Calcium phosphate injection of symptomatic bone marrow lesions of the knee: what is the current clinical evidence?

BACKGROUND: Chronic bone marrow lesions (BML) in the weight-bearing portions of the knee are often associated with symptomatic degenerative arthritis resulting in pain and dysfunction. Injection of bone substitute material like calcium phosphate has been described. Whilst some studies have reported encouraging results others have shown limited benefit of this technique. AIM: The aim was to collate the available evidence on the injection of calcium phosphate and systematically evaluate the results to answer the questions encountered in clinical decision making: (1) does it provide effective long-lasting pain relief to avoid further surgical intervention? (2) which factors (patient/surgical) significantly influence the outcome? and (3) does it adversely affect the outcomes of subsequent arthroplasty? METHODS: A literature search was performed to identify the studies describing the clinical outcomes of calcium phosphate injection for treatment of BML. We evaluated the reported clinical outcomes with respect to pain, function and complications. Isolated case reports and studies with no objective assessment of clinical outcomes were excluded. RESULTS: We noted 46 articles in the current literature of which 8 described clinical outcomes of calcium phosphate injection. Mean (plus/minus SD) score on the visual analog scale (VAS) has been reported to improve from 7.90 (± 0.38) to 2.76 (± 0.90), whereas the International Knee Documentation Committee (IKDC) score improved from 30.5 (SD not reported (NR)) to 53.0 (SD NR). Pre and post procedure Short form survey (SF-12) scores were 29.8 (SD NR) and 36.7 (SD NR), respectively. In one study, scores on the Tegner Lysholm knee scoring scale improved in 12 out of 22 patients, whereas the remainder had no change in symptoms. Extravasation of calcium phosphate into the joint was the most common complication, whereas no adverse effect has been reported on subsequent arthroplasty. CONCLUSION: Limited data from the published studies would suggest that calcium phosphate injection of BML may potentially improve pain and function. However, no evidence is currently available to clearly identify patient/surgical factors that may influence the long-term outcomes of this procedure. Hence pragmatic, prospective studies with stratified patient cohorts and robust reporting of outcome measures are essential to improve the understanding of the indications and clinical effectiveness of this novel procedure.

Evaluating the communities care program: best practice for rigorous research to evaluate gender based violence prevention and response programs in humanitarian settings.

BACKGROUND: Gender-based violence (GBV) is a significant issue for women and girls in humanitarian settings. Innovative primary prevention programs are being developed and implemented with existing response programs to change harmful social norms that sustain GBV in humanitarian settings. Social norms are expectations of how women, men, girls and boys should behave, who should have power and control over behavior, and how families and communities value women and girls and support their rights and opportunities. METHODS: The United Nations Children's Fund (UNICEF) led Communities Care program is a primary prevention and response program designed from the understanding that within the context of conflict and displacement, there is an opportunity for positive change in social norms that support gender equity, and decrease GBV. The goal is to support communities in humanitarian settings to create healthy, safe and peaceful environments with quality response services for women and girls by transforming harmful social norms that uphold violence into norms that promote dignity, equity, and non-violence. CONCLUSION: This manuscript will highlight the use of best practices in GBV research to rigorously evaluate the Communities Care program in two diverse in humanitarian settings, Somalia and South Sudan.

A human-driven decline in global burned area.

Fire is an essential Earth system process that alters ecosystem and atmospheric composition. Here we assessed long-term fire trends using multiple satellite data sets. We found that global burned area declined by 24.3 ± 8.8% over the past 18 years. The estimated decrease in burned area remained robust after adjusting for precipitation variability and was largest in savannas. Agricultural expansion and intensification were primary drivers of declining fire activity. Fewer and smaller fires reduced aerosol concentrations, modified vegetation structure, and increased the magnitude of the terrestrial carbon sink. Fire models were unable to reproduce the pattern and magnitude of observed declines, suggesting that they may overestimate fire emissions in future projections. Using economic and demographic variables, we developed a conceptual model for predicting fire in human-dominated landscapes.

