Receiver-operating characteristic (ROC) analysis was originally developed during World War II to analyse classification accuracy in differentiating signal from noise in radar detection. Recently, the methodology has been adapted to several clinical areas heavily dependent on screening and diagnostic tests, in particular, laboratory testing, epidemiology, radiology, and bioinformatics. ROC analysis is a useful tool for evaluating the performance of diagnostic tests and more generally for evaluating the accuracy of a statistical model (e.g., logistic regression, linear discriminant analysis) that classifies subjects into 1 of 2 categories, diseased or non diseased. Its function as a simple graphical tool for displaying the accuracy of a medical diagnostic test is one of the most well-known applications of ROC curve analysis.The closer the ROC curve is to the upper left corner, which has 100% sensitivity and 100% specificity, the higher the overall accuracy of the diagnostic test.

Meta-analysis is a quantitative, formal, epidemiological study design used to systematically assess previous research studies to derive conclusions about that body of research. Outcomes from a meta-analysis may include a more precise estimate of the effect of treatment or risk factor for disease, or other outcomes, than any individual study contributing to the pooled analysis. The examination of variability or heterogeneity in study results is also a critical outcome.The benefits of meta-analysis include a consolidated and quantitative review of a large, and often complex, sometimes apparently conflicting, body of literature. The specification of the outcome and hypotheses that are tested is critical to the conduct of meta-analyses, as is a sensitive literature search.Important medical questions are typically studied more than once, often by different research teams in different locations. In many instances, the results of these multiple small studies of an issue are diverse and conflicting, which makes the clinical decision-making difficult. The need to arrive at decisions affecting clinical practise fostered the momentum toward evidence-based medicine. Evidence-based medicine may be defined as the systematic, quantitative, preferentially experimental approach to obtaining and using medical information. Therefore, meta-analysis, a statistical procedure that integrates the results of several independent studies, plays a central role in evidence-based medicine.

Ipratropium bromide is an antimuscarinic drug used in the management of acute asthma and COPD. It can provide short-term relief in chronic asthma, but short-acting β2agonists act more quickly and are preferred.The BTS guidelines recommend that nebulised ipratropium bromide (0.5 mg 4-6 hourly) can be added to β2agonist treatment for patients with acute severe or life-threatening asthma or those with a poor initial response to β2 agonist therapy.The aerosol inhalation of ipratropium can be used for short-term relief in mild chronic obstructive pulmonary disease in patients who are not already using a long-acting antimuscarinic drug (e.g. tiotropium).Its maximum effect occurs 30-60 minutes after use; its duration of action is 3-6 hours, and bronchodilation can usually be maintained with treatment three times per day.The commonest side effect of ipratropium bromide is dry mouth. It can also trigger acute closed-angle glaucoma in susceptible patients. Tremor is commonly seen with β2agonists but not with antimuscarinics. Ipratropium bromide should be used with caution in: Men with prostatic hyperplasia and bladder-outflow obstruction (worsened urinary retention has been reported in elderly men), People with chronic kidney disease (CKD) stages 3 and above (because of the risk of drug toxicity), People with angle-closure glaucoma (nebulised mist of antimuscarinic drugs can precipitate or worsen acute angle-closure glaucoma)

The mean incubation period for P. falciparum is 12 days.WHO World Malaria Report 2019 states that an estimated 228 million cases of malaria occurred worldwide in 2018, and reports steadily decreasing the number of cases since 2010. In 2018, nineteen sub-Saharan African countries and India carried approximately 85% of the global malaria burden. The most prevalent and pathogenic malaria parasite, most commonly associated with severe illness and death, especially in the WHO African region, accounting for 99.7% malaria cases, is P. falciparum.The vector for Plasmodium spp. is a female Anopheles mosquito that inoculates sporozoites contained in her salivary glands into the puncture wound when feeding. Sporozoites enter peripheral bloodstream and are uptake by hepatocytes, where they undergo an asexual pre-erythrocytic liver-stage as liver schizonts lasting up to 2 weeks before the onset of the blood stage.Intravenous or intramuscular artesunate is the first-line treatment in all patients worldwide and should be used for at least 24 hours and until the oral medication is tolerated.

