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.     

Diabetes insipidus and adipsic hypernatremia in a patient with a craniopharyngioma

A fourteen-year male patient presented a retrochiasmatic craniopharyngioma. Aer transcranial surgical resection, the patient had diabetes insipidus, which presented an interphase with manifestations of inadequate secretion of ADH. The patient was adequately treated with intranasal desmopresin, but aer i.v. fluid replacement was withdrawn, severe dehydration occurred. This was attributed to loss of the thirst reflex, due to surgical lesion of the lamina terminalis, where the osmoreceptor neurons are located. This case underscores the complications with body fluids and osmolality which may occur after surgery of hypothalamic lesions; i.e. diabetes insipidus (which may have a triphasic course), and adipsia, an infrequent complication due to absence of thirst.     

Expression of Bcl-2 by human bone marrow mast cells and its overexpression in mast cell leukemia

Bcl-2 protein plays a major role in the prevention of programmed cell death of differentiating cells. In the present study, the expression of cytoplasmic bcl-2 by human Bone Marrow Mast Cells (BMMC) from both normal and pathological bone marrow samples was examined. A total of 35 subjects corresponding to 9 healthy volunteers, 8 cases of adult indolent systemic mast cell disease (SMCD), 4 cases of pediatric mastocytosis (PM), 11 cases of hematological malignancies (HM), 2 cases of reactive bone marrow, and 1 case of mast cell leukemia (MCL) were analyzed. The expression of bcl-2 was studied using quantitative three-color flow cytometry. We also studied the molecular configuration of the bcl-2 gene and other relatives by Southern blot and polymerase chain reaction (PCR) in the MCL case. Bcl-2 expression was detected in BMMC from all samples analyzed. No significant differences on the expression of bcl-2 were detected between BMMC from healthy subjects and patients with SMCD, PM, HM, and reactive bone marrow. By contrast, bcl-2 protein was overexpressed in BMMC from MCL patient without gene rearrangement. Our results show that bcl-2 protein was constitutively expressed by BMMC. BMMC from MCL display overexpression of bcl-2, which could not be related to molecular rearrangements involving the bcl-2 gene. The expression of this protein by mature MC may play a role in the prevention of MC apoptosis and thus help to explain the long survival of these cells. The overexpression of bcl-2 by BMMC in MCL may help to explain their resistance to chemotherapy-induced apoptosis.     

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.

     

The importance of anosmia,ageusia and age in community presentation of symptomatic and asymptomatic SARS-CoV-2 infection in Louisiana,USA; a cross-sectional prevalence study

ObjectiveWhile many seroprevalence studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been performed, few are demographically representative. This investigation focused on defining the nature and frequency of symptomatic and asymptomatic SARS-CoV-2 infection in a representative, cross-sectional sample of communities in Louisiana, USA.MethodsA sample of 4778 adults from New Orleans and Baton Rouge, Louisiana were given a survey of symptoms and co-morbidities, nasopharyngeal swab to test for active infection (PCR), and blood draw to test for past infection (IgG). Odds ratios, cluster analysis, quantification of virus and antibody, and linear modelling were used to understand whether certain symptoms were associated with a positive test, how symptoms grouped together, whether virus or antibody varied by symptom status, and whether being symptomatic was different across the age span.ResultsReported anosmia/ageusia was strongly associated with a positive test; 40.6% (93/229) tested positive versus 4.8% (218/4549) positivity in those who did not report anosmia/ageusia (OR 13.6, 95% CI 10.1–18.3). Of the people who tested positive, 47.3% (147/311) were completely asymptomatic. Symptom presentation clustered into three groups; low/no symptoms (0.4 ± 0.9, mean ± SD), highly symptomatic (7.5 ± 1.9) or moderately symptomatic (4.0 ± 1.5). Quantity of virus was lower in the asymptomatic versus symptomatic group (cycle number 23.3 ± 8.3 versus 17.3 ± 9.0; p < 0.001). Modelling the probability of symptoms showed changes with age; the highest probability of reporting symptoms was 64.6% (95% CI 50.4–76.5) at age 29 years, which decreased to a probability of 49.3% (95% CI 36.6–62.0) at age 60 years and only 25.1% (95% CI 5.0–68.1) at age 80 years.ConclusionAnosmia/ageusia can be used to differentiate SARS-CoV-2 infection from other illnesses, and, given the high ratio of asymptomatic individuals, contact tracing should include those without symptoms. Regular testing in congregant settings of those over age 60 years may help mitigate asymptomatic spread.