Long-term outcome in an uncemented, hydroxyapatite-coated total knee replacement: a 15- to 18-year survivorship analysis.

A consecutive series of patients with a hydroxyapatite-coated uncemented total knee replacement (TKR) performed by a single surgeon between 1992 and 1995 was analysed. All patients were invited for clinical review and radiological assessment. Revision for aseptic loosening was the primary outcome. Assessment was based on the Knee Society clinical score (KSS) and an independent radiological analysis. Of 471 TKRs performed in 356 patients, 432 TKRs in 325 patients were followed for a mean of 16.4 years (15 to 18). The 39 TKRs in 31 patients lost to follow-up had a mean KSS of 176 (148 to 198) at a mean of ten years. There were revisions in 26 TKRs (5.5%), of which 11 (2.3%) were for aseptic loosening. Other further surgery was carried out on 49 TKRs (10.4%) including patellar resurfacing in 20, arthrolysis in 19, manipulation under anaesthetic in nine and extensor mechanism reconstruction in one. Survivorship at up to 18 years without aseptic loosening was 96% (95% confidence interval 91.9 to 98.1), at which point the mean KSS was 176 (134 to 200). Of 110 knees that underwent radiological evaluation, osteolysis was observed in five (4.5%), one of which was revised. These data indicate that uncemented hydroxyapatite-coated TKR can achieve favourable long-term survivorship, at least as good as that of cemented designs.

Meniscal repair in anterior cruciate ligament reconstruction: a long-term outcome study.

PURPOSE: To study the long-term outcome of patients who have undergone inside-out, vertical stacked mattress suture repair of meniscal tears combined with anterior cruciate ligament (ACL) reconstruction. METHODS: From a database of ACL reconstructed patients, consecutive patients undergoing concomitant meniscal repair and ACL reconstruction between 1991 and 1999 were identified. Patients with previous ACL or meniscal pathology were excluded. Two age- and sex-matched cohorts who had undergone combined ACL reconstruction and menisectomy and who had undergone ACL reconstruction with normal menisci were identified for comparison. Outcome scoring included IKDC and Lysholm scores for the meniscal repair group. Two sample t-tests and chi-square tests were used to compare the IKDC subjective scores, with a minimum level of significance set at 5% (P = 0.05). RESULTS: Fourty-four patients were identified for analysis with a median follow-up of 10 years (7.7-12.6). Patients undergoing ACL reconstruction combined with meniscal repair had a mean IKDC of 84.2 compared with a mean score of 70.5 (P = 0.008) in patients who had undergone menisectomy and 88.2 (P = 0.005) in patients with intact menisci. 86.2% of patients with ACL reconstruction and meniscal repair had Lysholm score of between 80 and 100%. Sixty-nine percent follow-up was achieved. Survival analysis by life table method shows a best case of 89% 10-years survival. CONCLUSIONS: This study demonstrates that good long-term outcomes can be obtained in patients up to over 12 years after combined ACL reconstruction and meniscal repair. Improved functional scores can be achieved when compared with ACL reconstruction and menisectomy. The authors advocate repair of meniscal tears during ACL reconstruction unless there is complex tearing, radial tearing or plastic deformation of the remaining meniscus. LEVEL OF EVIDENCE: III.

Where is the F in MCH? Father involvement in African American families.

OBJECTIVES: To: 1) review the historical contexts and current profiles of father involvement in African American families; 2) identify barriers to, and supports of, involvement; 3) evaluate the effectiveness of father involvement programs; and 4) recommend directions for future research, programs, and public policies. METHODS: Review of observational and interventional studies on father involvement. RESULTS: Several historical developments (slavery, declining employment for Black men and increasing workforce participation for Black women, and welfare policies that favored single mothers) led to father absence from African American families. Today, more than two thirds of Black infants are born to unmarried mothers. Even if unmarried fathers are actively involved initially, their involvement over time declines. We identified multiple barriers to, and supports of, father involvement at multiple levels. These levels include intrapersonal (eg, human capital, attitudes and beliefs about parenting), interpersonal (eg, the father's relationships with the mother and maternal grandmother), neighborhoods and communities (eg, high unemployment and incarceration rates), cultural or societal (eg, popular cultural perceptions of Black fathers as expendable and irresponsible, racial stratification and institutionalized racism), policy (eg, Earned Income Tax Credit, Temporary Assistance for Needy Families, child support enforcement), and life-course factors (eg, father involvement by the father's father). We found strong evidence of success for several intervention programs (eg, Reducing the Risk, Teen Outreach Program, and Children's Aid Society - Carrera Program) designed to prevent formation of father-absent families, but less is known about the effectiveness of programs to encourage greater father involvement because of a lack of rigorous research design and evaluation for most programs. CONCLUSION: A multi-level, life-course approach is needed to strengthen the capacity of African American men to promote greater involvement in pregnancy and parenting as they become fathers.