Damage to the obturator nerve results in weak adduction of the hip with lateral swinging of the limb during walking due to unopposed abduction.

Propofol’s most frequent side effect is hypotension, which affects 17% of paediatric patients and 26% of adults. This is attributable to systemic vasodilation as well as a decrease in preload and afterload. Propofol has a little negative inotropic impact as well. The drop in blood pressure is dosage-dependent and is more noticeable in the elderly, thus this should be expected.

A posterior cerebral stroke will most likely result in a contralateral homonymous hemianopia with macular sparing.

Staphylococcus aureus = Gram-positive coccusBacillus cereus = Gram-positive bacillusCampylobacter jejuni = Gram-negative bacillusEscherichia coli = Gram-negative bacillusIn Gram staining, crystal violet is a purple stain that is used to stain the bacteria first. The stained bacteria are decolorized and then stained with a red stain, which is safranin. Bacteria with thick cell walls keep the purple stain and are called Gram-positive. Thin-walled bacteria are easily decolorized so when safranin, the red stain, is placed on the organisms, they become red or Gram-negative. Neisseria species appear as Gram-negative diplococci because they form pairs and their adjacent ends are flattened that is why they are also described to have a coffee-bean or kidney-bean shape.

Benign enlargement of the prostate is common in men older than 50 years. The cause is possibly an imbalance in the hormonal control of the gland. The median lobe of the gland enlarges upward and encroaches within the sphincter vesicae, located at the neck of the bladder. The leakage of urine into the prostatic urethra causes an intense reflex desire to micturate. The enlargement of the median and lateral lobes of the gland produces elongation and lateral compression and distortion of the urethra so that the patient experiences difficulty in passing urine and the stream is weak. Back-pressure effects on the ureters and both kidneys are a common complication. The enlargement of the uvula vesicae (owing to the enlarged median lobe) results in the formation of a pouch of stagnant urine behind the urethral orifice within the bladder. The stagnant urine frequently becomes infected, and the inflamed bladder (cystitis) adds to the patient’s symptoms.In all operations on the prostate, the surgeon regards the prostatic venous plexus with respect. The veins have thin walls, are valveless, and are drained by several large trunks directly into the internal iliac veins. Damage to these veins can result in a severe haemorrhage.

Overdosing on calcium-channel blockers should always be taken seriously and regarded as potentially fatal. Verapamil and diltiazem are the two most lethal calcium-channel blockers in overdose. These work by binding the alpha-1 subunit of L-type calcium channels, preventing calcium from entering the cell. In cardiac myocytes, vascular smooth muscle cells, and islet beta-cells, these channels play an important role.The following summarises the toxicity of calcium-channel blockers:Cardiac effectsVascular smooth muscle tone affectsMetabolic effectsExcessive negative inotropy: myocardial depressionNegative chronotropy: sinus bradycardiaNegative dromotropy: atrioventricular node blockadeDecreased afterloadSystemic hypotensionCoronary vasodilationHypoinsulinaemiaCalcium channel blocker-induced insulin resistance

Antibiotics that are bactericidal kill bacteria, while antibiotics that are bacteriostatic limit their growth or reproduction. The antibiotics grouped into these two classes are summarized in the table below:Bactericidal antibioticsBacteriostatic antibioticsVancomycinMetronidazoleFluoroquinolone, such as ciprofloxacinPenicillins, such as benzylpenicillinCephalosporin, such as ceftriaxoneCo-trimoxazoleTetracyclines, such as doxycyclineMacrolides, such as erythromycinSulphonamides, such as sulfamethoxazoleClindamycinTrimethoprimChloramphenicol

