65), 'Plant and Machine Operators and Assemblers' (OR: 1.26; 95 % CI 1.01-1.56), and 'Elementary Occupations' (OR:1.33; 95 % CI 1.12-1.58). More specifically, the increased risk was observed for 'Metal, Machinery and Related Trades Workers', 'Handicraft and Printing Workers', 'Drivers and Mobile Plant Operators', and 'Laborers in Mining, Construction, Manufacturing and Transport'. CONCLUSION: Our findings suggest that certain occupations may be at a higher risk of BMC. Some fraction of BMC can be prevented by reducing exposure to hazardous agents used in these occupations. Further research is needed to identify which exposures are responsible for the increased risk. Moreover, tobacco control and early detection activities can be focused towards these occupations as tobacco consumption is also high in them, which may also be the reason for increased risk observed in these groups.

Evaluating a Digital Mental Health Intervention (Wysa) for Workers' Compensation Claimants: Pilot Feasibility Study.

OBJECTIVE: This study examines the feasibility and acceptability of an AI-led digital mental health intervention in a Workers' Compensation (WC) program, Wysa for Return to Work. METHODS: Self-reported demographic data and responses to psychosocial screening questions were analyzed alongside participants' app usage through which four key outcomes were measured: recruitment rate, onboarding rate, retention, and engagement. RESULTS: The data demonstrated a high need for psychosocial interventions among injured workers, especially women, young adults, and those with high severity injuries. Those with more psychosocial risk factors had a higher rate of onboarding, retention, and engagement, and those with severe injuries had higher retention. CONCLUSIONS: Our study concluded that Wysa for Return to Work, the AI-led digital mental health intervention that delivers a recovery program using a digital conversational agent, is feasible and acceptable for a return-to-work population.

Wellness Following Wins and Losses Based on Psychological Hardiness in Division I Women's Lacrosse.

Psychological hardiness encompasses three components: commitment, control, and challenge, and illustrates how individuals respond to stressors. Analyzing athletes' responses to wins and losses, depending on their psychological hardiness level, may provide insight of the impact of game outcome on student-athlete wellness. The purpose of this study was to examine postgame subjective wellness scores based on level of psychological hardiness following wins and losses in collegiate female lacrosse athletes. Players (n = 17) took the Dispositional Resilience Scale Scale-15 (DRS-15) at the start of the academic year and were grouped based on hardiness level: above average (AH) and below average (BA). Participants took a daily wellness survey rating their overall wellness, energy level, muscle soreness, stress level, and sleep quality. RM-ANOVA indicated no difference in post-game wellness scores between hardiness groups (Lambda(5,11) = 1.073, p = .426, ES = .328), by game outcome (Lambda(5,11) = 2.361, p = .109, ES = .518), or an interaction between hardiness and outcome of game (Lambda(5,11) = 1.421, p = .291, ES = .392). No hardiness group differences were found for overall wellness or sub-scores. These results show subjective wellness scores decrease collectively after a loss versus a win but refute prior studies as hardy players did not experience significantly less stress than their less hardy counterparts. Future studies should be conducted to assess wellness after differing game outcomes over many seasons to assist coaching staff on the subjective, psychological impacts of game.

Successful outcome following allogeneic hematopoietic stem cell transplantation in adults with primary immunodeficiency.

The primary immunodeficiencies (PIDs), rare inherited diseases characterized by severe dysfunction of immunity, have been successfully treated by allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in childhood. Controversy exists regarding optimal timing and use of Allo-HSCT in adults, due to lack of experience and previous poor outcomes. Twenty-nine consecutive adult patients, with a mean age at transplant of 24 years (range, 17-50 years), underwent Allo-HSCT. Reduced-intensity conditioning (RIC) included fludarabine (Flu)/melphalan/alemtuzumab (n = 20), Flu/busulfan (Bu)/alemtuzumab (n = 8), and Flu/Bu/antithymocyte globulin (n = 1). Stem cell donors were matched unrelated donors or mismatched unrelated donors (n = 18) and matched related donors (n = 11). Overall survival (OS), event-free survival, transplant-related mortality (TRM), acute and chronic graft-versus-host disease incidence and severity, time to engraftment, lineage-specific chimerism, immune reconstitution, and discontinuation of immunoglobulin replacement therapy were recorded. OS at 3 years for the whole cohort was 85.2%. The rarer PID patients without chronic granulomatous disease (CGD) achieved an OS at 3 years of 88.9% (n = 18), compared with 81.8% for CGD patients (n = 11). TRM was low with only 4 deaths observed at a median follow-up of 3.5 years. There were no cases of early or late rejection. In all surviving patients, either stable mixed chimerism or full donor chimerism were observed. At last follow-up, 87% of the surviving patients had no evidence of persistent or recurrent infections. Allo-HSCT is safe and effective in young adult patients with severe PID and should be considered the treatment of choice where an appropriate donor is available.

