Minor change in the sulcus angle during the first six years of life: a prospective study of the femoral trochlea development in dysplastic and normal knees.

PURPOSE: The aetiology of femoral trochlear dysplasia is unknown. The aim of this prospective cohort study was to describe trochlear development in a newborn population during the first six years of life. METHODS: In an earlier study, the femoral trochlea was examined by ultrasound in 174 newborns. A dysplastic trochlea was defined with a sulcus angle (SA) above 159°. Two groups were defined, one group of 15 knees with SA > 159° (dysplastic group), and one group of 101 knees with SA < 159° (non-dysplastic group). In the present follow-up study, the children were further examined at six, 18 and 72 months. RESULTS: There was a statistically significant difference in the SA between the dysplastic and the non-dysplastic group at all follow-ups (p < 0.001). A small but statistically significant change in the SA between 0 to 72 months was detected for the dysplastic knees (p = 0.032) and for the controls (p < 0.001). CONCLUSION: Only minor changes in the anatomy of the femoral trochlea from newborn to age six years were found. A dysplastic trochlea at birth remains shallow and the anatomy does not change from normal to dysplastic during the same time span. LEVEL OF EVIDENCE: II.

Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax (ABT-263), a dual inhibitor of Bcl-2 and Bcl-XL , in patients with cancer.

WHAT IS KNOWN AND OBJECTIVE: Navitoclax, a first-in-class small molecule Bcl-2 family inhibitor, is metabolized in vitro by the hepatic microsomal cytochrome P450 (CYP) enzymes CYP3A4. Drugs that affect CYP3A4 may therefore have an impact on the pharmacological profile of navitoclax. This study evaluated the effects of co-administration of a potent CYP3A4 inducer rifampin on the pharmacokinetic and safety profiles of navitoclax. METHODS: This open-label, fixed-sequence, 2-period study was performed in twelve subjects with non-haematologic or haematologic malignancy that was relapsed or refractory to standard therapy. A 7-day washout period separated the two treatment periods. On Study Day 1 and Day 8, subjects received a single 250 mg oral dose of navitoclax. Rifampin 600 mg was administrated once daily (QD) on Study Day 4 through Day 10. Blood samples for navitoclax assay were collected prior to dosing (0 h) and at a series of time points through 72 h after dosing on Study Day 1 and Day 8. RESULTS AND DISCUSSION: Co-administration of a single 250 mg dose of navitoclax with 600 mg QD doses of rifampin had a negligible effect on the maximum plasma concentration (Cmax ) of navitoclax [ratio of geometric least square means: 0·84 (90% CI: 0·61-1·16)] but moderately decreased the area under the plasma concentration-time curve (AUC) of navitoclax [ratio of geometric least square means: 0·59 (90% CI: 0·44-0·80)]. Rifampin did not affect the half-life of navitoclax. Co-administration of rifampin did not appear to significantly change the safety profile of navitoclax in the limited number of patients evaluated in this study. WHAT IS NEW AND CONCLUSION: Co-administration navitoclax with rifampin moderately decreased navitoclax AUC, which could be partly due to the induction effect of rifampin on CYP3A4. Further assessment on the mechanism of drug interaction is warranted.

Awareness of implicit attitudes.

Research on implicit attitudes has raised questions about how well people know their own attitudes. Most research on this question has focused on the correspondence between measures of implicit attitudes and measures of explicit attitudes, with low correspondence interpreted as showing that people have little awareness of their implicit attitudes. We took a different approach and directly asked participants to predict their results on upcoming Implicit Association Test (IAT) measures of implicit attitudes toward 5 social groups. We found that participants were surprisingly accurate in their predictions. Across 4 studies, predictions were accurate regardless of whether implicit attitudes were described as true attitudes or culturally learned associations (Studies 1 and 2), regardless of whether predictions were made as specific response patterns (Study 1) or as conceptual responses (Studies 2-4), and regardless of how much experience or explanation participants received before making their predictions (Study 4). Study 3 further suggested that participants' predictions reflected unique insight into their own implicit responses, beyond intuitions about how people in general might respond. Prediction accuracy occurred despite generally low correspondence between implicit and explicit measures of attitudes, as found in prior research. Altogether, the research findings cast doubt on the belief that attitudes or evaluations measured by the IAT necessarily reflect unconscious attitudes.

