Evidence of survival benefit was often ambiguous in randomized trials of cancer treatments.

OBJECTIVES: The objective of the study is to estimate the proportion of statistically significant survival improvements reported in randomized trials of cancer treatments that are also compatible with a clinically negligible benefit. STUDY DESIGN AND SETTING: This is a cross-sectional study of reports of randomized clinical trials of cancer treatments that reported a statistically significant increase in overall survival, published in leading journals between 2009 and 2019. The main outcome variable was the hazard ratio (HR) for overall survival and its upper 95% confidence limit. An HR of 0.95 implies an absolute survival gain ≤1.9%, and an HR of 0.90 implies an absolute survival gain ≤3.8%; we reasoned that such survival gains can be considered clinically negligible, given the potential toxicity of oncologic treatments. RESULTS: Among 234 trial results, the mean point estimate of the HR was 0.664, and all HRs were below 0.90. The mean upper 95% confidence limit for the HR was 0.897, but 37.6% of the values were ≥0.95, and 59.0% were ≥0.90. These proportions were lower when overall survival was the primary outcome of the trial (29.9% ≥ 0.95 and 51.3% ≥ 0.90). CONCLUSIONS: Considering only point estimates of HRs, all trials reported clinically meaningful improvements in overall survival. However, the upper confidence limits of a large proportion of HRs were also compatible with clinically negligible survival gains. Acknowledging the uncertainty regarding treatment benefits presents a challenge for the reporting of trial results and for clinical decision-making.

Factors associated with patient willingness to participate in anaesthesia clinical trials: a vignette-based cross-sectional study.

BACKGROUND: Clinical trials are essential to improve knowledge of anesthesia and perioperative medicine. Unfortunately, many studies face participant-recruitment issues and fail to include the planned number of participants. There is limited published data about how information delivered about the study or how the experiences and attitudes of prospective participants influence willingness to participate. The purpose of this study was to identify such factors in the domain of anesthesia care. METHODS: We performed a cross-sectional study at the Geneva University Hospitals (Switzerland) using a newly developed paper-based questionnaire on a sample of outpatients with a recent hospital stay and that were aged over 18 years, confident speaking French and free of any disease that could hinder participation. We explored patient personal factors, such as current health, past exposure to clinical research and anesthesia, as well as study-related factors. Six different scenarios for clinical studies were assessed. Linear regression modeling was used to assess the specific association between personal and study-related factors and willingness to participate in the studies described in the scenarios. RESULTS: On the 1318 eligible patients, 398 fully completed the questionnaire. Multivariable adjustment revealed that factors related to altruistic values (ß, 9.6, 95% CI 3.4 to 15.7, P = 0.002), to the feeling of benefiting from a more effective treatment (ß, 4.7, 95% CI 0.2 to 9.2, P = 0.041) and to the absence of fear about double blinding (ß, 5.7, 95% CI 1.3 to 10.2, P = 0.012) were positively associated with willingness to participate. Conversely, concerns about drug-related adverse effects (ß, - 11.7, 95% CI - 16.9 to - 6.5, P < 0.001) and anxiety about surgery (ß, - 5.2, 95% CI - 10.0 to - 0.5, P = 0.031) were negatively associated with willingness to participate. CONCLUSION: Our study was based on vignettes illustrating typical scenarios of clinical trials performed in anesthesia. However, their similarities with real studies still remains hypothetical and our results should be interpreted as such. Nevertheless, the study contributes to improve understanding of factors that may act as incentives or barriers to participation in clinical trials. It highlights the importance of providing appropriate information and reassurance to patients.

Zika Virus Infection during Pregnancy and Effects on Early Childhood Development, French Polynesia, 2013-2016.

Congenital Zika virus syndrome consists of a large spectrum of neurologic abnormalities seen in infants infected with Zika virus in utero. However, little is known about the effects of Zika virus intrauterine infection on the neurocognitive development of children born without birth defects. Using a case-control study design, we investigated the temporal association of a cluster of congenital defects with Zika virus infection. In a nested study, we also assessed the early childhood development of children recruited in the initial study as controls who were born without known birth defects,. We found evidence for an association of congenital defects with both maternal Zika virus seropositivity (time of infection unknown) and symptomatic Zika virus infection during pregnancy. Although the early childhood development assessment found no excess burden of developmental delay associated with maternal Zika virus infection, larger, longer-term studies are needed.

