Incidence of catheter-related thrombosis in acute leukemia patients: a comparative, retrospective study of the safety of peripherally inserted vs. centrally inserted central venous catheters.

Central venous catheters are a leading cause of upper-extremity deep vein thrombosis. Concomitant severe thrombocytopenia makes anticoagulation for catheter-related thrombosis (CRT) in patients with acute leukemia (AL) a challenge. Incidence of CRT has been reported to be increased in those with peripherally inserted central catheters (PICC) vs. those with centrally inserted ones (CICC). Our objective is to compare the incidence rate of CRT in leukemia inpatients who received either a PICC vs. CICC. We retrospectively reviewed adult inpatients admitted to hematology wards with a new diagnosis of AL and who received either a PICC or a CICC. Baseline patient and catheter characteristics were recorded. Our primary outcome was the incidence rate of CRT in each group. The secondary outcomes included rates of infectious and mechanical complications. Six hundred sixty-three patients received at least one PICC (338) or CICC (325) insertion. A total of 1331 insertions were recorded, with 82 (11.7 %) and 41 (6.5 %) CRT in the PICC and CICC groups, respectively. The incidence rates were 1.89 and 0.52 per 1000 catheter day in the PICC and CICC groups, respectively. A PICC, when compared to CICC, was a significant risk factor for CRT (sHR 2.5, p < 0.0001). The prevalence and incidence rates of CRT in our AL patients were higher than predicted for a general cancer patient population. These rates were higher in the PICC group compared to the CICC group. We recommend careful consideration of thrombotic and bleeding risks of AL inpatients when choosing a central venous catheter.

Association of symptoms and breast cancer in population-based mammography screening in Finland.

The study purpose was to assess association of symptoms at screening visits with detection of breast cancer among women aged 50-69 years during the period 2006-2010. Altogether 1.2 million screening visits were made and symptoms (lump, retraction, secretion etc.) were reported either by women or radiographer. Breast cancer risk was calculated for each symptom separately using logistic regression [odds ratio (OR)] and 95% confidence intervals (CIs). Of the 1,198,410 screening visits symptoms were reported in 298,220 (25%) visits. Breast cancer detection rate for women with and without symptoms was 7.8 per 1,000 and 4.7 per 1,000 screening visits, respectively, whereas lump detected 32 cancers per 1,000 screens. Women with lump or retraction had an increased risk of breast cancer, OR = 6.47, 95% CI 5.89-7.09 and OR = 2.19, 95% CI 1.92-2.49, respectively. The sensitivity of symptoms in detecting breast carcinoma was 35.5% overall. Individual symptoms sensitivity and specificity ranged from, 0.66 to 14.8% and 87.4 to 99.7%, respectively. Of 5,541 invasive breast cancers, 1,993 (36%) reported symptoms at screen. Breast cancer risk among women with lump or retraction was higher in large size tumors (OR = 9.20, 95% CI 8.08-10.5) with poorly differentiated grades (OR = 5.91, 95% CI 5.03-6.94) and regional lymph nodes involvement (OR = 6.47, 95% CI 5.67-7.38). This study was done in a setting where breast tumors size is generally small, and symptoms sensitivity and specificity in diagnosing breast tumors were limited. Importance of breast cancer symptoms in the cancer prevention and control strategy needs to be evaluated also in other settings.

Sensitivity, effect and overdiagnosis in screening for cancers with detectable pre-invasive phase.

Studies on cancer screening often evaluate the performance by indirect indicators. In case the screening detects pre-invasive lesions, they may be a mixture of benefit of sensitivity and effect as well as of harm of overdiagnosis. Here, we develop the formulae for the sensitivity, the effect and overdiagnosis in screening for pre-invasive lesions of cancer. Sensitivity is the ability of screening to identify a progressive lesion at the level of test (relevant for the laboratory), episode (relevant in the clinic) and programme (relevant at the population level). Effect is reduction of cancer incidence in those screened (efficacy) and in the target population (effectiveness). The sensitivity is estimated by interval cancers between two consecutive screens (incidence method) and the effect by interval cancers and cancers detected at the subsequent screen. Overdiagnosis is estimated as the detection rate of pre-invasive lesions minus the rate of invasive cancer prevented by screening in one screening round. All the indicators are corrected for nonattendance and selective attendance by disease risk. The population to be followed and the period of follow-up are defined for each indicator separately. Data on cervix cancer screening with Papnet® automation device are given as an example. Estimation of sensitivity and effect are consistent with the purpose of the screening to prevent invasive disease. We further define the purpose at the level of laboratory, clinical medicine and public health and derive six estimators corresponding to the specific purposes considered in our article.

