25/03 Flashcards
Amino-glycoside abx examples and moa
30s
gent
strepto
Macrolides example and moa
50s 23srRNA
Azithromycin, clarithromycin, and erythromycin
Warfarin moa
Vit k epoxide reductase inhib
Most common trisomy of miscarriage
T16
When to test for FM hemorrhage testing
from 20/40
Week one embryology summary
ZB and Molly had a blast (implantation)
Week two embryology summary
TEEM
Trophoblast (sinking syncitio, circular cyto)
Embryoblast (Epi - amnioticcavity, hypo - exocoleon endo YS - next E
Exocoelomic memb - primary YS from hypoblast
Maternal cap invasion via lacunae (d9-13)
Journey of primordial germ cells
Form from wall of YS (endoderm) 2/40
Migrate into embryo to gonadal ridges and diff into oogonia 6/40
When does oocyte complete meiosis 1 and 2
from puberty
@ LH surge - completion of Meiosis 1–> 3 hours PRE ovulation
@ fertilisation - completion of Meiosis 2 –> zygote
spermatogenic cycle time
Spermatogenesis –> 70 days
New groups of spermatogonia arise every 16 days (spermatogenic cycle).
Oocytes
7 million at 20/40
2 million at birth
20 - 40 000 at puberty
Which HIV antiretroviral therapy classes contains drugs which may affect the efficacy of oral emergency contraception?
Non-nucleoside reverse transcriptase inhibitors
Only some
The enzyme inducing NNRTIs include:
Efavirenz
Nevirapine
Etravirine
In this circumstance, the Cu-IUD should be offered. If this is unacceptable or contraindicated, double-dose LNG-EC should be considered, although the effectiveness is unknown. Double-dose UPA-EC is not recommended by the FSRH.
NNRTIs which don’t cause enzyme induction include Doravirine and Rilpivirine.
CHC and cholestasis
Glucuronide metabolites of oestrogen (particularly from EE) impair bilirubin metabolism and excretion. This happens to a lesser extent with endogenous oestrogens which are metabolised much faster
This risk is considerably smaller now due to lower doses of ethinylestradiol in modern CHC preparations.
CHC use is a UKMEC 2 for patients with a history of obstetric cholestasis and a UKMEC 3 with a history of CHC induced cholestasis.
cytochrome P450 inducers
Would reduce conc of contraception - failure
Phenytoin
Rifampicin
Carbamazepine
Alcohol
Barbiturates
St. Jonno’s weeds
Plus:
Steroids: dexamethasone, prednisolone, glucocorticoids
Others: cigarette smoke
Antiepileptics: topiramate
Antifungals: griseofulvin
Antiretrovirals: ritonavir (can also act as an enzyme inhibitor), Plus NNRTIs include:
Efavirenz
Nevirapine
Etravirine
STRONG
Steroids
Topiramate
Ritonavir
Other ARV: NNRTIs this time, include: Efavirenz Nevirapine Etravirine
Nicotine
Griseofulvin
cytochrome P450 inhibitors
Would increase conc of contraception - toxicity
SSRIs
macrolides
verapamil
omeprazole
ciprofloxacin
isoniazid
amiodarone
diltiazem
imidazole (+Azoles: ketoconazole, fluconazole)
grapefruit juice
Plus:
Antibiotics: sulfonamides, metronidazole, chloramphenicol
Cimetidine
Sodium valproate
CANCEL
Cimetidine
Antibiotics: sulfonamides, metronidazole, chloramphenicol
Na Valproate
Chrysanthemum allergy
Permethrin
Lactational Amenorrhoea (LAM): Physiology
Suckling disrupts GnRH pulsatility leading to reduced LH release by the anterior pituitary
This prevents the LH surge and inhibits ovulation
FSH is still released resulting in variable levels of follicular activity, however reduced LH levels impedes oestrogen synthesis
Mechanoreceptors in the breast alveoli stimulate prolactin and oxytocin release from the pituitary
Prolactin stimulates milk production and disrupts GnRH release
Oxytocin activates milk release from the mammary alveoli into the lactiferous ducts via contraction of myoepithelial cells
When the frequency of suckling reduces, GnRH pulsatility can resume, permitting the LH surge which leads to ovulation
