MTX +dual DMARD compared to MTX + etarnecept

My original comments published in http://www.nejm.org/doi/full/10.1056/NEJMoa1303006#t=comments


The study showed a very promising results for triple therapy (methotrexate plus sulphasalazine plus hydroxychloroquine) with no difference significantly compared to methotrexate and etarnecept. The study potentially will give impact to management of rheumatoid arthritis as conventional triple therapy is much cheaper than methotrexate and etarnecept . Firstly combination conventional triple therapy potentially cheaper than methotrexate plus biologics. Secondly the initiating of triple therapy with relatively higher dose as starter therapy compared with normal treatment of DMARD with tapering dose according to response to therapy. NICE guideline only suggest initiate methotrexate with at least one other DMARD. I find this study commencing the aggressive therapy with the results of severe adverse events been observed ( 1mortality in biologics arm and severe infection in both arm). There is not mentioned folate in addition of methotrexate to prevent side effect of methotrexate . I personally suggest and conduct a routine chest radiograph before initiate biologics as pulmonary tuberculosis is relatively common in Malaysia.

Dabigatran post-AF ablation may be riskier than warfarin

Periprocedural anticoagulation in patients undergoing radiofrequency ablation for atrial fibrillation may entail a small but statistically increased risk of stroke or transient ischemic attack, according to a meta-analysis of 10 observational cohort studies.
The meta-analysis, which included 1,501 patients on periprocedural dabigatran (Pradaxa) and 2,356 on warfarin, had dual primary end points.
 One was stroke or TIA, which occurred in 0.7% of the dabigatran group, compared with 0.2% of those on warfarin – a statistically significant difference (P = .0007), Dr. Benjamin A. Steinberg reported at theannual meeting of the Heart Rhythm Society.

Major bleeding, was recorded in 1.6% of the dabigatran group, with a closely similar 1.7% incidence in the warfarin group.

Rates of cardiac tamponade, a secondary end point, were also similar: 1.1% with dabigatran and 0.9% with warfarin.
Conclusion: Dabigatran posted higher risk of stroke periprocedural anticoagulation with equal risk of bleeding and tamponade comparing to warfarin

Ceftaroline (Zinforo) a new toy for MRSA skin infection ?

Ceftaroline- a new generation of cephalosporin

Bactericidal

Block PBP

Addictive to other antibiotic, least interaction

Professor Lipman

CANVAS study showed effective against MRSA  complicated soft tissue infection compared to vancomycin  and aztreonem. Study showed non inferiority to Vancomycin and aztreonem

Treatment 5-14 days

FOCUS I and II – study showed effective towards CAP. No clinical data regarding MRSA CAP.

New combination produce –ceftaroline + avibactem –enhanced gram –ve cover.

Intensive Talk with Prof Falagas

Summary:
Bacteria develop multiple resistance to antibiotic
By:
1)producing B-lactamase
2)overexpression efflux pump to release extra antibiotic
3)antibiotic modify enzyme
4)ribosomal mutation
Thus appear all superbug such as ESBL, carbapenemase producing klebsiella etc
Pt infected with ESBL +ve had relative risk 1.85 of mortality compared to normal bugs
Treatment of commonest bugs in ICU –Acinetobacter spp.
Recommended to do C+S with MIC
Therapy promptly early
Start therapy right at beginning
Modification therapy as nessasary (de-escalation) early
Tigercycline- a new agt
It evades tetracycline efflux pump and ribosomal protective mechanism
Bacteriostatic
That is limitation no good blood level for therapeutic
Varied response to acinetobacter
Imipenem –launch with 4g/day
Recommend 2g/d as reduce seizure
Not enough as moderate susceptible organism need 1g qid .
Recommended for high MIC acinetobacter to give prolong infusion meropenem 1 g tds as long as 3 hr compared with 30min normally given.
Study proved similar dose with prolong infusion better outcome
Colistin monotherapy
Got 52% isolates for acinetobacter were polymycin only susceptible
The rest need colistin and one other antibiotic (rec add carbapenem)
As highest % of survival
Benault et al. showed Obesity highest rate septic shock
Partly related with leptin def
DM
FOsfamycin-good for Klebsiella spp and pseudomonas spp.
Another talk by gastro
If NDM1 may give fosfamycin + carbapenem.
UGIB
Commonest cause H. pylori followed by NSAID, Antiplatelet
Risk of UGIB-age, multiple co-morbidity and H/O peptic ulcer
If pt got cardiovascular problem, may restart antipltelet after 4-5 days of peptic ulcer