Limited reduction in Clostridioides difficile and Methicillin-Resistant Staphylococcus aureus with the use of an aerosolized hydrogen peroxide disinfection system in tertiary health care facilities in Alberta, Canada.

BACKGROUND: Nonmanual room disinfection systems may reduce the transmission of infections. A variety of systems have emerged; however, a paucity of evidence exists to make an evidence-informed decision for the implementation of a specific system. Alberta Health Services assessed one of these systems. METHODS: A quasi-experimental prepost design assessed an aerosolized hydrogen peroxide disinfection system on 6 units at 3 acute care facilities in Alberta. To assess clinical effectiveness an interrupted time-series analysis with Poisson distribution compared changes in hospital-acquired Clostridioides difficile infection (HA-CDI) and hospital-acquired Methicillin-resistant Staphylococcus aureus (HA-MRSA) between preintervention, intervention, and postintervention periods. To assess operational feasibility cleaning turnaround time, time to operate, and utilization were considered. A participatory research framework was used to understand the benefits and challenges of operationalization. RESULTS: Incidence rate ratio (IRR) of HA-CDI decreased by 25.7% on FMC-A and 6.9% on RAH-B. Following withdrawal, the IRR of HA-CDI continued to decrease. IRR of HA-MRSA decreased by 25.0% on RAH-B. Following withdrawal, the IRR of HA-MRSA continued to decrease. None of the results were statistically significant. The average time to operate was 3.2 hours. Utilization was between 1.7% and 25.6%. Most staff reported benefits and challenges. DISCUSSION: None of the changes observed in HA-CDI and HA-MRSA after the introduction of the aerosolized hydrogen peroxide system were statistically significant. While most respondents reported multiple benefits and challenges in using the system, the core challenge was delays in inpatient admissions due to the time operate the system. CONCLUSION: Successful implementation of a nonmanual room disinfection system as an addition to standard cleaning and disinfection requires significant investment and must consider a variety of factors.

Changes in Survival Outcomes of Patients With Neuroendocrine Neoplasms Over the Past 15 Years: A Real-World Study.

BACKGROUND: The past 2 decades have observed a number of advances in therapeutic approaches to patients with neuroendocrine neoplasms (NENs). This study aims to assess whether survival outcomes have changed among patients with NENs over the past 15 years, in a real-world, population-based study. MATERIALS AND METHODS: We accessed administrative databases within the province of Alberta, Canada, and we reviewed patients with invasive NENs diagnosed 2004 to 2019. Patients were classified according to the year of diagnosis into 3 groups: 2004 to 2008; 2009 to 2013; and 2014 to 2019. Kaplan-Meier survival estimates were used to compare overall survival (OS) according to different baseline characteristics (including the year of diagnosis). Multivariable Cox regression modeling was used to examine factors associated with the risk of death in this cohort. RESULTS: We included a total of 3431 patients in the study cohort. Using multivariable Cox regression analysis, the following factors were associated with worse survival: older age at diagnosis (hazard ratio [HR]: 3.45; 95% CI [confidence interval]: 2.74-4.35), male sex (HR: 1.38; 95% CI: 1.21-1.56), lung primary site (HR for lung vs. appendicular primary: 1.39; 95% CI: 1.01-1.92), Stage 4 disease (HR: 2.80; 95% CI: 2.38-3.30), South zone of the province (HR for South zone vs. Calgary zone: 1.85; 95% CI: 1.49-2.30), and higher comorbidity index (HR for ≥3 vs. 0: 2.66; 95% CI: 2.19-3.24). Although Kaplan-Meier method showed significant difference in OS according to diagnosis period, multivariable regression model showed that the period of diagnosis did not appear to impact OS (HR for diagnosis period 2004 to 2009 vs. 2014 to 2019: 1.04; 95% CI: 0.89-1.22). CONCLUSIONS: Over the study period (2004 to 2019), patients diagnosed during later periods did not appear to experience better OS compared with patients diagnosed at an earlier time.

A comparison of surgical site infections following total hip replacement and total knee replacement surgeries identified by Infection Prevention and Control and the National Surgical Quality Improvement Program in Alberta, Canada.