Note: the mechanism behind LAM is poorly understood. Hyperprolactinaemia is associated but not the sole cause of LAM
serum ENG level
to inhibit ovulation
@5-6 weeks
@ 12 months
@3 years
Ovulation inhibition:
Ovulation-inhibition is achieved when serum etonogestrel ≥90 pg/ml (normally occurs within 1 day of insertion)
Etonogestrel concentration peaks 2 weeks post insertion before declining
PER day
Average release rate:
60-70 μg/day at weeks 5-6 (6 = 60)
35-45 μg/day by 12 months (middle of above an below 45 at one year)
25-30 μg/day by 3 years (3 = 30)
Lamotrigine and contraception
CONTRA ON LAMO
(1) E2 on LAMO
» Estrogen in combined hormonal contraception appears to induce glucuronidation of lamotrigine, significantly reducing serum lamotrigine levels.
»Conversely, there could be a risk of lamotrigine toxicity during any hormone-free interval taken.
» (Although - effect of CHC on lamotrigine may be reduced if an individual is also taking valproate)
(2) PROG on LAMO
Desogestrel might increase exposure to lamotrigine .
LAMO ON CONTRAC
lamotrigine could reduce effectiveness of hormonal contraception
If need to use CHC - dose might need to increase, serum levels monitored, no HFI, and monitor levels when stopped too.
lamotrigine toxicity = dizziness, ataxia, diplopia
Need condoms if using
CHC, POP, IMP
DMPA and IUDs ok
IUC post abortion
second trimester abortion is a UKMEC category 2.
The Ulnar Nerve: Anatomical course
Originates from nerve roots C8-T1 before emerging from the medical cord of the brachial plexus
Descends down the arm, medial to the brachial artery
Approximately half-way down the arm, the ulnar enters the posterior compartment where it travels posteriorly and medial to the humerus
It then passes behind the medical epicondyle via the cubital tunnel where it is vulnerable to damage before entering the forearm
Ulnar nerve injury
Paraesthesia of the dorsal and palmer aspects of the fifth and medial aspect of the fourth digit
Adductor pollicis paralysis (Froment’s sign)
Hypothenar atrophy
Paralysis of the interossei muscles (intrinsic muscles of the hand)
Claw hand deformity (flexion at the proximal and distal interphalangeal joints of the 4th and 5th digits)
c atoms in
spiro
prog
steroids
test
oest
spuro 24
Progesterone 21
Mineralocorticoids 21
Cortisol 21
Testosterone 19
Oestrogens 18
Incubation Period for
Zika
Chickenpox/ Rubella/ Parvovirus
CMV
Zika
1 week
Chickenpox/ Rubella/ Parvovirus
2 weeks
CMV
3 weeks
How to diagnose VZV
VZV-specific IgG becomes detectable from d4
(most people present day 3)
(1) acute and convalescent (>7 days) serology
(2) PCR of vesicle fluid
How to rx VZV
Exposed
Bloods for VZV ab –> non immune –> Aciclovir d7-14
(second line VZIG up to d10)
Rash
If <24 hours for Aciclovir
VZIG not given
If infected in month before birth - try to delay at least 7 days before birth and bb to be treated if w/in 7d
CMV mum and baby symptoms
Mum:
asymp. high ALT
Bb:
1. Microcephephaly
2. Visual retinitis
3. SNHL
4. Rash
5. Perivent calcs
Parovirus 19 (fifths)
Parvovirus B19 infection occurs via the globoside (P antigen) receptor, the main glycolipid of erythroid cells, which induces apoptosis.
anemia-associated fetal hydrops –> treatable with in utero treatment with blood transfusion
Placental trophoblasts and erythroid precursor cells have been reported to express globoside (P antigen), which is necessary for parvovirus B19 infectivity, and to show apoptotic activity as a result of infection –> abruption
Parovirus ix
If comes into contact <20/40:
- Test for past infection
If IgG is detected and the IgM assay is negative she may be reassured that she is immune; if susceptible she should have further sample in 4 weeks. - If seroconversion - additional ultrasound scans should be performed for the next 10–12 weeks.
