What Does the Population Attributable Fraction Mean?

Recent controversy over the disagreement of population attributable fraction estimates for the obesity–total mortality relation has made the concept of attributable fraction visible in both scientific and popular news. Most of the attention in writings on the attributable fraction has focused on technical matters of estimation and on ensuring a causal relationship between exposure and outcome. Yet some of the most illuminating questions about the attributable fraction have to do with another causal question and how the measure is to be interpreted in light of the answer to this question: What interventions are available to cause the assumed reduction in risk among the exposed and the consequent estimated reduction in disease burden? In this paper, I discuss the limitations to the common interpretations of the attributable fraction and argue that these limitations cannot be overcome merely by better statistical modeling or by use of better data sets. They must be addressed through discussion of specific interventions and the hypothesized causal consequences of such specified interventions

Some Sex Hormone Profiles are Consistent over Time in Normal Menstruating Women: Implications for Sports Injury Epidemiology

Purpose-It is unclear whether sex hormone profiles obtained in two consecutive months are consistent within women. Month-to-month consistency in daily, nadir, peak and mean hormone concentrations during the early follicular and luteal phases in recreationally active, young eumenorrheic women was prospectively examined. Methods-60 healthy, non-smoking women who reported normal and consistent menstrual cycles lasting 26–32 days for the past 6 months were followed prospectively to obtain serum samples for the first 6 days of menses and for 8 days after a positive ovulation test over two consecutive months. Month-to-month consistency of daily concentrations of oestradiol (pg/ml), progesterone (ng/ml), testosterone (ng/dl), sex hormone-binding globulin (nmol/l) and free androgen index were determined using linear mixed models. Month-to-month consistency in nadir, peak and mean concentrations were then assessed using intraclass correlation coefficients and SEM to more precisely examine intraindividual consistency. Results-Linear mixed models revealed stable hormone concentrations across cycles and cycles by day. Reliability estimates for nadir, peak, mean menses and mean postovulatory concentrations range from 0.56 to 0.86 for oestradiol, 0.44 to 0.91 for progesterone, 0.60 to 0.86 for testosterone, 0.88 to 0.97 for sex hormone-binding globulin and 0.78 to 0.91 for free androgen index. Conclusions-Hormone profiles were reproducible over two consecutive months. To reduce month-to-month intraindividual variations and improve measurement consistency, it is recommended that multiple samples be taken over consecutive days as opposed to a single sample

Relationships Between Lower Extremity Alignment and the Quadriceps Angle

Objective: To determine the extent to which select lower extremity alignment characteristics of the pelvis, hip, knee, and foot are related to the Q angle. Design: Descriptive cohort study design.Setting: Applied Neuromechanics Research Laboratory. Participants: Two hundred eighteen participants (102 males, 116 females). Assessment of Risk Factors: Eight clinical measures of static alignment of the left lower extremity were measured by a single examiner to determine the impact of lower extremity alignment on the magnitude of Q angle. Main Outcome Measures: Q angle, pelvic angle, hip anteversion, tibiofemoral angle, genu recurvatum, tibial torsion, navicular drop, and femur and tibia length. Results: Once all alignment variables were accounted for, greater tibiofemoral angle and femoral anteversion were significant predictors of greater Q angle in both males and females. Pelvic angle, genu recurvatum, tibial torsion, navicular drop, and femur to tibia length ratio were not significant independent predictors of Q angle in males or females. Conclusions: Greater femoral anteversion and tibiofemoral angle result in greater Q angle, with changes in tibiofemoral angle having a substantially greater impact on the magnitude of the Q angle compared with femoral anteversion. As such, the Q angle seems to largely represent a frontal plane alignment measure. As many knee injuries seem to result from a combination of both frontal and transverse plane motions and forces, this may in part explain why Q angle has been found to be a poor independent predictor of lower extremity injury risk

A Comparison of Cyclic Variations in Anterior Knee Laxity, Genu Recurvatum, and General Joint Laxity across the Menstrual Cycle

Changes in anterior knee laxity (AKL), genu recurvatum (GR) and general joint laxity (GJL) were quantified across days of the early follicular and early luteal phases of the menstrual cycle in 66 females, and the similarity in their pattern of cyclic variations examined. Laxity was measured on each of the first 6 days of menses (M1–M6) and the first 8 days following ovulation (L1–L8) over two cycles. The largest mean differences were observed between L5 and L8 for AKL (0.32?mm), and between L5 and M1 for GR (0.56°) and GJL (0.26) (p?<?0.013). At the individual level, mean absolute cyclic changes in AKL (1.8?±?0.7?mm, 1.6?±?0.7?mm), GR (2.8?±?1.0°, 2.4?±?1.0°), and GJL (1.1?±?1.1, 0.7?±?1.0) were more apparent, with minimum, maximum and delta values being quite consistent from month to month (ICC2,3? =?0.51–0.98). Although the average daily pattern of change in laxity was quite similar between variables (Spearman correlation range 0.61 and 0.90), correlations between laxity measures at the individual level were much lower (range -0.07 to 0.43). Substantial, similar, and reproducible cyclic changes in AKL, GR, and GJL were observed across the menstrual cycle, with the magnitude and pattern of cyclic changes varying considerably among females