Gene therapy for Wiskott-Aldrich syndrome in a severely affected adult.

Until recently, hematopoietic stem cell transplantation was the only curative option for Wiskott-Aldrich syndrome (WAS). The first attempts at gene therapy for WAS using a ϒ-retroviral vector improved immunological parameters substantially but were complicated by acute leukemia as a result of insertional mutagenesis in a high proportion of patients. More recently, treatment of children with a state-of-the-art self-inactivating lentiviral vector (LV-w1.6 WASp) has resulted in significant clinical benefit without inducing selection of clones harboring integrations near oncogenes. Here, we describe a case of a presplenectomized 30-year-old patient with severe WAS manifesting as cutaneous vasculitis, inflammatory arthropathy, intermittent polyclonal lymphoproliferation, and significant chronic kidney disease and requiring long-term immunosuppressive treatment. Following reduced-intensity conditioning, there was rapid engraftment and expansion of a polyclonal pool of transgene-positive functional T cells and sustained gene marking in myeloid and B-cell lineages up to 20 months of observation. The patient was able to discontinue immunosuppression and exogenous immunoglobulin support, with improvement in vasculitic disease and proinflammatory markers. Autologous gene therapy using a lentiviral vector is a viable strategy for adult WAS patients with severe chronic disease complications and for whom an allogeneic procedure could present an unacceptable risk. This trial was registered at www.clinicaltrials.gov as #NCT01347242.

Efficacy of a novel oral formulation of sarolaner (Simparica™) against four common tick species infesting dogs in Europe.

The efficacy of single oral treatment of sarolaner (Simparica™, Zoetis), a novel isoxazoline compound, was evaluated against four tick species known to commonly infest dogs in Europe. Eight laboratory studies were conducted using adult purpose-bred Beagle dogs. In each study, 16 animals were randomly allocated to one of two treatment groups based on pre-treatment host-suitability tick counts. Dogs were infested with 50 unfed adult Dermacentor reticulatus (two studies), Ixodes hexagonus (three studies), Ixodes ricinus (two studies) or Rhipicephalus sanguineus (one study) ticks on Days -2, 5, 12, 19, 26 and 33. On Day 0, dogs were treated orally with placebo or sarolaner tablets providing the minimum dose of 2.0mg/kg bodyweight and tick counts were conducted 48h after treatment and after each subsequent weekly re-infestation. There were no treatment-related adverse reactions in any of the studies. Dogs in the placebo-treated group maintained tick infestations throughout the studies. Geometric mean live tick counts were significantly (P≤0.0001) lower in the sarolaner-treated group compared to the tick counts in the placebo group at all time-points. A single oral administration of sarolaner resulted in 100% efficacy against existing infestations of all tick species except R. sanguineus, for which the efficacy was 99.7%, within 48h. Efficacy against weekly re-infestations was ≥97.5% for all tick species for 35 days. Thus, a single dose of sarolaner administered orally at the minimum dosage of 2 mg/kg, resulted in ≥99.7% efficacy within 48h against existing tick infestations, and in ≥97.5% efficacy against weekly re-infestations, for at least 35 days after treatment. These studies confirmed that administration of the minimum dose of sarolaner will provide treatment of existing infestations and give at least one month of control against re-infestation by the common tick species affecting dogs in Europe.

Evaluation of the effectiveness of a novel oral formulation of sarolaner (Simparica™) for the treatment and control of fleas on dogs.