Pituitary
where is it
blood supply
embryological origin
hormones released
In sella turcica in sphenoid bone
Inferior hypophyseal artery (for posterior) and superior hypophyseal artery (for anterior)
Embryological origin
Anterior: ectodermal cells of the oropharynx in the primitive gut (weeks 4–5)–> Rathke pouch (craniopharyngiomas)
Posterior: neural crest cells
Post: Growth hormone, oxytocin
Somatotrophs
40–50% of the total cells in the anterior pituitary gland.
The half-life of GH in the circulation is about 20 minutes.
When is HPO axis established by
week 20
Warfarin birth defects
Hypoplasia of nasal bridge
Congenital heart defects
Ventriculomegaly
Agenesis of the corpus callosum
Stippled epiphyses
Carbimazole birth defects
Cho-anal atresia
GIT defects
Omphalocoele
Aplasia cutis
VS defects
Anticholinergics
examples
Oxybutanin (Oll M1-3)
Tolteridine (Two M2/3)
Sulfenacin (single M3) - competitive.
Anticholinergics contraindications
Pyloric stenosis
Urinary retention
UC
Myasthenia gravis
ACute closure glucoma
PUMA
Penis fascia
A
B
C
Albugnea - CC only
Bucks - penis
Colles - OP pernium
HPV screening
HPV testing and cytology triage
hrHPV pos
cyto abn - colp
cyto neg - recall 12 months (if hpv persists x 3 then colp)
hrHPV neg - routine recall
unavailable sample/ cytology inadequate - repeat 3 months (ref colp after second inadeq)
HPV screening
colposcopy (Including histopathology)
Colposcopy adequate
(1) No CIN on impression/ biopsy look back at htHPV/ cyto
»inadequate - 12recall
»LG cyto - 36recall
»HG/BL - MDT in 2 mo
(2) CIN 1+ on impression/ biopsy - manage as abnormal colp
(3) Colposcopy inadequate
» LG cytology - repeat colp in 12 months
» HG or borderline (endocervical) - LLETZ
HPV screening
Abn colposcopy
CIN1
Recall in 12 mo
(a) hrHPV neg: recall in 36 mo
(b) hrHPV pos: cyto
> cyto neg: recall in 12mo
Repeat above (a) + (b) and if cytology STILL neg then recall in 36 mo
> cyto abnormal
Refer to colp
HPV screening
Abn colposcopy
CIN2/3
Rx and recall in 6mo
TOC @6mo hrHPV NEG
36 mo recall
TOC @ 6mo hrHPV POS
Colp
Management based on findings
HPV screening
Abn colposcopy
CGIN
Rx and recall in 6mo
(A) NEG hrHPV TOC @6mo
Recall 12mo
Then if ok recall 36 mo and if POS then onto pathway below.
(B) POS hrHPV TOC @ 6mo
Cyto ABN - colp
Colp N: 10yr follow up (HPV pos at any point - for colp)
Colp ABN: GIN FU
Cyto N
Colp N - recall in12mo- repeat above (A) (B)
3 important types of bias
incidence-prevalence bias (cross-sectional)
loss-to-follow-up bias,
publication bias
Neyman bias
Type of selection bias
AKA incidence-prevalence bias
cross-sectional studies
extremely sick individuals or extremely healthy individuals are excluded from the final results of the study which may lead to biased results
Example 1: Sick individuals being excluded from a study
Case-control studies are most susceptible to this type of bias, but it can also occur in cohort studies and cross-sectional studies.
