Statistics

A population is the entire group to which we want to generalize our results.  A sample is a subset of the population that we actually study.

A numerical summary of a population is called a parameter, while the same numerical summary of a sample is called a statistic.

Sampling error is the sample-to-sample variability in a statistic. (Note that the term “error” here does not mean that anyone has made a mistake.  “Error” here just refers to variability.) In general we do not know the population parameters that we are interested in.  Instead, we have to draw conclusions about them based on sample statistics … usually from a single sample. In principle, any relationship that we observe in a sample could reflect nothing more than sampling error.  In other words, this sampling error hypothesis is a possible explanation for any relationship that we observe in a sample.  It could just be a random thing that happened for this particular sample, but it is not true in the population in general.

Central limit theorem states that 

• the random sampling distribution of means will always tend to be normal, irrespective of the shape of the population distribution from which the samples were drawn.

• the mean of the random sampling distribution of means is equal to the mean of the original population.

Statistical Relationships

There are two basic kinds of statistical relationships

• relationship  between two group means - null hypothesis testing
• relationships between two quantitative variables - correlation and regression

Correlational Techniques - two basic kinds of co-relational techniques:

• Correlation
• Regression

Correlation simply expresses the strength and direction of the relationship between two variables in terms of a correlation coefficient. For interval or ratio scale data, Pearson product-moment correlation ( r ) and for ordinal scale data, Spearman rank-order correlation ( p/rho ) are used. Both these correlational techniques are linear and so if there is a very strong nonlinear relationship between tow variables, these two coefficient will underestimate the true strength of the relationship. Visual inspection of scattergrams is therefore invaluable.




Types of Data:

Potassium Replacement

The total body potassium of an adult is about 3500 mmol (50 mmol/kg body weight), decreasing with age.

To calculate the amount of potassium supplement, one should have an estimate of the potassium deficit.

On average, a reduction of serum potassium by 0.3 mmol/l suggests a total body deficit of 100 mmol. Based on this formula, a patient with a serum potassium of 2.6 mmol/l needs at least 300 mmol of potassium for the correction of the deficit.

In calculating the total body potassium deficit one has to consider factors that can independently affect serum potassium. A patient with a serum potassium of 2.6 mmol/l has less total body deficit at blood pH of 7.5 than 7.3. The reason is that alkaline serum pH (that is, 7.5) can independently lower the serum potassium by intracellular shift.

Restless Legs Syndrome

Epidemiology:

• 10 % prevalence in general population and the prevalence increased with age
• Female predominance

Aetiology:

• Half of the patient reported family history
• Environmental Causes: Iron Deficiency, renal failure, peripheral neuropathy, diabetes mellitus, thyroid disorder, pregnancy, rheumatoid arthritis and fibromyalgia.

Diagnosis:
Current diagnostic criteria refer to four essential features and other supportive features of restless leg syndrome.

Required diagnostic criteria:

• An urge to move the legs, usually accompanied or caused by uncomfortable and unpleasant sensation in the legs.
• which begin or worsen during the periods of rest or inactivity such as lying or sitting.
• which are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues, and
• which are worse in the evening or night than during the day or only occur in the evening or night.

Supportive or associated features:

• Family history
• Response to dopaminergic therapy
• Periodic limb movements
• Disturbed sleep

Management:

Non-pharmacological method

• Assess iron deficiency. Ferritin level less than 50 umol/L is significant
• Reduce caffeine, alcohol or nicotine intake
• Compression stocking may improve the symptoms

Pharmacological method

• Dopamine Precursor: Levodopa ( plus carbidopa / benserazide ) intially 50 mg upto 100-200 mg. An important side effect is Augmentation ( increase in severity of symptoms with regular long term therapy ), which required stopping levodopa. Other side effect is rebound with recurrence of symptoms in the early morning, reflecting the end of drug action.
• Dopamine agonists: such as pergolide, cabergoline, bromocriptine and ropinirole. Augmentation is less common ( 30% ) compared to levodopa ( 70% ) Unlike levodopa, augmentation can be treated by giving divided doses and/or increasing the dosage.
• Low potency opioids such as tramadol are useful for intermittent or daily RLS symptoms.
• Benzodiazepines or benzodiazepines agonist
• Gabapentin is especially useful for painful variants of RLS.
  

