StATS: Answers to "Own Your Own" exercises in Statistical Evidence.
Here are answers to the exercises listed at the end of each chapter.
Chapter 1. Apples or Oranges?
1. Review the following abstracts, all from studies where randomization was not done. Speculate on the reason that randomization was not performed.
Body Fatness During Childhood and Adolescence and Incidence of Breast Cancer in Pre-Menopausal Women: A Prospective Cohort Study. Heather J Baer, Graham A Colditz, Bernard Rosner, Karin B Michels, Janet W Rich-Edwards, David J Hunter and Walter C Willett. Breast Cancer Research 2005, 7:R314-R325 doi:10.1186/bcr998. Introduction: Body mass index (BMI) during adulthood is inversely related to the incidence of pre-menopausal breast cancer, but the role of body fatness earlier in life is less clear. We examined prospectively the relation between body fatness during childhood and adolescence and the incidence of breast cancer in pre-menopausal women. Methods: Participants were 109,267 pre-menopausal women in the Nurses' Health Study II who recalled their body fatness at ages 5, 10 and 20 years using a validated 9-level figure drawing. Over 12 years of follow up, 1318 incident cases of breast cancer were identified. Cox proportional hazards regression was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for body fatness at each age and for average childhood (ages 5–10 years) and adolescent (ages 10–20 years) fatness. Results: Body fatness at each age was inversely associated with pre-menopausal breast cancer incidence; the multivariate RRs were 0.48 (95% CI 0.35–0.55) and 0.57 (95% CI 0.39–0.83) for the most overweight compared with the most lean in childhood and adolescence, respectively (P for trend < 0.0001). The association for childhood body fatness was only slightly attenuated after adjustment for later BMI, with a multivariate RR of 0.52 (95% CI 0.38–0.71) for the most overweight compared with the most lean (P for trend = 0.001). Adjustment for menstrual cycle characteristics had little impact on the association. Conclusion: Greater body fatness during childhood and adolescence is associated with reduced incidence of pre-menopausal breast cancer, independent of adult BMI and menstrual cycle characteristics.
This is an open source publication. The full free text is available at breast-cancer-research.com/content/7/3/R314.
Although the authors refer to this as a prospective study, the actual groups "most overweight" and "most lean" were defined using a retrospective recall of childhood and adolescent body fatness. So the comparision groups were intact at the start of the research study. Even if you could go back in time, there are great difficulties in assigning patients to randomly various body fatness groups. It is unreasonable to ask people to change their weight for the benefit of the research study. Robert DeNiro reported gained 60 pounds when he played the role of the aging boxer, Jake LaMotta in Raging Bull, but most of us can't easily put on or take off weight at will. There is also an ethical problem here. You can't ask people to place themselves at risk for various weight related diseases just because we need an overweight group for a research study. Instead you have to take individuals who unhappily find themselves in an overweight category because they have a genetic predisposition to gain weight readily or they have a pathological weakness for chocolate.
Impact of a Nurses' Protocol-Directed Weaning Procedure on Outcomes in Patients Undergoing Mechanical Ventilation for Longer Than 48 Hours: A Prospective Cohort Study with a Matched Historical Control Group. Jean-Marie Tonnelier, Gwenaël Prat, Grégoire Le Gal, Christophe Gut-Gobert, Anne Renault, Jean-Michel Boles and Erwan L'Her. Critical Care 2005, 9:R83-R89 doi:10.1186/cc3030. Introduction: The aim of the study was to determine whether the use of a nurses' protocol-directed weaning procedure, based on the French intensive care society (SRLF) consensus recommendations, was associated with reductions in the duration of mechanical ventilation and intensive care unit (ICU) length of stay in patients requiring more than 48 hours of mechanical ventilation. Methods: This prospective study was conducted in a university hospital ICU from January 2002 through to February 2003. A total of 104 patients who had been ventilated for more than 48 hours and were weaned from mechanical ventilation using a nurses' protocol-directed procedure (cases) were compared with a 1:1 matched historical control group who underwent conventional physician-directed weaning (between 1999 and 2001). Duration of ventilation and length of ICU stay, rate of unsuccessful extubation and rate of ventilator-associated pneumonia were compared between cases and controls. Results: The duration of mechanical ventilation (16.6 ± 13 days versus 22.5 ± 21 days; P = 0.02) and ICU length of stay (21.6 ± 14.3 days versus 27.6 ± 21.7 days; P = 0.02) were lower among patients who underwent the nurses' protocol-directed weaning than among control individuals. Ventilator-associated pneumonia, ventilator discontinuation failure rates and ICU mortality were similar between the two groups. Discussion: Application of the nurses' protocol-directed weaning procedure described here is safe and promotes significant outcome benefits in patients who require more than 48 hours of mechanical ventilation.
This is an open source publication. The full free text is available at ccforum.com/content/9/2/R83.