Helicopter Emergency Ambulance Service (HEAS) transfer: an analysis of trauma patient case-mix, injury severity and outcome.

INTRODUCTION: A retrospective review of all patients transferred by helicopter ambulance to the Great Western Hospital over a 20-month period between January 2003 and September 2004 was undertaken to establish the case-mix of patients (trauma and non-trauma) transferred and the outcome. PATIENTS AND METHODS: Details of all Helicopter Emergency Ambulance Service (HEAS) transfers to this unit in the study time period were obtained from the three HEAS providers in the area and case notes were reviewed. RESULTS: There were 156 trauma patients transferred (total 193) in the study period with 111 cases identified for analysis with a mean age of 33 years (range, 1-92 years). Average Injury Severity Score on admission was 12 (range, 1-36). Forty-five patients were discharged home from the emergency department, 24 cases had operation, 10 patients required ICU care and 2 were pronounced dead in the emergency department. Average hospital stay following HEAS transfer was 2.97 days (range, 0-18 days). DISCUSSION: Helicopter ambulance transfer in the acute setting is of debated value. Triage criteria are at fault if as many as 41% of patients transferred are being discharged home from casualty having incurred the financial cost of helicopter transfer. We suggest that the triage criteria for helicopter emergency transfer should be reviewed.

Severe knee osteoarthritis: a randomized controlled trial of acupuncture, physiotherapy (supervised exercise) and standard management for patients awaiting knee replacement.

OBJECTIVE: To evaluate the effects of standardized western acupuncture and physiotherapy on pain and functional ability in patients with severe osteoarthritic knee pain awaiting knee arthroplasty. METHODS: Three-arm, assessor-blind, randomized controlled trial. PARTICIPANTS: 181 patients awaiting knee arthroplasty. INTERVENTIONS: acupuncture for 6 weeks; physiotherapy for 6 weeks; standardized advice. MAIN OUTCOME MEASURES: Oxford Knee Score questionnaire (OKS) (primary); 50 m timed walk, and duration of hospital stay following knee arthroplasty. RESULTS: There was no baseline difference between groups. At 7 weeks, there was a 10% reduction in OKS in the acupuncture group which was a significant difference between the acupuncture and the control group: Mean (s.d.) acupuncture 36.8 (7.20); physiotherapy 39.2 (8.22); control 40.3 (8.48) (P = 0.0497). These effects were no longer present at 12 weeks. There was a trend (P = 0.0984) towards a shorter in-patient stay of 1 day for the physiotherapy group [mean 6.50 days (s.d. 2.0)] compared with the acupuncture group [mean 7.77 days (s.d. 3.96)]. CONCLUSIONS: We have demonstrated that patients with severe knee osteoarthritis can achieve a short-term reduction in OKS when treated with acupuncture. However, we failed to demonstrate any other clinically or statically significant effects between the groups. Both interventions can be delivered effectively in an out-patient group setting at a district general hospital. Further study is needed to evaluate the combined effects of these treatments.

Microvascular complications and the diabetic pregnancy.

Without strict glycemic control, diabetic pregnancies are frequently complicated by spontaneous abortion, stillbirth, or congenital malformation. Retrospective studies have been largely reassuring that pregnancy does not accelerate morbid outcomes in women with diabetic vascular disease. Improved outcomes of high-risk pregnancy in women with pregestational, type 1, or type 2 diabetes mellitus remain challenging, depending on a comprehensive and multidisciplinary team approach and extensive preconception counseling.

