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4:1 triamcinolone intra sheath injection for diabetic flexor tenosynovitis ( trigger finger - tf)Vol:12 4:1 Triamcinolone intra sheath injection for diabetic flexor enosynovitis
(Trigger finger - TF).
TF is caused by a disproportion between the flexor tendon and its
surrounding tendon sheath, in which smooth gliding of the flexor tendon within its sheath is restricted. The incidence in the general population is 1-2% while that in diabetics is 10 – 20%. Steroid injections for TF in non diabetics is reported to be effective with success rates varying from 40 – 90%. The success rate in diabetics is less. The difference is attributed to disturbances of collagen metabolism in diabetic flexor tendon sheaths. This may be due to accumulation of advanced glycation end products, increased cross linking of collagen with resistance to collagenase, increased oxidative stress or increased hydration of collagen mediated by the polyol pathway. The efficacy of this injection is related to the A1C value - > 8.0% indicates a poor response to Triamcinolone injection. Ref: Kameyama M et al Diabetes Care 2006 Nov; 29 (11) : 2512 – 2514.
Is Rosiglitazone safe in the first trimester?.
Pre clinical studies found no increase in congenital malformations in rats and rabbits treated with 19 and 73 times the human dose resp. Patients with polycystic ovaries and anovulation can be treated with metformin ( to decrease insulin resistance) and with clomiphene. Since glitazones also decrease insulin resistance, it is an attractive alternative for lean PCOS patients. But is it safe for the would be mother to be exposed to it prior to or during the first trimester before the presence of pregnancy is established?. Three cases of women exposed to rosiglitazone have now been published. In the first case, a 35 yr old woman was exposed to it until the 8th week of pregnancy. The second case was a woman exposed from weeks 13 – 17. The third case took rosiglitazone up to the 5th week of gestation. All three mothers delivered normal babies. Comment: These case reports suggest that rosiglitazone is not teratogenic in
humans, similar to rats and rabbits. Further studies are however required before
glitazones are recommended for PCOS women who intend to have babies.
Ref: Choi J.S. et al Diabetes Care 2006 Sept ; 29 (9): 2176.
4:3 At what age does diabetes become a coronary artery disease equivalent?.
Haffner showed that patients with diabetes without CAD had a seven year
cardiovascular risk equivalent to a non diabetic who had experienced CAD. This led
to the conclusion that diabetes should be treated as a CAD equivalent.
A study in Onatrio, Canada, in 379,003 adults with diabetes, and 9,018,082 non
diabetics was undertaken. It was found that the risk of cardiovascular disease was
higher in diabetic men and women at all age groups. The transition to a high risk
category – defined by an event rate equivalent to a 10 year risk > 20% or by an event
rate equivalent to that associated with previous MI occurred at a younger age for
men and women with diabetes, than those without diabetes ( mean difference 14.6
years). For the outcome of acute MI, stroke or death from any cause diabetic men
and women entered the high risk category at ages 47.9 and 54.3 years resp. When
coronary or carotid revascularization was added to these end points, diabetic men
and women entered the high risk category at ages 41 and 48 years resp. However the
risk for acute MI and death in diabetic men reached the equivalent of that for non
diabetic men with previous MI only after age 50 years.
Comment: Diabetes confers an equivalent risk about 15 years before non
diabetics. In general people with diabetes aged < 40 yrs do not seem to have a high
absolute risk of CVD. Diabetes seems to confer a risk equivalent to previous MI
only in men > 50 years. Whether these findings can be extrapolated to populations
of different ethnic origins such as South Asians has to be determined.
Ref: Booth G.L. et al Lancet 2006; 368: 29 -36.
4:4 Is pramlintide useful in the treatment of Type 1 Diabetics who are
already on intensive insulin therapy?.