Iterative algorithms for metal artifact reduction in children with orthopedic prostheses: preliminary results.

BACKGROUND: Increased computational power allows computed tomography (CT) software to process very advanced mathematical algorithms to generate better quality images at lower doses. One such algorithm, iterative metal artifact reduction (iMAR) has proven to decrease metal artifacts seen in CT images of adults with orthopedic implants. OBJECTIVES: To evaluate artifact reduction capability of the algorithm in lower-dose pediatric CT compared to our routine third-generation advanced modeled iterative reconstruction (ADMIRE) algorithm. MATERIALS AND METHODS: Thirteen children (11-17 years old) with metal implants underwent routine clinically indicated CT. Data sets were reconstructed with an iMAR algorithm. Hounsfield units and image noise were measured in bone, muscle and fat in the streak artifact (near the implant) and at the greatest distance from the artifact (far from the implant). A regression model compared the effects of the algorithm (standard ADMIRE vs. iMAR) near and far from the implant. RESULTS: Near the implant, Hounsfield units with iMAR were significantly different in our standard ADMIRE vs. iMAR for bone, muscle and fat (P<0.001). Noise was significantly different in standard ADMIRE vs. iMAR in bone (P<0.003). Far from the implant, Hounsfield units and noise were not significantly different for ADMIRE vs. iMAR, for the three tissue types. CONCLUSION: These preliminary results demonstrate that iMAR algorithms improves Hounsfield units near the implant and decreases image noise in bone in low-dose pediatric CT. It does this without changing baseline tissue density or noise far from the implant.

Descriptive epidemiology of parkinsonism in the Canton of Geneva, Switzerland.

OBJECTIVES: A large descriptive cross-sectional population-based prevalence study as well as a retrospective incidence study were undertaken to ascertain the frequency of Parkinson's Disease (PD) and other types of degenerative and non-degenerative parkinsonism in the Canton of Geneva, Switzerland. METHODS: An extensive case-finding approach including records from public hospitals, private neurologists and nursing homes was utilized. All patients with a diagnosis of parkinsonism established between 2003 and 2012 were included. Diagnosis of parkinsonism was ascertained by a movement disorders specialist, based on published and validated consensus diagnostic criteria. RESULTS: A total of 1235 living patients with parkinsonism were identified, from which 80% presented with a degenerative form and 20% with a non-degenerative form of parkinsonism. Among the former, PD was the most frequent diagnosis (81%, age-adjusted prevalence: 183/105 inhabitants, age-adjusted average annual incidence: 20/105/year) followed by dementia with Lewy bodies (9%), progressive supranuclear palsy (3.9%), multisystem atrophy (1.9%) and corticobasal syndrome (1.4%). Among non-degenerative parkinsonism, drug-induced parkinsonism was the most frequent diagnosis (43.4%), followed by vascular parkinsonism (37%), normal pressure hydrocephalus (5.1%) and parkinsonism in the context of a psychiatric disorder or functional parkinsonism (3.8%). Crude, age-, sex-specific and age-adjusted prevalence and incidence of all types of parkinsonism are detailed for each diagnosis. CONCLUSION: This is the first Swiss population-based epidemiological study of PD and parkinsonism. It provides an extensive overview of the prevalence and incidence of degenerative and non-degenerative forms of parkinsonism. These data may assist clinicians with their clinical workup.

Respiratory changes in subclavian vein diameters predicts fluid responsiveness in intensive care patients: a pilot study.