A patient suffering from acute ischemic stroke can commonly present with hypertensive emergencies. Thrombolytic therapy is contraindicated in a patient with:1. Systolic blood pressure greater than 185 mmHg2. Diastolic blood pressure greater than 110 mmHgBut delaying thrombolytic therapy is associated with increased morbidity in patients with acute ischemic stroke. Managing high blood pressure in acute ischemic stroke requires a slower and more controlled reduction in BP. In the presence of an ischaemic stroke, rapid reduction of MAP can compromise blood flow, causing further ischemia and worsening of the neurological deficit.Intravenous labetalol is the agent of choice. The dose is 10 mg IV over 1-2 minutes. This dose can be repeated, or an infusion can be set up that runs at 2-8 mg/minute. Thrombolysis can be performed once the blood pressure is brought down to less than 180/105 mmHg.A nitrate infusion (for example, Isoket) can be used as an alternative in patients with contraindications to the use of beta-blockers (e.g., asthma, heart block, cardiac failure).

Cefotaxime (or ceftriaxone) are indicated first line in:- Blind treatment of meningitis in patients > 3 months (with amoxicillin if patient > 50 years)- Meningitis caused by meningococci- Meningitis caused by pneumococci- Meningitis caused by H. influenzae- Severe or invasive salmonellosis- Typhoid fever- Gonorrhoea- Gonococcal arthritis- Haemophilus influenzae epiglottitis

Anti-HCV IgG antibodies indicate exposure to hepatitis C but this could be acute, chronic or resolved infection. If the antibody test is positive, HCV RNA should be tested for, which if positive indicates that a person has current infection with active hepatitis C.

Klebsiellais a genus of non-motile,Gram-negative, rod-shaped bacteriawith a prominent polysaccharide-based capsule. They are routinely found in the nose, mouth and gastrointestinal tract as normal flora, however, they can also behave as opportunistic pathogens.Infections with Klebsiella spp. areusually nosocomial. They are an important cause of ventilator-associated pneumonia (VAP), urinary tract infection, wound infection and bacteraemia. Outbreaks of infections with Klebsiellaspp. in high-dependency units have been described and are associated with septicaemia and high mortality rates. Length of hospital stay and performance of invasive procedures are risk factors forKlebsiellainfections.Primary pneumonia withKlebsiella pneumoniaeis a rare,severe, community-acquired infection associated with a poor outcome.Klebsiella rhinoscleromatis causes a progressive granulomatous infection of the nasal passages and surrounding mucous membranes. This infection is mainly seen in the tropics.Klebsiella ozanae is a recognised cause of chronic bronchiectasis.Klebsiella organisms are resistant to multiple antibiotics including penicillins. This is thought to be a plasmid-mediated property. Agents with high intrinsic activity againstKlebsiellapneumoniaeshould be selected for severely ill patients. Examples of such agents include third-generation cephalosporins (e.g cefotaxime), carbapenems (e.g. imipenem), aminoglycosides (e.g. gentamicin), and quinolones (e.g. ciprofloxacin). These agents may be used as monotherapy or combination therapy. Aztreonam may be used in patients who are allergic to beta-lactam antibiotics.Species with ESBLs (Extended spectrum beta-lactamase) are resistant to penicillins and also cephalosporins such as cefotaxime and ceftriaxone.

Ion channels are pore-forming protein complexes that facilitate the flow of ions across the hydrophobic core of cell membranes. They are present in the plasma membrane and membranes of intracellular organelles of all cells, and perform essential physiological functions. They provide a charged, hydrophilic pore through which ions can move across the lipid bilayer. They are selective for particular ions and their pores may be opened or closed. Because of this ability to open and close, ion channels allow the cell to have the ability to closely control the movement of ions across the membrane. Gating refers to the transition between an open and closed ion channel state, and is brought about by a conformationational change in the protein subunits that open or close the ion-permeable pore. Ion channels can be:1. voltage-gated these are regulated according to the potential difference across the cell membrane or2. ligand-gated – these are regulated by the presence of a specific signal molecule.