The efficacy of a single oral dose of a novel isoxazoline, sarolaner (Simparica™, Zoetis), for the treatment and control of flea infestations on dogs was confirmed in five laboratory studies. The studies were conducted using adult purpose-bred Beagles and/or mixed breed dogs. All animals were individually identified and housed, and were allocated randomly to treatment with either placebo or sarolaner (eight to 10 per group) based on pretreatment parasite counts. Three studies used cat flea (Ctenocephalides felis felis) strains recently isolated from the field from the US, EU, or Australia; in the fourth study a laboratory strain (KS1) with documented tolerance to a number of insecticides such as fipronil, imidacloprid, and permethrin was used. In the fifth study, dogs were infested with dog fleas, Ctenocephalides canis. Dogs were treated orally on Day 0 with a placebo or a sarolaner tablet providing a minimum dose of 2mg/kg. Dogs were infested with approximately 100 unfed, adult fleas prior to treatment and at weekly intervals post-treatment. Comb counts were conducted to determine the numbers of viable fleas at 24h after treatment and after each subsequent infestation. Efficacy against C. felis and C. canis was 99.8-100% from treatment through Day 35. In all five studies, elimination of existing infestations was achieved within 24h after dosing, with only a single live C. felis found on one dog on Day 1. Similarly, control of flea challenges was achieved within 24h after infestation throughout the 35day study periods, with only single live C. felis found on two dogs on Day 28 in one study, and on a single dog on Day 35 in another study. There were no adverse reactions to treatment with sarolaner. These studies confirmed that a single oral dose of sarolaner at 2mg/kg provided highly effective treatment of existing C. felis infestations and persistent control of C. felis on dogs for 35days after treatment. Efficacy equivalent to that seen with C. felis was confirmed against C. canis and a known insecticide-tolerant strain of C. felis.

Two-Stage Priming of Allogeneic Natural Killer Cells for the Treatment of Patients with Acute Myeloid Leukemia: A Phase I Trial.

UNLABELLED: Human Natural Killer (NK) cells require at least two signals to trigger tumor cell lysis. Absence of ligands providing either signal 1 or 2 provides NK resistance. We manufactured a lysate of a tumour cell line which provides signal 1 to resting NK cells without signal 2. The tumor-primed NK cells (TpNK) lyse NK resistant Acute Myeloid Leukemia (AML) blasts expressing signal 2 ligands. We conducted a clinical trial to determine the toxicity of TpNK cell infusions from haploidentical donors. 15 patients with high risk AML were screened, 13 enrolled and 7 patients treated. The remaining 6 either failed to respond to re-induction chemotherapy or the donor refused to undergo peripheral blood apheresis. The conditioning consisted of fludarabine and total body irradiation. This was the first UK trial of a cell therapy regulated as a medicine. The complexity of Good Clinical Practice compliance was underestimated and led to failures requiring retrospective independent data review. The lessons learned are an important aspect of this report. There was no evidence of infusional toxicity. Profound myelosuppression was seen in the majority (median neutrophil recovery day 55). At six months follow-up, three patients treated in Complete Remission (CR) remained in remission, one patient infused in Partial Remission had achieved CR1, two had relapsed and one had died. One year post-treatment one patient remained in CR. Four patients remained in CR after treatment for longer than their most recent previous CR. During the 2 year follow-up six of seven patients died; median overall survival was 400 days post infusion (range 141­910). This is the first clinical trial of an NK therapy in the absence of IL-2 or other cytokine support. The HLA-mismatched NK cells survived and expanded in vivo without on-going host immunosuppression and appeared to exert an anti-leukemia effect in 4/7 patients treated. TRIAL REGISTRATION: ISRCTN trial registry ISRCTN11950134.

Confirmation of the efficacy of a novel fipronil spot-on for the treatment and control of fleas, ticks and chewing lice on dogs.