A 29 week DBPC study randomized 296 patients to pramlintide or placebo as an adjunct to insulin. During initiation pramlintide was escalated from 15 to 60 mcg/meal in 15 mcg increments with recommended reductions of 30 – 50% in meal time insulin. Insulin was subsequently adjusted to optimize glycaemic control. End points included safety, change in A1C, post prandial glucose, insulin dose, weight and tolerability. The A1C was decreased by a mean of 0.5%. It also significantly reduced post prandial glucose excursions. Weight reduced by about 1.3Kg and the meal time insulin dose by 28%. Nausea however was reported in 63 % and was mild to moderate in intensity. Severe hypoglycaemia rates were low(0.5%). Comment: Pramlintide treated patients experienced reductions in post prandial
glucose excursions and weight, not achievable with insulin therapy alone and the
mealtime insulin dose was reduced. A1C reductions however were moderate and
comparable to placebo.
Ref: Edelman S.et al Diabetes Care 2006 Oct; 29 (10): 2189 – 2195.
Prevention or delay of progression from IGT to Type 2 DM – a
This study identified 17 randomized trials involving 8,084 participants with IGT. 12 trials evaluated life style interventions (LSI) - mainly exercise and weight loss, and 12 evaluated pharmacologic interventions ( mainly Metformin and Acarbose). Follow up was for about 4 years. The pooled hazard ratio for developing diabetes was 0.51 with life style intervention, 0.70 with oral anti diabetic drugs (ODD) and 0.44 for Orlistat. All these results were statistically significant and translated to the number needed to treat (NNT) for benefit as 6.4 for LSI, 10.8 for ODD and 5.4 for Orlistat. Comment : This study confirms that several interventions can delay the progression
to Type 2 DM. However the protective effects lasted only as long as the intervention
was in place - a delay rather than a true protective effect. This indicates that these
interventions require long term use to be truly effective. The recently concluded
DREAM trial which used Rosiglitazone showed that it was also useful for
prevention of DM in IGT patients and the subsequent wash out studies indicated that
the effect lasted only as long as the drug was given.
Ref: Gillies C.L. et al BMJ 2007 Feb 10; 334: 299.
4:6 Diabetes risk with antihypertensive medication.
Researchers conducted a network meta analysis to study new onset diabetes in
22 long term randomized anti hypertensive drug trials involving 143, 158 subjects.
When diuretics were used as the reference, the risk for incident diabetes was
significantly lower with ARBs (OR 0.57) ACEIs (OR 0.67), CCBs (OR 0.75) and
placebo (OR 0.77). There was a non significant lower incidence with Beta blockers
(OR0.90). Compared with placebo, only ARBs were associated with significantly
reduced risk for incident diabetes (OR0.75) and only diuretics with significantly
increased risk (OR 1.30).
Comment: In the 3-5 years of follow up, diuretics had the highest risk of incident
diabetes and ARBs the lowest risk. The absolute differences between the different
antihypertensive drugs never exceeded 3.6%. However even this risk increase might
matter in high risk populations such as those who are obese, have an IGT with FPG
between 110 – 125mg/dl and those with a family history of Type 2DM.
Ref: Elliott and Meyer P.M. Lancet 2007 Jan 20; 369: 201 – 207.
Bariatric surgery for adolescents.
2744 adolescent procedures were performed in the US from 1996 to 2003 and the numbers are increasing. Most patients were female, had no comorbid conditions and were operated at urban and teaching hospitals. Major complications ( most of them respiratory) occurred in 5.5% of patients. Compared with adults comorbidity, lengths of stay and hospital charges were lower. Comment: Outcome data are needed to assess optimal timing and long term effects
of this procedure in adolescents.
Ref: Tsai W.S. et al Arch.Pediatr. Adolesc. Med 2007 March ; 161: 217 – 221.
Does recombinant PTH (rPTH) prevent vertebral fractures?.
In a previous study rPTH ( teriparatide) increased bone mineral density (BMD)
and reduced the incidence of new vertebral fractures among post menopausal
women with prior vertebral fractures (NEJ Med 2001; 344: 1434). Now in a new
multinational trial researchers examine the effect of rPTH on the incidence of
fracture in 2,679 post menopausal women with osteoporosis , 81% of whom had no
prior vertebral fracture. The dose was 100mcg sc or placebo daily for 18 months.
The drug maker funded the study and performed the statistical analysis. Numerous
possible financial conflicts of interest were reported .
