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P Abraham

Publications and source records attributed to P Abraham.

At least 19 recordsLinked to original sources
PubMed2006

The cost effectiveness of treatment modalities for thyrotoxicosis in a U.K. center.

OBJECTIVE: This study determined the cost effectiveness of treating thyrotoxicosis using thionamide therapy, radioiodine or surgery in the United Kingdom. DESIGN: One hundred thirty-five patients diagnosed with thyrotoxicosis (62% Graves' disease, 7% nodular disease, 5% thyroiditis, and 27% unknown aetiology) referred in 12 months were offered a fully informed choice of treatment modality. Thirteen patients with transient thyrotoxicosis were subsequently excluded from the analysis. Seventy-four patients (61%) received an 18-month course of thionamide therapy, 43 received radioiodine therapy (35%), and 5 had a thyroidectomy (4%) within the first year of diagnosis as their primary treatment. A successful outcome ("cure") was defined as euthyroidism 12 months after thionamide therapy or euthyroidism or hypothyroidism on thyroxine replacement at 24 months following radioiodine or thyroidectomy. Costs were calculated for outpatient attendances, laboratory tests, and initial and subsequent treatments. MAIN OUTCOME: In the thionamide group 73% were "cured" at 30 months after initiating treatment compared to 95% in the radioiodine group and 100% treated by thyroidectomy at 24 months. Cost per "cure" was calculated to be 3,763 pounds (5,644 dollars) per patient who received thionamides, 1,375 pounds (2,063 dollars) per patient given radioiodine and 6,551 pounds (9,826 dollars) per patient who underwent thyroidectomy. CONCLUSION: The most cost-effective primary treatment modality for thyrotoxicosis is radioiodine.

Antithyroid Agents↗
PubMed2006

Validation of a new device for transcutaneous oxygen pressure recordings in real and simulated exercise tests.

AIM: Measurement of transcutaneous oxygen pressure (tcpO2) is of interest in critical limb ischemia at rest and also during exercise in patients suffering proximal claudication or claudication of questionable origin. The recent commercialization of the computerized multiprobe-TCM400 device (Radiometer, Copenhagen, DK) appears attractive for exercise tests but comparison with the previous devices has not been reported. Indeed, the final endpoint for the physician is to be sure that a new apparatus will not interfere with the results observed in patients. METHODS: Using a 5 probe-TCM400 and 5 single probe-TCM3s, simultaneous recordings of tcpO2 were performed: 1) in vitro during 25 simulated exercises and 2) in vivo during exercise treadmill tests in 27 vascular patients. We analyzed resting (REST), minimal absolute (MIN) and DROP (limb-changes minus chest-changes) values. TcpO2 absolute and DROP profiles were analyzed through cross-correlation to detect response delays between the devices. RESULTS: In simulated tests, the Pearson coefficient of correlation between TCM400 and TCM3 was r=0.99 for REST, MIN and minimal DROP. In treadmill tests, the Pearson coefficient of correlation between TCM400 and TCM3 was significantly higher with minimal DROP (r=0.88) than with REST (r=0.63) or MIN (r=0.7). A 15 s delay was observed with TCM3 as compared to TCM400 responses for both tcpO2 and DROP profiles. The rmax(2) of the cross-correlation was 0.74 and 0.67 for tcpO2 and DROP, respectively. CONCLUSIONS: Our observations underline the limits of the clinical in vivo comparison of 2 transcutaneous devices. Despite the differences observed in absolute values during in vivo tests with simultaneous recordings (assumed to rely on physiological and not technical problems), we suggest that TCM400 is valid for exercise tests with the advantage of improved user interface, automatic memorization and integrated multiple probes of this newly commercially available apparatus.

Blood Gas Monitoring, Transcutaneous↗
PubMed2005

Crossed retroperitoneal approach to the internal iliac artery: a preliminary anatomical study.

The internal iliac arteries (IIA), and especially the distal segment, course very deep in the pelvis and are generally difficult to access surgically. The recent development of simple and reliable methods to investigate proximal ischemia of the lower extremities has led to discovery of more candidates for elective revascularization of the IAA. The classic approaches to the IAA, i.e., the transperitoneal and homolateral retroperitoneal routs have certain disadvantages. We present a new crossed retroperitoneal approach to the IAA and the results of such method in six cadavers. In all six cases, the entire IAA could be exposed without any particular problems. This novel approach to the IAA seems to be both simple and reproducible.