A novel spot-on formulation containing fipronil (Eliminall(®)/Exproline vet™) Spot-on Solution for Dogs, Pfizer Animal Health, registered and manufactured by Krka, d.d, Novo mesto) was evaluated in three laboratory studies to confirm efficacy against fleas, ticks and chewing lice on dogs for at least one month. Control of two laboratory strains of cat flea (Ctenocephalides felis), two tick species (Rhipicephalus sanguineus and Dermacentor reticulatus) and the chewing louse (Trichodectes canis) was evaluated. In all studies, dogs were randomly allocated to treatment groups and compared with untreated dogs. The studies also included a commercial, comparator product containing fipronil (Frontline(®) spot-on, Merial Limited). All treatments were applied to the skin at one spot between the scapulae on Day 0. In the studies, dogs were infested with fleas and/or ticks prior to treatment and then reinfested at weekly intervals for up to 8 weeks after treatment and evaluated for efficacy at 2 days (48 h) after treatment and each reinfestation. These studies confirmed that treatment with the novel fipronil spot-on at the proposed commercial dose rate rapidly reduced existing infestations of fleas, ticks and chewing lice on dogs. Treatment provided control of reinfesting fleas for up to 8 weeks, up to 4 weeks control of ticks, and control of chewing lice.

Efficacy of a novel fipronil spot-on for the treatment and control of induced infestations of adult cat fleas (Ctenocephalides felis) and castor bean ticks (Ixodes ricinus) on cats.

Cat fleas (Ctenocephalides felis) and the castor bean tick (Ixodes ricinus) cause discomfort and health effects due to bites and ingestion of blood and they serve as vectors for several animal and human pathogens. Effectiveness of a novel 10 % w/v fipronil spot-on (Eliminall®/Exproline vet™, marketed by Pfizer Animal Health and registered and manufactured by Krka, d.d., Novo mesto) was confirmed against these parasites on experimentally infested cats. Two parallel, unicentre and masked controlled studies were conducted with European mixed breed and mixed sex cats. Cats were allocated randomly to one of two treatment groups based on either pre-treatment flea counts (study 1) or pre-treatment tick counts (study 2). In each of the study, eight animals served as control, while another eight animals were treated once topically with the unit label dose of 50 mg fipronil per cat (10.6-23.8 mg/kg). At each reinfestation, animals were infested with approximately 100 fleas or 60 ticks to achieve adequate infestation rates. Parasites were removed and counted on days 2, 9, 16, 23, 30 and 37, 48 h after the treatment or experimental infestation. Excellent effectiveness was demonstrated on day 2 (100 and 94 % efficacy against fleas and ticks, respectively) and lasted for up to 5 weeks (efficacy ≥96 %) against fleas and up to 4 weeks against ticks (efficacy ≥94 %). The product was well tolerated and no adverse reactions were observed.

Warfarin management using point-of-care testing in a university-based internal medicine resident clinic.

INTRODUCTION: The primary endpoint was to determine whether point-of-care (POC) International Normalization Ratio (INR) testing would increase the percentage of patients in the therapeutic range. The secondary endpoint was to determine how POC Testing (POCT) would affect the time to intervention (the amount of time it took to contact a patient who had an INR outside the therapeutic range and make the appropriate warfarin adjustment). METHODS: Over an 11-month time period, the authors implemented an anticoagulation-focused quality improvement initiative based on the internal medicine resident continuity clinic. The initiative was designed as a single site before and after study. RESULTS: The proportion of INR values within the therapeutic range before the implementation of POCT (predesign phase) was 25%. After the implementation of POCT (postdesign phase), the percentage of therapeutic INR was 50% (P = 0.005). The time to intervention in the predesign phase was 4 days while intervention was accomplished during the same visit that the blood was sampled in the postdesign phase of this study. The number needed to treat was 4 to obtain a therapeutic INR. CONCLUSION: The results of this quality improvement study showed significant improvement in the percentage of patients who were in the therapeutic range with the use of POCT. Time to intervention was also markedly improved with the addition of POCT. The authors believe that this is the first study showing such results in an internal medicine academic clinic.

Cytomegalovirus-specific CD8+ T cells targeting different peptide/HLA combinations demonstrate varying T-cell receptor diversity.

Cytomegalovirus (CMV) infection and reactivation pose a serious threat for patients after haematopoietic stem cell transplantation. We have previously shown that CD8(+) T cells targeting different CMV epitopes correlate with protection at different threshold frequencies in those patients. To investigate if this may relate to a different quality of these cells here we analyse the T-cell receptor diversity of pp50 (245-253)/HLA-A*0101 specific CD8(+) T cells with that of CD8(+) T cells targeting various pp65 peptides. The results from this pilot study show differences in the breadth of the T-cell receptor usage of the different cell populations. We observe for the first time that the T-cell receptor Vß CDR3 spectratypes used by CMV pp50 (245-253)/HLA-A*0101-specific CD8(+) T cells can reach higher numbers than those used by CD8(+) T cells targeting various pp65 peptides in our patient cohort. This merits further investigation into the effectiveness of the different CMV-specific T cells and their impact on immunosenescence, which is important to eventually define the most useful source of adoptive therapy and monitoring protocols for cytomegalovirus-specific immune responses.

