Omitted variable bias occurs when a statistician passes over one or more relevant variables from the study.

Publication bias occurs in publish academic research. it occurs when the results of the study effect the decision whether to publish or not.

Expectation bias occurs when the expectation of a researcher about the results effect the behaviour of the participants. Expectations may come from communication and experiences.

Work up bias occurs in the study of diagnostic test validity, whether a gold standard procedure has been used. work up bias can seriously affect the specificity of the test.

Recall bias introduced when participants in a study are systematically more or less likely to recall and relate information on exposure depending on their outcome status. Recall bias is more potential for Case-control studies.

Colligative properties are properties of solutions that depend on the number of dissolved particles in solution. They do not depend on the identities of the solutes.

All of the above have colligative properties with the exception of depression of melting point.

The osmolality from the concentration of a substance in a solution is measured by an osmometer. The freezing point of a solution can determines concentration of a solution and this can be measured by using a freezing point osmometer. This is applicable as depression of freezing point is directly correlated to concentration.

Vapour pressure osmometers, which measure vapour pressure, may miss certain volatiles such as CO2, ammonia and alcohol that are in the solution

The use of a freezing point osmometer provides the most accurate and reliable results for the majority of applications.

Colligative properties does not include melting point depression . Mixtures of substances in which the liquid phase components are insoluble, display a melting point depression and a melting range or interval instead of a fixed melting point.

The magnitude of the melting point depression depends on the mixture composition.

The melting point depression is used to determine the purity and identity of compounds. EMLA (eutectic mixture of local anaesthetics) cream is a mixture of lidocaine and prilocaine and is used as a topical local anaesthetic. The melting point of the combined drugs is lower than that individually and is below room temperature (18°C).

ARR= (Risk factor associated with the new drug group) — (Risk factor associated with the currently available drug)

So,

ARR= (24/120)-(60/240)

ARR= 0.2-0.25

ARR= 0.05 (Numerical Value)

ARR= 5%

The normal distribution is a symmetrical, bell-shaped distribution in which the mean, median and mode are all equal.

The passive leg raising (PLR) manoeuvre is a method of altering left and right ventricular preload and it is done with real-time measurement of stroke volume. It is a simple, quick, relatively unbiased, and accurate bedside test to guide fluid management and avoid fluid overload.

Pulse pressure variation (PPV), Stroke volume variation (SVV), superior vena cava diameter variation (threshold 36%) and end-expiratory occlusion test are used for dynamic tests of fluid responsiveness.

PPV is derived peripherally from the arterial pressure waveform.

Stroke volume variation (SVV) can be derived peripherally through pulse contour analysis of the arterial waveform. PPV and SVV have a threshold of 12% but since they are not used in patients who have cardiac arrhythmias, are spontaneous breathing, and in ventilated patients with low lung compliance and tidal volumes, they are of limited value.

The tests of fluid responsiveness’ accuracy is determined by calculating the area under the receiver operating characteristic curve (UROC) obtained by plotting the sensitivity of the parameter in predicting fluid responsiveness vs. 1-specificity.

Under optimal conditions, the ability to determine the need for fluid is best with PPV>SVV>LVEDA>CVP.

Central venous pressure (CVP) is a static test of preload (not preload responsiveness) and a key determinant of cardiac function. The left ventricular end-diastolic area (LVEDA) a static test of fluid responsiveness, is derived using echocardiography

Number needed to treat is a measure of the impact of a treatment or intervention that is often used to communicate results to patients, clinicians, the public and policymakers. It states how many patients need to be treated for one additional patient to experience an adverse outcome (e.g. a death).

It is calculated as the inverse of the absolute risk reduction and is rounded to the next highest whole number.

The absolute risk reduction is 8% (16% – 8%). 100/8 = 12.5, so rounding up the next integer this gives at NNT of 13. i.e. you would need to give the new drug to 13 people to ensure that you prevented one death.

The standard error of the mean (SEM) is a measure of the spread expected for the mean of the observations – i.e. how ‘accurate’ the calculated sample mean is from the true population mean. The relationship between the standard error of the mean and the standard deviation is such that, for a given sample size, the standard error of the mean equals the standard deviation divided by the square root of the sample size.

SEM = SD / square root (n)

where SD = standard deviation and n = sample size

Amyl nitrate is part of the treatment of cyanide poisoning. The short acting nitrate causes oxidation of Fe2+ in haemoglobin to Fe3+ in methaemoglobin. Methaemoglobin combines with cyanide (cyanmethemoglobin), which reacts with sodium thiosulfate to convert nontoxic thiocyanate and methaemoglobin.