The heart sounds are as a result of the various parts of the cardiac cycle.Heart Sound – Phase of Cardiac Cycle – Mechanical Event:1st heart sound – Systole starts – there is closure of the atrioventricular (mitral & tricuspid) valves2nd heart sound – Systole ends – there is closure of the semilunar (aortic and pulmonary) valves3rd heart sound – Early diastole – this is caused by rapid flow of blood from the atria into the ventricles during the ventricular filling phase4th heart sound – Late diastole – this is caused by filling of an abnormally stiff ventricle in atrial systole

Due to their increased risk of cardiovascular adverse events, coxibs and diclofenac are contraindicated in people with ischaemic heart disease, cerebrovascular disease, peripheral arterial disease and mild, moderate, or severe heart failure. Other NSAIDs are only contraindicated in people with severe heart failure. Selective inhibition of COX-2 is associated with less gastrointestinal intolerance. In single doses NSAIDs have analgesic activity comparable to that of paracetamol, therefore given their side effect profile, paracetamol is preferred, particularly in the elderly. Pain relief starts soon after taking the first dose and a full analgesic effect should normally be obtained within a week, whereas an anti-inflammatory effect may not be achieved (or may not be clinically assessable) for up to 3 weeks. Mefenamic acid has only very mild anti-inflammatory properties.

During quiet respiration, the approximate position of the right oblique fissure can be marked by a line on the thoracic wall that begins at the spinous process of vertebra T4, crosses the fifth intercostal space laterally and then follows the contour of rib 6 anteriorly.

CREST syndrome is usually associated with anti-centromere antibodies.Primary biliary cirrhosis is associated with anti-mitochondrial antibodies.Sjogren’s syndrome is associated with anti-Ro and anti-La antibodies.Polymyositis is associated with anti-Jo1 antibodies.Anti-double stranded DNA antibodies are highly characteristic of systemic lupus erythematosus (SLE). They are a group of anti-nuclear antibodies (ANA) that target double stranded DNA and are implicated in the pathogenesis of lupus nephritis.

Clinical features of hypoglycaemia: Autonomic  symptoms: Sweating, feeling hot, anxiety/agitation, palpitations, shaking, paraesthesia, dizzinessNeuroglycopaenic symptoms: Weakness, blurred vision, difficulty speaking, poor concentration, poor coordination, drowsiness, confusion, seizures, comaOther symptoms: Nausea, fatigue, hunger

Erysipelas is a rare infection of the skin and subcutaneous tissues observed frequently in elderly patients. It is characterized by an acute spreading skin lesion that is intensely erythematous with a plainly demarcated but irregular edge. It is most commonly caused by Streptococcus pyogenes or Group A Streptococcus (GAS).GAS are susceptible to penicillin, which remains the drug of choice for treatment. For patients allergic to penicillin, erythromycin can be used.S. pyogenes colonizes the throat and skin on humans, making these sites the primary sources of transmission. Infections resulting from S. pyogenes include pharyngitis, scarlet fever, skin or pyodermal infections, and other septic infections. In addition, the sequelae rheumatic fever and acute glomerulonephritis can occur as a result of infection with S. pyogenes.Agammaglobulinemia is mostly associated with S. pneumoniae.The M protein is attached to the peptidoglycan of the cell wall and extends tothe cell surface. The M protein is essential for virulence. The polysaccharide capsule is characteristic of S. pneumoniae.

Cellulitis is most commonly caused by bacteria from the group Aß-hemolytic streptococcus. Cellulitis can be caused by animal bites. For uncomplicated cellulitis, flucloxacillin is the first-line antibiotic. Because it is beta-lactamase stable, it is efficient against Staphylococcus aureus.