At 18 months, BMD in the PTH group increased at the lumbar spine and hip but decreased at the distal radius compared to the placebo group. Significantly fewer women in the PTH group than in the placebo group had a new or worsened vertebral fracture (1.4% vs 3.4%). The study groups did not differ significantly in rates of non vertebral fractures. Hypercalciuria, hypercalcaemia and nausea were significantly more common in the teriparatide group. Comment: Although the results suggest that PTH can prevent fractures, the effects
ere modest and side effects were common. The administration as a sc injection and
high cost make it unlikely to become a first line treatment option.
Ref: Greenspan S.L. et al Ann.Intern. Med 2007 March 6; 146: 326 – 339.
Changes in lung function with inhaled insulin (II) – Exubera.
600 adults with Type 1 diabetes were randomized to receive pre meal inhaled insulin or pre meal sc short acting insulin. Both groups also received long acting basal insulin. At 3 months, mean FEV1 had declined by 0.05 litres in the II group and 0.03 litres in the sc insulin group – a small but statistically significant difference. However after 3 months and through 24 months, the FEV1 declined at the same rate in both groups. For diffusing capacity, the same pattern was noted – a small initial decline, but no further separation between groups during moths 3 – 24. Cough occurred more frequently in the II group ( 38% vs 13%). Glycaemic control was similar in the two groups. Comment: This study demonstrates that II induces small changes in pulmonary
function shortly after the start of treatment. However, changes do not appear to
progress after 3 months. Patients are advised to have spirometry before starting II,
after 6 months of treatment and annually thereafter. II is not recommended for
patients with underlying lung disease and in contraindicated in smokers.
Ref: Skyler J.S. et al Diabetes Care 2007 Mar; 30: 579 – 85.
MRI of the opposite breast in women with breast cancer.
MRI is more sensitive than mammography for detecting breast cancer. In a multicentre study, the yield of MRI of the other breast in 969 women with recently diagnosed breast cancer and no clinical or mammographic evidence of abnormality were studied. The following outcomes were noted. a) MRI detected contralateral breast cancer in 30 patients. During the ensuing year three additional patients were detected after a negative MRI (sensitivity 91% with 3 false negatives). b) Positive predictive value was 21 % and negative predictive value was 99%. Comment: MRI detected contralateral breast cancer in about 3% of women
with recently diagnosed breast cancer but no clinical or mamographic findings in
the other breast. The findings are potentially important for at least two reasons. First,
when contralateral breast cancer is discovered concurrently, the woman can undergo
simultaneous treatment and avoid a second course of treatment later. Second, for
women who are considering prophylactic contralateral mastectomy, as those with
positive BRCA genes, the high negative predictive value of a negative MRI might
argue against that prophylactic procedure. Some concerns regarding the high rate of
false positive MRI results, leading to many biopsies of benign lesions and the lack
of expertise in breast MRI in many clinical centres have been expressed.
Ref: Lehman C.D. et al N.E.J.Med 2007 March 29; 356: 1295 – 1303.
4:11 Rosiglitazone may increase risk for MI
A meta-analysis of 42 ramdomized trials studied the effect of Rosi on MI and cardio
vascular death, and compared it with other Glucose lowering drugs or placebo.
Rosi was associated with a significantly increased risk for MI compared with
controls(OR 1.43;p=0.03). In addition an increased risk for CV death in the Rosi
group almost reached statistical significance (OR 1.64;p=0.06)
Comments: This meta-analysis has several methodological limitations. However
one needs to be alert to the possibility of increased risk for coronary events with
Rosi. Does this represent a class effect? The options now for the physicians are
Stop Rosi and consider other drug classes. Substitute pioglitazone which has a proven track record in preventing cardiovascular events (as shown by the secondary prevention trial viz the RO ACTIVE trial), and has a better effect on the lipid profile. To continue Rosi in patient who appeared to benefit from it and wait for the verdict of the RECORD trial, which will look specifically at rosiglitazone’s cardio vascular event risk. Ref: Nissen SE and Wolski K, NEJ Med 2007 Jun14;356;2457-71
Observation vs Surgery for asymptomatic primary hyper
Nowadays PHPT may be diagnosed incidentally in routine blood screening. Some believe that many asymptomatic patients actually have subtle symptoms In a Scandinavian trial, 191 patients with mild PHPT with mean serum calcium 10.8mg / dl,were randomized to observation or surgery. After the follow up of 2 years, quality of life was not significantly different in the 2 groups. Psychological assessment also showed no difference. However bone density improved at the lumbar spine and the femoral neck, but not at the radius, in the surgical group. Mean serum calcium remained stable in the “observation only” group. Comment: In this RCT, Surgery did not improve quality of life in mild PHPT.