Methaemoglobin is formed when the iron in haemoglobin is converted from the reduced state (Fe2+) to the oxidized state (Fe3+). The oxidized form of haemoglobin (Fe3+) does not bind oxygen as readily as Fe2+, but has high affinity for cyanide. It also results to high affinity of bound oxygen to haemoglobin, thus leading to tissue hypoxia. Arterial oxygen tension is normal despite observations of cyanosis and dyspnoea. Methemoglobinemia can be treated with methylene blue and vitamin C.

Carboxyhaemoglobin can be due to carbon monoxide poisoning. In such cases, patients experience headache and dizziness, but do not develop cyanosis.

2,3-diphosphoglycerate causes a shift in the oxygen dissociation curve to the right, decreasing haemoglobin’s affinity to oxygen to facilitate unloading of oxygen to the tissues.

Glutamic acid decarboxylase is responsible for the catalyses of glutamate to gamma-aminobutyric acid (GABA)

Catechol-o-methyl transferase catalyses the degradation and inactivation of dopamine into 3-methoxytyramine, epinephrine into metanephrine, and norepinephrine into normetanephrine and vanylmethylmandelic acid (VMA).

Monoamine oxidase catalyses the oxidation of norepinephrine to vanylmethylmandelic acid (VMA) and serotonin to 5-hydeoxyindole acetic acid (5-HIAA).

Cholinesterase functions to catalyse the split of acetylcholine into choline and acetic acid.

Calcium is a very important ion and is involved in:
-cell homeostasis
-coagulation
-muscle contraction
-neuronal impulse transmission/membrane stabilization
-bone formation and skeletal strength
-secretion processes

99% is found in bone and 1% in the plasma. Of the 1% that is in the plasma
-45% is free ionized calcium
-45% is bound to proteins, mainly Albumin
-10% is present as an anion complex

Reduced levels of IONIZED calcium give rise to features of hypocalcaemia , resulting in increased excitability of membranes. This results when the total calcium concentration goes below 2 mmol/L.

Features of mild to moderate hypocalcaemia are:
-paraesthesia (peri-oral, fingers)
-tetany
-spasm
-muscle cramps
-ECG changes (prolonged QT)
-Trousseau’s sign (inflation of tourniquet induces carpopedal spasm)
-Chvostek’s sign (tapping the facial nerve – cranial nerve VII – causes facial muscle twitch/spasm)

Features of severe hypocalcaemia are:
-cardiogenic shock and congestive cardiac failure due to reduced myocardial contractility
respiratory distress due to bronchospasm, agitation, confusion, seizures

Features of hypercalcaemia (remember ‘bones, stones, groans and psychic moans’):
-Abdominal pain
-Vomiting
-Constipation
-Polyuria
-Polydipsia
-Depression
-Lethargy
-Anorexia
-Weight loss
-Hypertension
-Confusion
-Pyrexia
-Calcification in the cornea
-Renal stones
-Renal failure
-Decreased Q-T interval
-Cardiac shock/collapse

Mixed venous oxygen content (CvO2) is the oxygen concentration in 100mL of mixed venous blood taken from the pulmonary artery. It is usually 12-17 mL/dL (70-75%). It is represented mathematically as:

CvO2 = (1.34 x Hgb x SvO2 x 0.01) + (0.003 x PvO2)

Where,

1.34 = Huffner’s constant
Hgb = Haemoglobin level (g/dL)
SvO2 = % oxyhaemoglobin saturation of mixed venous blood
PvO2 = 0.0225 = mL of O2 dissolved per 100mL plasma per kPa, or 0.003 mL per mmHg

Therefore,

CvO2 = (1.34 x 10 x 70 x 0.01) + (0.003 x 50)

CvO2 = 9.38 + 0.15 = 9.53 mL/100mL

With respect to oxygen transport in cells, almost all oxygen is transported within erythrocytes. There is limited solubility and only 1% is carried as solution. Thus, the amount of oxygen transported depends upon haemoglobin concentration and its degree of saturation.

Haemoglobin is a globular protein composed of 4 subunits. Haem is made up of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds – one is with oxygen and the other with a polypeptide chain.
There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but can bind to CO2 and hydrogen ions.
The beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules.