Ways to prevent
1. Use incident cases rather than prevalent cases.
2. Use follow-up studies.
Publication bias
only studies which have statistically significant positive results get published and the statistically insignificant or negative studies does not get published.
What type of bias does blinding minimise?
observer
what type of bias does randomisation minimise
selection
How long does CL last
14 days if no preg
4 mo if preg
Sperm cycle how many days
16 days
which vaccines are recomb
Hep B
HPV
Men B
Use yeast / bacterial cells - infect virus into them - use surface proteins for vaccine
Vaccines in preg and what types of vaccines are they
Pertusis
Toxoid
From 16/40
Flu
Seasonal
inactivated flu vaccine are available - QIVe, QIVc, and QIV-HD -
» split virion, inactivated
» Dont get nose spray as is a LAIV
» Egg allergy!!
RSV
28/40
Recombinant
Not advised:
CG (vaccination against tuberculosis)
MMR (measles, mumps and rubella)
oral typhoid
yellow fever
Epithelium of male urethra
Prostatic - transitional
(SV - pseudostrat columnar)
Membranous - transitional/ pseudostrat columnar
Penile - pseudostrat columnar
(BU - simple columnar)
Meatus / Nav fossa - stratified squamous
BS male urethra
LN
Pros: inf ves a (II)
Mem: BU a (int pud)
Pen: int pud
LN
Pro and memb: obt and int iliac
pen: sup inguinal
Where are the BU glands found?
@ level of memb urethra in deep perineal pouch
F urethra
A/N/L
A: int pud
N: vesicle plexus and pud
LN: int iliac
Ligs of penis
Suspensory: erectile bodies -> PS
Fundi - sling: linea -> PS
Where is the spermatic cord in relation to epiG vessels
Lat and inferior
Fasial layers spermatic cord
Ext spermatic fasc - ext oblique
Cremasteric fasc - int oblique
Int spermatic spermatic fasc - transversalis fasc
Cremasteric A and N
A ilioinguinal
N G branch of GF
Testes BS
Testicular a (inguinal canal)
Cremasteric (inf hypoG)
VD a (inf vesical - int iliac)
Renal function and PrEP
> 90 and <40 - annual
60–90 OR >40 OR RF renal impairment - 6monthly
<60 specific input
Mgen TOC/ abstinence
aabstinence 14d from beginning of rx
TOC in 5 weeks from beg in rx
Mife moa and CI
1, decid
2, increase sens PG
3, Cervix soft
CI
Hypothyroid
CAI/ asthma - antiglucocorticoid
Enzyme inducers
ART CP450 inducers
Some NNRTIs
Efavirenz (EFV)
Nevirapine (NVP)
Etravirine (ETR)
Efavirenz(could consider IMP, or 2xEE to make up 50 cont)
Ok: Doravirine, Rilpivirine
Reduced contraceptive effectiveness
ARVs that inhibit cytochrome P450
Boosted PIs (boosted protease inhibitors)
Atazanavir/ritonavir (ATV/r)
Lopinavir/ritonavir (LPV/r)
Darunavir/ritonavir (DRV/r)
Atazanavir/cobicistat (ATV/c)
Darunavir/cobicistat (DRV/c)
Ritonavir inhibits some cytochrome P450 enzymes and induces others.
Cobicistat inhibits cytochrome P450.
(1) Ritonavir - inhibits CYP3A4 but induces glucuronidation enzymes –> increase progestogen exposure but to reduce EE (through glucuronidation).
(2) Cobicistat (more specific CYP3A) - no inducing properties –> increase both progestogen and EE exposure.
Note: in elvitegravir (II)/cobicistat - EE levels lower
SAFE ARV to use with hormonal contraception.
