ISSLS PRIZE in Clinical Science 2023: comparison of degenerative MRI features of the intervertebral disc between those with and without chronic low back pain. An exploratory study of two large female populations using automated annotation.

OBJECTIVES: The relationship of degeneration to symptoms has been questioned. MRI detects apparently similar disc degeneration and degenerative changes in subjects both with and without back pain. We aimed to overcome these problems by re-annotating MRIs from asymptomatic and symptomatics groups onto the same grading system. METHODS: We analysed disc degeneration in pre-existing large MRI datasets. Their MRIs were all originally annotated on different scales. We re-annotated all MRIs independent of their initial grading system, using a verified, rapid automated MRI annotation system (SpineNet) which reported degeneration on the Pfirrmann (1-5) scale, and other degenerative features (herniation, endplate defects, marrow signs, spinal stenosis) as binary present/absent. We compared prevalence of degenerative features between symptomatics and asymptomatics. RESULTS: Pfirrmann degeneration grades in relation to age and spinal level were very similar for the two independent groups of symptomatics over all ages and spinal levels. Severe degenerative changes were significantly more prevalent in discs of symptomatics than asymptomatics in the caudal but not the rostral lumbar discs in subjects < 60 years. We found high co-existence of degenerative features in both populations. Degeneration was minimal in around 30% of symptomatics < 50 years. CONCLUSIONS: We confirmed age and disc level are significant in determining imaging differences between asymptomatic and symptomatic populations and should not be ignored. Automated analysis, by rapidly combining and comparing data from existing groups with MRIs and information on LBP, provides a way in which epidemiological and 'big data' analysis could be advanced without the expense of collecting new groups. LEVEL OF EVIDENCE I: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

The Third National Health and Morbidity Survey: prevalence of obesity, and abdominal obesity among the Malaysian elderly population.

Obesity is an emerging public health threat in the elderly population in developing countries. Hence, the Third National Health and Morbidity Survey has assessed 4746 individuals aged 60 years and older recruited through a household survey to determine the prevalence of adiposity using body mass index and waist circumference. The national's prevalence of overweight and obesity in men was 29.2% (95% confidence interval [CI] = 27.2-31.3) and 7.4% (95% CI = 6.4-8.6), respectively. However, the prevalence decreased with age. The figures in women were 30.3% (95% CI = 28.5-32.1) and 13.8% (95% CI = 12.5-15.2), respectively. The prevalence of abdominal obesity was 21.4% (95%CI = 20.2-22.6), with 7.7% (95% CI = 6.7-9.0) in men and 33.4% (95% CI = 31.4-35.3) in women. Predictors of adiposity include the following: Malay and Indian ethnicity, higher education level, higher household income, from urban area, and being married. In conclusion, adiposity affects about one third of the Malaysian elderly population, especially those of the younger age group, women, and those with higher socioeconomic status.

Elevated serum CA 19-9 in association with Hashimoto thyroiditis.

Tumour markers are widely used in clinical practice. Elevated tumour markers can be observed in both malignant and benign conditions. Therefore, it is important for clinicians to be aware of the association of tumour markers with various disorders so that unnecessary investigations can be avoided without missing the malignant disorders. A 58-year-old woman who presented with weight loss and elevated carbohydrate antigen 19-9 (CA19-9) was referred to our hospital for evaluation and was subsequently diagnosed with Hashimoto thyroiditis. Investigations for underlying malignancy were negative. The CA19-9 level normalised subsequently, with restoration of the euthyroid state.

Lower gastrointestinal bleeding: an unusual manifestation of inguinal hernia.

Inguinal hernia is a common condition that usually presents with swelling and mild groin discomfort. Complications include bowel obstruction and strangulation. We report a case of a 50 year-old man who developed lower gastrointestinal bleeding secondary to an indirect inguinal hernia. Colonoscopy showed an ileocecal valve polyp, florid inflammation of cecum and ascending colon and ulcerations of the terminal ileum. Histology showed nonspecific colitis and angiodysplasia of the polyp. Surgical correction of the hernia led to the resolution of the endoscopic changes. The trauma associated with intermittent herniation of small bowel probably led to ischemia, resulting in the observed changes.

A 3 year retrospective review of intrauterine insemination, using cryopreserved donor spermatozoa and cycle monitoring by urinary or serum luteinizing hormone measurements.

Insemination with donor spermatozoa is an integral part of infertility treatment. For the last 3 years in our unit, intrauterine insemination with donor spermatozoa (IUID) has been used in preference to vaginal insemination. In this retrospective study, patients were offered an initial course of five single intrauterine inseminations with cryopreserved donor spermatozoa and treatment was then reviewed. A total of 389 patients received 1465 inseminations. In all, 1119 cycles were monitored using luteinizing hormone serum analyses and 346 cycles using the urine home test kits. The clinical pregnancy rate per insemination for the cycles monitored by the serum assay was 18.0% (202/1119) compared with the urine cycles (13.7%, 46/346) (P <05). The pregnancy loss rate was not significantly different (14.4%, 29/202 and 21.7%, 10/46) (serum and urine cycles respectively). The viable clinical pregnancy rate was significantly higher (P <03) for the serum cycles than for the cycles using the urinary monitoring (15.5%, 173/1119 and 10.4%, 36/346 respectively). The cycles monitored by serum assay had a significantly higher cumulative viable clinical pregnancy rate (P <0001) of 70.2% after nine inseminations compared with the urine monitored cycles of 54.8%. The majority of patients opted for the serum cycles, with a minority self-selecting the urine cycles mainly for travelling convenience. The explanation for the significant differences between the viable clinical pregnancy rates per insemination and the cumulative viable clinical pregnancy rates may be due to the sensitivity of the urine home test kit or the patients' interpretation of the result.