It is, perhaps, possible to assign patients to receive either a nurse protocol-directed weaning procedure or a conventional physician-directed weaning. I suspect, however, that there are some practical difficulties. First, healthcare providers may balk at having to be responsible for two different weaning protocols simultaneously. Second, once you get greater involvement from the nurses, they may find it difficult to step back into a presumably more passive role that the conventional weaning required. Third, once you learn a new approach, it may be impossible to "unlearn" it for half of your patients. There are approaches that can sometimes work in this situation. First, you can recruit 10 or 20 separate hospital ICUs and randomly assign half of them to transition to the nurse protocol-directed weaning procedure early. The other half would serve as a control group for several months before they too transition to the new procedure. That's a rather expensive study to conduct, but it would not require any healthcare provider to juggle two different procedures at the same time.
Extravascular Lung-Water in Patients with Severe Sepsis: A Prospective Cohort Study. Greg S Martin, Stephanie Eaton, Meredith Mealer and Marc Moss. Critical Care 2005, 9:R74-R82 doi:10.1186/cc3025. Introduction: Few investigations have prospectively examined extravascular lung water (EVLW) in patients with severe sepsis. We sought to determine whether EVLW may contribute to lung injury in these patients by quantifying the relationship of EVLW to parameters of lung injury, to determine the effects of chronic alcohol abuse on EVLW, and to determine whether EVLW may be a useful tool in the diagnosis of acute respiratory distress syndrome (ARDS). Methods: The present prospective cohort study was conducted in consecutive patients with severe sepsis from a medical intensive care unit in an urban university teaching hospital. In each patient, transpulmonary thermodilution was used to measure cardiovascular hemodynamics and EVLW for 7 days via an arterial catheter placed within 72 hours of meeting criteria for severe sepsis. Results: A total of 29 patients were studied. Twenty-five of the 29 patients (86%) were mechanically ventilated, 15 of the 29 patients (52%) developed ARDS, and overall 28-day mortality was 41%. Eight out of 14 patients (57%) with non-ARDS severe sepsis had high EVLW with significantly greater hypoxemia than did those patient with low EVLW (mean arterial oxygen tension/fractional inspired oxygen ratio 230.7 ± 36.1 mmHg versus 341.2 ± 92.8 mmHg; P < 0.001). Four out of 15 patients with severe sepsis with ARDS maintained a low EVLW and had better 28-day survival than did ARDS patients with high EVLW (100% versus 36%; P = 0.03). ARDS patients with a history of chronic alcohol abuse had greater EVLW than did nonalcoholic patients (19.9 ml/kg versus 8.7 ml/kg; P < 0.0001). The arterial oxygen tension/fractional inspired oxygen ratio, lung injury score, and chest radiograph scores correlated with EVLW (r2 = 0.27, r2 = 0.18, and r2 = 0.28, respectively; all P < 0.0001). Conclusions: More than half of the patients with severe sepsis but without ARDS had increased EVLW, possibly representing subclinical lung injury. Chronic alcohol abuse was associated with increased EVLW, whereas lower EVLW was associated with survival. EVLW correlated moderately with the severity of lung injury but did not account for all respiratory derangements. EVLW may improve both risk stratification and management of patients with severe sepsis.
This is an open source publication. The full free text is available at ccforum.com/content/9/2/R74.
There's a bit of ambiguity on what represents the exposure group and what represents the control group. You could say that the researchers are comparing patients with and without acute respiratory distress syndrome (ARDS), or you could say that the patients are comparing patients with and with extravascular lung water (EVLW). I prefer the second interpretation, but I would not quibble with someone who offered the first interpretation. Why could this study not be randomized? It would be impossible (and unethical if it were possible) to induce a randomly selected group of patients to develop EVLW. Instead you have to take those patients who are unfortunate enough to develop EVLW on their own and see what their prognosis is relative to patients who are fortunate enough not to develop EVLW.
Breast Implants Following Mastectomy in Women with Early-Stage Breast Cancer: Prevalence and Impact on Survival. Gem M Le, Cynthia D O'Malley, Sally L Glaser, Charles F Lynch, Janet L Stanford, Theresa HM Keegan and Dee W West. Breast Cancer Res 2005, 7:R184-R193 doi:10.1186/bcr974. Background: Few studies have examined the effect of breast implants after mastectomy on long-term survival in breast cancer patients, despite growing public health concern over potential long-term adverse health effects. Methods: We analyzed data from the Surveillance, Epidemiology and End Results Breast Implant Surveillance Study conducted in San Francisco–Oakland, in Seattle–Puget Sound, and in Iowa. This population-based, retrospective cohort included women younger than 65 years when diagnosed with early or unstaged first primary breast cancer between 1983 and 1989, treated with mastectomy. The women were followed for a median of 12.4 years (n = 4968). Breast implant usage was validated by medical record review. Cox proportional hazards models were used to estimate hazard rate ratios for survival time until death due to breast cancer or other causes for women with and without breast implants, adjusted for relevant patient and tumor characteristics. Results: Twenty percent of cases received postmastectomy breast implants, with silicone gel-filled implants comprising the most common type. Patients with implants were younger and more likely to have in situ disease than patients not receiving implants. Risks of breast cancer mortality (hazard ratio, 0.54; 95% confidence interval, 0.43–0.67) and nonbreast cancer mortality (hazard ratio, 0.59; 95% confidence interval, 0.41–0.85) were lower in patients with implants than in those patients without implants, following adjustment for age and year of diagnosis, race/ethnicity, stage, tumor grade, histology, and radiation therapy. Implant type did not appear to influence long-term survival. Conclusions: In a large, population-representative sample, breast implants following mastectomy do not appear to confer any survival disadvantage following early-stage breast cancer in women younger than 65 years old.