Health Assessment in Aboriginal and Torres Strait Islander People

Life Style:
Alcohol Consumption - Hazardous ingestion of alcohol is more prevalent among indigenous Australian males and females aged 35–44 years than among the general population.

• Strongly advise pregnant women and those likely to conceive to abstain from alcohol.
• Base assessment of problem drinking follow by brief interventional counselling commencing at a young age (14–15 years). Repeat opportunistically at least annually, but care is needed to avoid jeopardising the client’s ongoing relationship with the health care provider.
• Simple advice about safe drinking
• Referral to specialist service or therapist
  

Smoking - Indigenous Australian adults from age 18 years are approximately twice as likely to be current smokers than non-Indigenous adults.

• Advise smokers at a higher risk of developing smoking related complications and those with smoking related disease about the benefits of quitting.
• Offer smokers support including self help health promotion materials.

Immunisation:
Influenza - Influenza and secondary pneumonia contribute to the much higher rates of hospitalisation for respiratory diseases among Indigenous Australians.

• Offer annual influenza vaccination from age 50 years.
• Offer annual influenza vaccination to clients with chronic illness from age 6 months.

Pneumococcal - The rate of invasive pneumococcal disease in the Aboriginal and Torres Strait Islander population far exceeds that in the non-Indigenous population. Some reported rates have been the highest ever recorded in the world.

• The 7vPCV is recommended for all Aboriginal and Torres Strait Islander children as part of the Australian Standard Childhood Vaccination Schedule.
• Offer 23vPPV with a single repeat vaccination 5 years after the initial dose from age 50 years.
• The 23vPPV is specifically recommended for Aboriginal and Torres Strait Islander clients aged 15–49 years who smoke or who have chronic illnesses (eg. chronic cardiac, renal and pulmonary disease, diabetes and/or alcohol related problems). Re-vaccination is required after 5 years, and again 10 years later or at 50 years, whichever is later.

Screening:
Pap smear - Cervical cancer is the most common cause of death due to cancer among Aboriginal women. There is an overall mortality rate that is more than nine times greater than that of non-Aboriginal women.

• Screen women who have no symptoms or history suggestive of cervical pathology with Pap tests every 2 years.
• Commence Pap tests for all women who have ever been sexually active at 18–20 years or 2 years after their first sexual intercourse, whichever is later.

Mammogram - Aboriginal and Torres Strait Islander women may be less likely than other women to be diagnosed with breast cancer. However, the incidence of breast cancer may be increasing.

• Screen women aged 50–69 years using mammography every 2 years.
• Advise women aged 40–49 years that there may be a small benefit in mammography screening when weighed against factors such as their age (the benefits of screening may increase through the decade), family history, possible risk factors, personal concerns, levels of anxiety, inconvenience, cost, and discomfort.
• Clinical breast examination is not recommended for breast cancer screening alone or in place of mammography.

Eye:
Visual Acuity - The Aboriginal and Torres Strait Islander population has a higher risk of developing cataracts than the general Australian population.

• Screen adults (from age 40 years) for reduced visual acuity at least every 2 years. The need for cataract surgery and/or correction of any refractive errors should be identified.

Active trachoma - Active trachoma is endemic in the Aboriginal populations of northern and
central Australia, and predominantly affects children.

• Perform an opportunistic eye examination as part of any child health assessment where trachoma affects a community.
• Single dose azithromycin is the treatment of choice for active trachoma.

Trichiasis - Trichiasis affects a significant proportion of the elderly Aboriginal population (defined as aged >50 years) in remote areas of northern and central Australia.

• Screen for trichiasis as part of the routine annual examination from age 40 years if the region is or has been endemic for trichiasis.
• Refer for surgery when trichiasis is present.

Vascular Health:
Blood Pressure -

• Measure BP of adults (>18 years) at every visit (ensuring BP has been measured at least annually).
• Screening may commence earlier (from 15 years) in regions known to have a high prevalence of hypertension from this age.
• Screen 6-monthly for those with diabetes or target organ damage.

Physical activity -

• Recommend moderate intensity physical activity (such as brisk walking) of 30 minutes or more on most, if not all, days of the week. The total 30 minutes may be accumulated in shorter bouts, such as three 10-minute walks.

Cholesterol and lipids -

• Commence lipid screening at age 18 years and continue annually thereafter.
• Those whose cholesterol levels are raised but who are at low to moderate absolute risk of CVD should be given dietary and other lifestyle advice and monitored more closely over the next year.