The present pilot study investigated whether respiratory variation in subclavian vein (SCV) diameters correlates with fluid responsiveness in mechanically ventilated patients. Monocentric, prospective clinical study on fluid responsiveness in adult sedated, mechanically ventilated ICU patient, monitored with the PiCCO™ system (Pulsion Medical System, Germany), and requiring a fluid challenge (FC). A 10-min fluid bolus of 500 mL of 0.9% saline was administered. Cardiac output (CO) and dynamic parameters [stroke volume variation (SVV) and pulse pressure variation (PPV)] measured by transpulmonary thermodilution and pulse contour analysis (PiCCO™) as well as classical hemodynamic parameters were recorded at baseline and after FC. Fluid responsiveness was described as an increase in CO of ≥ 15%. Ultrasound measurements obtained in the subclavian long-axis view were used to calculate the SCVvariability index. A cut-off value for SCV variation for the prediction of fluid responsiveness was determined using receiver operating curve (ROC) analysis. Nine of 20 FCs (45%) induced an increase in CO of ≥ 15%. At baseline, the SCVvariability index was greater in responders than in non-responders (34.0 ± 21.4 vs. 9.0 ± 5.5; p = 0.0005). Diagnostic performance for the SCVvariability index revealed a cut-off value of 14 with a sensitivity of 100% [Confidence interval (CI) 95% (90; 100)] and a specificity of 82% [CI 95% (48; 98)] for the prediction of fluid responsiveness. Other parameters, such as SVV and PPV, could not predict fluid responsiveness. The correlation coefficient between CO variation and the SCVvariability index was 0.73 (p < 0.001). The SCVvariability index was a reliable, non-invasive parameter for the prediction of fluid responsiveness at the bedside of mechanically ventilated, critically ill patients in this pilot study.

Lack of association between fingernail selenium and thyroid cancer risk: a case-control study in French Polynesia.

BACKGROUND: Numerous studies have suggested that selenium deficiency may be associated with an increased risk for several types of cancer, but few have focused on thyroid cancer. MATERIALS AND METHODS: We examined the association between post-diagnostic fingernail selenium levels and differentiated thyroid cancer risk in a French Polynesian matched case-control study. Conditional logistic regression models were used to estimate odds ratios and 95% confidence intervals. RESULTS: The median selenium concentration among controls was 0.76 µg/g. Significantly, we found no association between fingernail selenium levels and thyroid cancer risk after conditioning on year of birth and sex and additionally adjusting for date of birth (highest versus lowest quartile: odds-ratio=1.12, 95% confidence interval: 0.66-1.90; p-trend=0.30). After additional adjustment for other covariates, this association remained non-significant (p-trend=0.60). When restricting the analysis to thyroid cancer of 10 mm or more, selenium in nails was non-significantly positively linked to thyroid cancer risk (p-trend=0.09). Although no significant interaction was evidenced between iodine in nails and selenium in nails effect (p=0.70), a non-significant (p-trend =0.10) positive association between selenium and thyroid cancer risk was seen in patients with less than 3 ppm of iodine in nails. The highest fingernail selenium concentration in French Polynesia was in the Marquises Islands (M=0.87 µg/g) and in the Tuamotu-Gambier Archipelago (M=0.86 µg/g). CONCLUSIONS: Our results do not support, among individuals with sufficient levels of selenium, that greater long-term exposure to selenium may reduce thyroid cancer risk. Because these findings are based on post-diagnostic measures, studies with prediagnostic selenium are needed for corroboration.

Differentiated thyroid carcinoma risk factors in French Polynesia.

BACKGROUND: To investigate differentiated thyroid cancer risk factors in natives of French Polynesia is of interest because of the very high incidence of this cancer in the archipelago. MATERIALS AND METHODS: To assess the role of various potential risk factors of thyroid cancer in the natives of French Polynesia we performed a case-control study. The study included almost all the French Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 (n=229) and 373 French Polynesian control individuals from the general population without cancer. RESULTS: Thyroid radiation dose received from nuclear fallout before the age of 15, a personal history of neck or/and head medical irradiation, obesity, tallness, large number of children, an artificial menopause, a familial history of thyroid cancer, a low dietary iodine intake, and having a spring as the main source of drinking water were found to be significant risk factors. No roles of smoking habits, alcohol consumption, iodine containing drugs, and exposure to pesticides were evidenced. CONCLUSIONS: Except for smoking, differentiated thyroid carcinoma risk factors in natives of French Polynesia are similar to those in other populations. Our finding on the role of having a spring as a drinking water origin is coherent with some other studies and could be due to geological factors.

Long-term cardiovascular mortality after radiotherapy for breast cancer.

