In a double-blind study of 24 healthy volunteers treated with daily doses of 150 mg flurbiprofen, 600 mg phenylbutazone, 2.1 g aspirin, or placebo for 7 days, assessments were made of faecal blood loss before, during and after treatment. Measurementl body showed that aspirin produced the greatest degree of blood loss. Although both flurbiprofen and phenylbutazone produced greater blood loss than did placebo, the difference from pre-treatment values was not significant, and the levels returned almost to normal in the post-treatment period.
Aims:
No meta-analysis is available which has holistically analyzed efficacy and safety of once weekly thyroxine (OWT) vs. standard daily therapy (SDT) with regards to managing primary hypothyroidism. We undertook this meta-analysis to address this knowledge gap.
Methods:
Electronic databases were searched for clinical trials involving hypothyroid patients receiving OWT in intervention arm, and SDT in control arm. Primary outcome was to evaluate changes in serum thyroid stimulating hormone. Secondary outcomes were to evaluate alterations in total tetra-iodothyronine (TT4), total tri-iodothyronine (TT3), free T4 (FT4), free T3 (FT4), heart rate (HR), cardiac function, symptomatology, and adverse events.
Results:
From initially screened 159 studies, data from four trials involving 294 patients were analyzed. Patients of OWT had significantly higher thyroid stimulating hormone (TSH) [mean difference (MD) +1.85 mU/L (95% confidence interval, CI: 0.95–2.75);
P
< 0.01;
I
2
= 63%], comparable TT4 [MD -0.87 mcg/dl (95% CI: -2.98–1.24);
P
= 0.42;
I
2
= 65%], and significantly lower TT3 [MD -15.7 ng/dl (95% CI: -29.9–1.51);
P
= 0.03;
I
2
= 90%], following 6-weeks therapy. TT4 [MD 3.05 mcg/dl (95% CI: 1.44–4.66);
P
< 0.01], and FT4 [MD 0.56 ng/dl (95% CI: 0.04–1.08);
P
= 0.03;
I
2
= 66%] were significantly higher 2 h after thyroxine intake, in people on OWT compared to SDT. TT4 levels were significantly higher 4 h after thyroxine intake in OWT as compared to SDT [MD 0.70 ng/dl (95% CI: 0.52–0.88);
P
< 0.01]. Following 4–8 h of intake of thyroxine, isovolumetric contraction time [MD 3.62 ms (95% CI: 1.93–5.31);
P
< 0.01;
I
2
= 0%] and aortic ejection time/pre-ejection period ratio [MD 0.01 (95% CI: 0.00–0.02);
P
= 0.02;
I
2
= 0%], were significantly higher in people on OWT as compared to SDT.
Conclusion:
OWT is associated with less efficient control of hypothyroidism at 6 weeks and may be associated with supraphysiologic elevation of thyroid hormone levels along with transient echocardiographic changes in some patients following 2-4 h of thyroxine intake.
Aims:
No Cochrane meta-analysis with grading of evidence is available on use of hydroxychloroquine (HCQ) in type-2 diabetes (T2DM). This meta-analysis evaluated the efficacy and safety of HCQ in T2DM.
Methods:
Electronic databases were searched using a Boolean search strategy: ((hydroxychloroquine) OR (chloroquine*)) AND ((diabetes) OR (“diabetes mellitus”) OR (glycemia) OR (glucose) OR (insulin)) for studies evaluating hydroxychloroquine for glycemic control in T2DM. The primary outcome was a change in glycated haemoglobin (HbA1c). The secondary outcomes were changes in other glycemic/lipid parameters and adverse effects.
Results:
Data from 11 randomized controlled trials (RCTs) (3 having placebo as controls [passive controls] and 8 having anti-diabetes medications as controls [active controls]) involving 2,723 patients having a median follow-up of 24 weeks were analyzed. About 54.54% of the RCTs were of poor quality as evaluated by the Jadad scale. The performance bias and detection bias were at high risk in 63.64% of the RCTs. The HbA1c reduction with HCQ was marginally better compared to the active (mean differences [MD]-0.17% [95%, CI:-0.30–-0.04;
P
=0.009;
I
2
=89%; very low certainty of evidence, VLCE]), and passive (MD-1.35% [95%CI:-2.10–-0.59;
P
=0.005;
I
2
=74%]) controls. A reduction in fasting glucose (MD-16.63mg/dL[95%, CI: -25.99 – -7.28mg/dL;
P
<0.001;
I
2
=97%;VLCE]) and post-prandial glucose [MD -8.41mg/dL (95%CI: -14.71 – -2.12mg/dL;
P
=0.009;
I
2
=87%;VLCE]), appeared better with HCQ compared to active controls. The total adverse events (risk ratio [RR]0.93 [95% CI:0.68–1.28];
P
=0.65;
I
2
=66%) were not different with HCQ compared to the controls.
Conclusion:
The routine use of HCQ in T2DM cannot be recommended based on the current evidence.
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