Limping Child

A limp is an abnormal gait pattern, as a result of pain, weakness or deformity of the musculoskeletal system.

It is useful to assess the child by considering common presenting conditions at each age group.

• Toddler (1 - 4 years)
• Child (4 - 10 years)
• Adolescent (10 - 16 years)
  

At all ages the following MUST be considered

• TRAUMA
• TUMOUR
• INFECTION

Type of Limp:

The gait has two phases - stance phase and swing phase.

• Antalgic gait - the stance phase is shortened and the patient hurries off the painful side.
• Trendelenburg gait - is due to weakness of the hip abductor muscles and the body tends to lurch to the affected side. The lurching gait may be unilateral or bilateral. If the condition is bilateral, waddling is seen, with the trunk swaying from side to side. The causes may involve an abnormal hip joint such as in developmental dysplasia of the hip, congenital coxa vara or Perthes’ disease. It may also be caused by muscle weakness such as in polio, cerebral palsy or spina bifida.
• Stiff knee gait - is characterised by loss of knee motion resulting in circumduction and pelvic elevation on the affected side during the swing phase. This may be caused by knee disorders to minimise the motion of a painful knee.
• Short-leg gait - the head and pelvis fall as the body weight is taken on the short leg. This may be difficult to detect if the discrepancy is less than 2 cm. The gait may be disguised by tilting of the pelvis and by holding the ankle of the short leg in a plantar flexed position. To compensate for difference in leg lengths, circumduction of the leg on the long side may occur instead. A heel raise corrects the gait.

Common Causes of Limping in Children:
Toddler (1 - 4 years)

• Developmental - Developmental dysplasia of the hip,Perthes disease
• Infection - Osteomyelitis, Septic arthritis
• Inflammatory - Irritable hip (transient synovitis)
• Trauma - Accidental or non-accidental
• Tumour - Ewing's sarcoma, Secondaries
• Neurological - Cerebral palsy

Child (4 - 10 years)

• Developmental - Perthes disease
• Infection - Osteomyelitis, Septic arthritis
• Inflammatory - Juvenile rheumatoid arthritis, Irritable hip (transient synovitis)
• Trauma - Accidental or non-accidental
• Tumour - Ewing's sarcoma, Secondaries

Adolescent (10 - 16 years)

• Developmental - Residual effects from childhood and toddler conditions, Tarsal coalition, Slipped upper femoral epiphysis (SUFE)
• Infection - Osteomyelitis, Septic arthritis
• Inflammatory - Juvenile rheumatoid arthritis, Irritable hip (transient synovitis)
• Trauma - Accidental ( sport related )
  
• Tumour - Osteosarcoma

Clinical Assessment:
History including antenatal, perinatal and postnatal history, developemental history, trauma and features of infection
Examination:

• Gait
• Walk on toes and heel
• Trendelenburg test
• Spine examination
• An assessment of leg lengths can be determined by palpating the anterior superior iliac spines or the posterior superior iliac spines. If there is any significant tilting of the pelvis, level the pelvis by placing an appropriate height block under the foot on the short side.
• The hip, knee and ankle joints are examined and a neurological assessment is undertaken.

Checking for Non-adherence

Definitions:
Compliance/Adherence/Concordance - the extent to which a patient acts in accordance with the prescribed interval and dose of a dosing regimen.
Persistence - the duration of time from initiation to discontinuation of therapy.
Adherence: may also be defined as the combination of both compliance and persistence.

The validated Morisky questionnaires can help you identify non-adherence in patients, and gives an insight into the nature of any non-adherence.

4 points questionaire:

• Do you ever forget to take your medication?
• Are you careless at times about taking your medication?
• When you feel better, do you sometimes stop taking your medication?
• Sometimes, if you feel worse when you take your medication, do you stop taking it?

Premenstrual Syndrome

Premenstrual syndromeis a cyclical disorder of young and middle-aged women, which is characterized by emotional and physical symptoms that consistently occur during the luteal phase of the menstrual cycle.

• Affective Symptoms: Depression, Sadness, Irritability, Anger, Anxiety, Tension, Appetite Change and Food Cravings, Change in sexual interest
• Cognitive Symptoms: Impaired concentration, confusion, forgetfulness, temper outburst
  
• Fluid Retention: Breast tenderness or swelling, weight gain, abdominal bloating or swelling, swelling of extremities
  
• General Somatic Symptoms: Fatigue, Dizziness, vertigo, nausea and insomnia
  

Women with more severe affective symptoms are classified as having premenstrual dysphoric disorder.

