Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.     

Obstetric anal sphincter injury: prospective evaluation of incidence

PURPOSE: An obstetrically damaged anal sphincter is the principal cause of the development of fecal incontinence in otherwise healthy females. Reports suggest that such damage complicates as many as 35 percent of primiparous vaginal deliveries, with 13 percent of first-time mothers becoming symptomatic. In maternity units delivering 3,000 patients annually, it would follow that 390 symptomatic patients would develop new symptoms each year. This incidence of dysfunction does not reflect current clinical practice. We have investigated this discrepancy to establish the actual incidence of anal sphincter trauma associated with childbirth. METHODS: During a six-week period, 159 females (105 primiparous and 54 para-I) were prospectively assessed postnatally using a standardized symptom questionnaire, endoanal ultrasound, and anal manometry. This group constituted 84 percent of all eligible deliveries occurring in the unit during the study period. RESULTS: One patient developed fecal urgency after this delivery; there were no reports of fecal incontinence. Anal sphincter injuries were identified ultrasonically in 6.8 percent of primiparous patients, 12.2 percent of para-I patients having vaginal deliveries, and 83 percent of patients having forceps deliveries overall. Manometric data provided confirmatory evidence, with significantly reduced maximum squeeze pressures in patients with a disrupted anal sphincter (P<0.0005). CONCLUSIONS: A symptom questionnaire is inadequate to identify anal sphincter injuries. The incidence of sphincter injury in relation to vaginal delivery has been overestimated in previous published work. This study demonstrates that the true incidence is 8.7 percent overall and that symptoms of sphincter dysfunction are uncommon this is in keeping with current clinical practice.     

A qualitative study of clinical reasoning in physiotherapy with preterm infants and their parents: Action and interaction

Background: Physiotherapists (PTs) in primary health care provide services to preterm infants and their parents after hospital discharge. The service should be collaborative and individualized to meet the family’s needs. In this study, we analyze pediatric PTs’ collaborative work in the clinical setting and investigate the PTs’ emerging clinical reasoning (CR) in interaction with the infant and parent(s).

Methods: The study is based on observations of 20 physical therapy sessions and 20 interviews with PTs. We performed a systematic content analysis informed by enactive theory regarding the interactions and co-creation of meaning.

Results and Discussion: CR emerged in reciprocity with the PTs’ interaction with the infant and parent(s). Based on the sensitivity to the infant’s motor abilities and signs of engagement as well as the parents’ need of support and education, the PTs individualized and reasoned about their therapeutic approach. This interactional CR was vulnerable: infant disengagement, parent expectations, and PT preoccupations could obfuscate interactions and hamper CR.

Conclusion: Through mutuality and engagement with the infant and parent(s), the PTs allow the autonomy of interaction to emerge and shape the translation of CR into successful therapeutic actions and learning together with the infant and parent(s).     

Drug eluting stents: maximising benefit and minimising cost

A policy of selective implantation of drug eluting stents, in a minority of lesions most likely to benefit, seems to be a rational way to employ this new and currently costly technology.     

Feasibility and Timing of Prehospital Administration of Reteplase in Patients with Acute Myocardial Infarction

Background: In myocardial infarction patients undergoing thrombolysis, treatment delays negatively impact outcomes. This pilot study was conducted to determine the feasibility and timing of field administration of intravenous double bolus reteplase in patients with ST-elevation myocardial infarction. Methods: Sixty three patients with symptoms and EKG changes consistent with acute myocardial infarction of less than six hours duration received the first bolus of reteplase before arriving at the emergency department. A second bolus of reteplase was given in the emergency department. Subsequent resolution of ST-segment elevation was measured. Mean time from symptom onset to paramedic dispatch, and paramedic arrivals to first bolus of reteplase were measured. The mean time from the first bolus of reteplase to heparin bolus in an emergency department was also measured. All patients with evidence of ST-elevation and suspected acute myocardial infarction gave consent for the thrombolytic therapy. There were no refusals of therapy among those candidates eligible for thrombolysis. Results: The mean times from the first bolus of reteplase to heparin bolus in the emergency department was substantially longer than the in-field times. Resolution of ST-segment elevation was recorded in 52 of the 63 patients and the times of resolution ranged from five minutes after the first bolus dose to 190 minutes after the second bolus of reteplase. Resolution of ST-segment elevation and relief of pain occurred almost simultaneously. Conclusions: These results demonstrated that in-field administration of thrombolytic therapy is a viable option to reduce the delay from symptom onset to initiation of thrombolysis. They demonstrated that satisfactory resolution of ST-segment elevation can be recorded in the field. The reduction in mortality observed in this study is comparable to previously published studies on inpatients. Abbreviated Abstract. This open-label pilot study was conducted to determine the feasibility and timing of field administration of intravenous double-bolus reteplase and to measure subsequent resolution of ST elevation in 63 patients with symptoms and ECG changes consistent with acute myocardial infarction for less than 6 hours. These results demonstrated that in-field administration of thrombolytic therapy is a viable option to reduce the delay from symptom onset to initiation of thrombolytic therapy.     

