Kurt Schmidlin

Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials.

BACKGROUND Erythropoiesis-stimulating agents reduce anaemia in patients with cancer and could improve their quality of life, but these drugs might increase mortality. We therefore did a meta-analysis of randomised controlled trials in which these drugs plus red blood cell transfusions were compared with transfusion alone for prophylaxis or treatment of anaemia in patients with cancer. METHODS Data for patients treated with epoetin alfa, epoetin beta, or darbepoetin alfa were obtained and analysed by independent statisticians using fixed-effects and random-effects meta-analysis. Analyses were by intention to treat. Primary endpoints were mortality during the active study period and overall survival during the longest available follow-up, irrespective of anticancer treatment, and in patients given chemotherapy. Tests for interactions were used to identify differences in effects of erythropoiesis-stimulating agents on mortality across prespecified subgroups. FINDINGS Data from a total of 13 933 patients with cancer in 53 trials were analysed. 1530 patients died during the active study period and 4993 overall. Erythropoiesis-stimulating agents increased mortality during the active study period (combined hazard ratio [cHR] 1.17, 95% CI 1.06-1.30) and worsened overall survival (1.06, 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 for mortality during the active study period, and I(2) 7.1%, p=0.33 for overall survival). 10 441 patients on chemotherapy were enrolled in 38 trials. The cHR for mortality during the active study period was 1.10 (0.98-1.24), and 1.04 (0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients given different anticancer treatments (p for interaction=0.42). INTERPRETATION Treatment with erythropoiesis-stimulating agents in patients with cancer increased mortality during active study periods and worsened overall survival. The increased risk of death associated with treatment with these drugs should be balanced against their benefits. FUNDING German Federal Ministry of Education and Research, Medical Faculty of University of Cologne, and Oncosuisse (Switzerland).

Influence of residual pockets on progression of periodontitis and tooth loss: Results after 11 years of maintenance

BACKGROUND Limited evidence exists on the significance of residual probing pocket depth (PPD) as a predictive parameter for periodontal disease progression and tooth loss. AIM The aim of this study was to investigate the influence of residual PPD >or=5 mm and bleeding on probing (BOP) after active periodontal therapy (APT) on the progression of periodontitis and tooth loss. MATERIAL AND METHODS In this retrospective cohort, 172 patients were examined after APT and supportive periodontal therapy (SPT) for 3-27 years (mean 11.3 years). Analyses were conducted using information at site, tooth and patient levels. The association of risk factors with tooth loss and progression of periodontitis was investigated using multilevel logistic regression analysis. RESULTS The number of residual PPD increased during SPT. Compared with PPD<or=3 mm, PPD=5 mm represented a risk factor for tooth loss with odds ratios of 5.8 and 7.7, respectively, at site and tooth levels. The corresponding odds ratios for PPD=6 mm were 9.3 and 11.0 and for PPD>or=7 mm 37.9 and 64.2, respectively. At patient level, heavy smoking, initial diagnosis, duration of SPT and PPD>or=6 mm were risk factors for disease progression, while PPD>or=6 mm and BOP>or=30% represented a risk for tooth loss. CONCLUSION Residual PPD>or=6 mm represent an incomplete periodontal treatment outcome and require further therapy.

Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis

Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition.

Peri‐implantitis susceptibility as it relates to periodontal therapy and supportive care