Aetiology:

• The role of ovarian hormones is unclear, but symptoms often improve when ovulation is suppressed.
• Some evidence suggests that the disorder is related to enhanced sensitivity to progesterone in women with underlying serotonin deficiency.

Management:

Premenstrual syndrome and premenstrual dysphoric disorder are diagnoses of exclusion; therefore, alternative explanations for symptoms must be considered before either diagnosis is made.

PMS also must be distinguished from simple premenstrual symptoms (e.g., bloating, breast tenderness) that do not interfere with daily functioning and are characteristic of normal ovulatory cycles.

When PMS or PMDD is suspected, patients should be instructed to keep a premenstrual daily symptom diary for several consecutive months.

Non-pharmacological Therapies: should be offered to all patients and includes education, supportive therapy, rest, exercise, dietary modifications such as low fat, high fibre diet with reduced salt, sugar and caffeine.

Pharmacologic Therapies:

• Selective Serotonin Reuptake Inhibitor - Administration only during the luteal phase decreases drug cost, minimizes drug exposure and side effects, and may be more acceptable to some women. For intermittent therapy, fluoxetine or sertraline can be given during the 14 days before the menstrual period, or treatment can be initiated just before the expected onset of symptoms.

• Diuretics - Spironolactone is the only diuretic that has been shown to effectively relieve PMS symptoms such as breast tenderness and fluid retention.

• Non-steroidal Anti-inflammatory Drugs - mefanamic acid and naproxen sodium have been the most studied.

Dysmenorrhoea

Dysmenorrhoea is painful menstruation and may be

• primary in the absence of detectable pelvic pathology
  
• secondary to organic pelvic disease.

Primary Dysmenorrhoea

Dysmenorrhea is thought to be caused by the release of prostaglandins in the menstrual fluid, which causes uterine contractions and pain. Vasopressin also may play a role by increasing uterine contractility and causing ischemic pain as a result of vasoconstriction.

Risk Factors:
* Age < 20 years
* Attempts to lose weight
* Depression/anxiety
* Disruption of social networks
* Heavy menses
* Nulliparity
* Smoking

Clinical Features:
* Age - 6 - 12 months after the onset of menarche
* Onset - 24 hrs before menstruation and rarely persists for more than 48 - 72 hours.
* Pain - in the lower abdomen which may radiate to the inner surface of the thigh and lower back.
* Nausea and vomiting may be prominent, due to a prostaglandin effect or as a result of severe pain.

Treatment:

Nonsteroidal anti-inf lammatory drugs (NSAIDs): are the best-established initial therapy for dysmenorrhea. They have a direct analgesic effect through inhibition of prostaglandin synthesis, and they decrease the volume of menstrual f low.

Hormonal therapies:
# Oral Contraceptive Pills - it acts by reducing prostaglandin release during menstruation.
# Other - Depo-medroxyprogesterone acetate injection and levonorgestrel intrauterine device (Mirena).

Complementary and Alternative Medicines:
# Thiamine at a dosage of 100 mg daily was found to be effective in treating dysmenorrhea in a double-blind RCT of more than 500 East Indian women aged 12 to 21 years with moderate to severe symptoms.
# The Japanese herbal remedy toki-shakuyakusan (TSS) has been shown in an RCT to be better than placebo in the treatment of women with dysmenorrhea.

Life Style Modification:
# Low-fat vegetarian diet decreases duration and intensity of dysmenorrhea.
# Some studies have reported a benefit with exercise.

Secondary Dysmenorrhoea

It is uncommon before the age of 25 years.

The precise clinical picture is determined by the underlying cause.

A history that is inconsistent and/or physical findings of a pelvic mass, abnormal vaginal discharge, or pelvic tenderness that is not limited to the time of the menstrual period suggest a diagnosis of secondary dysmenorrhea.

Glaucoma

Glaucoma and IOP elevation are not synonymous.

Glaucoma is characterized by damage to the optic nerve that results in visual field loss regardless of the IOP level.

Many patients with elevated IOP show no evidence of optic nerve damage or visual field loss. This condition is known as "ocular hypertension." Much debate exists as to when glaucoma therapy should be initiated in patients with mild ocular hypertension alone.