OBJECTIVE: To understand how the different data collections methods of the Alberta Health Services Infection Prevention and Control Program (IPC) and the National Surgical Quality Improvement Program (NSQIP) are affecting reported rates of surgical site infections (SSIs) following total hip replacements (THRs) and total knee replacements (TKRs). DESIGN: Retrospective cohort study. SETTING: Four hospitals in Alberta, Canada. PATIENTS: Those with THR or TKR surgeries between September 1, 2015, and March 31, 2018. METHODS: Demographic information, complex SSIs reported by IPC and NSQIP were compared and then IPC and NSQIP data were matched with percent agreement and Cohen's κ calculated. Statistical analysis was performed for age, gender and complex SSIs. A P value <.05 was considered significant. RESULTS: In total, 7,549 IPC and 2,037 NSQIP patients were compared. The complex SSI rate for NSQIP was higher compared to IPC (THR: 1.19 vs 0.68 [P = .147]; TKR: 0.92 vs 0.80 [P = .682]). After matching, 7 SSIs were identified by both IPC and NSQIP; 3 were identified only by IPC, and 12 were identified only by NSQIP (positive agreement, 0.48; negative agreement, 1.0; κ = 0.48). CONCLUSIONS: Different approaches to monitor SSIs may lead to different results and trending patterns. NSQIP reports total SSI rates that are consistently higher than IPC. If systems are compared at any point in time, confidence on the data may be eroded. Stakeholders need to be aware of these variations and education provided to facilitate an understanding of differences and a consistent approach to SSI surveillance monitoring over time.

Cervical cancer patterns with automation-assisted and conventional cytological screening: a randomized study.

The purpose was to evaluate alternative cytological screening methods in population-based screening for cervical cancer up to cancer incidence and mortality outcome. Automation-assisted screening was compared to conventional cytological screening in a randomized design. The study was based on follow-up of 503,391 women invited in the Finnish cervical cancer screening program during 1999-2003. The endpoints were incident cervical cancer, severe intraepithelial neoplasia and deaths from cervical cancer. One third of the women had been randomly allocated to automation-assisted screening and two thirds to conventional cytology. Information on cervical cancer and severe neoplasia were obtained through 1999-2007 from a linkage between screening and cancer registry files. There were altogether 3.2 million woman-years at risk, and the average follow-up time was 6.3 years. There was no difference in the risk of cervical cancer between the automation-assisted and conventional screening methods; the relative risk (RR) of cervical cancer between the study and control arm was 1.00 (95% confidence interval [CI] = 0.76-1.29) among all invited and 1.08 (95% CI = 0.76-1.51) among women who were test negative at entry. Comparing women who were test negative with nonscreened, RR of cervical cancer incidence was 0.26, 95% CI = 0.19-0.36 and of mortality 0.24 (0.13-0.43). Both methods were valid for screening. Because cervical cancer is rare in our country, we cannot rule out small differences between methods. Evidence on alternative methods for cervical cancer screening is increasing and it is thus feasible to evaluate new methods in large-scale population-based screening programs up to cancer outcome.

A Greenwood formula for standard error of the age-standardised relative survival ratio.

The age-standardised relative survival ratio is used to compare population-based cancer survival patterns when the population age structures differ. Traditionally, the direct standardisation method based on age-specific relative survival ratios has been used. In a new method [Brenner H, Arndt V, Gefeller O, Hakulinen T. An alternative approach to age adjustment of cancer survival rates. Eur J Cancer 2004;40:2317-22], weighted observations depending on the age structures of the study and standard populations are used to substitute the patients leading to a use of weighted counts. The relative survival ratio is then calculated in the conventional way. However, no standard error of the age-standardised relative survival estimate has been reported. In this paper, we introduce a generalisation of the well-known Greenwood formula for that purpose. This method is also applicable for the observed survival and particularly when the observed survival probabilities of the patient population differ by age stratum. The traditional Greenwood formula is a special case of the method when no specific weights are used and the observed survival probability is the same in each stratum. Data from the Finnish Cancer Registry are used for illustration.

Choosing the net survival method for cancer survival estimation.

BACKGROUND: A new net survival method has been introduced by Pohar Perme et al. (2012 [4]) and recommended to substitute the relative survival methods in current use for evaluating population-based cancer survival. METHODS: The new method is based on the use of continuous follow-up time, and is unbiased only under non-informative censoring of the observed survival. However, the population-based cancer survival is often evaluated based on annually or monthly tabulated follow-up intervals. An empirical investigation based on data from the Finnish Cancer Registry was made into the practical importance of the censoring and the level of data tabulation. A systematic comparison was made against the earlier recommended Ederer II method of relative survival using the two currently available computer programs (Pohar Perme (2013) [10] and Dickman et al. (2013) [11]). RESULTS: With exact or monthly tabulated data, the Pohar-Perme and the Ederer II methods give, on average, results that are at five years of follow-up less than 0.5% units and at 10 and 14 years 1-2% units apart from each other. The Pohar-Perme net survival estimator is prone to random variation and may result in biased estimates when exact follow-up times are not available or follow-up is incomplete. With annually tabulated follow-up times, estimates can deviate substantially from those based on more accurate observations, if the actuarial approach is not used. CONCLUSION: At 5 years, both the methods perform well. In longer follow-up, the Pohar-Perme estimates should be interpreted with caution using error margins. The actuarial approach should be preferred, if data are annually tabulated.

