Re: Rachel

- All pregnant women should be screened for gestational diabetes unless they are in a low-risk group. (at 28th week)

- Women at high risk for gestational diabetes are those
- >25 years of age;
- those with a body mass index > 25 kg/m2,
- maternal history of macrosomia or gestational diabetes,
- positive diabetes in a first-degree relative;
- high-risk ethnic group (African American, Hispanic, Native American).

- two-step strategy for establishing the diagnosis of gestational diabetes involves
- administration of a 50-g oral glucose challenge with a single serum glucose
measurement at 60 min.
- <7.8 mmol/L (<140 mg/dL) = normal.
- > 7.8 mmol/L (>140 mg/dL) = administration of a 100-g oral glucose challenge
with serum glucose measurements obtained in the
fasting state, and at 1, 2, and 3 h.
- Normal = <5.8 mmol/L (<105 mg/dL), 10.5 mmol/L
(190 mg/dL), 9.1 mmol/L (165 mg/dL), and 8.0
mmol/L (145 mg/dL), respectively.

- Pregnant women with gestational diabetes are at increased risk of:
- preeclampsia,
- delivering infants who are large for their gestational age,
- birth lacerations.
- (after birth) fetuses are at risk of hypoglycemia and birth trauma (brachial
plexus) injury.

--> Treatment of gestational diabetes with a two-step strategy of dietary intervention followed by insulin injections if diet alone does not adequately control blood sugar [fasting glucose < 5.6 mmol/L (<100 mg/dL) and 2-h post-prandial <7.0 mmol/L (<126 mg/dL)] is associated with a decreased risk of birth trauma for the fetus. (Usuaully, most pregnant mothers' glucose levels are controlled by diet modification alone. Compliance to these diet restrictions are usually the culprit for high blood sugar.)

- For women with gestational diabetes, within the 10 years after the index pregnancy there is a 80% (Malaysia) risk of being diagnosed with diabetes. All women with a history of gestational diabetes should be counseled about prevention strategies and have an annual screening for diabetes (according to Malaysian CPG).

- In general, during the first trimester, the initial insulin requirement is 0.7 units/kg per d. By late pregnancy, patients generally require 1 unit/kg per d.

--> Generally, 2/3 of the total insulin dose is given in the morning and 1/3 in the evening. Usually, 2/3 of the morning dose consists of NPH (NPH = Humulin N: intermediate type)and 1/3 of regular insulin. The evening dose consists of half NPH and half regular insulin. Determination of the exact amount of insulin for each pregnant woman is done on a case-by-case basis. Start with the safe amount of insulin units by using the formula above (Usually 1 unit/kg per day), and slowly increase/decrease by 4 units if the blood sugar level results are high/low respectively.

--> Usage of metformin:
- Recent evidence suggests that glyburide or metformin are safe and effective
alternatives. However...
- Fetal, neonatal, and maternal outcomes have been evaluated following maternal
use of metformin for the treatment of GDM and type 2 diabetes. Available
information suggests that metformin use during pregnancy may be safe as long as
good glycemic control is maintained; however, many studies used metformin
during the second or third trimester only.
- Therefore, until further research is done (on the 1st trimesters), treatment
with oral hypoglycemics in Malaysia (and many other countries) is NOT advocated
as the routine 1st line treatment(as it increases the risk of congenital
malformations. ), as Insulin is the drug of choice for the control of diabetes
mellitus during pregnancy.

Shock! A brief overview.

Prof: What is the first line therapeutic strategy for those in shock?
Student: Administration of intravenous fluids.

Prof: That is right. But what if the blood pressure remains low in spite of fluid resuscitation?
Student: Give vasoconstrictors.

Prof: Right again. What are the vasoconstrictors commonly used for shock?
Student: Dopamine, Dobutamine and Norepinephrine.

Prof: Which is better - dopamine or norepinephrine?
Student: I am not sure.