Glaucoma may manifest as

• Optic disc changes – cupping resulting from reduced width of the neuroretinal rim or notch-like nerve-head deficit with associated nerve fibre layer irregularities – detectable loss and thinning
• Visual field losses
• Usually both of the above, but the disc changes often precede the field loss.

There are two main types of glaucoma:

• Open angle – most commonly primary open-angle glaucoma
• Closed angle.

Management:

Screening: RACGP does not recommend routine screening of glaucoma with tonometer or visual field testing. However, high risk patients should be referred for further assessment every 12 months.

• a family history of glaucoma
• age ≥60 years
• high myopia >8 diopters
• diabetes
  
• history of long term steroid use

The aim of treatment of open-angle glaucoma is to normalise IOP and thus stabilise disease. Clinical trials indicate that the lower the IOP, the greater the likelihood of achieving stable disease.

Pharmacological Method -

When a topical medication is chosen as first-line therapy in a patient with primary open-angle glaucoma, a stepped approach is used. Thus, a single topical agent is given up to its maximum dosage, as tolerated, before another agent is added or a different agent is tried.

A prostaglandin derivative, or ß-blocker are most commonly chosen, and should be used at the lowest possible concentration, and as infrequently as possible while achieving the desired outcome.

ß-blockers

Non-selective ß-blocker - timolol 0.25% or 0.5% lowers IOP by reducing aqueous secretion.

Selective ß₁-adrenegic-blocking agent betaxolol is nearly as effective as timolol, but has the advantage of having little effect on the cardiopulmonary system.

Combining a topical and systemic ß-blocker can increase the risk of ß-blocker-related side effects. For patients taking an antihypertensive medication the possibility of low nocturnal blood pressure should be considered. Nocturnal hypotension has been linked to progression of glaucoma.

Prostaglandin derivatives

The synthetic prostaglandins – latanoprost, travoprost, bimatoprost – lower IOP by increasing aqueous outflow through the uveo-scleral pathway.

They commonly cause hyperaemia and can increase the length of eyelashes and can increase periorbital skin pigmentation.

α ₂-adrenergic agents

These agents – aproclonidine, brimonidine – stimulate α 2-receptors in the ciliary epithelium to reduce the formation of aqueous humour, and enhancing uveoscleral outflow. In long term treatment aproclonidine tends to diminish in efficacy over time and both agents have a relatively high incidence of local allergy.

Carbonic anhydrase inhibitors

Both topical – dorzolamide, brinzolamide and oral – acetezolamide – carbonic anhydrase inhibitors are used in the treatment of glaucoma, where they decrease the formation of aqueous humour, presumably by slowing the formation of bicarbonate ions resulting in reductions in sodium and fluid transport.

Miotics

Miotics – pilocarpine, carbachol – were the traditional agents used to treat glaucoma. They act by stimulating cholinergic receptors, reducing IOP by contraction of the ciliary muscle causing pressure on the trabecular meshwork and a consequent increase in the outflow.

Surgical Therapy:

• Laser therapies
• Selective laser trabeculoplasty
• Peripheral laser iridotomy
• Filtration surgery

It is essential for the best outcomes that all patients be followed-up on a regular basis. After initiation of therapy patients should be seen at 2–4 week intervals until control of IOP is achieved.

Once IOP has been controlled patients should be reviewed every 3–6 months.

Early Detection Of Prostate Cancer

Men who are between the ages of 50 - 75 years and men older than 40 years with family history of prostate cancer are most likely to benefit from the early detection of prostate cancer.

For early detection digital rectal examination and prostate specific antigen are required.

Chance of prostate cancer given positive PSA test is one in three and chance of cancer given both abnormal PSA and DRE test is one in two.

Prostate cancer can still be present with normal PSA.

• Interpretation of PSA testing:

Age 50th centile 95th centile
40 - 49 .....0.65..............2.0
50 - 59......0.85............. 3.0
60 - 69......1.39..............4.0
70 - 79.......1.64..............5.5

Men whose PSA above 50th centile but below the 95th centile have been shown to be at higer long term risk of prostate cancer compared with those below the median.

PSA velocity which is calculated by meansuring PSA over 12 - 18 months can suggest the higer risk if it is over 0.75 ng/ml/yr.

Precentage of free PSA: Prostate cancer is likely if FTP is below 10% and a low risk if FTP is over 25%.