Gaussian distribution, also known as normal distribution, is the most important probability distribution in statistics because it fits many natural phenomena. The normal distribution is a probability function that describes how the values of a variable are distributed. Below are its characteristics:(1) Bell-shaped and symmetrical about the mean(2) The mean, median, mode are all equal(3) The total area under the curve and above the x-axis is equal to 1(4) It has long tapering tails extending infinitely but never touching the x-axis(5) It is determined by its parameters: its mean and standard deviation(6) The standard deviation becomes a more meaningful quality than merely being a measure of dispersionThe mean is the most common measure of central tendency. It is the sum of all observed values divided by the number of observation, and is also known as the ‘average’.The median is the value that falls in the middle position when the observations are ranked in order from the smallest to the largest. If the number of observations is odd, the median is the middle number. If it is even, the median is the average of the two middle numbers.The mode is the value that occurs with the greatest frequency in a set of observations, and is commonly used in public health statistics, such as the top 10 causes of mortality.

The maximum daily dose of paracetamol in an adult is 4 grams. Doses greater than this can lead to hepatotoxicity and, less frequently, acute kidney injury. Early symptoms of paracetamol toxicity include nausea, vomiting, and abdominal pain, and usually settle within 24 hours. Symptoms of liver damage include right subcostal pain and tenderness, and this peaks 3 to 4 days after paracetamol ingestion. Other signs of hepatic toxicity include encephalopathy, bleeding, hypoglycaemia, and cerebral oedema.

ACE inhibitors should be used with caution in patients of Afro-Caribbean descent who may respond less well; calcium channel blockers are first line for hypertension in these patients. ACE inhibitors have a role in the management of diabetic nephropathy. ACE inhibitors are contraindicated in pregnant women. ACE inhibitors inhibit the breakdown of bradykinin; this is the cause of the persistent dry cough. Blocking ACE also diminishes the breakdown of the potent vasodilator bradykinin which is the cause of the persistent dry cough. Angiotensin-II receptor blockers do not have this effect, therefore they are useful alternative for patients who have to discontinue an ACE inhibitor because of persistent cough.

Both ventilation and perfusion increase towards the lung base, because of the effects of gravity, but the gravitational effects are greater on perfusion than ventilation and therefore there is a regional variation in V/Q ratio from lung apex (high V/Q) to lung base (low V/Q). In a pure shunt, there is normal perfusion but absent ventilation and the V/Q ratio = 0. In a true shunt increasing oxygen fraction has no effect because the oxygen-enriched air fails to reach the shunted blood. An increased A-a gradient is seen in V/Q mismatch.

Majority of carbohydrates are broken down into monosaccharides (glucose, fructose galactose) and are absorbed by the small intestine. Enzymes released from the brush border break down carbohydrate. Some carbohydrates, such as cellulose, are not digested at all, despite being made of multiple glucose units. This is because the cellulose is made out of beta-glucose that makes the inter-monosaccharide bindings different from the ones present in starch, which consists of alpha-glucose. Humans lack the enzyme for splitting the beta-glucose-bond.The principal brush border enzymes are dextranase and glucoamylase. Other brush border enzymes are maltase, sucrase, and lactase.Pancreatic amylase breaks down some carbohydrates (notably starch) into oligosaccharides. Dextranase and glucoamylase, then further break down oligosaccharides.Trypsin aids in digestion of protein.Chymotrypsin is a proteolytic enzyme that digests proteinCarboxypeptidase hydrolyses the first peptide or amide bond at the carboxyl or C-terminal end of proteins and peptides

Neutropenia is defined as a total neutrophil count of < 2.0 x 109/l.It can be caused by:Viral infectionsCollagen disease e.g. SLE and RAChemotherapy and radiotherapyHypersplenismMarrow infiltrationVitamin and folate deficiencyDrug reactionsDrugs that cause neutropenia include flecainide, phenytoin, carbimazole, indomethacin and co-trimoxazole.

The first line treatment for acute gout includes NSAIDs like diclofenac, indomethacin or naproxen. In patients in whom NSAIDs are contraindicated, not tolerated or ineffective, colchicine is an alternative. In those who cannot tolerate or who are resistant to NSAIDs and colchicine, oral or parenteral corticosteroids are an effective alternative. In acute monoarticular gout, intra-articular injection of a corticosteroid can be used occasionally. In acute gout. allopurinol is not used in the actual treatment, but its use should be continued during an acute attack if the patient is already established on long term therapy.