Determination of naltrexone dosage for narcotic agonist blockade in detoxified Asian addicts.

Thirty-eight, adult, male, detoxified, Malaysian opiate addicts participated in this double-blind clinical evaluation of naltrexone. Addicts from three ethnic groups: Chinese, Malays, and Indians received a weekly regimen of naltrexone (100 mg on Days 1 and 3, and 150 mg on Day 5). Subjects were randomly assigned to receive intravenous challenge with either 25 mg heroin or placebo 12, 24, 48, and 72 h after the third naltrexone dose. Physiological and subjective parameters were measured at each challenge interval. Results indicated that naltrexone was effective in blocking the physiological and psychological effects of heroin for at least 48 and 72 h, respectively, in detoxified Malaysian opiate addicts. The efficacy of naltrexone did not differ among the three ethnic groups evaluated in this study.

Multiple-dose pharmacokinetic study of proguanil and cycloguanil following 12-hourly administration of 100 mg proguanil hydrochloride.

A pharmacokinetic study with 12-hourly doses of 100 mg proguanil hydrochloride over 15 days has been conducted in six adult male Malaysian volunteers. Steady state for proguanil was established after the fourth dose on Day 2, for the active metabolite cycloguanil as from Day 3 inclusive. The steady state mean peak concentration of proguanil was 1201.6 +/- 132.4 nmol/l, the mean trough concentration 650.0 +/- 58.1 nmol/l. The corresponding values for cycloguanil were 317.0 +/- 44.4 nmol/l (mean peak) and 230.8 +/- 35.1 nmol/l (mean trough). The profiles and peak/trough ratios of proguanil and cycloguanil with 12-hourly dosing offer better prospects for protection against malaria than those obtained with 24-hourly doses of 200 mg proguanil hydrochloride, the current routine in malaria chemoprophylaxis.

Chemosuppression of malaria by the triple combination mefloquine/sulfadoxine/pyrimethamine: a field trial in an endemic area in Malaysia.

Malaria, particularly that due to chloroquine-resistant Plasmodium falciparum, which requires management with antimalarial drugs capable of protecting against multiresistant strains, has emerged in Malaysia. A study was carried out to assess the efficacy and tolerability of 2 dosages of mefloquine/sulfadoxine/pyrimethamine (MSP; RO 13-5112) compared to Fansidar in a malaria endemic area. 914 subjects in 3 random groups were studied. Occurrence of malaria was assessed both clinically as well as by blood films. Plasma drug levels were also measured. The results showed that the low dose of MSP was completely effective in suppressing parasitaemia. 2.7% of the study population reported adverse drug reactions, the lowest incidence being in subjects on the low dose; their blood chemical profiles were also the least affected. The plasma levels of pyrimethamine and sulfadoxine achieved in the low dose group were slightly higher than expected, but there was no significant difference in bioavailability. The study showed that, for chemoprophylaxis, a low dose of MSP provided effective protection with minimal side effects.

Single dose kinetic study of the triple combination mefloquine/sulphadoxine/pyrimethamine (Fansimef) in healthy male volunteers.

A single dose pharmacokinetic study of a combined antimalarial formulation of mefloquine, sulphadoxine and pyrimethamine (Fansimef) has been performed in 10 healthy adult male Malaysian volunteers. The dose consisted of two tablets containing 250 mg mefloquine base, 500 mg sulphadoxine base and 25 mg pyrimethamine base each. Plasma concentrations of mefloquine and pyrimethamine were measured by GC-ECD, those of sulphadoxine by h.p.l.c. Time to peak concentrations (mean +/- s.d. for mefloquine (5.70 +/- 0.95 h), sulphadoxine (3.75 +/- 2.03 h) and pyrimethamine (3.30 +/- 1.98 h) were similar to those observed by others after administration of the single compounds. This was also true for elimination half-lives (t1/2). The t1/2s for mefloquine, sulphadoxine and pyrimethamine were 387 +/- 98 h, 255 +/- 61 h and 114 +/- 42 h, respectively.

Relative bioavailability of the hydrochloride, sulphate and ethyl carbonate salts of quinine.

The hydrochloride, sulphate and ethylcarbonate salts of quinine were given in single oral doses (600 mg base equivalent) to nine healthy male subjects according to a cross-over design. No statistically significant differences were noted in the plasma drug concentration-time profiles although inter- and intra-subject variation in AUC, Cmax and tmax values was appreciable. The ethylcarbonate salt may be preferred for use in paediatric patients because of its neutral taste.