Knee Joint Laxity and Its Cyclic Variation Influence Tibiofemoral Motion during Weight Acceptance

Purpose - To better understand how sex differences in anterior knee joint laxity (AKL) impact knee joint biomechanics, we examined the consequence of greater absolute baseline (males and females) and cyclic increases in AKL during the menstrual cycle (females) on anterior tibial translation (ATT) as the knee transitioned from non-weight bearing (NWB) to weight bearing (WB) conditions, while also controlling for genu recurvatum (GR). Methods - Males and females (71F,48M;18-30 years) were measured for AKL and GR, and underwent measurement of ATT. Females were tested on the days of their cycle when AKL was at its minimum (T1) and maximum (T2); males were matched in time to a female with similar AKL. Linear regressions examined relationships between absolute baseline (AKLT1, GRT1) and cyclic changes (?=T2-T1; AKL?, GR?)(females only) in knee laxity with ATT as measured at T1 and T2, and ? (T2-T1) (females only). Results - AKL and GR increased in females, but not males, from T1 to T2. Greater AKLT1 and GRT1 predicted greater ATTT1 and ATTT2 in males (R2=21.0, P<.007). The combination of greater AKLT1, AKL? and less GR? predicted greater ATTT1 and ATTT2 in females (R2=12.5-13.1, P<.05), with AKL? being a stronger predictor (coefficient, P-value) of ATTT2 (0.864, P=.027) compared to ATTT1 (0.333, P=.370). AKL? was the sole predictor of ATT? (R2=.104; 0.740, P=.042). Conclusions - Greater absolute baseline and cyclic increases in AKL were consistently associated with greater ATT produced by transition of the knee from NWB to WB. As the ACL is the primary restraint to ATT, these findings provide insight into possible mechanisms by which greater AKL may be associated with at risk knee biomechanics during the weight acceptance phase of dynamic tasks

Joint Laxity Is Related to Lower Extremity Energetics during a Drop Jump Landing

Purpose: To examine the relationships between anterior knee laxity (AKL), genu recurvatum (GR), and general joint laxity (GJL) with sagittal plane energetics in males and females during a drop jump task. Methods: A total of 68 females and 50 males were measured for AKL, GR, and GJL and were instrumented to obtain neuromuscular and biomechanical data on their dominant limb during the initial landing phase of a 45-cm drop jump. Multiple linear regressions determined the extent to which the three joint laxity variables combined to predict hip, knee, and ankle work absorption and stiffness. Associations between joint laxity and joint kinematics, joint kinetics, and muscle activation amplitudes were also investigated to further interpret significant relationships. Results: Higher AKL and GJL and lower GR combined to predict greater knee work absorption (R2= 0.210, ? = 0.002) and stiffness (R2 = 0.127, ? = 0.033) and lower ankle stiffness (R2= 0.115, ? = 0.048) in females. These associations were modulated through greater peak knee extensor moments and flexion angles, lower hamstring activation, and lower ankle extensor moments. In males, joint laxity had little impact on knee energetics, but a significant association was observed between greater GJL and decreased ankle stiffness (R2= 0.209, ? = 0.012), a product of both greater peak ankle flexion and decreased ankle extensor moment. Conclusions: Females with greater AKL and GJL and lower GR demonstrated a landing strategy that increased work absorption and stiffness about the knee, whereas females with greater GR demonstrated a landing style that reduced knee work absorption and stiffness. The findings suggest that AKL, GR, and GJL may represent distinct risk factors and support the need to consider more comprehensive laxity profiles as they relate to knee joint function and anterior cruciate ligament injury risk

Glucose-6-phosphate dehydrogenase-derived NADPH fuels superoxide production in the failing heart.