There was a trend for improve BMD with surgery. However these patients on
observation need to have life long monitoring with BP, serum calcium, X-ray KUB
for calculi, intact PTH and BMD estimations on a regular basis.
Ref: Bollerslev J etal ,J Clin Endocrinol Metab 2007May;92;1687-92
4:13 Surgery for undescended testes and risk for testicular cancer – age
Most experts recommend that Orchiopexy should be performed before the age of 2
years, because some research has suggested a link between testicular cancer and
older age at surgery.
In a Swedish study it was found that compared with risk in the general population,
the risk for testicular cancer among those who underwent surgery before age 13 was
increased (RR 2.2). This 2fold increased risk was noted for patients treated at all
ages before 13. After the age of 13, the risk for cancer increased significantly
Comment: These data clearly support the current recommendations that orchiopexy
for undescended testes should be performed during first few years of life.
Ref: Pettersson A etal NEJ Med 2007 May 3;356;1835-41
Insulin Glargine vs Rosiglitazone – Quality of life (QOL) outcomes
In this study, oral Rosi and a single daily injection of insulin glargine as add on
therapy for 217 patients with type 2 DM, whose glycaemic control was inadequate
with metformin and sulphonylurea was compared.
Improvement in QOL at 24 weeks was equal in both groups. However improvements in a total symptoms score and a total symptom distress score were significantly greater in the insulin group than in the Rosi group. Several individual symptoms such as mood, vision and fatigue, also showed greater improvement with the insulin. There were no differences between groups for other symptoms eg: cognitive, neuropathic,cardiovascular. Comment: Add on therapy with insulin glargine, to failed combined metformin +
SU therapy, appears to improve health related QOL to greater extent than
Re: Vinik AI & Zhang Q , Diabetes Care 2007 Apr;30;795-800
Bone loss and glitazones
The Manufacturers of the 2 currently available glitazones – Rosi and Pio have issued
letters to health care providers, warning that these medications may cause an
increased risk of fracture in women
In December 2006, the ADOPT trial reported a higher risk of fractures in diabetic women randomized to Rosi than in women randomized to metformin or glibenclamide. The proportion of women reporting a fracture was 9.3 % for Rosi, 5.1% for metformin 3.5% for glibenclamide (RR=2.18,significant). Among male participants, the fracture distribution was similar across treatments. Pioglitazone also may have negative skeletal effects in women but not in men. Takeda noted that among women the fracture incidence was 1.9 per 100 persons years vs 1.1for those using placebo or anther active drug. Total hip bone density decreased significantly on Rosi within 14 weeks in
postmenopausal women, who were on 18mg/d, in study published in Jan 2007.
Similar observations were found in any women taking a glitazone in the Health ABC
study. Rosi may also cause bone loss in older men.