Ethnicity and social deprivation independently influence metabolic control in children with type 1 diabetes

AIMS/HYPOTHESIS: This study was performed to evaluate the influence of ethnicity and socioeconomic status (SES) on metabolic control in a population-based cohort of children with type 1 diabetes mellitus, and to evaluate whether any relationship between ethnicity and HbA(1c) is mediated by SES. METHODS: We performed a retrospective review of all patients under age 16 years with type 1 diabetes (n = 555) from 1995 to 2005 in the greater Auckland region, New Zealand. Diabetes care variables and HbA(1c) values were collected prospectively, during clinic visits. RESULTS: The mean population HbA(1c) was 8.3 +/- 1.3%. Maori and Pacific patients had poorer metabolic control than their European counterparts (9.1% and 9.3% vs 8.1%, p < 0.001) and higher rates of moderate to severe hypoglycaemia (31.1 and 24.8 vs 14.9 events/100 patient-years, p = 0.03). In multiple linear regression analysis, both ethnicity and SES were independently associated with HbA(1c) (p < 0.001). Other factors associated with higher HbA(1c) level were longer duration of diabetes, higher insulin dose, lower BMI z score and less frequent blood glucose monitoring (p < 0.001). CONCLUSIONS/INTERPRETATION: Both ethnicity and SES independently influenced metabolic control in a large, unselected population of children with type 1 diabetes. Irrespective of SES, Maori and Pacific youth with type 1 diabetes were at greater risk of both moderate to severe hypoglycaemia and long-term complications associated with poor metabolic control.     

What are We Measuring When We Test Strain Differences in Anxiety in Mice?

We examined measures of locomotor and anxiety-like behavior in male and female mice of 15 inbred strains on the elevated-plus maze, light/dark transition box and open field. Strain differences were found on all measures of locomotor activity and anxiety. Strain means for measures of locomotor activity on the three apparatus were significantly correlated, but strain means for commonly used measures of anxiety were not correlated. Principal component analysis revealed a common locomotor activity factor, which accounted for 28.6 % of the variance, but no common anxiety factor. Species-typical behaviors (defecations, stretch-attend postures, grooming) accounted for smaller proportions (<11 %) of the variance. These results plus comparisons with previously published data suggest that the elevated-plus maze, light/dark box and open field measure different facets of anxiety, and that the reliability of genetic differences on anxiety is highly dependent on apparatus, procedural variables and laboratory factors. Locomotor activity, however, is a stable trait that differs across strains and is reliably measured in different apparatus and laboratories. We conclude that anxiety traits of inbred mouse strains are best reflected by species-typical behaviors in each apparatus. These results suggest that new ways of measuring trait anxiety are required in order to determine the neural and genetic correlates of anxiety-like behaviour in mice.     

Age-dependent neurological phenotypes in a mouse model of PRRT2-related diseases

Paroxysmal kinesigenic dyskinesia is an episodic movement disorder caused by dominant mutations in the proline-rich transmembrane protein PRRT2, with onset in childhood and typically with improvement or resolution by middle age. Mutations in the same gene may also cause benign infantile seizures, which begin in the first year of life and typically remit by the age of 2 years. Many details of PRRT2 function at the synapse, and the effects of mutations on neuronal excitability in the pathophysiology of epilepsy and dyskinesia, have emerged through the work of several groups over the last decade. However, the age dependence of the phenotypes has not been explored in detail in transgenic models. Here, we report our findings in heterozygous and homozygous Prrt2 knockout mice that recapitulate the age dependence of dyskinesia seen in the human disease. We show that Prrt2 deletion reduces the levels of synaptic proteins in a dose-dependent manner that is most pronounced at postnatal day 5 (P5), attenuates at P60, and disappears by P180. In a test for foot slippage while crossing a balance beam, transient loss of coordination was most pronounced at P60 and less prominent at age extremes. Slower traverse time was noted in homozygous knockout mice only, consistent with the ataxia seen in rare individuals with biallelic loss of function mutations in Prrt2. We thus identify three age-dependent phenotypic windows in the mouse model, which recapitulate the pattern seen in humans with PRRT2-related diseases.