Clinicians' implicit ethnic/racial bias and perceptions of care among Black and Latino patients.

PURPOSE: We investigated whether clinicians' explicit and implicit ethnic/racial bias is related to black and Latino patients' perceptions of their care in established clinical relationships. METHODS: We administered a telephone survey to 2,908 patients, stratified by ethnicity/race, and randomly selected from the patient panels of 134 clinicians who had previously completed tests of explicit and implicit ethnic/racial bias. Patients completed the Primary Care Assessment Survey, which addressed their clinicians' interpersonal treatment, communication, trust, and contextual knowledge. We created a composite measure of patient-centered care from the 4 subscales. RESULTS: Levels of explicit bias were low among clinicians and unrelated to patients' perceptions. Levels of implicit bias varied among clinicians, and those with greater implicit bias were rated lower in patient-centered care by their black patients as compared with a reference group of white patients (P = .04). Latino patients gave the clinicians lower ratings than did other groups (P <.0001), and this did not depend on the clinicians' implicit bias (P = .98). CONCLUSIONS: This is among the first studies to investigate clinicians' implicit bias and communication processes in ongoing clinical relationships. Our findings suggest that clinicians' implicit bias may jeopardize their clinical relationships with black patients, which could have negative effects on other care processes. As such, this finding supports the Institute of Medicine's suggestion that clinician bias may contribute to health disparities. Latinos' overall greater concerns about their clinicians appear to be based on aspects of care other than clinician bias.

Assessment of biases against Latinos and African Americans among primary care providers and community members.

OBJECTIVES: We assessed implicit and explicit bias against both Latinos and African Americans among experienced primary care providers (PCPs) and community members (CMs) in the same geographic area. METHODS: Two hundred ten PCPs and 190 CMs from 3 health care organizations in the Denver, Colorado, metropolitan area completed Implicit Association Tests and self-report measures of implicit and explicit bias, respectively. RESULTS: With a 60% participation rate, the PCPs demonstrated substantial implicit bias against both Latinos and African Americans, but this was no different from CMs. Explicit bias was largely absent in both groups. Adjustment for background characteristics showed the PCPs had slightly weaker ethnic/racial bias than CMs. CONCLUSIONS: This research provided the first evidence of implicit bias against Latinos in health care, as well as confirming previous findings of implicit bias against African Americans. Lack of substantive differences in bias between the experienced PCPs and CMs suggested a wider societal problem. At the same time, the wide range of implicit bias suggested that bias in health care is neither uniform nor inevitable, and important lessons might be learned from providers who do not exhibit bias.

A phase I study of an oral simulated FOLFOX with high dose capecitabine.

BACKGROUND: A phase I study of high-dose capecitabine given over 2 days, along with oxaliplatin, bolus 5FU and leucovorin (LV), was designed to simulate FOLFOX6 without the need for infusional 5FU. METHODS: Schedule A included oxaliplatin 100 mg/m(2), 5FU 400 mg/m(2), and LV 20 mg/m(2) (all given IV on days 1 and 15, 28 day cycle). Capecitabine was administered orally every 8 h x 6 doses, days 1 and 15. Schedule B excluded 5FU and LV, maintaining oxaliplatin and capecitabine. Pharmacokinetics were performed for capecitabine for 6 patients on each schedule. RESULTS: 36 patients were treated. The dose-limiting toxicities seen included nausea, dehydration, fatigue, hypotension and confusion. Minimal palmar-plantar erythrodysesthesia was seen. Myelosuppression was common, but not a dose limiting toxicity. The pharmacokinetic parameters for capecitabine were unaltered. CONCLUSION: Using capecitabine to mimic FOLFOX6 is feasible and well tolerated with a toxicity profile that differs from standard 14-day capecitabine dosing, with less palmar-plantar erythrodysesthesia. The phase II dose for capecitabine in combination with oxaliplatin, 5FU, and LV is 1,500 mg/m(2)/dose or 2,250 mg/m(2)/dose in the absence of bolus 5FU/LV.

Universal or selective screening of the neonatal hip using ultrasound? A prospective, randomised trial of 15,529 newborn infants.