The oxygen dissociation curve (ODC) describes the relationship between the percentage of saturated haemoglobin and partial pressure of oxygen in the blood.
Of note, it is not affected by haemoglobin concentration.

Chronic anaemia causes 2, 3 DPG levels to increase, hence shifting the curve to the right

Haldane effect – Causes the ODC to shift to the left. For a given oxygen tension there is increased saturation of Hb with oxygen i.e. Decreased oxygen delivery to tissues.
This can be caused by:
-HbF, methaemoglobin, carboxyhaemoglobin
-low [H+] (alkali)
-low pCO2
-ow 2,3-DPG
-ow temperature

Bohr effect – causes the ODC to shifts to the right = for given oxygen tension there is reduced saturation of Hb with oxygen i.e. Enhanced oxygen delivery to tissues. This can be caused by:
– raised [H+] (acidic)
– raised pCO2
-raised 2,3-DPG
-raised temperature

The correlation coefficient gives us the idea about relation between two parameters. i.e. to what extent change in parameter A could prompt a change in parameter B. The numerical value of correlation coefficient could not be greater than 1.

pH is the negative log to the base 10 of hydrogen ion concentration:

So, what power produces the answer?

pH = – log10 [H+]

Making [H+] the subject:

[H+] = 10-pH

Substituting, [H+] = 10-7

One nanomole = 1 x 10-9 or 0.000000001

10-7 = 1x 0.0000001 or 10 x 0.00000001 or 100 x 0.000000001

100 nanomole

Sodium-chloride symporter inhibitor.

The thiazide sensitive sodium chloride symporter is inhibited by thiazides at the proximal portion of the distal convoluted tubule leading to increased sodium and water excretion. Increased delivery of sodium to the distal portion of the distal convoluted tubule promotes potassium loss. This is why thiazides are associated with hyponatraemia and hypokalaemia.

Carbonic anhydrase inhibitors are used mainly in the treatment of glaucoma. They act on the proximal convoluted tubule to promote bicarbonate, sodium and potassium loss.

Sodium potassium chloride symporter is inhibited by Loop diuretics.
Epithelial sodium channels are inhibited by Amiloride.
Drugs which lead to nephrogenic diabetes insipidus such as lithium and demeclocycline, are Inhibitors of vasopressin.

The following are the pharmacokinetic properties of drugs with a low hepatic extraction ratio:

Changes in liver blood flow have no effect on drug clearance.
When given orally, drug clearance is extremely sensitive to changes in protein binding, intrinsic metabolism, and excretion, and there is no first-pass metabolism.

Warfarin and phenytoin are two drugs with low hepatic extraction ratios.

The following are the pharmacokinetic properties of drugs with a high hepatic extraction ratio:

When taken orally, undergo extensive first-pass metabolism; drug clearance is dependent on liver blood flow, and drug clearance is less sensitive to changes in protein binding and intrinsic metabolism.

Morphine, lidocaine, propranolol, and etomidate are examples of drugs with high hepatic extraction ratios.

Functional residual capacity (FRC) is 1.7 to 3.5L/kg

A capacity is the sum of two or more volumes. The total lung capacity (TLC) is total sum of the volume of gas present in all lung compartments upon maximum inspiration. It is represented mathematically as:

Total lung capacity (TLC) = Vital capacity (VC) + Residual volume (RV)

The residual volume (RV) is the volume of gas still present within the lung post maximum exhalation. It cannot be measured by spirometry, but can be using a body plethysmograph and also with the helium dilution technique.

Closing capacity (CC) is the volume of gas within the lungs at which small airways close upon expiration. It increases with age and is especially important when it surpasses the FRC as it causes changes in ventilation/perfusion mismatch and hypoxia.
In the supine position, a patient with a normal body mass index and no history of lung pathology, the CC equals the FRC at approximately 44, and at approximately 66 at standing position.

Recall bias introduced when participants in a study are systematically more or less likely to recall and relate information on exposure depending on their outcome status.

In procedure bias, the researcher decides assignment of a treatment versus control and assigns particular patients to one group or the other non-randomly. This is unlikely to have occurred in this case, although it is not mentioned specifically.

Self Selection or volunteer bias occur when those subjects are selected to participate in the study who are not the representative of the entire target population. those subjects may be from high socio-economic status and practice those activities or lifestyle that improves their health.

Lead-time bias occurs when a disease is detected by a screening test at an earlier time point rather than it would have been diagnosed by its clinical appearance. In this bias, earlier detection improves the survival time in the intervention group.