OBJECTIVE To assess the long-term survival of implants inserted in periodontally susceptible patients and to investigate the influence of residual pockets on the incidence of peri-implantitis and implant loss. MATERIALS AND METHODS For 70 patients, comprehensive periodontal treatment was followed by installation of 165 Straumann Dental implants. Subsequently, 58 patients entered a University supportive periodontal therapy (SPT) program and 12 had SPT in a private practice. The follow-up time ranged from 3 to 23 years (mean 7.9 years). Bleeding on probing (BOP), clinical attachment level (CAL), and peri-implant probing depths (PPD) were evaluated at baseline (T0), completion of active treatment (T1), and at follow-up (T2). Peri-implant bone levels were assessed on radiographs at T2. Patients were categorized as having implants not affected by peri-implantitis (non-PIP), or affected by peri-implantitis (PIP). RESULTS From 165 implants inserted, six implants were lost, translating into a cumulative survival rate of 95.8%. Solid screw implants yielded significantly higher survival rates than the hollow cylinder and hollow screw implants (99.1% vs. 89.7%). Implants lost due to peri-implant infection were included in the PIP groups. When peri-implantitis (PPD ≥ 5 mm, BOP+) was analyzed, 22.2% of the implants and 38.6% of patients had one or more implants affected by peri-implantitis. Using the peri-implantitis definition (PPD ≥ 6 mm, BOP+), the prevalence was reduced to 8.8% and 17.1%, respectively. Moreover, all these implants demonstrated significant (≥ 2 mm) bone loss at T2. At T1, the non-PIP group had significantly (P = 0.011) fewer residual pockets (≥ 5 mm) per patient than the PIP group (1.9 vs. 4.1). At T2, the PIP group displayed an increased number of residual pockets compared to T1, whereas in the non-PIP group, the number remained similar to T1. At T2, mean PPD, mean CAL and BOP were significantly higher in the PIP group compared with the non-PIP group. The prevalence of peri-implantitis was lower in the group that was in a well organized SPT at the University. CONCLUSIONS In periodontitis susceptible patients, residual pockets (PPD ≥ 5 mm) at the end of active periodontal therapy represent a significant risk for the development of peri-implantitis and implant loss. Moreover, patients in SPT developing re-infections are at greater risk for peri-implantitis and implant loss than periodontally stable patients.

Maxillary sinus floor elevation using the (transalveolar) osteotome technique with or without grafting material. Part I: Implant survival and patients' perception.

OBJECTIVES To analyze the survival and success rates of implants installed utilizing the (transalveolar) osteotome technique, to compare peri-implant soft tissue parameters and marginal bone levels of osteotome-installed implants with implants placed using standard surgical procedures, and to evaluate patient-centered outcomes. MATERIAL AND METHODS During 2000 to 2005, 252 Straumann dental implants were inserted in 181 patients. The surgical technique was a modification of the original osteotome technique presented by Summers. In addition to the clinical examination, the patients were asked to give their perception of the surgical procedure, utilizing a visual analogue scale. RESULTS The cumulative survival rate of the osteotome-installed implants after a mean follow-up time of 3.2 years, was 97.4% (95% confidence intervals: 94.4-98.8%). From the 252 implants inserted, three were lost before loading and another three were lost in the first and second year. According to residual bone height the survival was 91.3% for implant sites with < or =4 mm residual bone height, and 90% for sites with 4 mm and 5 mm, when compared with that of 100% in sites with bone height of above 5 mm. According to implant length the survival rates were 100% for 12 mm, 98.7% for 10 mm, 98.7% for 8 mm and only 47.6% for 6 mm implants. Soft tissue parameters (pocket probing depth, probing attachment level, bleeding on probing and marginal bone levels) did not yield any differences between the osteotome-installed and the conventionally placed implants. More than 90% of the patients were satisfied with the implant therapy and would undergo similar therapy again if necessary. The cost associated with implant therapy was considered to be justified. CONCLUSION In conclusion, the osteotome technique was a reliable method for implant insertion in the posterior maxilla, especially at sites with 5 mm or more of preoperative residual bone height and a relatively flat sinus floor.