Integrase strand transfer inhibitors (INSTIs) Dolutegravir (DTG)
Raltegravir (RAL),
Bictegravir (BIC)
abotegravir (CAB)
ARV that cause hepatotoxicity and lactic acidosis in preg
STAVUDINE
DIDANOSINE
ARV that causes NT defects
Efavirenez
Dolglutavir
recommendation for first-line PEP
two NRTIs: tenofovir disoproxil fumarate and emtricitabine
one II: raltegravir.
Subclinical hypothyroidism management in preg
TSH > 4 give thyroxine
TSH > 2.5 reg monitoring from 7/40
Factor 5 leiden
resistance to activated protein C
A506G mutation on factor V
APC resistance test
A-E of cervical ectopic
Absent sliding sign
Barrel shaped cervix
Colour doppler (bf around gs)
Down GS below internal os
Empty uterus
Interstitial ectopic
Empty uterus
POC/GC laterally to round lig/ UT junction
<5mm myometrium surrounds GS in all planes
Interstitial line sign
Chemicals that stop and stimulate puberty
Pre pub : GABA, neuroP Y
Post pub: glutamate, kisspeptin, leptin (47kg)
Clit nerve supply
Sens dorsal n - pudendal
ANS U-V plexus - inferior hypoG
Cardinal ligament
Cervix –> lateral wall @ ischial spine
Carries: uterine a/v, hypoG, ureters
Tests to do in RM
RM - APL and CAL
Second trimester loss - PTGM, protein S, factor V
Attrition bias
Lost to follow up differ from those who stay in
Procedure bias
Different arms treated differently
Alpha value
cut off to compare P so see if P is small enough to be stat signif
Probability of making a t1 error
T1 error
false pos
true nul which u reject
claiming signif when not
increased by bias
Manage by doing repeat studies
Alpha/ p value
T2 errors
False neg
Insufficient power
Sample size, Beta, 1-power
Power
the probability of finding a difference between groups if it did exist
AUDIT 6
Identify issue
Obtain standards
Collect data
Compare with standards
Implement change
Re-audit
GDPR
6 things
- Lawful/ fair
- Specific
- Relevant
- Accurate
- Time
- Secure
Article 6 of GDPR
Personal data
- consent
- contract
- legal
- vital interest
- public interest
- legitimate interest
Article 9
Health data
One from A6 plus confidentiality
Antiemetics MOA
Cyclizine
Promethazine
histamine h1 r antagonists
Ondansatron
serotonin 5-HT3 r antagonists
Prochloperazine
Metaclopramide (also 5-HT3 r antagonists)
dopamine d2 antagonists
Craniophryngioma
Rathke cleft (ant pit)
- increased ICP
- Hypopit and DI
- Visual field defect
Effect of prevalence on P+N PV
Prev increases , NPV decrease, PPV increase
Anatomy - lateral walls of pelvic cavity
Obt internus
Piriformis
What do superficial and deep perineal n supply
Superficial - post labia
Deep - 1/5 lower vag and perineum
External genitalia A/V/N/L
A
Internal pudendal (internal iliac) - dorsal clit
External pudendal (femoral) - perineal and labial skin
V
Int/ ext pudendal
L
Femoral - superficial inguinal LN –> int iliac
N
ANT: ilioinguinal and GF
POST: pudendal and post cut n of thigh
BULB/CLIT: PNS uterovag n plexus
Vagina A/N/L
A
uterina and vaginal a+v (from internal iliac)
L
upper 1/3: ext iliac
middle 1/3: common/ int iliac
lower 1/3: sup inguinal and perirectal
N
PNS hypogastric
Somatic pudendal (deep perineal) - lower 1/5
Histology: nondisordered proliferative and disordered proliferative endometrium
Non-disordered proliferative
Tubular glands and abundant stroma (S>G)
Columnar cells with pseudostratified hyperchromatic nuclei and mitosis
Disordered proliferative (from anov cycles)
Haphazard shaped glands (branching cystically, dilated)
Abundant stroma (G:S ration <2:1)
Cytology same as hyperplasia w/out atypia
Histology: Hyperplasia w/out atypia
Gland crowding (G:S>2:1) simple–> complex
Normal nuclei / cytology (elongate, dense, polarised nuclei)
Histology: Hyperplasia w/ atypia
Gland crowding (G:S>2:1) complex b2b glands
Cytologically altered nuclei (round, large, pleomorphic, loss of polarity, vesicular chromatin, nucleoli)
Histology: Endometriod carcinoma
Stromal invasion: one of
1. Loss of intervening stroma
2. Irregular infil myometrium
3. Solid non-squamous epithelial growth
4. Papillary architecture / villus gland growth
Standard deviation
For normally distributed data.