The aim of this study was to evaluate whether universal (all neonates) or selective (neonates belonging to the risk groups) ultrasound screening of the hips should be recommended at birth. We carried out a prospective, randomised trial between 1988 and 1992, including all newborn infants at our hospital. A total of 15 529 infants was randomised to either clinical screening and ultrasound examination of all hips or clinical screening of all hips and ultrasound examination only of those at risk. The effect of the screening was assessed by the rate of late detection of congenital or developmental hip dysplasia in the two groups. During follow-up of between six and 11 years, only one late-detected hip dysplasia was seen in the universal group, compared with five in the subjective group, representing a rate of 0.13 and 0.65 per 1,000, respectively. The difference in late detection between the two groups was not statistically significant (p = 0.22). When clinical screening is of high quality, as in our study, the effect of an additional ultrasound examination, measured as late-presenting hip dysplasia, is marginal. Under such circumstances, we consider that universal ultrasound screening is not necessary, but recommend selective ultrasound screening for neonates with abnormal or suspicious clinical findings and those with risk factors for hip dysplasia.

Good results after treatment with the Frejka pillow for hip dysplasia in newborns: a 3-year to 6-year follow-up study.

Because there is no consensus with regard to the efficiency of the Frejka pillow in the treatment of hip joint dysplasia in newborns, the aim of the present study was to evaluate our results with this device. During the 3-year period 1988 to 1990, the Frejka pillow was used in 108 newborns with clinically unstable hips verified by ultrasonography. There were three treatment failures (2.8%), defined as infants who needed additional treatment with an abduction splint or hip-spica cast. Avascular necrosis of the femoral head occurred in one patient (0.9%). At an age of 3 years to 6 years, 85 of the children attended a follow-up examination. An intoeing gait was observed in 17% and slightly reduced hip mobility in 20% of the patients. Compared with normal children, the patients had somewhat lower coverage of the femoral head by radiography, indicated by a lower centre-edge angle and a higher migration percentage, but the coverage was within the normal range in all cases. The mean anteversion angle was larger than that of normal children but only three patients had abnormally high anteversion angles. In conclusion, the results with the Frejka pillow were good, with few treatment failures and complications, and it is the most simple abduction device for the parents to handle. More rigid devices like the von Rosen splint seem to involve a slightly lower failure rate, but a higher risk of avascular necrosis. Therefore, we recommend the Frejka pillow when treatment is started within a few days of birth.

New therapies, new directions: advances in the systemic treatment of metastatic colorectal cancer.

Colorectal cancer is the second leading cause of cancer death and it is clear that patients with metastatic disease have better quality of life and survival when given treatment. Despite four decades of experience of treating patients with fluorouracil, there remains considerable controversy about the optimum dose and scheduling, as well as biomodulation with leucovorin and methotrexate. However, irrespective of the dose and schedule, overall survival times are poor--about 1 year. Disappointingly, oral agents with similar mechanisms to fluorouracil do not improve survival rates in comparison with fluorouracil and leucovorin treatment. Irinotecan and oxaliplatin are newer agents that have improved the response rates for patients with metastatic disease when they are added to flurouracil and leucovorin. The combination of irinotecan, fluorouracil, and leucovorin has also improved overall survival. These are small advances in the fight against colorectal cancer, and further drug development is necessary.

The natural history of hip abnormalities detected by ultrasound in clinically normal newborns: a 6-8 year radiographic follow-up study of 93 children.

Ultrasound screening for hip dysplasia or dislocation has revealed a group of children with clinically normal hips, but with abnormal or suspicious ultrasound. During the 3-year period 1988-90, we found 170 children with this combination. We evaluated the natural history of these hips. 93 children were examined clinically and with standard radiography 6-8 years after birth. The center edge (CE) angle of Wiberg and migration percentage (MP) were measured on the radiographs. 87 children had not undergone any treatment, whereas treatment with an abduction orthosis had been initiated at approximately 4 months of age because of persisting dysplasia in 6 cases. All hips were radiographically normal at this follow-up. The mean CE value was 24 degrees (SD 6.5) and the mean MP was 13% (SD 5.2). 73 children had no complaints in their lower extremities, whereas 12 had intoeing gait, 1 had outtoeing gait, 2 had hip or knee pain, and 5 had other complaints not relevant to hip dysplasia. We conclude that infants with sonographically abnormal or suspicious hips, but with normal clinical findings, do not need immediate treatment because spontaneous resolution occurs in most of them. Postponement of treatment in the few with persistent dysplasia does not seem to affect the outcome.