Significance of Periodontal Risk Assessment in the recurrence of periodontitis and tooth loss

AIM To investigate the association of the Periodontal Risk Assessment (PRA) model categories with periodontitis recurrence and tooth loss during supportive periodontal therapy (SPT) and to explore the role of patient compliance. MATERIAL AND METHODS In a retrospective cohort, PRA was performed for 160 patients after active periodontal therapy (APT) and after 9.5 +/- 4.5 years of SPT. The recurrence of periodontitis and tooth loss were analysed according to the patients risk profile (low, moderate or high) after APT and compliance with SPT. The association of risk factors with tooth loss and recurrence of periodontitis was investigated using logistic regression analysis. RESULTS In 18.2% of patients with a low-risk profile, in 42.2% of patients with a moderate-risk profile and in 49.2% of patients with a high-risk profile after APT, periodontitis recurred. During SPT, 1.61 +/- 2.8 teeth/patient were lost. High-risk profile patients lost significantly more teeth (2.59 +/- 3.9) than patients with moderate- (1.02 +/- 1.8) or low-risk profiles (1.18 +/- 1.9) (Kruskal-Wallis test, p=0.0229). Patients with erratic compliance lost significantly (Kruskal-Wallis test, p=0.0067) more teeth (3.11 +/- 4.5) than patients compliant with SPT (1.07 +/- 1.6). CONCLUSIONS In multivariate logistic regression analysis, a high-risk patient profile according to the PRA model at the end of APT was associated with recurrence of periodontitis. Another significant factor for recurrence of periodontitis was an SPT duration of more than 10 years.

Transalveolar maxillary sinus floor elevation using osteotomes with or without grafting material. Part II: radiographic tissue remodeling

OBJECTIVES To evaluate the pattern of tissue remodeling after maxillary sinus floor elevation using the transalveolar osteotome technique with or without utilizing grafting materials. METHODS During the period of 2000-2005, 252 Straumann dental implants were inserted using the transalveolar sinus floor elevation technique in a group of 181 patients. For 88 or 35% of those implants, deproteinized bovine bone mineral with a particle size of 0.25-1 mm was used as the grafting material, but for the remaining 164 implants, no grafting material was utilized. Periapical radiographs were obtained with a paralleling technique and digitized. Two investigators, who were blinded to whether grafting material was used or not, subsequently evaluated the pattern of tissue remodeling. RESULTS The mean residual bone height was 7.5 mm (SD 2.2 mm), ranging from 2 to 12.7 mm. The mean residual bone height for implants placed with grafting material (6.4 mm) was significantly less compared with the implants installed without grafting material (8.1 mm). The implants penetrated on average 3.1 mm (SD 1.7 mm) into the sinus cavity. The measured mean radiographic bone gain using the transalveolar technique without grafting material was significantly less, 1.7 mm (SD 2 mm) compared with a mean bone gain of 4.1 mm (SD 2.4 mm), when grafting material was used. Furthermore, the probability of gaining 2 mm or more of new bone was 39.1% when no grafting material was used. The probability increased to 77.9% when the implants were installed with grafting material. CONCLUSION When the transalveolar sinus floor elevation was performed without utilizing grafting material, only a moderate gain of new bone could be detected mesial and distal to the implants. On the other hand, when grafting material was used, a substantial gain of new bone was usually seen on the radiographs.

Incidence and risk factors of HIV-related non-Hodgkin's lymphoma in the era of combination antiretroviral therapy: a European multicohort study.

BACKGROUND Incidence and risk factors of HIV-associated non-Hodgkins lymphoma (NHL) are not well defined in the era of combination antiretroviral therapy (cART). METHODS A total of 56,305 adult HIV type-1 (HIV-1)-infected patients who started cART in 1 of 22 prospective studies in Europe were included. Weibull random effects models were used to estimate hazard ratios (HRs) for developing systemic NHL and included CD4(+) T-cell counts and viral load as time-updated variables. RESULTS During the 212,042 person-years of follow-up, 521 patients were diagnosed with systemic NHL and 62 with primary brain lymphoma (PBL). The incidence rate of systemic NHL was 463 per 100,000 person-years not on cART and 205 per 100,000 person-years in treated patients for a rate ratio of 0.44 (95% confidence interval [CI] 0.37-0.53). The corresponding incidence rates of PBL were 57 and 24 per 100,000 person-years (rate ratio 0.43, 95% CI 0.25-0.73). Suppression of HIV-1 replication on cART (HR 0.60, 95% CI 0.44-0.81, comparing < or =500 with 10,000-99,999 copies/ml) and increases in CD4(+) T-cell counts (HR 0.30, 0.22-0.42, comparing > or =350 with 100-199 cells/microl) were protective; a history of Kaposis sarcoma (HR 1.70, 1.08-2.68, compared to no history of AIDS), transmission through sex between men (HR 1.57, 1.19-2.08, compared with heterosexual transmission) and older age (HR 3.71, 2.37-5.80, comparing > or =50 with 16-29 years) were risk factors for systemic NHL. CONCLUSIONS The incidence rates of both systemic NHL and PBL were substantially reduced in patients on cART. Timely initiation of therapy is key to the prevention of NHL in the era of cART.