Aged↗
PubMed2005

Structure-activity relationship of trihexyphenidyl analogs with respect to the dopamine transporter in the on going search for a cocaine inhibitor.

A series of trihexyphenidyl (THP) analogs were used to search for a derivative that could serve as a cocaine inhibitor. A compound that blocks binding of the cocaine analog carboxyfluorotropane (CFT), allows dopamine uptake and exhibits low side effects could serve as a good candidate for that purpose. All analogs were tested for the extent to which they inhibit CFT binding, dopamine uptake and n-methyl scopolamine (NMS) binding. Several structure-function relationships emerged. Methylation/halogenation of THP's benzene ring enhanced the compound's ability to block CFT binding in comparison to its ability to block dopamine uptake (5a-e). Replacement of the cyclohexyl ring with a benzene ring tended to create compounds that had lower affinities to the dopamine transporter (7b compared to THP, 7d compared to 5h, 7c compared to 8c) and modification of THP's piperidine ring tended to enhance affinity to the dopamine transporter (5f-h, 8a, 8c). One analog (5f) that showed little muscarinic activity indicating that it would probably have few side effects was investigated for its effects as an in vivo cocaine inhibitor. However, it showed few antagonistic effects in vivo. Nevertheless, this work greatly elucidates the structure-function relationships required for potential cocaine inhibitors and so lays out promising directions for future research.

Carbonic Anhydrase Inhibitors↗
PubMed2005

Cathodal current-induced vasodilation to single application and the amplified response to repeated application in humans rely on aspirin-sensitive mechanisms.

Assumed to rely on an axon reflex, the current-induced vasodilation (CIV) interferes with the microvascular response to iontophoretic drug delivery. Mechanisms resulting in CIV are likely different at the anode and at the cathode. While studies have been conducted to understand anodal CIV, little information is available on cathodal CIV. The present study investigates CIV observed following 0.1-mA cathodal applications on forearms of healthy volunteers and the possible mechanisms involved. Results are expressed in percentage of the cutaneous heat-induced maximal vascular conductance [%MVC (means +/- SE)]. 1) The amplitude of CIV was proportional to the duration of cathodal currents for periods of <1 min: r = 0.99. 2) Two current applications of 10 s, with 10-min interstimulation interval, induced a higher peak value of CIV (79.1 +/- 8.6% MVC) than the one obtained with all-at-once 20-s current application (39.5 +/- 4.3% MVC, P < 0.05). This amplified vascular response due to segmental application was observed for all tested interstimulation intervals (up to 40 min). 3) Two hours and 3 days following pretreatment with 1-g oral aspirin, the CIV observed following cathodal application, as well as the difference of cathodal CIV amplitude between all-at-once and segmented applications, were reduced. These findings suggest a role of prostaglandins, not only released from endothelial or smooth muscle cells, as direct vasodilator and/or as a sensitizer. Thus aspirin pretreatment could be used to decrease CIV resulting from all-at-once and repeated cathodal application and facilitate the study of the specific vascular effect induced by the drug delivered.

Administration, Oral↗
PubMed2005

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: July 2004. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Twenty-three randomised trials involving 3115 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% versus 58%) than six month therapy (Odds ratio (OR) 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR 0.75, 95% CI 0.39 to 1.43). Twelve trials examined the effect of Block-Replace versus Titration regimen. The relapse rates were similar in both groups at 51% in the Block-Replace group and 54% in the Titration group (Peto OR 0.86, 95% CI 0.68 to 1.08). Participants reporting rashes (10% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine with continued low dose antithyroid therapy after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio 0.58, 95% CI 0.05 to 6.21). Four studies considered the addition of thyroxine alone after initial therapy with antithyroid drugs. There was no significant difference in the relapse rates between the groups after 12 months follow-up with relapse rates being 31% (88/282) with thyroxine and 29% (82/284) with placebo (Peto OR 1.15, 95% CI 0.79 to 1.67). AUTHORS' CONCLUSIONS: The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. The incidence of hypothyroidism was not reported and there were no deaths reported in the study populations.