The use of ultrasound in determining the initiation of treatment in instability of the hip in neonates.

We have evaluated the effect of the use of ultrasound in determining the initiation of treatment in neonatal instability of the hip. A total of 99 newborn infants (1.5% of all live births) with neonatal hip instability did not have treatment from birth, but were re-examined at eight to 15 days. In the 31 who had persisting clinical instability and ultrasound abnormality, treatment was then started with a Frejka pillow. The hips in the remaining 68 infants showed spontaneous clinical stabilisation and improvement of the ultrasound findings. Treatment was therefore withheld. There was a marked trend towards normal development in mildly unstable hips, whereas no hips with severe instability did so spontaneously. Further follow-up showed normal development in all the hips which had been treated, and in all except five of the 68 untreated infants. These five infants showed persistent hip dysplasia on both ultrasound and radiological examination at four to five months of age. Treatment with an abduction splint was then started and their hips developed normally. Ultrasound is very useful in deciding on treatment if the examiners have adequate experience with the method. Its use substantially reduces the rate of treatment. Spontaneous resolution occurred in more than half of the unstable hips. Since five of the untreated infants developed hip dysplasia a strict follow-up is essential to identify and treat these cases.

TAT results in a longitudinal study of bereaved college students.

The authors analyzed projective data obtained from 141 college students who wrote stories on three separate occasions to selected cards from the Thematic Apperception Test (TAT). The students included 46 members of support groups for bereaved college students, 34 members of a bereavement control group, and 61 nonbereaved students. The study used a repeated-measures pretest-posttest control group design to gather longitudinal data about the trajectory of bereavement with and without support group intervention. Coders, who reached consistently high interrater reliability, looked for themes of death, grief, coping, and affiliation in the stories. Multivariate analysis of variance (MANOVA) and repeated-measures MANOVA tests were applied to analyze coding results. Overall MANOVA results indicated significant group differences in the responses to the TAT cards. Repeated-measures MANOVA found group differences in use of themes of death and grief and found Group x Time differences in maintaining a sense of self-efficacy while in a crisis. A majority of the stories contained affiliation imagery but without any group differences in the use of such imagery.

Ultrasonography of clinically unstable hips. A prospective study of 143 neonates at birth and early follow-up.

We evaluated the ability of ultrasonography to reduce the treatment rate of hips with clinical instability or uncertain findings at birth. Among 9,514 live births during the period 1988-1990, unstable hips were detected in 143 neonates by the Ortolani and Barlow tests, whereas the physical examination was inconclusive in 59 cases. These 202 neonates were also examined by ultrasound and instability was confirmed in 108 neonates who were treated with the Frejka pillow. The mean femoral head coverage (FHC) was 37%, indicating slight subluxation in the majority of unstable hips. The remaining 94 infants had normal ultrasonographic findings and were not treated. Their mean FHC was 53% and all these hips developed normally, except in 2 girls, who were treated with an abduction splint from age 4-5 months because subluxation developed. We conclude that ultrasound improved the reliability of the neonatal hip evaluation, thus markedly reducing the number of treated infants. Sonography also reduced the use of radiography during followup.

Relationship between symptoms of jumper's knee and the ultrasound characteristics of the patellar tendon among high level male volleyball players.

This study assessed the ultrasound characteristics of the patellar tendon in two groups of volleyball players, one group without knee symptoms and one group with symptoms of jumper's knee. Of 47 male elite players, 25 were diagnosed to have current and seven to have had previous symptoms of jumper's knee, as determined by clinical examination. Since some players had bilateral problems, there were 34 knees with current problems and nine with previous problems. Seven of the 30 knees with a clinical diagnosis of jumper's knee in the patellar tendon had normal ultrasound findings, and ultrasound changes believed to be associated with jumper's knee (tendon thickening, echo signal changes, irregular paratenon appearance) were observed in 12 of 51 knees without symptoms. Specific ultrasound findings such as paratenon changes, hypoechoic zones or pathological tendon thickness proximally did not correlate significantly with the degree or the duration of symptoms. This study suggests that the specificity and sensitivity of ultrasonography is low in the evaluation of patients with mild symptoms of jumper's knee.

Hip abnormalities detected by ultrasound in clinically normal newborn infants.