OBJECTIVES: This study sought to investigate long-term cardiovascular mortality and its relationship to the use of radiotherapy for breast cancer. BACKGROUND: Cardiovascular diseases are among the main long-term complications of radiotherapy, but knowledge is limited regarding long-term risks because published studies have, on average, <20 years of follow-up. METHODS: A total of 4,456 women who survived at least 5 years after treatment of a breast cancer at the Institut Gustave Roussy between 1954 and 1984 were followed up for mortality until the end of 2003, for over 28 years on average. RESULTS: A total of 421 deaths due to cardiovascular diseases were observed, of which 236 were due to cardiac disease. Women who had received radiotherapy had a 1.76-fold (95% confidence interval [CI]: 1.34 to 2.31) higher risk of dying of cardiac disease and a 1.33-fold (95% CI: 0.99 to 1.80) higher risk of dying of vascular disease than those who had not received radiotherapy. Among women who had received radiotherapy, those who had been treated for a left-sided breast cancer had a 1.56-fold (95% CI: 1.27 to 1.90) higher risk of dying of cardiac disease than those treated for a right-sided breast cancer. This relative risk increased with time since the breast cancer diagnosis (p = 0.05). CONCLUSIONS: This study confirmed that radiotherapy, as delivered until the mid-1980s, increased the long-term risk of dying of cardiovascular diseases. The long-term risk of dying of cardiac disease is a particular concern for women treated for a left-sided breast cancer with contemporary tangential breast or chest wall radiotherapy. This risk may increase with a longer follow-up, even after 20 years following radiotherapy.

Pooled analysis of two case-control studies in New Caledonia and French Polynesia of body mass index and differentiated thyroid cancer: the importance of body surface area.

BACKGROUND: New Caledonia and French Polynesia have among of the world highest thyroid cancer incidence rates. Studies have demonstrated a relationship between anthropometric parameters and the prevalence of cancer. In this study we evaluated further the relationship between body mass index (BMI) and other anthropometric parameters on the incidence of thyroid cancer in the New Caledonia and French Polynesia populations. METHODS: We performed a pooled analysis of two case-control studies in New Caledonia and French Polynesia. We included a total of 554 cases (65 men and 489 women) of differentiated thyroid cancers and 776 population control subjects matched on sex, age, and study. Anthropometric factors (height, weight, BMI, body fat percentage [BF%], and body surface area [BSA]), at age 18 and before diagnosis, were analyzed by conditional logistic regression, adjusting for other independent risk factors. RESULTS: A high proportion of cases (73%) were overweight (25-29.9 kg/m(2)) or obese (≥30 kg/m(2)) before diagnosis of thyroid cancer (against 57% of control subjects). An increased risk of thyroid cancer was observed with greater height, weight, BMI, BF%, and BSA. The association of thyroid cancer risk with height, weight, BMI, and BF% did not remain when adjustment was made for BSA. By comparison, the odds ratios for the highest versus the lowest quartile of BSA at age 18 were 3.97 (95% confidence interval, 2.57-6.15; p < 0.001) for women and 4.06 (95% confidence interval, 1.03-16.06; p = 0.04) for men. The association between thyroid cancer risk and each of anthropometric factors did not depend on tumor size or menopausal status before diagnosis. CONCLUSION: Among anthropometric factors, BSA plays a dominant role in thyroid cancer risk and explains the apparent role of BMI.

Family history of thyroid cancer and the risk of differentiated thyroid cancer in French polynesia.