Prof: Vasoconstrictors differ in their degree of alpha adrenergic, beta adrenergic and dopaminergic effects. Dopamine and norepinephrine (noradrenaline) both have alpha and beta adrenergic effects but norepinephrine stimulates alpha adrenergic receptors more than beta adrenergic receptors. Stimulation of alpha receptors will bring up the blood pressure more effectively but at the cost of reduced splanchnic and renal blood flow. Dopamine also stimulates dopaminergic receptors which norepinephrine does not. Stimulation of dopaminergic receptors helps to improve blood flow to the internal organs and kidney but has a deleterious effect on the hypothalamic pituitary axis because it results in reduced prolactin and growth hormone levels. So you can see that there are good and bad points for both norepinephrine and dopamine. A study was published in the March 2010 issue of the New England Journal of Medicine which compared the effect of these two vasoconstrictor agents in shock. You can read the article HERE. You can see from it that both these agents are good as initial therapy for shock. But based on this study it would be preferable to use norepinephrine rather than dopamine for cardiogenic shock.

2 better than 1?

There is enough evidence to suggest that lowering LDL cholesterol helps decrease the incidence of coronary artery disease. It is a bit of a surprise therefore to learn from the ENHANCE trial that a greater degree of LDL cholesterol lowering with the combination of Ezetimibe and Simvastatin, when compared to Simvastatin alone, did not have any significant impact on the carotid intima-media thickness.

The IMPROVE IT trial is now underway to study if this combination of Ezetimibe and Simvastatin will be better than Simvastatin alone in reducing cardiovascular events.

For now, there is no evidence to recommend that the combination of ezetimibe plus simvastatin is better than a statin alone for patients with elevated LDL cholesterol levels.

Note:
Exetimibe is a drug that lowers LDL cholesterol by reducing intestinal absorption of cholesterol.

Simvastatin is a drug that lowers LDL cholesterol by affecting a key enzyme in the liver.

Carotid intima-media thickness is a marker of atherosclerosis in the carotid artery.

Rosiglitazone, from Hero to Zero.

In the years that followed the launch of rosiglitazone, there were many papers on its usefulness for patients with diabetes. There were papers that showed the drug’s effectiveness in reducing blood sugar when used alone example and also when used in combination with sulphonylureas example or metformin example . Some other notable trials that showed beneficial effects of rosiglitazone were the DREAM trial and the ADOPT trial. In the DREAM trial investigators showed that rosiglitazone could reduce the development of diabetes in those who had impaired fasting glucose or impaired glucose tolerance while the ADOPT trial showed that rosiglitazone was better than metformin or a sulphonylurea in maintaining glycemic control as monotherapy.

Problems with the drug began to surface in 2007. In early 2007, the first reports that rosiglitazone was associated with osteoporosis and an increased fracture risk appeared - See here. Then, in June 2007 a meta analysis published in the New England Journal of Medicine showed that patients on rosiglitazone had a greater risk of suffering a myocardial infarction - (Read the article).

Food for thought

Reference: The Lancet

Lung cancer (teratment)

- The treatment of lung cancer is dependent on the type and stage of cancer.
- The treatment explained here is only a summary:

1) Non-small cell lung cancer

* Stages IA, IB, IIA, IIB & some IIIA :

- basically the tumour is resected with / without removal of the lymph nodes in the mediastinum.
- post-operative radiotherapy is only advocated for selective patients.(with N2 disease if no neoadjuvant chemotherapy)

* Stage IIIA & IIIB

- The treatment for this stage of lung cancer is a little more complicated in that it depends also on the nature of the tumour i.e. bulky, with/without chest wall invasion,etc.
- It is suffice to say that resection of tumour is followed up with chemotherapy or radiotherapy.

* Stage IV & more advanced IIIB

- For this stage, radiotherapy to site of the involved area for relieve of symptoms.
- Chemotherapy for ambulatory patients.
- Resection of primary tumour and tumour spread (metastases) will be considered.

2) Small cell lung cancer

- limited stage (good performance status) : chemotherapy + chest radiotherapy
- Extensive stage (good performance status) : combination chemotherapy
- complete tumour responders (all stages) : consider prophylactic cranial radiotherapy
- Poor-performanc-status patients (all stages) :modified-dose combination, palliative care.

3) All patients

- radiotherapy for brain metastases, spinal cord compression, weight bearing lytic bony lesions, symptomatic local lesions.
- encourage to stop smoking.
- supportive care during chemotherapy.

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