We have followed the natural progress of newborn infants in whom ultrasound examination showed abnormalities in hips which appeared to be clinically normal. Over six years we saw 306 such children out of 9952 examined (31 per 1000 live births). The examination was repeated at two to three months and those who still showed an abnormality were followed up further. At four to five months a standard radiograph was obtained, and treatment began if this and another ultrasound scan were both abnormal. At this stage, 291 infants had normal hips. In the 15 infants with abnormal hips there was no pronounced deterioration, none developed a frank dislocation, and all became normal after treatment in an abduction splint. Newborn infants with abnormal and suspicious ultrasound findings who are normal on clinical examination do not need treatment from birth; most of these hips will settle spontaneously. Treatment can be postponed until the age of four to five months unless clinical instability develops or ultrasound shows dislocation. The criteria for treatment should be based on measurements by both ultrasound and radiography: both should show an abnormality before intervention is considered necessary.

Isokinetic muscle performance in healthy female handball players and players with a unilateral anterior cruciate ligament reconstruction.

A total of 114 healthy female European team handball players in the elite to second division with no previous ACL injury, and the uninjured legs of 22 females with a unilaterally reconstructed ACL (the injury sustained while playing handball; mean time from reconstruction 15 months) were examined with a Biodex isokinetic testing device. Five extensions and flexions at lower speed (60 degrees/s) and 15 repetitions at higher speed (240 degrees/s) were performed. Gravity-corrected peak torque values for flexion and extension were obtained, and hamstrings-to-quadriceps ratios (H/Q) were calculated at both speeds. Compared with the control group, the uninjured legs of the injury group showed 8% weaker quadriceps muscles and 14% higher H/Q ratios at higher speed. The other between-group comparisons were not significant. These differences could have been developed by strength reduction after the injury in the noninjured limb due-to-insufficient rehabilitation, by a weaker musculature in the patient group already initially, or by both mechanisms. If the second option is true, the finding may indicate that weak quadriceps musculature is one of the risk factors for anterior cruciate ligament injuries. The study establishes additional normative data on hamstrings and quadriceps torque on high-level female handball players.

Ultrasonographic evaluation of breech presentation as a risk factor for hip dysplasia.

In order to gain more information of breech position as a risk factor for congenital hip dysplasia or dislocation, the hips of 408 newborns delivered in the breech position were examined by ultrasound. Clinical examination was performed by both experienced paediatricians and orthopaedic surgeons. The infants were re-examined by ultrasound at 2-3 months of age. Twenty-five newborns (6.1%) had neonatal hip instability. Breech presentation as a risk factor was confirmed, with first borns, breech position with extended knees, and high birthweight as special high-risk groups. Ultrasound showed subluxation in most of the unstable hips. The main benefit of using ultrasound was that direct visualization permitted more reliable evaluation, especially when the clinical findings were uncertain. Normal ultrasound findings in false positive and uncertain Ortolani tests reduced the frequency of unnecessary treatment. Because ultrasound was used in follow-up, the need of radiography was reduced. There were no late-detected cases of hip dysplasia or dislocation, indicating that routine follow-up is not necessary in breech infants with normal hips at birth, provided that the neonatal screening is optimal.

Surgical treatment of medial tibial stress syndrome (shin splint) by fasciotomy of the superficial posterior compartment of the leg.

From September 1988 to June 1990, 35 athletes were treated for medial tibial stress syndrome (shin splint) by fasciotomy of the superficial posterior compartment of the leg. Thirty-two patients were available for the follow-up, including self-assessment, clinical examination and activity scoring. The mean postoperative observation time was 16 months. Thirteen patients were performing sports at top international or top national level; 19 patients were competing at different lower levels. Twenty-three patients improved, 7 were unchanged and 2 had poor results.

Intercondylar notch width and the risk for anterior cruciate ligament rupture. A case-control study in 46 female handball players.

We measured the intercondylar notch of the femur in female handball players from radiographs of 20 players with previous unilateral anterior cruciate ligament injury, and 26 controls without injury. The groups were comparable regarding age, height, weight and level of performance. Intercondylar fossa radiographs were obtained in a posteroanterior axial position. The anterior opening of the intercondylar notch was narrower in the healthy knee of the injured group compared to the controls. There was an increased risk of anterior cruciate ligament injury associated with decreasing notch opening: female handball players with 17 mm or less anterior notch width were 6 times more susceptible to anterior cruciate ligament injury compared to players with wider notch width.