How data is spread around average.
±1 SD includes 68.2% of the data
±2 SD includes 95.4%,
±3 SD includes 99.7%.
(Jay Z was sick and late (68%) which got him fired from his nine to five (95%) job, giving him 99 problems but 7up (99.7%) wasn’t one.)
Sometimes used wrong ie in non-normally distributed data: A simple check for a normal distribution is to see if 2 SDs away from the mean are still within the possible range for the variable.
Forest plot
Statistics which test differences
parametric tests
non-parametric tests
Chi-squared
Parametric tests
T test
Numeric plus categorical variable (2 categories). Comparison of 2 means. p value.
Analysis of variance (ANOVA)
Numeric value plus categorical variable (3 or more categories). Comparison of 3+ means. p value.
Chi test
2 categorical variables. Comparison.
Correlation
2 numeric variables. How they relate / association.
non-parametric tests
Rather than comparing the values of the raw data,
statisticians “rank” the data and compare the ranks.
“Mann–Whitney U test”
The “Wilcoxon signed rank test”, “Kruskal Wallis”
and “Friedman” tests are other non-parametric tests.
CHI-SQUARED/ χ2
Tests to analyze
contingency tables
χ2 test,
Fisher’s exact test»_space; best choice as it always gives the exact P value, particularly where the
numbers are small.
Kolmogorov Smirnov
normality test that examines if variables are normally distributed
> > see whether parametric stats can be used
Correlation
Where there is a linear relationship between two
variables there is said to be a correlation between
them. The strength of that relationship is given by the
“correlation coefficient”. “r”
The “Pearson correlation coefficient”, Pearson’s r, is
used if the values are sampled from “normal”
populations (page 9). Otherwise the “Spearman
correlation coefficient” is used. However, the
interpretation of the two is the same
R2 is sometimes given. As it is the square of the r
value, and squares are always positive, you cannot
use it to tell whether the graph slopes up or down. does tell you is how much of the variation in
one value is caused by the other
Regression
Linear regression
A regression line is the “best fit” line through the
data points on a graph.
The regression coefficient gives the “slope” of the
graph, in that it gives the change in value of one
outcome, per unit change in the other.
y = a + bx
The regression
coefficient and constant can be given with their
“standard errors”.
Logistic regression
Poisson Regression Poisson regression is mainly used to study waiting times or time between rare events.
Cox proportional hazards regression model The
Cox regression model (page 60) is used in survival analysis where the outcome is time until a certain event.
Regression or correlation?
Correlation measures the strength of the association
between variables.
Regression quantifies the association. It should only
be used if one of the variables is thought to precede or cause the other.
Survival analysis techniques
the time until a single event occurs (e.g. death or dc from hospi)
Life table. A life table is a table of the proportion of
patients surviving over time. Life table methods look at the data at a number of fixed time points and calculate the survival rate at those times.
» The most commonly used method is
Kaplan–Meier.
The Kaplan–Meier approach recalculates the
survival rate when an end event (e.g. death) occurs in the data set, i.e. when a change happens rather than at fixed intervals.
» The test to compare the survival between two
groups on KM is called the “log rank test”
THE COX REGRESSION
MODEL
Also known as the proportional hazards survival model.
investigate the
relationship between an event (usually death) and
possible explanatory variables, for instance smoking status or weight.