cognition after carotid endarterectomy or stenting

A neurology 77 published a interesting report regarding the topic above.
divided in 2 arms -one for CEA ( carotid endarterectomy) , another CAS (carotid artery stenting)
the NIHSS (NIH stroke scale) assessed at baseline and 1 daY postprocedure. Modifie RANKIN SCALE at baseline, 1 and 6 month. Cognition assessed in the week before procedure and 6 months later.Pt also assessed for mood using Beck depression inventory II.
MRI with DWI performed 1 to 3 days before and 3 days thereafter to assessnew ischemic lesion.]

Result:significant decrease in cogntion sumscore after CAS from baseline to 6 month
NO significant decrease score after CEA.
The mean difference between changes was not statistically significant.
the worst cogntion functioning inpt treated with CAS consistent with higher rate NEW ischemic DWI lesion after CAS

Peripheral neuropathy

Peripheral neuropathy or polyneuropathy-diffuse peripheral lesion, often symmetrical
Onset-
Childhood-CMT
Adult-diabetes
Older adult- paraproteinemia
Acute onset-AIDP, porphyria, toxic, vasculitis,tick paralysis, diphtheria
Chronic-B 12 def, paraproteinemia, diabetes.
Symptom-
Motor-distal weakness predominates.
Sensory-tingling (positive), numbness (negative)
Autonomic-orthostatic lightheadedness, gastroparesis, sweating abnormalities
Diff diagnosis by pattern
Pattern 1 : symmetrical ,prox and distal weakness + sensory loss
CIDP, vasculitis
Pattern 2 : symmetrical distal weakness +sensory loss
DM, drug and toxin, hereditary neuropathies, amyloidosis , paraproteinemia
Pattern 3: Asymmertical distal weakness and numbness
Infectious neurpathy, multifocal trauma, entrapment, vasculitic
Pattern 4: asymmetrical distal or prox weakness without sensory loss
Multifocal motor neuropathy, motor neuron disease, inclusion body myolitis
Pattern 5: asymmetric prox and distal weakness with sensory loss
Malignant infiltration, polyradiculopathy, HNPP
Pattern 6: symmetric small fibre sensory neuropathy without weakness
DM, amyloid, HIV
Pattern 7 marked proprioception loss
HIV, B6 toxicity, sjogren, paraneoplastic
Pattern 8: Neuropathywith cranial nerve involve
HIV,lyme, AIDP, sarcoidosis, malignant infiltration,antiGd1b neuropathy
Acute neuropathies
Guillain barre
Vasculitic neuropathic
Acute intermittent porphyria
Diphteria
Heavy metal
Tick paralysis
Chronic:
Mononeuropathic –trauma entrapment’
Multiple mononeuropathic- vasculitic
Polyarteritis nodosa
Sjogren
Wegener grnulomatosis
HNPP
Multifocal motor neuropathic
Polyneuropathic
DM,
Nutritional eg B12, B6, B1 def ,
Alcoholic
CIDP
Paraneoplstic
Paraproteinemia
Infectious-HIV, CMV, lyme, leprosy
Sarcoid
Metabolic- renal, hepatic or hypothyroid
Heavy metal- arsenic, lead, mercury
Drug- vincristine, flagyl, sisplatin , amiodarone,