A simple clinical test of flexor pollicis longus rupture.

Rupture of the tendon of flexor pollicis longus is suspected when active flexion of the interphalangeal joint of the thumb is not possible. This can be a result of trauma but, when spontaneous, diagnostic confusion can exist as incomplete palsy of the anterior interosseous nerve can present in a similar way. We describe a simple clinical sign which can differentiate between these conditions.

Bioenergetic consequences of accumulating the common 4977-bp mitochondrial DNA deletion.

Mutations and deletions in mitochondrial DNA (mtDNA) lead to a number of human diseases characterized by neuromuscular degeneration. Accumulation of truncated mtDNA molecules (delta-mtDNA) lacking a specific 4977-bp fragment, the common deletion, leads to three related mtDNA diseases: Pearson's syndrome; Kearns-Sayre syndrome; and chronic progressive external ophthalmoplegia (CPEO). In addition, the proportion of delta-mtDNA present increases with age in a range of tissues. Consequently, there is considerable interest in the effects of the accumulation of delta-mtDNA on cell function. The 4977-bp deletion affects genes encoding 7 polypeptide components of the mitochondrial respiratory chain, and 5 of the 22 tRNAs necessary for mitochondrial protein synthesis. To determine how the accumulation of delta-mtDNA affects oxidative phosphorylation we constructed a series of cybrids by fusing a human osteosarcoma cell line depleted of mtDNA (rho0) with enucleated skin fibroblasts from a CPEO patient. The ensuing cybrids contained 0-86% delta-mtDNA and all had volumes, protein contents, plasma-membrane potentials and mitochondrial contents similar to those of the parental cell line. The bioenergetic consequences of accumulating delta-mtDNA were assessed by measuring the mitochondrial membrane potential, rate of ATP synthesis and ATP/ADP ratio. In cybrids containing less than 50-55% delta-mtDNA, these bioenergetic functions were equivalent to those of cybrids with intact mtDNA. However, once the proportion of delta-mtDNA exceeded this threshold, the mitochondrial membrane potential, rate of ATP synthesis, and cellular ATP/ADP ratio decreased. These bioenergetic deficits will contribute to the cellular pathology associated with the accumulation of delta-mtDNA in the target tissues of patients with mtDNA diseases.

Cutaneous larva migrans associated with water shoe use.

It has been long suspected that footwear is protective against cutaneous larva migrans. This case report describes a woman who developed cutaneous larva migrans despite wearing 'protective' footwear. We forward a hypothesis by which recently popular water shoes may actually be conducive to the development of cutaneous larva migrans rather than having a protective function.

Sexual content-induced delay with double-entendre words.

Seventy-three men and 72 women made lexical decisions to target words that followed sentences constructed so that the last word was a sexual double-entendre. Prime target relatedness, erotic versus nonerotic target, stimulus onset asynchrony, and participant's gender were varied in a between-subjects design. A second analysis that substituted sentence context for prime target relationship also was conducted. Data were collected on the emotionality and social acceptability of priming sentences and target words. Results revealed that, as with previous research on neutral words, prime target relatedness facilitated lexical decisions. Additionally, there was evidence of slowing in making lexical decisions when erotic material was presented or was part of a contextual bias. This delay was accentuated in women. A model that proposes that sexual words evoke a more complex processing sequence is presented. The model suggests that appraisal and checking or editing mechanisms, which are accentuated in women, help explain the phenomenon.

In vivo efficacies of levofloxacin and ciprofloxacin in acute murine hematogenous pyelonephritis induced by methicillin-susceptible and-resistant Staphylococcus aureus strains.