This is an open source publication. The full free text is available at breast-cancer-research.com/content/7/2/R184.
Like choices about the type of birth control used, personal preferences to use/avoid breast implants are quite strong and most women would rather not leave the choice in the hands of another person, much less in the hands of random coin flip. The large sample size, almost 5,000 women, and the long follow-up time (a median of more than 12 years) make it impractical to randomize. It would just cost too much to contact and enroll that many women and the expense of regularly checking these women over a twelve plus year time frame would be even worse. Finally, the study was retrospective, which means that the choice of implants was made before the researchers even started collecting their data.
Pregnancy Weight Gain and Breast Cancer Risk. Tarja I Kinnunen, Riitta Luoto, Mika Gissler, Elina Hemminki and Leena Hilakivi-Clarke. BMC Women's Health 2004, 4:7 doi:10.1186/1472-6874-4-7. Background: Elevated pregnancy estrogen levels are associated with increased risk of developing breast cancer in mothers. We studied whether pregnancy weight gain that has been linked to high circulating estrogen levels, affects a mother's breast cancer risk. Methods: Our cohort consisted of women who were pregnant between 1954–1963 in Helsinki, Finland, 2,089 of which were eligible for the study. Pregnancy data were collected from patient records of maternity centers. 123 subsequent breast cancer cases were identified through a record linkage to the Finnish Cancer Registry, and the mean age at diagnosis was 56 years (range 35 – 74). A sample of 979 women (123 cases, 856 controls) from the cohort was linked to the Hospital Inpatient Registry to obtain information on the women's stay in hospitals. Results: Mothers in the upper tertile of pregnancy weight gain (>15 kg) had a 1.62-fold (95% CI 1.03–2.53) higher breast cancer risk than mothers who gained the recommended amount (the middle tertile, mean: 12.9 kg, range 11–15 kg), after adjusting for mother's age at menarche, age at first birth, age at index pregnancy, parity at the index birth, and body mass index (BMI) before the index pregnancy. In a separate nested case-control study (n = 65 cases and 431 controls), adjustment for BMI at the time of breast cancer diagnosis did not modify the findings. Conclusions: Our study suggests that high pregnancy weight gain increases later breast cancer risk, independently from body weight at the time of diagnosis.
This is an open source publication. The full free text is available at www.biomedcentral.com/1472-6874/4/7.
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Racial Variations in Processes of Care for Patients with Community-Acquired Pneumonia. Eric M Mortensen, John Cornell and Jeff Whittle. BMC Health Services Research 2004, 4:20 doi:10.1186/1472-6963-4-20. Background: Patients hospitalized with community acquired pneumonia (CAP) have a substantial risk of death, but there is evidence that adherence to certain processes of care, including antibiotic administration within 8 hours, can decrease this risk. Although national mortality data shows blacks have a substantially increased odds of death due to pneumonia as compared to whites previous studies of short-term mortality have found decreased mortality for blacks. Therefore we examined pneumonia-related processes of care and short-term mortality in a population of patients hospitalized with CAP. Methods: We reviewed the records of all identified Medicare beneficiaries hospitalized for pneumonia between 10/1/1998 and 9/30/1999 at one of 101 Pennsylvania hospitals, and randomly selected 60 patients at each hospital for inclusion. We reviewed the medical records to gather process measures of quality, pneumonia severity and demographics. We used Medicare administrative data to identify 30-day mortality. Because only a small proportion of the study population was black, we included all 240 black patients and randomly selected 720 white patients matched on age and gender. We performed a re-sampling of the white patients 10 times. Results: Males were 43% of the cohort, and the median age was 76 years. After controlling for potential confounders, blacks were less likely to receive antibiotics within 8 hours (odds ratio with 95% confidence interval 0.6, 0.4–0.97), but were as likely as whites to have blood cultures obtained prior to receiving antibiotics (0.7, 0.3–1.5), to have oxygenation assessed within 24 hours of presentation (1.6, 0.9–3.0), and to receive guideline concordant antibiotics (OR 0.9, 0.6–1.7). Black patients had a trend towards decreased 30-day mortality (0.4, 0.2 to 1.0). Conclusion: Although blacks were less likely to receive optimal care, our findings are consistent with other studies that suggest better risk-adjusted survival among blacks than among whites. Further study is needed to determine why this is the case.
This is an open source publication. The full free text is available at www.biomedcentral.com/1472-6963/4/20.
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Chapter 2. Who was left out?
Answers for this and remaining chapters not yet prepared.
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