Clinical and biochemical prediction of early fatal outcome following hip fracture in the elderly

Hip fracture, a moderate musculoskeletal trauma, is associated with a high postoperative mortality. Most patients are elderly, with comorbid conditions and often with heart disease. The objective of this study was to find out if clinical parameters and analyses of specific muscle enzymes could predict three month postoperative mortality. A total of 302 patients above 75 years of age with hip fracture were consecutively enrolled. Baseline information on age, sex and comorbidity assessed with the American Society of Anesthesiologists (ASA) score was obtained before surgery. Creatine kinase (CK), myocardium-specific creatine kinase (CK-MB) and troponin T (TnT) were analysed from venous blood, collected the day before surgery (−1) and postoperatively, within 24 hours (0) and on days one (+1) and four (+4). The overall three month mortality was 19.5%. Multivariate analyses showed that age, male sex and comorbidity (ASA) correlated with mortality (p = 0.027, p = 0.002, p < 0.001, respectively). Surgery induced a two- to threefold increase of CK and CK-MB but without any correlation with mortality. However, high TnT levels >0.04 μg/l correlated significantly with death (days −1, +1 and +4, p = 0.003, p = 0.005 and p = 0.003, respectively). Multivariate analyses, adjusted for age, sex and ASA category, confirmed this correlation (day +4, p = 0.008). Thus, in elderly patients with comorbidities undergoing hip fracture surgery information on sex, age, ASA category and postoperative laboratory analyses on TnT provide the clinicians with useful information on patients at risk of fatal outcome.     

Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS)

Using population-based data from Sweden, we identified all multiple myeloma (MM) patients (n = 8740) and 5652 monoclonal gammopathy of undetermined significance (MGUS) patients diagnosed between 1986 and 2005. We calculated standardized incidence rates (SIRs) for all subsequent hematologic and nonhematologic malignancies for MM patients diagnosed before/after 1995 (introduction of high-dose melphalan/autologous stem cell transplantation [HDM-ASCT]) and 2000 (introduction of immunomodulatory drugs [IMiDs]), respectively. MM patients had an 11.51-fold (95% confidence interval: 8.19-15.74) increased risk of acute myeloid leukemia (AML)/myelodysplastic syndromes (MDS); risk was very similar before/after 1995 and 2000, respectively. MGUS patients had an 8.01-fold (5.40-11.43) increased risk of AML/MDS. Risk was confined to IgG/IgA, while no IgM MGUS patients developed AML/MDS; patients with monoclonal-protein (M-protein) concentrations > 1.5 g/dL (SIR = 11.12; 3.61-25.96) had higher risk than those < 1.5 g/dL (SIR = 4.67; 1.71-10.16). An excess risk of nonmelanoma skin cancer was observed subsequent to both MM (SIR = 2.22; 1.74-2.80) and MGUS (SIR = 3.30; 2.76-3.90). Our novel observations of an excess risk for AML/MDS following IgG/IgA (but not IgM) MGUS, and the highest risk associated with M-protein concentrations > 1.5 g/dL, support a role for nontreatment-related factors in plasma cell dyscrasias. AML/MDS risk following MM was the same before/after the introduction of HDM-ASCT. Longer follow-up is needed to characterize second tumor risks in the IMiD era.     

Assessing physical function in adult acquired major upper-limb amputees by combining the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome Questionnaire and clinical examination

Østlie K, Franklin RJ, Skjeldal OH, Skrondal A, Magnus P. Assessing physical function in adult acquired major upper-limb amputees by combining the Disabilities of the Arm, Shoulder and Hand (DASH) Outcome Questionnaire and clinical examination.

Objectives

To describe physical function in adult acquired major upper-limb amputees (ULAs) by combining self-assessed arm function and physical measures obtained by clinical examinations; to estimate associations between background factors and self-assessed arm function in ULAs; and to assess whether clinical examination findings may be used to detect reduced arm function in unilateral ULAs.

Design

Survey: postal questionnaires and clinical examinations.

Setting

Norwegian ULA population. Clinical examinations performed at 3 clinics.

Participants

Questionnaires: population-based sample (n=224; 57.4% response rate). Clinical examinations: combined referred sample and convenience sample of questionnaire responders (n=70; 83.3% of those invited). Survey inclusion criteria: adult acquired major upper-limb amputation, resident in Norway, mastering of spoken and written Norwegian.

Interventions

Not applicable.

Main Outcome Measures

The Disabilities of the Arm, Shoulder and Hand (DASH) Outcome Questionnaire, and clinical examination of joint motion and muscle strength with and without prostheses.

Results

Mean DASH score was 22.7 (95% confidence interval [CI], 20.3–25.0); in bilateral amputees, 35.7 (95% CI, 23.0–48.4); and in unilateral amputees, 22.1 (95% CI, 19.8–24.5). A lower unilateral DASH score (better function) was associated with paid employment (vs not in paid employment: adjusted regression coefficient [aB]=−5.40, P=.033; vs students: aB=−13.88, P=.022), increasing postamputation time (aB=−.27, P=.001), and Norwegian ethnicity (aB=−14.45, P<.001). At clinical examination, we found a high frequency of impaired neck mobility and varying frequencies of impaired joint motion and strength at the shoulder, elbow, and forearm level. Prosthesis wear was associated with impaired joint motion in all upper-limb joints (P<.006) and with reduced shoulder abduction strength (P=.002). Impaired without-prosthesis joint motion in shoulder flexion (ipsilateral: aB=12.19, P=.001) and shoulder abduction (ipsilateral: aB=12.01, P=.005; contralateral: aB=28.82, P=.004) was associated with increased DASH scores.