HIV-1-related Hodgkin lymphoma in the era of combination antiretroviral therapy

The risk of Hodgkin lymphoma (HL) is increased in patients infected with HIV-1. We studied the incidence and outcomes of HL, and compared CD4⁺ T-cell trajectories in HL patients and controls matched for duration of combination antiretroviral therapy (cART). A total of 40 168 adult HIV-1-infected patients (median age, 36 years; 70% male; median CD4 cell count, 234 cells/μL) from 16 European cohorts were observed during 159 133 person-years; 78 patients developed HL. The incidence was 49.0 (95% confidence interval [CI], 39.3-61.2) per 100,000 person-years, and similar on cART and not on cART (P = .96). The risk of HL declined as the most recent (time-updated) CD4 count increased: the adjusted hazard ratio comparing more than 350 with less than 50 cells/μL was 0.27 (95% CI, 0.08-0.86). Sixty-one HL cases diagnosed on cART were matched to 1652 controls: during the year before diagnosis, cases lost 98 CD4 cells (95% CI, -159 to -36 cells), whereas controls gained 35 cells (95% CI, 24-46 cells; P < .0001). The incidence of HL is not reduced by cART, and patients whose CD4 cell counts decline despite suppression of HIV-1 replication on cART may harbor HL.

Impact of unlinked deaths and coding changes on mortality trends in the Swiss National Cohort

BackgroundResults of epidemiological studies linking census with mortality records may be affected by unlinked deaths and changes in cause of death classification. We examined these issues in the Swiss National Cohort (SNC).MethodsThe SNC is a longitudinal study of the entire Swiss population, based on the 1990 (6.8 million persons) and 2000 (7.3 million persons) censuses. Among 1,053,393 deaths recorded 1991–2007 5.4% could not be linked using stringent probabilistic linkage. We included the unlinked deaths using pragmatic linkages and compared mortality rates for selected causes with official mortality rates. We also examined the impact of the 1995 change in cause of death coding from version 8 (with some additional rules) to version 10 of the International Classification of Diseases (ICD), using Poisson regression models with restricted cubic splines. Finally, we compared results from Cox models including and excluding unlinked deaths of the association of education, marital status, and nationality with selected causes of death.ResultsSNC mortality rates underestimated all cause mortality by 9.6% (range 2.4% - 17.9%) in the 85+ population. Underestimation was less pronounced in years nearer the censuses and in the 75–84 age group. After including 99.7% of unlinked deaths, annual all cause SNC mortality rates were reflecting official rates (relative difference between −1.4% and +1.8%). In the 85+ population the rates for prostate and breast cancer dropped, by 16% and 21% respectively, between 1994 and 1995 coincident with the change in cause of death coding policy. For suicide in males almost no change was observed. Hazard ratios were only negligibly affected by including the unlinked deaths. A sudden decrease in breast (21% less, 95% confidence interval: 12% - 28%) and prostate (16% less, 95% confidence interval: 7% - 23%) cancer mortality rates in the 85+ population coincided with the 1995 change in cause of death coding policy.ConclusionsUnlinked deaths bias analyses of absolute mortality rates downwards but have little effect on relative mortality. To describe time trends of cause-specific mortality in the SNC, accounting for the unlinked deaths and for the possible effect of change in death certificate coding was necessary.