Youth empowerment in context: exploring tensions in school-based yPAR.

In much of the youth empowerment literature, researchers focus on the relationship between youth and adults involved in empowerment programs while neglecting the broader social framework in which these relationships and the program itself functions. Utilizing an ecological model, the current research examines the tensions that surfaced in attempts to create an empowering setting in an after-school PAR program with fifth-graders. Challenging assumptions about youth, structural challenges, and conflicting theories of change are highlighted. Results examine the role of sociocultural context as PAR researchers attempt to create a setting in which students gain skills to become change agents within their school. The study suggests that youth empowerment is a context dependent process that requires attention to a multiplicity of factors that influence possibilities for empowerment via second order change.

The role of Vδ2-negative γδ T cells during cytomegalovirus reactivation in recipients of allogeneic stem cell transplantation.

Reactivation of cytomegalovirus (CMV) remains a serious complication after allogeneic stem cell transplantation, but the role of γδ T cells is undefined. We have studied the immune reconstitution of Vδ2negative (Vδ2neg) γδ T cells, including Vδ1 and Vδ3 subsets and Vδ2positive (Vδ2pos) γδ T cells in 40 patients during the first 24 months after stem cell transplantation. Significant long-term expansions of Vδ2neg but not Vδ2pos γδ T cells were observed during CMV reactivation early after transplantation, suggesting direct involvement of γδ T cells in anti-CMV immune responses. Similarly, significantly higher numbers of Vδ2neg γδ T cells were detected in CMV-seropositive healthy persons compared with seronegative donors; the absolute numbers of Vδ2pos cells were not significantly different. The expansion of Vδ2neg γδ T cells appeared to be CMV-related because it was absent in CMV-negative/Epstein-Barr virus-positive patients. T-cell receptor-δ chain determining region 3 spectratyping of Vδ2neg γδ T cells in healthy subjects and patients showed restricted clonality. Polyclonal Vδ2neg cell lines generated from CMV-seropositive healthy donors and from a recipient of a graft from a CMV-positive donor lysed CMV-infected targets in all cases. Our study shows new evidence for role of γδ T cells in the immune response to CMV reactivation in transplantation recipients.

Incidence and dynamics of Epstein-Barr virus reactivation after alemtuzumab-based conditioning for allogeneic hematopoietic stem-cell transplantation.

BACKGROUND: Reactivation of Epstein-Barr virus (EBV) infection and posttransplant lymphoproliferative disorder (PTLD) pose a significant risk after T-cell-depleted (TCD) allogeneic hematopoietic stem-cell transplantation (HSCT). The pattern of EBV reactivation in patients receiving allogeneic HSCT, incorporating in vivo or in vitro alemtuzumab as the method of TCD, is not known. METHODS: Monitoring for EBV DNA was performed by quantitative polymerase chain reaction on whole blood in 111 consecutive adults undergoing HSCT using alemtuzumab-based TCD. Patients with more than 40,000 copies/mL were screened for PTLD, followed by the withdrawal of immunosuppression and a single infusion of rituximab. RESULTS: The 2-year cumulative incidence of EBV DNAemia was 40.3%. In vivo alemtuzumab was associated with earlier EBV reactivation than in vitro alemtuzumab (100-day incidence 22.7% vs. 2.8%, P=0.006). Eighteen patients (16%) had EBV DNAemia of more than 40,000 copies/mL. In evaluable patients, the initial rate of increase in EBV DNA levels was significantly faster in those who went on to treatment with rituximab than in patients who were left untreated (mean doubling time 3.5 days vs. 4.2 days, P=0.003). Rituximab treatment induced rapid declines in EBV DNA with an average half-life of 1.2+/-0.7 days. Only one patient (0.9%) had histologic confirmation of PTLD and subsequently attained a complete remission with rituximab that persists at 18 months. CONCLUSIONS: Alemtuzumab-based TCD is associated with a high frequency of EBV reactivation but a low (<1%) risk of PTLD using a strategy of preemptive rituximab therapy.