Kidney cancer risk in oil refining in Finland: a nested case-referent study.

OBJECTIVE: The purpose of this study was to assess whether occupational exposure to hydrocarbons in the oil-refining activity increases the risk of kidney cancer. METHODS: This case-referent study was nested within the cohort of employees in the oil refinery industry in Finland in 1967 to 1982 (n = 9454). The final data included 30 cases of kidney cancer and 81 age- and sex-matched referents. RESULTS: There was a threefold increase in the kidney cancer risk for exposure to hydrocarbons in crude oil (odds ratio, 3.1; confidence interval, 1.1 to 8.9; 11 exposed cases). The risk was associated with the highest cumulative exposure category to hydrocarbons in crude oil. CONCLUSIONS: Occupational exposure in oil refining, particularly to crude oil, may increase kidney cancer risk. The study assessed historical exposures; further information needs to be collected for evaluating current exposures.

Survival of Sami cancer patients.

OBJECTIVES: The incidence of cancer among the indigenous Sami people of Northern Finland is lower than among the Finnish general population. The survival of Sami cancer patients is not known, and therefore it is the object of this study. STUDY DESIGN: The cohort consisted of 2,091 Sami and 4,161 non-Sami who lived on 31 December 1978 in the two Sami municipalities of Inari and Utsjoki, which are located in Northern Finland and are 300-500 km away from the nearest central hospital. The survival experience of Sami and non-Sami cancer patients diagnosed in this cohort during 1979-2009 was compared with that of the Finnish patients outside the cohort. METHODS: The Sami and non-Sami cancer patients were matched to other Finnish cancer patients for gender, age and year of diagnosis and for the site of cancer. An additional matching was done for the stage at diagnosis. Cancer-specific survival analyses were made using the Kaplan-Meier method and Cox regression modelling. RESULTS: There were 204 Sami and 391 non-Sami cancer cases in the cohort, 20,181 matched controls without matching with stage, and 7,874 stage-matched controls. In the cancer-specific analysis without stage variable, the hazard ratio for Sami was 1.05 (95% confidence interval 0.85-1.30) and for non-Sami 1.02 (0.86-1.20), indicating no difference between the survival of those groups and other patients in Finland. Likewise, when the same was done by also matching the stage, there was no difference in cancer survival. CONCLUSION: Long distances to medical care or Sami ethnicity have no influence on the cancer patient survival in Northern Finland.

Detection rates of precancerous and cancerous cervical lesions within one screening round of primary human papillomavirus DNA testing: prospective randomised trial in Finland.

OBJECTIVE: To compare the detection rates of precancerous and cancerous cervical lesions by human papillomavirus (HPV) DNA testing and by conventional cytology screening. DESIGN: Prospective randomised trial. Two cohorts were followed over one screening round of five years, screened initially by primary HPV DNA testing or by primary Pap test. SETTING: Population based programme for cervical cancer screening in Finland. PARTICIPANTS: Women aged 25-65 years invited for screening in 2003-07 (101,678 in HPV arm; 101,747 in conventional cytology arm). INTERVENTION: Women were randomly allocated (1:1) to primary HPV DNA screening followed by cytology triage if they had positive results, or to primary cytology screening. Screening method was disclosed at the screening visit. Trial personnel involved were aware of all test results. MAIN OUTCOME MEASURES: Cumulative detection rates of cervical intraepithelial neoplasia (CIN), adenocarcinoma in situ (AIS), and invasive cervical cancer before the second screening (after five years) or before 31 December 2008. Lesions detected at screening and during the five year interval were included. RESULTS: 1010 and 701 precancerous or cancerous lesions were detected during an average follow-up of 3.6 years in the HPV and cytology arms, respectively. Among invited women, the hazard ratio was 1.53 (95% confidence interval l.28 to 1.84) for CIN grade 1, 1.54 (1.33 to 1.78) for CIN 2, 1.32 (1.09 to 1.59) for CIN 3 or AIS, and 0.81 (0.48 to 1.37) for cervical cancer. In 25-34 year old participants, the cumulative hazard (or cumulative detection rate) was 0.0057 (0.0045 to 0.0072) for HPV screening versus 0.0046 (0.0035 to 0.0059) for conventional screening; corresponding data for women aged 35 years and older were 0.0022 (0.0019 to 0.0026) and 0.0017 (0.0014 to 0.0021), respectively. CONCLUSIONS: Primary HPV DNA screening detects more cervical lesions than primary cytology within one screening round of five years. Even if the detection rate of CIN 3 or AIS increased in the HPV arm in both age groups, the absolute difference in cumulative rates in women aged 35 years or older was small. By carefully selecting age groups and screening intervals, HPV screening could increase the overall detection rate of cervical precancerous lesions only slightly. However, these findings should be interpreted in the context of the high level of opportunistic screening that occurs in Finland. TRIAL REGISTRATION: International Standard Randomised Controlled Trial ISRCTN23885553.