The question mentions a quantitative, ratio scale data set. The use of mean would be ideal under normal circumstances, however, in this situation median is preferred as it is less sensitive to the skewness of data. The median is usually preferred to other measures of central tendency when your data set is skewed (i.e., forms a skewed distribution)

Codeine is easily absorbed from the gastrointestinal tract and converted to morphine and norcodeine in the liver via O- and N-demethylation. Morphine and norcodeine are excreted almost entirely by the kidney, primarily as conjugates with glucuronic acid.

By glucuronidation, phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 converts morphine to morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) (UGT2B7).

Approximately 60% of morphine is converted to M3G, with the remaining 6-10% converted to M6G. M3G is inactive, but M6G is said to be 4 to 650 times more potent on the MOP receptor than morphine.

When codeine is consumed, cytochrome P450 2D6 in the liver converts it to morphine (CYP2D6).

Some people have DNA variations that increase the activity of this enzyme, causing codeine to be converted to morphine more quickly and completely than in others. After taking codeine, these ultra-rapid metabolisers are more likely to have higher than normal levels of morphine in their blood.

Respiratory depression/obstruction can be caused by high levels of morphine and M6G, especially in people who have a history of obstructive sleep apnoea. The estimated number of ultra-rapid metabolisers ranges from 1 to 7 per 100 people, but some ethnic groups may have as many as 28 per 100 people.

A compound that contains an asymmetric centre (chiral atom or chiral centre) and thus can occur in two non-superimposable mirror-image forms (enantiomers) are called chiral compounds.

Desflurane, Halothane, and isoflurane are chiral compounds but Sevoflurane is not a chiral compound.

Closing capacity refers to volume of gas within the lungs at which the conducting small airways begin to close, that is, the point during expiration when small airways close.

It is calculated mathematically as:

Closing capacity = Closing volume (CV) + Residual volume (RV)

Functional residual capacity (FRC) is the volume of gas still present within the lungs post expiration.

Closing capacity is lower than the functional residual capacity in younger adults, but begins to rise to eventually equal, and then exceed it with increasing age (at about middle age), increasing intrabdominal pressure, decreasing blood flow in the pulmonary system and parenchymal disease within the pulmonary system.

An agonist is a molecule with intrinsic efficacy and affinity for a receptor. The ability of a drug-receptor interaction to produce a maximal response is referred to as intrinsic efficacy or activity. Efficacy also refers to a drug’s ability to have a therapeutic or beneficial effect. Although the potencies of morphine and fentanyl differ, they both have the same intrinsic efficacy.

The amount of drug required to produce a given effect is referred to as potency. If drug X is effective in a dose of 100 mcg, its potency is greater than if drug Y is effective in a dose of 10 mg.

The therapeutic index, also known as the margin of safety, is a ratio of the lethal or serious side effect dose of a drug divided by the therapeutic dose of the same drug.

The term bioavailability refers to the ability of a substance to be absorbed. The area under a curve (AUC) of a graphic plot of plasma concentration and time is used to calculate oral bioavailability. It’s used to figure out how much of a drug to take and when to take it.

Approximately 20% of halothane and 0.02% desflurane undergo hepatic biotransformation. Desflurane, halothane, and isoflurane are metabolised in the liver by cytochrome p450 to trifluoroacetate. Through an immunological mechanism involving trifluoroacetyl hapten formation, trifluoroacetate is thought to be responsible for hepatotoxicity.

Potency of inhaled anaesthetic agents is measured using the minimal alveolar concentration (MAC). The MAC of halothane is 0.74% while that of desflurane is 6.3%. The potency can also be compared using the oil: gas partition coefficient (224 and 18.7 for halothane and desflurane respectively).

Onset of action of volatile agents depends on the blood:gas partition coefficient. A lower blood:gas partition coefficient and insolubility in blood means faster onset and offset of action. The blood gas coefficient for halothane is 2.4 while that of desflurane is 0.42. Desflurane is less soluble than halothane in blood. Halothane has a pungent smell that can irritate the airway which limits its use for a gaseous induction especially in paediatric anaesthesia. desflurane is not pungent.

Desfluranes boiling point is only slightly above normal room temperature (22.8°C) making it extremely volatile while the boiling point of halothane is approximately 50.2°C.