BACKGROUND: Differentiated thyroid carcinoma is considered to be the nonhereditary cancer for which familial inheritance is the highest. To date, no familial aggregation analysis of this cancer has been performed in Maohi populations, which exhibit a very high incidence rate. Therefore, we evaluate the risk of differentiated thyroid cancer associated with a family history of thyroid cancer in natives of French Polynesia. METHODS: We investigated thyroid cancer incidence in the first-degree relatives of 225 cases of differentiated thyroid carcinomas diagnosed between 1979 and 2004 in patients born in French Polynesia, and 368 randomly selected population controls matched for sex and age, born and residing in French Polynesia. All but five thyroid cancers declared among relatives were validated. RESULTS: Twenty-four cases declared a family history of thyroid cancer, when compared with 11 controls. Individuals with an affected first-degree relative had a 4.5-fold (95% confidence interval [CI], 1.9-10.6) increased risk of differentiated thyroid cancer. This odds ratio (OR) was not significantly higher when a male first-degree relative was affected (OR, 10.0; 95% CI, 1.3-74.8) compared with a female (OR, 4.0; 95% CI, 1.5-10.3) and was not different for patients who had a nonaggressive thyroid microcarcinoma (OR, 3.5; 95% CI, 0.6-16.4) than those who had a larger cancer (OR, 6.0; 95% CI, 1.8-20.5). This OR was borderline significantly (p, 0.07) higher in Maohis (OR, 11.0; 95% CI, 2.4-48.8) than in individuals of mixed origin (OR, 2.1; 95% CI, 0.8-5.9). CONCLUSION: Our study shows that the familial inheritance of differentiated thyroid cancer is particularly high in Maohi populations.

Anthropometric factors in differentiated thyroid cancer in French Polynesia: a case-control study.

OBJECTIVES: French Polynesia has one of the world's highest thyroid cancer incidence rates. A case-control study among native residents of French Polynesia included 219 cases of differentiated thyroid cancers diagnosed between 1979 and 2004 (195 women/24 men) matched with 359 population controls (315 women/44 men) on the date of birth. METHODS: Anthropometric factors were analyzed by conditional logistic regression. RESULTS: The risk of thyroid cancer for women in the highest quartile of body mass index (BMI) before diagnosis and at age 18 was 2.3-fold higher (95% CI, 1.1-4.7 p = 0.04) and 2.3-fold higher (95% CI, 1.2-4.4 p < 0.01), respectively, compared with the lowest. Women who were overweight (BMI = 25-29.9 kg/m2) or obese (BMI > or = 30 kg/m2) at age 18 and before diagnosis had an increased risk compared with those with a normal lifelong weight (OR = 6.2; 95% CI, 2.5-15.5 p < 0.01). Results for excess weight appeared in similar directions for men, although the number of cases was too small to provide reliable estimates. Height was positively associated with thyroid cancer among men and women. CONCLUSION: This study shows the role of excess body weight, especially if the onset is during early adulthood, and elevated height in the risk of differentiated thyroid cancer in populations born in French Polynesia.

Reconstruction of individual radiation doses for a case-control study of thyroid cancer in French Polynesia.

Forty-one atmospheric nuclear weapons tests (plus five safety tests) were conducted in French Polynesia between 1966 and 1974. To evaluate the potential role of atmospheric nuclear weapons testing on a high incidence of thyroid cancer observed since 1985 in French Polynesia, a population-based case-control study was performed. The study included 602 subjects, either cases or controls, all aged less than 40 y at the end of nuclear weapons testing in 1974. Radiation doses to the thyroids of the study subjects were assessed based on the available historical results of radiation measurements. These were mainly found in the annual reports on the radiological situation in French Polynesia that had been sent to the UNSCEAR Secretariat. For each atmospheric nuclear weapons test that contributed substantially to the local deposition of radionuclides, the radiation dose to the thyroid from I intake was estimated. In addition, thyroid doses from the intake of short-lived radioiodines (132I, 133I, 135I) and 132Te, external exposure from gamma-emitted radionuclides deposited on the ground, and ingestion of long-lived Cs were reconstructed. The mean thyroid dose among the study subjects was found to be around 3 mGy while the highest dose was estimated to be around 40 mGy. Doses from short-lived iodine and tellurium isotopes ranged up to 10 mGy. Thyroid doses from external exposure ranged up to 3 mGy, while those from internal exposure due to cesium ingestion did not exceed 1 mGy. The dose estimates that have been obtained are based on a rather limited number of radiation measurements performed on a limited number of islands and are highly uncertain. A thorough compilation of the results of all radiation monitoring that was performed in French Polynesia in 1966-1974 would be likely to greatly improve the reliability and the precision of the dose estimates.

Menstrual and reproductive factors in the risk of differentiated thyroid carcinoma in native women in French Polynesia: a population-based case-control study.