Levofloxacin, the active L-isomer of ofloxacin, has demonstrated strong activity against Staphylococcus aureus both in vitro and in vivo. In a murine model of hematogenous pyelonephritis, the in vivo efficacies of levofloxacin and ciprofloxacin were evaluated against two methicillin-susceptible and two methicillin-resistant S. aureus strains. All four isolates had virtually identical susceptibilities to levofloxacin and ciprofloxacin. Pyelonephritis was induced in carrageenan-primed mice by an intravenous injection of 0.5 ml of 10(7) CFU of methicillin-susceptible S. aureus isolates per ml or 10(8) CFU of methicillin-resistant S. aureus isolates per ml. At 1 h postinfection, the mice were treated orally with levofloxacin or ciprofloxacin once a day or twice a day (total daily dose of 20 to 160 mg/kg of body weight) for 4 days. Mice were euthanized 24 h after the final treatment, and the kidneys were excised and weighed. The kidneys were prepared for histological examination or were homogenized to determine the numbers of CFU per gram of tissue quantitatively. The reduction in the mean log10 number of CFU per gram as a function of total daily dose was recorded. A dose-response analysis showed that levofloxacin was superior to ciprofloxacin for all four isolates at any dose or regimen tested, independent of the methicillin susceptibility of the isolates. By using an inverse prediction technique, the equivalent effective doses of levofloxacin (once a day) were less than those of ciprofloxacin (twice a day) by 5.2 and 3.2 times, respectively, for methicillin-susceptible S. aureus 9039 and 3087. For methicillin-resistant S. aureus 667 and 2878, the equivalent effective doses of levofloxacin (once a day) were less than those of ciprofloxacin (twice a day) by 4.1 and 6.4 times, respectively. In a separate study, histological examination of all infected, untreated mice showed moderate to marked hematogenous pyelonephritis. Levofloxacin-treated mice (40 mg/kg once a day) showed no evidence of pyelonephritis in the kidneys, whereas the kidneys of mice treated with the same dose of ciprofloxacin showed only a reduction in the severity of the lesions. Treatment with ciprofloxacin (80 mg/kg twice a day) demonstrated a histology comparable to that of treatment with levofloxacin (40 mg/kg once a day). Levofloxacin (40 mg/kg once a day) reduced the log10 numbers of CFU per gram by 5 log10; however, ciprofloxacin (80 mg/kg twice a day) reduced the numbers of CFU per gram by only 3 log10. In the present murine model of pyelonephritis, levofloxacin was superior to ciprofloxacin in preventing pyelonephritis and eradicating S. aureus.

Autoregressive spectral analysis of phrenic neurogram during eupnea and gasping.

During hypoxic gasping, the phrenic neurogram (PN) has a steeper rate of rise, an augmented amplitude, and a shorter duration than is seen during eupnea. Because hypoxia reduces neuronal activity, we hypothesized that gasping would be characterized in the frequency domain by enhanced low-frequency power compared with eupnea. Autoregressive (AR) spectral analysis of the PN in chloralose-anesthetized, vagotomized, peripherally chemodenervated cats was performed during eupnea and hypoxic gasping. During eupnea, significant spectral peaks were seen at 41 +/- 2 and 93 +/- 2 (SE) Hz. In all cats, the 41-Hz spectral peak disappeared during hypoxic gasping and was replaced by a high-power, low-frequency peak at 26 +/- 1 Hz. No consistent change in the frequency or power of the high-frequency spectral peak was seen during gasping. To determine whether changes in the AR spectrum of the PN during gasping result from augmented respiratory output, we compared the AR spectra of the PN during gasping, hypercapnia (end-tidal CO2 fraction = 0.09), and carotid sinus nerve stimulation. Unlike during gasping, there was no shift in power toward lower frequencies during hypercapnia and carotid sinus nerve stimulation. We conclude that the spectral characteristics of gasping, loss of the medium-frequency peak and the appearance of low-frequency (< 30-Hz) power, are unique to this respiratory pattern.

Respiration and medullary blood flow during sinusoidal hypoxia in the peripherally chemodenervated cat.