Antithyroid Agents↗
PubMed2005

Physiological effects of indomethacin and celecobix: an S-transform laser Doppler flowmetry signal analysis.

Conventional signal processing typically involves frequency selective techniques which are highly inadequate for nonstationary signals. In this paper, we present an approach to perform time-frequency selective processing of laser Doppler flowmetry (LDF) signals using the S-transform. The approach is motivated by the excellent localization, in both time and frequency, afforded by the wavelet basis functions. Suitably chosen Gaussian wavelet functions are used to characterize the subspace of signals that have a given localized time-frequency support, thus enabling a time-frequency partitioning of signals. In this paper, the goal is to study the influence of various pharmacological substances taken by the oral way (celecobix (Celebrex), indomethacin (Indocid) and placebo) on the physiological activity behaviour. The results show that no statistical differences are observed in the energy computed from the time-frequency representation of LDF signals, for the myogenic, neurogenic and endothelial related metabolic activities between Celebrex and placebo, and Indocid and placebo. The work therefore proves that these drugs do not affect these physiological activities. For future physiological studies, there will therefore be no need to exclude patients having taken cyclo-oxygenase 1 inhibitions.

Administration, Oral↗
PubMed2005

Systematic diagnostic approach to proximal-without-distal claudication in a vascular population.

BACKGROUND: Very few observations of proximal-without-distal claudication have been reported in the literature. This is likely due to the use of questionnaires limiting vascular claudication to the calves and to the problems encountered in attributing unexplained "buttock" claudication to a vascular origin. METHODS: During a 2 1/2-year period, we searched for proximal-without-distal exercise-related pain with the San Diego claudication questionnaire among some 2000 patients referred for lower limb arterial investigations. Of these patients, 97 presented no contraindication to treadmill testing and were investigated with exercise transcutaneous oxygen pressure (tcpO2). We used buttock tcpO2 (DROP index<-15 mm hg) to argue for the presence of ischemia on the corresponding side. RESULTS: Ischemia consistent with symptoms was found in 61 patients, whereas pain on one or both sides without underlying ischemia was found in 36 patients, suggesting a non-arterial origin of the symptoms. More than half of the patients with proximal-without-distal claudication and underlying exercise-related ischemia had been suffering for more than 2 years before they were referred to the laboratory. Eleven of the patients were treated. The treatment was successful in all but one of them. CONCLUSIONS: An important delay before diagnosis is frequently observed in proximal-without-distal claudication. TcpO2 is useful in attributing proximal exercise-related pain to a vascular origin. Given the number of detected and successfully treated patients in this small monocentric study, it is surprising that so few observations have been published to date, suggesting that proximal-without-distal arterial claudication is most likely an underestimated diagnosis.

Journal Article↗
PubMed2005

[Results of surgical treatment for renal artery dysplasia].

PURPOSES: To retrospectively assess functional results of surgical treatment for renal artery dysplasia. PATIENTS AND METHOD: From January 1992 to December 2001, 11 symptomatic patients including 9 women (mean age 47 years, range 23-67), underwent surgery for renal artery dysplasia. Three patients presented with normalized hypertension, three others presented with isolated systolic hypertension, and the five remaining presented with grade II or III hypertension. Angiograms showed evidence of dysplasia of 16 renal arteries. Six arteries showed stenosis (37.5%), four aneurysms (25%), four both (25%), and two arteries showed wall irregularities (12.5%). Endovascular revascularizations were performed in five patients (45%) during the treatment of six renal arteries (37.5%). All endovascular procedures were angioplasties without any stent placement. Six patients (55%) underwent conventional procedures (in situ or ex-situ surgery) for the treatment of seven renal arteries (44%). RESULTS: In the short term, the treatment had a significant decrease on the systolic arterial pressure (p=0.019) and in the number of drugs used (p=0.009), but was not significant in the diastolic arterial pressure (p=0.084). The benefits persisted after two years of follow-up (PAS, p=0.023, PAD, p=0.047, drugs p=0.03). Benefits persisted in all of the six patients who had had hypertension for less than five years. There was 60% functional failure in the treatment of the five patients with a more than five years history of hypertension. CONCLUSION: This study confirms the short and long term's beneficial results of the surgical treatment of symptomatic renal artery dysplasia. Rapid care of those patients should optimize the functional results.