The mechanism of bone loss is decreased osteoblast function. The Mesenchymal stem cells are increasingly allocated toward adipocytes and differntiation toward osteoblasts is decreased. Low levels of endogenous oestrogen may enhance the negative effect on bone. This contributes to the enhanced bone loss in postmenopausal women. In the ADOPT, where the mean age was 57 years, the annual fracure rate among women was double in Rosi uses vs the glibenclamide group. In an older cohort of diabetic women (average age72 ) the reported fracture rate for Rosi was 50% higher than in the 57 year group. This relative increase in fracture risk is similar to that observed with a 1 SD decrease in bone density. Therefore older postmenopausal women are at the greatest risk for fracture. Re: Schwartz AV & Sellmeyer DE , Diabetes Care Jun 2007;30(6):1670-71
4:16: Understanding bone mineral density reports
The T score compares the patient’ s BMD with that of a young adult
population while the Z score compares it with an age-matched population. For the diagnosis of osteoporosis and assessment of fracture risk, the T score should be used only in postmenopausal women and men older than 50 years. The diagnosis of osteoporosis in healthy pre-menopausal women or healthy men younger than 50 years should not be made on the basis of the BMD result alone. These patients should be compared with age and sex matched databases to derive Z scores. Osteoporosis may be diagnosed if there is a low BMD in the appropriate clinical setting (eg: glucocorticoid therapy, hypogonadism, fragility fracture, hyper parathyroidism) One of the most important numbers in a BMD report is the least significant change (LSC). This is defined as the smallest change that can occur in BMD that we are 95% sure is due to changes in the patient’s BMD and not to machine or patient failure. Only the LSC in absolute BMD (reported as grams per sq cm) should be used for serial comparisons. The average LSC for all technicians and densitometers used in an institution needs to be determined to eliminate the need for patient to be scanned on the same machine, by the same technician, when serial assessments are performed. The absolute changes in BMD greater than the LSC at the site of interest is likely represent a real change in BMD. Undetected compression in the lumbar spine may spuriously elevate the BMD measurement. However, a low T score at 2 or more vertebrae, despite the presence of some degenerative joint disease, may still be of use to the clinician, who can conclude the lumbar spine BMD is the same or worse than the measured value. The fracture risk assessment should be based on several clinical risk factors in addition to BMD. Notable examples include age, prior fragility fracture, history of smoking, chronic steroid use, history of falls and low body weight. Ref: Kennel K A & O’Connor M K Endocrinology Update Mayo Clinic 2006-1(3): 1-
4: 17: When should an ultra sound guided fine needle aspiration cytology
(FNAC) on the thyroid be performed?
US guided FNAC is valuable for small nodules (less than 1.5cm) and essential for all non-palpable nodules, helping to ensure proper needle placement for precise sampling and avoiding cystic areas in complex nodules. It is also helpful to select for biopsy, those nodules which are more likely to be malignant (hypo echoic nodules with microcalcifications, irregular borders, increased vascular flow, greater height than width or rapid growth). Ref: Gharib H et al Endocrinology Update May Clinic 2006 –1(3-4)
4:18 Oestrogen therapy and coronary artery calcification (CAC)
The Women’s Health Initiative (WHI) examined the relationship between oestrogen therapy and CAC. 1064 women aged 50-59 at randomization to either conjugated equine oestrogen (CEO) 0.625mg/d or placebos were studied. 7.4 years of treatment and 1.3years after the trial was completed (8.7years after randomization) CAC scores were measured. The results showed that the CAC was lower among women receiving oestrogen (83vs123). This difference was significant. Ref: NEJ Med 2007;356:2591-202
4:19: What are the sexual functions that are improved by testosterone treatment?
Spontaneous sexual thoughts
Attentiveness to erotic auditory stimuli
Frequency of daytime erections
Duration, magnitude and frequency of nocturnal penile erections
Overall sexual activity scores
Volume of ejaculate
No improvement or insufficient evidence
Erectile response to visual erotic stimulus
Therapeutic response to selective phosphodiasterase inhibitors
Ref: Bhasin S et al Lancet 2007 Feb 17,369:597-611
4:20: A new use of Bisphonate therapy – Idiopathic sporadic tumoral calcinosis
ISTC is a dense, nodular calcareous mass in the peri articular subcutaneous tissue.
This most often occurs around the hips, elbows, shoulders or feet. It consists of
calcium hydroxy apatite crystals surrounded by a foreign body giant cell and
histocytic reaction. Three distinct varieties of ISTC are seen.
b) Metabolic- where calcium x phosphate product is high. (CRF, hypervitaminosis
Bisphosphonates for several months orally may be successful in eradicating the
Ref: Jacob J J et al, Endocrine Practice, 2007 March/April; 13(2): 182-186
Compiled by :- Dr. Henry N. Rajaratnam
MD, FCCP, FRCP (Lond), (Hon) FRACP, (Hon) FSLCGP, FACE
Our Journey through TBI (Traumatic Brain Injury) On June 11, 2006 Gary had come home from working with our brother-in-law Tim when he started to act out of character. I was on the phone with his mum Joan and thought he was playing around with me. Joan said “put him on the phone” But, at that point his face and right side of his body started drooping, he was having a stroke. Joan s