The “HR” is the ratio of the hazard (chance of
something harmful happening) of an event in one group of observations divided by the hazard of an event in another group. A HR of 1 means the risk is
1 × that of the second group, i.e. the same. A HR of 2 implies twice the risk.
Statistics which analyze clinical investigations and screening
Sensitivity, specificity and predictive value 62
Level of agreement and Kappa
Likelihood ratio
If the test is positive, how much more likely
the patient is to have the disease than not have it.
Kappa is often seen written as k
comparison of how well people or tests agree
and is used when data can be put into ordered
categories.
Typically it is used to look at how accurately a test
can be repeated.
Example: If the same cervical smear slides are examined by the cytology
departments of two hospitals and k = 0.3, it suggests that there is little
agreement between the two laboratories.
» “ordinal data”
(if continuous data use
“intra-class correlation coefficient” )
Incidence
The number of new cases of a condition over a given
time as a percentage of the population.
Example: Each year 15 people in a practice of 1000 patients develop Brett’s palsy.
15/ 1000 x 100 = yearly incidence of 1.5%
Prevalence (= Point Prevalence Rate)
The existing number of cases of a condition at a
single point in time as a percentage of the population.
E.g. At the time of a study 90 people in a practice of 1000 patients were suffering from Brett’s palsy (15 diagnosed in the last year plus 75
diagnosed in previous years).
Power
The power of a study is the probability that it would detect a statistically significant difference.
Bayesian statistics
mathematical tools to rationally update our subjective beliefs in light of new data or evidence.
Heterogeneity
Important in systematic reviews and meta-analyse
Clinical heterogeneity
differences in the specific research question
Methodological heterogeneity
variability in study design and in the risk of bias
Statistical heterogeneity
ariability in the “true” intervention effects
consequence of (c) or (m)
Statistical heterogeneity - how to calculate?
Cochran’s Q statistic
form of chi-squared test of the null hypothesis that the true effect in all included studies are the same
I-Squared Test
uses Cochran’s Q statistic to give a percentage score for heterogeneity, with higher percentages indicating greater heterogeneity
Funnel plots
type of scatterplot
X-axis: Typically represents the effect size of the intervention (e.g., odds ratio, mean difference). often odds ratio (logs scale)
Y-axis: Represents a measure of study size or precision, often the STANDARD ERROR or inverse variance.
A symmetrical funnel plot suggests no publication bias or heterogeneity, while asymmetry (a “bite” out of the funnel) suggests potential bias.
Heterogenicity - funnel plots show variability in the effect sizes of different studies, which can be an indicator of heterogeneity.
Causes of asymmetry on a funnel plot
Non-reporting bias: less likely to be published if not statistically significant, or if the effect size is very small or non-existent.
Poor methodological quality leading to exaggerated effects: Studies with inferior methods may show larger effect estimates of an intervention than would have been observed in a well-designed study.
True heterogeneity: Sometimes a significant benefit of an intervention can only be observed in patients who are at high risk for the outcome targeted by the intervention. These high-risk patients are more likely to be included in small, early trials, leading to asymmetry in the funnel plot.
Artefactual: Certain effect estimates, such as odds ratios or standardised mean differences, are inherently correlated with their standard errors. This correlation can create a false asymmetry in a funnel plot even when there is no bias.
Chance: With a small number of studies and their heterogeneity (variation), the analysis of the relationships between studies in a meta-analysis is more prone to false positives. This can affect the symmetry of the funnel plot.
Publication Bias
failure to publish the results of a study on the basis of the direction or strength of the study findings.
studies which have statistically significant positive results get published and the statistically insignificant or negative studies does not get published.
Funnel plots help identify if smaller studies are more likely to show larger effects (positive or negative), which could indicate that studies with significant results are more likely to be published, leading to a skewed view of the overall effect.