In the failing heart, NADPH oxidase and uncoupled NO synthase utilize cytosolic NADPH to form superoxide. NADPH is supplied principally by the pentose phosphate pathway, whose rate-limiting enzyme is glucose 6-phosphate dehydrogenase (G6PD). Therefore, we hypothesized that cardiac G6PD activation drives part of the excessive superoxide production implicated in the pathogenesis of heart failure. Pacing-induced heart failure was performed in eight chronically instrumented dogs. Seven normal dogs served as control. End-stage failure occurred after 28 +/- 1 days of pacing, when left ventricular end-diastolic pressure reached 25 mm Hg. In left ventricular tissue homogenates, spontaneous superoxide generation measured by lucigenin (5 microM) chemiluminescence was markedly increased in heart failure (1338 +/- 419 vs. 419 +/- 102 AU/mg protein, P < 0.05), as were NADPH levels (15.4 +/- 1.5 vs. 7.5 +/- 1.5 micromol/gww, P < 0.05). Superoxide production was further stimulated by the addition of NADPH. The NADPH oxidase inhibitor gp91(ds-tat) (50 microM) and the NO synthase inhibitor L-NAME (1 mM) both significantly lowered superoxide generation in failing heart homogenates by 80% and 76%, respectively. G6PD was upregulated and its activity higher in heart failure compared to control (0.61 +/- 0.10 vs. 0.24 +/- 0.03 nmol/min/mg protein, P < 0.05), while superoxide production decreased to normal levels in the presence of the G6PD inhibitor 6-aminonicotinamide. We conclude that the activation of myocardial G6PD is a novel mechanism that enhances NADPH availability and fuels superoxide-generating enzymes in heart failure

Reproductive and Hormonal Risk Factors for Ductal Carcinoma In situ of the Breast

One-fifth of all newly diagnosed breast cancer cases are ductal carcinoma in situ (DCIS), but little is known about DCIS risk factors. Recent studies suggest that some subtypes of DCIS (high grade, or comedo) share histopathologic and epidemiologic characteristics with invasive disease, while others (medium or low grade, or non-comedo) show different patterns. To investigate whether reproductive and hormonal risk factors differ among comedo and non-comedo types of DCIS and invasive breast cancer, we used a population-based case-control study of 1808 invasive and 446 DCIS breast cancer cases and their age and race frequency-matched controls (1564 invasive and 458 DCIS). Three or more full-term pregnancies showed a strong inverse association with comedo-type DCIS (odds ratio (OR) = 0.53, 95% confidence interval (CI) = 0.30, 0.95) and a weaker inverse association for non-comedo DCIS (OR = 0.73, 95% CI = 0.42, 1.27). Several risk factors (age at first full-term pregnancy, breastfeeding, and age at menopause) demonstrated similar associations for comedo-type DCIS and invasive breast cancer, but different associations for non-comedo DCIS. Ten or more years of oral contraceptive showed a positive association with comedo-type DCIS (OR = 1.31, 05% CI 0.70, 2.47) and invasive breast cancer (OR = 2.33, 95% CI 1.06, 5.09), but an inverse association for noncomedo DCIS (OR = 0.51, 95% CI 0.25-1.04). Our results support the theory that comedo-type DCIS may share hormonal and reproductive risk factors with invasive breast cancer, while the etiology of non-comedo DCIS deserves further investigation

A Comparison of Cyclic Variations in Anterior Knee Laxity, Genu Recurvatum, and General Joint Laxity across the Menstrual Cycle

. A comparison of cyclic variations in anterior knee laxity, genu recurvatum and general joint laxity across the menstrual cycle. Journal of Orthopaedic Research, 28, 1411Research, 28, -1417 Abstract: Changes in anterior knee laxity (AKL), genu recurvatum (GR) and general joint laxity (GJL) were quantified across days of the early follicular and early luteal phases of the menstrual cycle in 66 females, and the similarity in their pattern of cyclic variations examined. Laxity was measured on each of the first 6 days of menses (M1-M6) and the first 8 days following ovulation (L1-L8) over two cycles. The largest mean differences were observed between L5 and L8 for AKL (0.32 mm), and between L5 and M1 for GR (0.56°) and GJL (0.26) (p &lt; 0.013). At the individual level, mean absolute cyclic changes in AKL (1.8 ± 0.7 mm, 1.6 ± 0.7 mm), GR (2.8 ± 1.0°, 2.4 ± 1.0°), and GJL (1.1 ± 1.1, 0.7 ± 1.0) were more apparent, with minimum, maximum and delta values being quite consistent from month to month (ICC 2,3 = 0.51-0.98). Although the average daily pattern of change in laxity was quite similar between variables (Spearman correlation range 0.61 and 0.90), correlations between laxity measures at the individual level were much lower (range −0.07 to 0.43). Substantial, similar, and reproducible cyclic changes in AKL, GR, and GJL were observed across the menstrual cycle, with the magnitude and pattern of cyclic changes varying considerably among females. Article: Joint laxity continues to be a variable of interest as we seek to uncover the underlying risk factors for ACL injury in females