The hypothesis that hypoxic respiratory depression is mediated by changes in medullary blood flow (MBF) was assessed in 18 anesthetized, paralyzed, vagotomized, peripherally chemodenervated, ventilated cats exposed to sinusoidal hypoxic hypoxia. In nine cats, the dynamic response of the central respiratory controller to hypoxia was studied by varying the cycle time of sinusoidal hypoxia (cycle time = 2.5, 4, 6, 10, and 15 min). Peak phrenic neurogram amplitude (PNA) followed sinusoidal oscillations in the hypoxic input [arterial O2 saturation (SaO2)] at all cycle times. The relationship between PNA and SaO2 was expressed as the transfer function of the system and was approximated as a first-order differential equation with a time constant of 78 +/- 1 s, a value consistent with a previous measurement of the time constant of the change in respiration following a change in brain blood flow. In a separate study, MBF was continuously measured during sinusoidal hypoxia (cycle time = 6 min; n = 9) with a laser-Doppler flow probe to directly assess the role of MBF in production of hypoxic respiratory depression. PNA and MBF followed SaO2 oscillations during sinusoidal hypoxia. Infusion of sodium nitroprusside (20 micrograms.kg-1.min-1 iv) increased MBF by 30-40% and abolished MBF oscillations during subsequent sinusoidal hypoxia but had no effect on PNA oscillations. We conclude that the increase in brain blood flow seen during sinusoidal hypoxia is not the primary cause of the accompanying central hypoxic respiratory depression.

Respiratory and sympathetic activity during recovery from hypoxic depression and gasping in cats.

In peripherally chemodenervated, vagotomized, chloralose-anesthetized cats, hypoxia can produce central cardiorespiratory depression or excitation depending on severity. We monitored phrenic and cervical sympathetic neurograms during either hypoxic depression or gasping and 30 min of subsequent isocapnic reoxygenation to determine whether the response of these outputs during hypoxia predicts their activity during recovery. Three levels of hypoxic response were produced in cats: 1) reduction of phrenic neurogram amplitude (PNA) by 30% [fractional inspired O2 (FIO2) = 14-18%)]; 2) production of phrenic apnea (FIO2 = 9-10%); and 3) hypoxic gasping (FIO2 = 6-8%). Recovery from the milder levels of hypoxia was characterized by transient (< 10 min) depression of PNA and inspiratory synchronous sympathetic activity. Respiratory frequency was unaffected or only transiently depressed. Tonic sympathetic activity was unaffected. During reoxygenation after gasping, both PNA and inspiratory synchronous sympathetic activity were initially increased by 80% over control levels and respiratory frequency was depressed. Tonic sympathetic activity increased during hypoxia but returned to control levels after a brief undershoot on reoxygenation. All variables returned to control levels within 15 min. Measurement of medullary extracellular K+ concentration ([K+]e) in a separate group of cats indicated that a significant increase in this variable was associated with hypoxic gasping but was not correlated with PNA augmentation during reoxygenation. We hypothesize that increased [K+]e coincident with gasping may trigger a postanoxic potentiation of respiratory premotor neurons similar to that described in hippocampus.

Activity of respiratory neurons during hypoxia in the chemodenervated cat.

Exposure of anesthetized paralyzed vagotomized peripherally chemodenervated cats to hypoxia results in initial depression and subsequent loss of the phrenic neurogram. To determine whether hypoxic respiratory depression results from the inhibition of respiratory premotor neurons by bulbospinal neurons of the Bötzinger complex (Böt-E neurons), extracellular recordings were made of dorsal and ventral respiratory group bulbospinal inspiratory neurons and Böt-E neurons during acute hypoxic hypoxia. All neurons recorded decreased firing rate during hypoxia. Böt-E neurons became silent before the loss of phasic phrenic activity during hypoxia and commenced firing before or coincident with the return of the phrenic neurogram during reoxygenation. Inspiratory neurons ceased firing coincident with phrenic silence. Dorsal respiratory group and ventral respiratory group neurons that had a late onset of firing with respect to the phrenic neurogram during normoxia fired progressively earlier in inspiration during hypoxia, an effect that was reversed during reoxygenation. These data are consistent with inhibition and/or disfacilitation as the mechanism of hypoxic respiratory depression but suggest that Böt-E neurons are not the source of this inhibition.