Adult↗
PubMed2005

Transcutaneous oxygen pressure measurements (tcpO2) at ankle during exercise in arterial claudication.

AIM: Although a time consuming technique, tcpO2 provides complementary information as compared to other tests. Simultaneous recording of systemic and peripheral oxygen pressure changes with exercise could be interesting to confirm that local hypoxemia is of arterial origin, but accuracy versus gold standard arteriography and objectively determined cut-off points to be used in arterial claudication at the ankle are not reported. METHODS EXPERIMENTAL DESIGN: retrospective plus prospective study. SETTING: institutional practice, ambulatory care. PATIENTS: 100 patients suffering stage 2 claudication (group A) were retrospectively studied to objectively define cut-off points derived from tcpO2 recordings to be used in exercise testing. Then, applicability and reproducibility of these cut-off points were analysed prospectively in another 50 patients (group B). INTERVENTION: tcpO2 was measured on both calves and with a chest reference electrode. Arteriography on each side was quoted positive for a diameter stenosis superior to 75% or occlusion on the aorto-popliteal axis or of all-3-calf arteries. RESULTS: The best performance was obtained with tcpO2 changes from rest at the calf normalised to eventual chest changes (DROP) during or following the treadmill test. Optimal cut-off point determined through ROC curve analysis for DROP was -15 mmHg in group A. Applying this cut-off point in group B provided a 86/84% sensitivity/specificity and showed excellent reproducibility. CONCLUSIONS: TcpO2 measurement on the calf during exercise could be useful in a selected population of patients with claudication of questionable vascular origin and/or when other non-invasive investigations cannot be performed.

Aged↗
PubMed2005

A pilot study for serological evidence of hantavirus infection in human population in south India.

BACKGROUND AND OBJECTIVES: Hantaviruses are rodent-borne viruses of the family Bunyaviridae that have been identified as aetiological agents of two human diseases, haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). There are no reports of hantavirus infections in humans from India, hence this pilot study was undertaken to provide the serological evidence of hantavirus infections in humans in south India. METHODS: Serum samples were obtained from individuals with acute febrile illness and from voluntary blood donors, majority of whom were from south India. Serum samples were tested for anti-hantavirus IgM using a commercial enzyme immunoassay (EIA). Samples found positive by the EIA were tested by an indirect immunofluorescence assay (IFA) using slides coated with Seoul virus (SEOV) infected cells as substrate. RESULTS: Of the 152 serum samples from individuals with pyrexic illness, 23 (14.7%) were positive for anti-hantavirus IgM by EIA. In contrast, only 5.7 per cent of healthy blood donors were positive by this assay. Eighteen of the 22 (82%) EIA-positive samples from patients were positive by the IFA assay. In contrast, only 2 of the 5 (40%) blood donor EIA positive samples were positive in the IFA assay. INTERPRETATION AND CONCLUSION: The finding of this study indicated the possible presence of hantavirus infections in the human population of India presenting both as asymptomatic and symptomatic infections. Further studies need to be done to confirm the findings on a larger sample using molecular techniques.

Fluorescent Antibody Technique, Indirect↗
PubMed2004

Prostaglandins participate in the late phase of the vascular response to acetylcholine iontophoresis in humans.

The participation of prostaglandins (PGs) in the cutaneous vasodilatation to acetylcholine (ACh) applied via iontophoresis is under debate. Using laser Doppler flowmetry, we studied the long lasting effect (20 min) of iontophoretic application (30 s; 0.1 mA) of ACh on the human forearm. Experiments were repeated (1) using deionized water instead of ACh to test the effect of current application, (2) after scopolamine treatment to inhibit muscarinic cholinergic receptors, and (3) 2 h, 3 days and 10 days following inhibition of PG synthesis with aspirin or a placebo control. Cutaneous vascular conductance (CVC) was calculated at rest (CVC(rest)), at peak vasodilatation in the first 5 min following ACh iontophoresis (CVC(peak)), and 20 min after iontophoresis (CVC(20)). The minimal CVC (CVC(min)) following iontophoresis was also determined. Cutaneous response to ACh displayed a biphasic pattern with an early and transient peak (CVC(peak): 62 +/- 8% of the maximal CVC induced by local heating (MVC)) followed by a long lasting slower vasodilatation (CVC(min): 44 +/- 6; CVC(20): 56 +/- 5%MVC). The current itself had no major effect. Scopolamine almost abolished both phases. The long lasting phase was aspirin sensitive but not the transient phase. At hour 2 post-aspirin, CVC(peak) was 61 +/- 10, CVC(min) 26 +/- 6 and CVC(20) 29 +/- 6%MVC. At day 3, CVC(peak) was 53 +/- 9, CVC(min) 22 +/- 3 and CVC(20) 25 +/- 4%MVC. At day 10, CVC(peak) was 67 +/- 10, CVC(min) 47 +/- 7 and CVC(20) 50 +/- 8%MVC. Placebo had no effect. We conclude that PGs participate in the vasodilator response following ACh iontophoresis. Previous non-steroidal anti-inflammatory drug treatments must be taken into account when studying the effect of ACh iontophoresis.