Cytomegalovirus-specific CD8(+) T cells targeting different HLA/peptide combinations correlate with protection but at different threshold frequencies.

Cytomegalovirus (CMV) causes significant morbidity and mortality in patients after haematopoietic stem cell transplantation (HSCT). Due to limitations of current antiviral therapies, alternative approaches, involving transfer of donor-derived CMV-specific CD8(+) T cells, have been considered. Levels of such cells correlating with protection against CMV infection and disease have only been reported in patients expressing HLA-A*0201 and HLA-B*0702. This is despite an increasing number of reports describing cells targeting CMV peptides presented by other human leucocyte antigens (HLAs). Considering several frequent HLA alleles, our findings suggest that HLA-A*2402/pp65 (341-349)- and HLA-B*3501/pp65 (123-131)-specific CD8+ T cells correlate with protection from CMV reactivation at significantly lower cell levels than HLA-A*0101/pp50 (245-253)- and HLAA* 0201/pp65 (495-503)-specific CD8+ T cells, both in HSCT recipients posttransplant and in healthy CMV seropositive volunteers. This may result from a differing efficiency of the responses restricted by the two sets of HLA alleles. These findings add to the knowledge of immunodominance and differences in antigen processing that are coordinated in individuals with different HLA alleles and have direct implications for therapy and monitoring in patients.

Cytomegalovirus-specific CD8(+) T cells targeting different HLA/peptide combinations correlate with protection but at different threshold frequencies.

Cytomegalovirus (CMV) causes significant morbidity and mortality in patients after haematopoietic stem cell transplantation (HSCT). Due to limitations of current antiviral therapies, alternative approaches, involving transfer of donor-derived CMV-specific CD8(+) T cells, have been considered. Levels of such cells correlating with protection against CMV infection and disease have only been reported in patients expressing HLA-A*0201 and HLA-B*0702. This is despite an increasing number of reports describing cells targeting CMV peptides presented by other human leucocyte antigens (HLAs). Considering several frequent HLA alleles, our findings suggest that HLA-A*2402/pp65 (341-349)- and HLA-B*3501/pp65 (123-131)-specific CD8(+) T cells correlate with protection from CMV reactivation at significantly lower cell levels than HLA-A*0101/pp50 (245-253)- and HLA-A*0201/pp65 (495-503)-specific CD8(+) T cells, both in HSCT recipients post-transplant and in healthy CMV seropositive volunteers. This may result from a differing efficiency of the responses restricted by the two sets of HLA alleles. These findings add to the knowledge of immunodominance and differences in antigen processing that are coordinated in individuals with different HLA alleles and have direct implications for therapy and monitoring in patients.

A randomized, controlled trial comparing ganciclovir to ganciclovir plus foscarnet (each at half dose) for preemptive therapy of cytomegalovirus infection in transplant recipients.

Forty-eight patients who provided 2 consecutive blood samples that tested positive for cytomegalovirus DNA by polymerase chain reaction (PCR) were randomized to receive either full-dose ganciclovir (5 mg/kg intravenously [iv] twice daily) or half-dose ganciclovir (5 mg/kg iv once daily) plus half-dose foscarnet (90 mg/kg iv once daily) for 14 days. In the ganciclovir arm, 17 (71%) of 24 patients reached the primary end point of being CMV negative by PCR within 14 days of initiation of therapy, compared with 12 (50%) of 24 patients in the ganciclovir-plus-foscarnet arm (P = .12). Toxicity was greater in the combination-therapy arm. In patients who failed to reach the primary end point, baseline virus load was 0.77 log10 higher, the replication rate before therapy was faster (1.5 vs. 2.7 days), and the viral decay rate was slower (2.9 vs. 1.1 days) after therapy. Bivariable logistic regression models identified baseline virus load, bone-marrow transplantation, and doubling time and half-life of decay as the major factors affecting response to therapy within 14 days. This study did not support a synergistic effect of ganciclovir plus foscarnet in vivo.