Don't run away; it's simple : PARALLEL Vs CROSS OVER DESIGNS IN RANDOMIZED CONTROLLED TRIALS

 CONTROLLED TRIALS 

⏸Parallel groups 

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(👳🏻🔷vs 👳▪️ ) Simple, head-to-head comparison of two or more treatments 

1️⃣Subjects are allocated at random to a single treatment or a single treatment programme for the duration of the trial 

🆓The groups are independent  of each other

 🔀Crossover trials 

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(💂🔷  ➡ ️vs  💂▪️)This involves a single group study, where each patient receives two more treatments in turn; i.e. Each patient acts as their own control and comparisons of treatments are made within patients 

2️⃣Two or more treatments are given to each patient in random order 

✅useful for chronic conditions  such as pain relief in long-term illness or the control of high blood pressure where the outcome can be assessed relatively quickly

✴️It may not be feasible for treatments for short-term illnesses that once treated are cured, for example antibiotics for infections

😃Advantages of parallel group designs

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✔️The comparison of the treatments takes place concurrently 

✔️Can be used for any condition, especially an acute condition which is cured or self-limiting such as an infection 

✔️No problem of carry-over effects 

😬Disadvantages of parallel group designs 

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✖️The comparison is between patients and so usually needs a bigger sample size than the equivalent cross-over trial 

😃Advantages of crossover designs 

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✔️Treatments are compared within patients and so differences between patients are accounted for explicitly 

✔️Usually need fewer subjects than the equivalent parallel group trials 

✔️Can be used to test treatments for chronic conditions 

😬Disadvantages of crossover designs 

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✖️Cannot be used for many acute illnesses 

✖️Carry-over effects need to be controlled 

✖️Likely to take longer than the equivalent parallel designs 

✖️Statistical analysis is more complicated if subjects do not complete all periods

ѦԀԀIṬIȎṄѦʟ IṄҒȎ➕ 

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🏃🏾In cross over trials, it is important to avoid the 'carry-over effect' of one treatment into the period in which the next treatment is allocated. 

↔️This is usually achieved by having a gap or 'washout period'  between treatments

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Trouble Shooting the Arterial Blood Pressure Tracing: OVER DAMPENING & UNDER DAMPENING ▪️▪️▪️▪️▪️

Over dampened tracing 

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⏺May result in an under-reading of pressures 

⏺This may cause an underestimation of the systolic pressure and overestimation of diastolic pressure. 

▶️Check the transducer position as it may be too high above RA. 

▶️Kinking of the catheter at the insertion site may also cause the waveform to become dampened. 

Under dampened tracing 

➖➖➖➖➖➖➖➖➖

⏺noted by a high initial spike in the waveform 

⏺because of inadequate damping of the transducer, which causes an excessive resonance in the system. 

⏺ May result in an overestimate of systolic pressure and an underestimate of diastolic pressure. 

▶️check the transducer position. It may be too low below the RA. 

Better to re-zero the transducer to atmospheric pressures, in both of the above situations

TRAMADOL AND ONDANSETRON: THEY ARE NOT A GOOD PAIR ! ; WHY FORCING THEM TO LIVE TOGETHER ?

Tramadol- highlights 

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✔️both opioid and non-opioid modes of action. . 

(1) inhibition of noradrenaline re-uptake 

(2)increased release and decreased re-uptake of serotonin in the spinal cord, and 

(3)a weak effect on mu opioid receptors

✔️The weak, opioid effect is mediated by an active metabolite, (+)-M1 (O-desmethyltramadol), formed via the genetically polymorphic P450 CYP2D6 iso-enzyme system. The biological activity of this system is variable, and individuals may be classified as extensive or poor metabolisers of tramadol. 

✔️Tramadol’s affinity for opioid receptors is about 6000 times weaker than morphine, but the (+)-M1 metabolite has an affinity about 200 times greater than tramadol. Poulsen et al. report much higher concentrations of the (+)-M1 metabolite and greater analgesic efficacy of tramadol in extensive metabolisers compared to poor metabolisers. Also noted was a reduction of nausea, vomiting and tiredness amongst poor metabolisers

Ondansetron-highlights

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✔️Ondansetron competitively antagonises serotonin, subtype 3 (5-HT3) receptors in the CTZ and enteric neurones. 