Microshock refers to ventricular fibrillation caused by miniscule amounts of currents or voltages (100-150 microamperes) passing through the myocardial tissue from external cables arising from electrical components within the cardiac muscle, for example, pacemaker electrodes or saline filled venous catheters.
The risk of shock changes with the construction of electrical equipment in question. The main classes of electrical equipment include: I: Appliances have a protective earth connected to an outer casing which prevents live elements from coming in contact with conductive elements. A fault in this equipment class will result in live elements coming in contact with the outer casing and allowing electrical flow into the protective earth. This triggers the protective fuse to disconnect the electric supply to the appliance.
II: These appliances have reinforced insulation. In the event of a fault which causes the first layer of insulation to fail, the second layer is able to prevent contact of live elements with outer casing.
III: These appliances have no insulation to provide safety, and rely solely on the use of separated extra low voltage source (SELV) which limits voltage to 25V AC or 60V DC allowing for a person to come in contact with it without risk of a shock under normal dry conditions. Under wet conditions, voltage supply should be lowered to reduce risk of shock. These devices have no risk of macroshocks, but some risk of microshocks.
Class I and II electrical appliances are further divided into subtypes developed to limit current leakage in the event of a singular fault:
B (body): Upper limit of current leakage is 500 µA. This current can cause skin tingling and microshocks, but is not sufficient to cause injury.
BF (body floating): These appliances have an isolating capacitor or transformer which separate the secondary circuit from the protective earth. The upper limit of current leakage is the same as type B.
CF (cardiac floating): Upper limit of leakage current during a singular fault is 50 microamps. It is least likely to result in a microshock

The ideal gas equation makes the following assumptions:

The gas particles have a small volume in comparison to the volume occupied by the gas.
Between the gas particles, there are no forces of interaction.
Individual gas particle collisions, as well as gas particle collisions with container walls, are elastic, meaning momentum is conserved.
PV = nRT
Where:

P = pressure
V = volume
n = moles of gas
T = temperature
R = universal gas constant

Helium is a monoatomic gas with a small helium atom. The attractive forces between helium atoms are small because the helium atom is spherical and has no dipole moment. Because helium atoms are spherical, collisions between them approach the ideal state of elasticity.

Most real gases behave qualitatively like ideal gases at standard temperatures and pressures. When intermolecular forces and molecular size become important, the ideal gas model tends to fail at lower temperatures or higher pressures. It also fails to work with the majority of heavy gases.

Helium, argon, neon, and xenon are noble or inert gases that behave the most like an ideal gas. Xenon is a noble gas with a much larger atomic size than helium.

Hawthorne effect explains the change in any behavioural aspect owing to the awareness that the person is being observed.
Simpson’s Paradox explains the association developed when the data from several groups is combined to form a single larger group.

The remaining terms are made up.

The following table shows the compartments and their relative oxygen reserve:
Compartment Factors Room air (mL) 100% O2 (mL)
Lung FAO2, FRC 630 2850
Plasma PaO2, DF, PV 7 45
Red blood cells Hb, TGV, SaO2 788 805
Myoglobin 200 200
Interstitial space 25 160

Oxygen reserves in the body, with room air and after oxygenation.

FAO2-alveolar fraction of oxygen rises to 95% after administration of 100% oxygen (CO2 = 5%)
FRC- Functional residual capacity – (the most important store of oxygen in the body) – 2,500-3,000 mL in medium sized adults
PaO2-partial pressure of oxygen dissolved in arterial blood (80 mmHg breathing room air and 500 mmHg breathing 100% oxygen)
DF -dissolved form (0.3%)
PV-plasma volume (3L)
TG-total globular volume (5L)
Hb-haemoglobin concentration
SaO2-arterial oxygen concentration (98% breathing air and 100% when preoxygenated)

Rifampicin is a derivative of a rifamycin (other derivatives are rifabutin and rifapentine). It is bactericidal against both dividing and non-dividing mycobacterium and acts by inhibiting DNA-dependent RNA polymerase. Thus this drug inhibits RNA synthesis.

The solid state of matter has a definite volume and shape and particles are packed closely together and are incompressible. Within this tight lattice, there is enough thermal energy to produce vibration of particles.

Liquids however have a volume but no definite shape. These particles are less tightly packed together. Although there is free movement within the volume, they are incompressible.

Gases, however, have no finite shape or volume and particles are free to move rapidly in a state of random motion. They are compressible and are completely shaped by the space in which they are held. Vapours exist as a gas phase in equilibrium with identical liquid or solid matter below its boiling point.

The most prevalent state of matter in the universe is plasma which is formed by heating atoms to very high temperatures to form ions.