French Polynesia has one of the world's highest incidence rates of thyroid cancer. A case-control study among native residents of French Polynesia included 201 women diagnosed with differentiated thyroid cancer before the age of 56 years, between 1981 and 2004, matched to 324 population controls on date of birth. Face-to-face interviews were conducted from 2002 to 2004. Odds ratios were calculated by using conditional logistic regression and were reported in the total group and by ethnic group ("Polynesian" vs. "mixed"). The risk of thyroid cancer increased with natural (odds ratio = 1.9) or artificial (odds ratio = 4.5) menopause compared with that associated with a premenopausal status and with number of births (p for trend = 0.03): odds ratios for one, two, three, four or five, six or seven, and eight or more births were, respectively, 0.90, 1.6, 2.3, 2.2, 2.7, and 1.7 compared with a nulliparous status. Similar results were observed for Polynesian women. No association was observed with irregular menstrual cycles, age at menopause, history of miscarriage or induced abortion, time since last birth, age at and outcome of first pregnancy, or breastfeeding. This study confirms the role of menstrual and reproductive factors in the risk of differentiated thyroid cancer in Pacific island populations.

Dietary patterns and blood pressure change over 5-y follow-up in the SU.VI.MAX cohort.

BACKGROUND: Although short-term effects of the Dietary Approaches to Stop Hypertension (DASH) diet on blood pressure have been shown in intervention studies, less is known about the long-term effects. OBJECTIVE: The aim was to study the relation between dietary patterns based on DASH diet characteristics and blood pressure (BP) and BP change in a clinical trial of antioxidants conducted in France from 1994 to 2002. DESIGN: Repeated 24-h dietary records were collected during the first year of follow-up. Dietary variables studied included fruit and vegetables, dairy products and fat (defined by Keys score), and two hypothesis-oriented scores based on the DASH diet. We performed a cross-sectional analysis of BP measured at the first clinical examination (1995-1996) in 4652 participants aged 35-63 y and a longitudinal analysis of BP change over a median follow-up of 5.4 y (n = 2341). RESULTS: The mean increases in systolic (SBP) and diastolic (DBP) BPs were 9.3 and 4.5 mm Hg, respectively. After adjustment for potential confounders, higher fruit and vegetable consumption was associated with lower SBP and DBP at first clinical examination (P for trend < 0.02 for both) and a lower 5-y increase in SBP (-2.1 mm Hg in the 4th compared with the 1st quartile; P for trend < 0.004) and DBP (-0.7 mm Hg in the 4th compared with the 1st quartile; P for trend < 0.03). The 2 DASH scores also were significantly associated with a lower BP at the first clinical examination and a lower BP increase. No significant relations were observed with dairy products or Keys score in either analyses. CONCLUSION: These results suggest that high fruit and vegetable intakes may be associated with a lower increase in BP with aging.

Prevalence, awareness, treatment, and control of hypertension in the elderly: the Three City study.

OBJECTIVE: To study management of hypertension in the elderly in a large population-based study and to evaluate the prevalence of hypertension and factors related to awareness, treatment, and control. DESIGN: The Three City study, a population-based study among 9693 non-institutionalized individuals aged 65 years and over. METHODS: Blood pressure was measured with an automated electronic device, and treatment assessed, during home interview. Hypertension was defined by a mean blood pressure of two measurements superior to or equal to 160/95 mmHg and/or the intake of antihypertensive medications. RESULTS: In the final working sample of 9090 people, 62% were hypertensive. More than two-thirds were aware of their hypertension and 81% were treated with antihypertensive drugs. Among 4573 treated hypertensive participants, 35% had a blood pressure over 160/95 mmHg and 69% over 140/90 mmHg. Women were more frequently aware of their hypertension, more frequently treated, and more frequently controlled than men. A history of cardiovascular disease, high body mass index, diabetes and high frequency of visits to the general practitioner were related to higher percentages of awareness and treatment. Among treated hypertensive patients, those with a history of cardiovascular events or who visited their general practitioner more often or who more often had their blood pressure measured were more frequently controlled. Awareness was strongly associated with treatment, but was inversely related to control of hypertension among treated hypertensive patients. CONCLUSIONS: Management of hypertension, and particularly its control among treated hypertensive patients, needs to be improved in people aged 65 years and over.