Acetylcholine↗
PubMed2004

Anodal current intensities above 40 microA interfere with current-induced axon-reflex vasodilatation in human skin.

When using iontophoresis, the 'non-specific' vasodilatation (NSV) that is observed as a result of C-fibre excitation is generally attributed to the local accumulation of protons under the anode. NSV following prolonged 100-microA anodal current application only appears after the current is stopped. Break excitation alone does not explain the delayed onset of this vasodilatation. We hypothesised that this delay could result from an anodal block and thus, that a minimal intensity would be required to achieve hyperpolarisation of primary afferent fibres (mainly C-fibres). Using laser Doppler flowmetry, cutaneous blood flow was recorded in the forearms of 8 healthy volunteers 2 min before current application, during the application and 20 min after stopping the monopolar anodal current. In protocol 1, after 2.5 min of current application at an intensity of 100 microA, the intensity was abruptly decreased to 0-80 microA for a second 2.5-min period. The onset of vasodilatation was only delayed at intensities >30 microA during this second period. In protocol 2, re-application of the current after a 50-second interruption (expected to allow for the occurrence of an axon reflex) did not interfere with the onset of vasodilatation. Thus: (1) the minimal intensity interfering with the axon reflex is far lower than that reported for C-fibre blockade in isolated nerves; (2) the results suggest that current application does not directly interfere with the vasodilator mechanisms induced by the axon reflex at the level of smooth muscle cells.

Adult↗
PubMed2004

Effects of murine-derived anti-methamphetamine monoclonal antibodies on (+)-methamphetamine self-administration in the rat.

Two murine-derived anti-methamphetamine monoclonal antibodies were studied as potential pharmacokinetic antagonists of (+)-methamphetamine self-administration by rats. Intravenous administration of a 1 g/kg dose of the lower affinity [antibody equilibrium dissociation constant (K(d)) = 250 nM] monoclonal antibody (mAb) designated mAb6H8, 1 day before the start of several daily 2-h self-administration sessions produced effects that depended on the dose of (+)-methamphetamine. mAb6H8 increased the rate of self-administration of a unit dose of 0.06 mg/kg (+)-methamphetamine, had little effect on the rate of self-administration of a unit dose of 0.03 mg/kg (+)methamphetamine, and lowered the rate of self-administration of a unit dose of 0.01 mg/kg (+)-methamphetamine to a level similar to that after saline substitution. mAb-induced changes in rates of self-administration occurred very early in self-administration sessions and lasted for 3 to 7 days. Intravenous administration of a 1 or a 0.6 g/kg dose of a higher affinity (K(d) = 11 nM) mAb designated mAb6H4, 24 h before the first of several self-administration sessions, produced very similar effects to the lower affinity mAb, despite the more than 20-fold greater affinity for (+)-methamphetamine. It is proposed that these anti-methamphetamine antibodies bind some of the self-administered (+)-methamphetamine before it can penetrate into brain, thereby reducing the amount of free drug available to function as a reinforcer. Although neither of these mAb medications are optimal antibodies for treating (+)-methamphetamine abuse, the experiments demonstrate that anti-(+)-methamphetamine monoclonal antibodies can attenuate the self-administration of the drug and suggest the potential of using monoclonal antibodies as pharmacokinetic antagonists of (+)-methamphetamine.

Adrenergic Agents↗
PubMed2004

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWERS' CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.

Antithyroid Agents↗