Merkel cell carcinoma - a population-based epidemiological study in Finland with a clinical series of 181 cases.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignancy of the skin, and its incidence is reported to be rising. The purpose of this study was to calculate its incidence and survival ratios, and to describe the clinical characteristics of Merkel cell carcinoma patients in Finland. METHODS: We calculated the incidence of MCC based on data from the Finnish Cancer Registry. In addition, patient files from hospitals and primary health care centres were reviewed for detailed data on the treatment and disease recurrence of 181 patients diagnosed with MCC in Finland during 1983-2004, and relative survival ratios were calculated for them. RESULTS: The incidence (per 100,000) of MCC in Finland in 1989-2008 was 0.11 for men and 0.12 for women, adjusted for age to the world standard population. The mean age at diagnosis was 76 years (range 27-100), and 69% of the patients were women. The most common site of the primary tumour was the head and neck (53%). No extra benefit was gained from a wide surgical margin (≥ 2 cm) compared to a margin of 0.1-0.19 cm, but an intralesional excision was more often associated with local recurrence. None of the patients with Stage I-II disease who had received postoperative radiotherapy to the tumour bed had a local recurrence. The 5-year relative survival ratio amongst men was 36% (95% confidence interval 20-54%), and amongst women 69% (56 to -82%). CONCLUSIONS: MCC is a rare disease in Finland, with incidence rates similar to those in the other Nordic countries. Our results support the view that complete excision with clear margins and post operative radiotherapy decrease local recurrences.

Age-standardisation of relative survival ratios of cancer patients in a comparison between countries, genders and time periods.

A recent method of age-standardisation of relative survival ratios for cancer patients does not require calculation of age-specific relative survival ratios, as ratios of age-specific proportions between the standard population and study group at the beginning of the follow-up are used to substitute the original individual observations. This method, however, leads to direct age-standardisation with weights that are different for each patient group if the general population mortality patterns for the groups are different. This is the case in international comparisons, and in comparisons between genders and time periods. The magnitude of the bias caused by the differences in general population mortality is investigated for comparisons involving European countries and the USA. Patients in each country are assumed to have exactly the same age-specific relative survival ratios as those diagnosed in Finland in 1985-2004. An application of a properly functioning age-standardisation method should then give exactly equal age-standardised relative survival ratios for each country. However, the recent method shows substantial differences between countries, with highest relative survival for populations, where the general population mortality in the oldest ages is the highest. This source of error can thus be a serious limitation for the use of the method, and other methods that are available should then be employed.

How to interpret the relative survival ratios of cancer patients.

It is common in population-based cancer registries to use the relative survival ratio to estimate patients' probabilities of surviving if their cancer were the only cause of death. Results from the recently proposed new methods of age-standardisation can be interpreted as ratios between the observed and expected survival proportions. Like the non-standardised ratios, these age-standardised relative survival ratios have, however, the desired probability interpretation only under a specific condition. The condition involved is the survival with respect to other causes up to the given point of follow-up. With different lengths of follow-up, this condition is also different. As a consequence, the non-standardised relative survival ratios and those standardised with the two newest methods produce, for different lengths of follow-up, mutually incomparable estimates with respect to age. Not accounting for this may, for example, lead to erroneous conclusions about the cure of the patients. The traditional method of age-standardisation does not have this problem of incomparability. Results of relative survival analyses of data from the Finnish Cancer Registry are used to illustrate this issue. To avoid overinterpretation and confusion, the different interpretations of the relative survival ratios, both non-standardised and age-standardised, must be known. For example, the very popular cumulative relative survival curves, consisting of consecutive cumulative relative survival ratios, should not be produced for the non-standardised ratios or for ratios age-standardised with the two newest methods. In practical applications, it is crucial to know which method of standardisation, and not only which standard population, has been in use.