Random error
error that occurs due to chance
e.g. sampling error
Central limit theorem
As sample size increases, standard deviation of the sampling distribution (standard error) decreases/ precision increases – this underlies funnel plots as wide bit at the bottom is little studies (with larger SE).
Systematic review vs meta-analysis
A systematic review is an article that synthesizes available evidence on a certain topic utilizing a specific research question, pre-specified eligibility criteria for including articles, and a systematic method for its production.
Whereas a meta-analysis is a quantitative, epidemiological study design used to assess the results of articles included in a systematic-review.
Hep C
Acute 0-6months
Chronic 6+months (2/3rds)
cirrhosis, liver failure, and hepatocellular carcinoma
antibody test (which indicates if a person has ever been infected with HCV) and HCV RNA test (to check if HCV infection is active and for genotype analysis)
Placental tf low, around 5% –>
How does hepatitis B differ in children and adults?
Hepatitis B infection acquired in adulthood leads to chronic hepatitis in less than 5% of cases, whereas infection in infancy and early childhood leads to chronic hepatitis in about 95% of cases.
Hep B and pregnancy
Screening for HBV in pregnancy should involve serological testing for
presence of hepatitis B surface antigen (HBsAg) -> if positive further serology: Ige markers and anti-HBc IgM
HIV, HCV and hepatitis delta co-infection
HBV DNA >200,000 IU/ml
antiviral treatment to reduce risk of HBV vertical
transmission from 24weeks
–> Tenofovir
In many women planning to conceive, antiviral treatment of HBV may be
deferred, providing there is minimal liver disease
Women on antiviral therapy for HBV prior to pregnancy should continue
treatment during and after pregnancy
Women who have conceived on entecavir should be offered the option to
switch to TD during pregnancy
Half life gnrh
2-4mins
What is randomisation and why is it important
process of assigning clinical trial participants to treatment groups such that each participation has a known (usually equal) chance of being assigned to any of the groups
successful randomisation requires that group assignment cannot be predicted in advance
knowledge of group allocation should be kept secure until after patient is enrolled; i.e. allocation concealment
lack of allocation concealment may affect the decision to recruit a patient and so distort the accuracy of the study’s findings ==> loss of internal validity due to bias from systematic variation
Randomisation is important to
(1) minimises selection bias
(2) balance known and unknown prognostic factors
(3) allow probability theory to express the likelihood that any difference in outcome between groups (other than intervention) reflects chance
(4) facilitates blinding of investigators, participants and evaluators
(5)trials that lack randomisation introduce bias (systematic variation)
Types of randomisation
Simple Randomisation: Equal chance for each patient, but may lead to imbalances, especially in small trials.
Block Randomisation: Ensures similar group sizes.
Stratification: Uses pre-identified confounding factors to balance groups, useful in small studies.
Minimisation: Not truly random, adjusts allocations to balance baseline characteristics. Useful when multiple confounders exist or randomisation is ethically problematic.
Publication Notes:
Only fully randomised trials are “randomised”; others are “non-randomised e.g. quasi”
Sequence generation method must be stated.
Report details of block randomisation, stratification, and minimisation if used
Anatomy of testicular artery
Course:
originate aa @ L2-L3 descend over psoas major
go into spermatic cord via the deep inguinal ring
In spermatic cord, pampiniform venous plexus surrounds a - countercurrent heat exchange system
A then reaches the posterior margin of the testis, splitting into two terminal branches supplying the testicular lobules.
Branches & Supply:
Ureteric branches (supply ureters)
Epididymal branches (supply the epididymis)
Superior & inferior polar branches (supply the testis, anastomosing with cremasteric and ductus deferens arteries)
Ovarian torsion
Torsion occurs when the ovary twists over the supporting ligaments
» infundibulopelvic (suspensory )ligament
» utero-ovarian (ovarian) ligament
Initially, the venous outflow is obstructed, and later arterial inflow is also interrupted due to increased swelling,
R>L
Over 5cm