Conclusions

Upper-limb loss clearly affects physical function. DASH score limitation profiles may be useful in individual clinical assessments. Targeted clinical examination may indicate patients with extra rehabilitational needs. Such examinations may be of special importance in relation to prosthesis function.     

Growth-inhibiting conditions slow growth plate senescence

The mammalian growth plate undergoes programmed senescence during juvenile life, causing skeletal growth to slow with age. We previously found that hypothyroidism in rats slowed both growth plate chondrocyte proliferation and growth plate senescence, suggesting that senescence is not dependent on age per se but rather on chondrocyte proliferation. However, one alternative explanation is that the observed slowing of growth plate senescence is a specific consequence of hypothyroidism. We reasoned that, if delayed senescence is a general consequence of growth inhibition, rather than a specific result of hypothyroidism, then senescence would also be slowed by other growth-inhibiting conditions. In this study, we therefore used tryptophan deficiency to temporarily inhibit growth in newborn rats for 4 weeks. We then allowed the animals to recover and studied the effects on growth plate senescence. We found that structural, functional, and molecular markers of growth plate senescence were delayed by prior tryptophan deficiency, indicating that the developmental program of senescence had occurred more slowly during the period of growth inhibition. Taken together with previous studies in hypothyroid rats, our findings support the hypothesis that delayed senescence is a general consequence of growth inhibition and hence that growth plate senescence is not simply a function of time per se but rather depends on growth.     

Concomitant use of medication with antiplatelet effects in patients receiving either rivaroxaban or enoxaparin after total hip or knee arthroplasty

Introduction

The RECORD programme compared oral rivaroxaban with enoxaparin for prevention of venous thromboembolism after elective total hip or knee replacement. This analysis compared the safety of concomitant use of specified medications with rivaroxaban and enoxaparin by evaluating postoperative bleeding rates from the pooled RECORD1-4 data.

Materials and methods

The co-medications were non-steroidal anti-inflammatory drugs and platelet function inhibitors, including acetylsalicylic acid (no dose restriction). The endpoints evaluated were the composite of major and non-major clinically relevant bleeding and any bleeding occurring after first oral study drug intake. The time relative to surgery was stratified into three time periods: day 1-3, day 4-7 and after day 7. Relative bleeding rate ratios for co-medication use versus non-use were derived using stratified Mantel-Haenszel methods and compared between rivaroxaban and enoxaparin groups.

Results

Co-medication use with rivaroxaban or enoxaparin resulted in non-significant increases in bleeding events. Respective rate ratios were not significantly different between rivaroxaban and enoxaparin for all bleeding endpoints with concomitant use of non-steroidal anti-inflammatory drugs (any bleeding, 1.22 vs 1.22; major and non-major clinically relevant bleeding, 1.28 vs 0.90) and with concomitant use of platelet function inhibitors/acetylsalicylic acid (any bleeding, 1.32 vs 1.40; major and non-major clinically relevant bleeding, 1.11 vs 1.13).

Conclusions

This explorative analysis indicates that there is no significant increase in bleeding risk for rivaroxaban compared with enoxaparin when co-administered with non-steroidal anti-inflammatory drugs or acetylsalicylic acid, although, because of low usage, the experience with platelet function inhibitors (except acetylsalicylic acid) was limited.     

Serum concentrations of opioids when comparing two switching strategies to methadone for cancer pain

Purpose

Our aim was to compare pharmacological aspects of two switching strategies from morphine/oxycodone to methadone; the stop and go (SAG) strategy in which methadone is started directly after the initial opioid has been stopped, and the 3-days switch (3DS), in which morphine/oxycodone is gradually changed to methadone by cross-tapering over 3 days.

Methods

Forty-two cancer patients with pain and/or opioid side effects were assessed in this randomised trial. Trough serum concentrations of methadone, morphine, morphine-6-glucuronide (M6G), and oxycodone were measured on days 1, 2, 3, 4, 7, and 14. Primary outcome was number of patients with methadone concentrations in apparent C_SS on day 4. Secondary outcomes were exposure to opioids during the first 3 days, interindividual variation of opioid concentrations, and correlation between methadone concentrations and pain intensity (PI) day 3.

Results

Thirty-five patients received methadone (16 in the SAG group, 19 in the 3DS group). The median preswitch morphine equivalent doses were 620 (range 350–2000) mg/day in the SAG group and 800 (range 90–3600) mg/day in the 3DS group (p?=?0.43);42% reached C_SS for methadone in the SAG group on day 4 compared with 22% in the 3DS group (p?=?0.42). The SAG group was significantly less exposed to morphine/M6G/oxycodone and significantly more exposed to methadone in the first 3 days. Methadone showed a low correlation with PI. More patients dropped out after intervention in the SAG group than in the 3DS group (38% vs. 5%; p?=?0.032). One SAG patient suffered from respiratory depression on day 5.

Conclusion

The SAG group was initially more exposed to methadone and less to the replaced opioids but without observed clinical benefit and with a higher dropout rate. Patients switched to methadone should be followed closely for the first 5 days, regardless of switching strategy.