✔️ Peripheral 5-HT3 receptors are also involved in nociceptive pathways and ondansetron may alter 5-HT3 nociceptive responses at the level of dorsal horn neurones

✔️ Ondansetron can block sodium channels in a similar fashion to local anaesthetic agents, and exhibit agonist activity at mu opioid receptors, thus resulting in a peripheral anti-nociceptive effect.

Tramadol + Ondansetron 

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✔️PONV due to Tramadol is often managed with a competitive serotonin antagonist, ondansetron

✔️ There is evidence that the concurrent use of these two drugs results in a mutual reduction of effect—tramadol is a less potent analgesic and ondansetron is a less effective as an antiemetic. 

✔️ But the effect of ondansetron on tramadol consumption diminished with time. 

✔️ De Witte et al. found a significant (50%) increase in cumulative tramadol consumption during the first post-operative hour when patients were given ondansetron along with Tramadol.

✔️ Ondansetron is, in part, metabolised by the CYP2D6 iso-enzyme system—an iso-enzyme system responsible for formation of an active tramadol metabolite that has analgesic effect . Competition for this metabolic pathway may result in a reduction in formation of the (+)-M1 metabolite of tramadol and a consequent reduction in analgesic efficacy.

DO YOU KNOW❓😳 additional points➕

✔️ There is animal and human evidence that both tramadol and ondansetron have local anaesthetic type properties.

✔️ Ondansetron was approximately fifteen times more potent than lignocaine and may well be a prototype molecule for the development of a new group of local anaesthetic agents. 

✔️ These findings are further supported in a human clinical study by Memis et al.which showed that tramadol and ondansetron both significantly reduced the pain associated with the injection of the neuromuscular blocking drug, rocuronium.

(Ref: J.H. Ye, W.C. Mui, J. Ren, T.E. Hunt, W.H. Wu, V.K. Zbuzek Ondansetron exhibits the properties of a local anesthetic. Anesth. Analg., 85 (1997), pp. 1116–1121)

✔️Tropisetron and granisetron are able to reverse an acetaminophen-mediated analgesia completely.

 

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References:

Anaesthesia. 2015 Feb;70(2):209-18. doi: 10.1111/anae.12948. Epub 2014 Dec 10.

The effect of ondansetron on the efficacy of postoperative tramadol: a systematic review and meta-analysis of a drug interaction.

Stevens AJ1, Woodman RJ, Owen H.

Ondansetron Inhibits the Analgesic Effects of Tramadol: A Possible 5-HT3 Spinal Receptor Involvement in Acute Pain in Humans

Arcioni, Roberto MD*,; della Rocca, Marco MD*,; Romanò, Sarah MD*,; Romano, Rocco MD†,; Pietropaoli, Paolo MD*, and; Gasparetto, Alessandro MD*

ScienceDirect Review

Aspects of tramadol and ondansetron interactions Bruce Hammonds, David A. Sidebotham, Brian J. Anderson,

📝BRAIN TUMOURS-SYMPTOMATOLOGY

📌Contralateral signs :  are associated with lesions in the posterior frontal area (motor) or anterior parietal lobe (sensory)

📌Lesions in the dominant hemisphere: Aphasia

📌Lesions in the non dominant hemisphere: Apraxia

📌Temporal lobe lesions : Focal seizures with auras and visual field defects

📌Frontal lobe lesions : Altered cognitive functioning and subtle personality changes

📌Subfrontal lesions : Anosmia

📌Sellar and Parasellar lesions: Visual field and Acuity problems , hypopituitarism, oversecretion syndromes (Cushing Syndrome, Acromegaly)

📌Tumours in relation to Ventricular system : Hydrocephalus , Raised ICP

📌Tumours of the brainstem and cerebellopontine angle : Cranial nerve palsies , long tract signs , secondary hydrocephalus

📌Lesions of Cerebellar vermis : Truncal ataxia

📌Lesions in Cerebellar hemisphere: Appendicular signs such as incoordination and nystagmus 

Reference:

Page :617-618, Bailey and Love’s , SHORT PRACTICE OF SURGERY , 24 th edition