Drug non-adherence and associated risk factors among Chinese geriatric patients in Hong Kong.

OBJECTIVES: To study the prevalence of drug non-adherence among Chinese elderly people and its associated risk factors. DESIGN: Cross-sectional survey. SETTING: Medical and Geriatrics specialist out-patient clinic in a regional hospital. PATIENTS: Elderly patients (> or =65 years) with chronic diseases requiring regular medications were selected by systematic sampling. MAIN OUTCOME MEASURES: Drug non-adherence; potential risk factors studied include patients' factors, availability of assistance, and prescription factors. RESULTS: Two hundred and nine elders participated with 84% response rate. Estimated mean prevalence rate of drug non-adherence was 37% (standard deviation, 7%). The risk factors for drug non-adherence were: (1) self-perceived adverse drug effects (odds ratio=2.5; 95% confidence interval, 1.2-5.2; P=0.017); (2) use of respiratory drugs (2.7; 1.0-7.5; P=0.048); (3) complicated drug regimens (7.4; 3.2-16.9; P<0.001); and (4) necessity to cut tablets (4.8; 2.1-10.7; P<0.001). Presence of caregiver/community nursing services assistance to pack medication (odds ratio=0.2; 95% confidence interval, 0.1-0.5; P=0.001), and the use of medication boxes (0.5; 0.3-1.0; P=0.050) were found to be the protective factors against drug non-adherence. CONCLUSION: Drug non-adherence is an important concern in patient management. Medication regimen should be simplified as far as possible, in particular to avoid cutting pills or use of different dosage at different timing. Patients receiving drugs for respiratory diseases should be the first target group for intervention. Patients should be encouraged to voice out their perceived adverse drug effects.

Laparoscopic repair of perforated duodenal ulcers: the"three-stitch" Graham patch technique.

BACKGROUND: "Three-stitch" laparoscopic Graham patch repair (LGPR) for perforated duodenal ulcer enjoyed the same advantage as open Graham patch repair. However, it was not a popular approach because it had problems of suture entanglement and difficult laparoscopic suturing and knotting. The authors describe their technique and results. METHODS: A prospective series from January 2000 to September 2004 was examined. In this study, 35 LGPRs were performed for 32 males and 3 females with a median age of 47 years (range, 18-76 years). RESULTS: No conversion occurred for any of the 35 LGPRs attempted. The median perforation size was 5 mm (3-10 mm), and the median operative time was 86 min (range, 55-163 min). The median time for ambulation was day 2, and the median time for discharge was day 4. Morbidity was 11%, involving one chest infection, one retention of urine, one pelvic collection, and one pyloric stenosis. There was no reoperation, leakage, or mortality. CONCLUSION: The authors' LGPR technique was safe and efficient, and might be the choice for laparoscopic repair of relatively large perforations.

Epithelioid schwannoma of the vestibular nerve.

Epithelioid schwannomas are rarely encountered intracranially, with only four cases involving the eighth nerve reported in the literature. Histological behaviour ranging from benign to aggressive has been described. We report a 45-year-old woman who presented with right-sided tinnitus and hearing impairment. Magnetic resonance imaging revealed a tumour in the right cerebellopontine angle with intracanalicular extension. The patient underwent retromastoid craniectomy with near-total tumour excision. Microscopical examination confirmed the diagnosis of epithelioid schwannoma of the vestibular nerve. Intraoperative findings of sharp circumscription, bland histological appearance, low proliferative activity, coupled with the indolent clinical course, point to the quiescent nature of the lesion in this case.

Clinical performance of computer-assisted detection (CAD system in detecting carcinoma in breasts of different densities.

OBJECTIVES: To determine the clinical performance of a computer-assisted detection (CAD) system in detecting carcinoma in breasts of different densities. MATERIALS AND METHODS: A total of 264 sets of bilateral screening mammograms taken in craniocaudal and medial-lateral oblique projections during the year 1997 were divided into four groups according to the BI-RADS density classification: fatty (pattern 1), scattered fibroglandular (pattern 2), heterogeneously dense (pattern 3) and extremely dense (pattern 4). Each group contained about 60% normal and 40% biopsy-proven cancer cases. Of the malignant cases, there were a mixture of mammographic findings including focal masses (<2.5 cm), asymmetrical density, architectural distortion or microcalcifications. Films with artefacts and obvious masses>2.5 cm were not included. The chosen cases were then digitized and analysed by the CAD system. Sensitivity was calculated as detection of cancer by at least one marker in at least one view. Specificity was calculated as the number of false-positive marks per image on normal cases. Statistical tests of significance were performed by using contingency tables and Chi square test. RESULTS: The CAD system detected 14 out of the total 15 cancer cases in totally fatty breasts with a sensitivity of 93.3% at a specificity of 1.3 false-positive marks per image. In breasts with scattered fibroglandular pattern, the sensitivity was 93.9% (31/33) and the specificity was 1.6 false-positive marks per image while in heterogeneously dense breasts, the sensitivity of the CAD system fell to 84.8% at a specificity of 1.6 false-positive marks per image. The sensitivity of the CAD system further dropped to 64.3% in markedly dense breasts while maintaining a specificity of 1.2 false-positive marks per image. The decrease in sensitivity in dense breast was found to be significant (p=0.046). CONCLUSION: The sensitivity of the CAD system deteriorated significantly as the density of the breast increased while the specificity of the system remained relatively constant.

Complex salvage procedures for severe lower extremity nerve pain.

From 1995 to 1999, the senior author did revision nerve release and vein wrapping (58 limbs in 58 patients) or peripheral nerve stimulation (62 limbs in 62 patients) to relieve intractable lower extremity nerve pain. Vein wrapping was done if the patient had temporary relief after a previous nerve release, if there was evidence of scarring around the nerve, and if nerve pain was triggered by mechanical stimulation. Peripheral nerve stimulation was done when previous nerve operations provided no relief or if the nerve pain was more constant and spontaneous without mechanical provocation. The duration of symptoms preoperatively averaged 52 months, and the number of previous peripheral neurosurgical interventions averaged 2.5. Postoperatively, the average pain improvement was rated as 60% for the patients who had vein wrapping and 41% for the patients who had peripheral nerve stimulation. Of the patients who had vein wrapping, 53% were satisfied, 14% were somewhat satisfied, and 33% were dissatisfied. Of the patients who had peripheral nerve stimulation, 61% were satisfied, 21% were somewhat satisfied, and 18% were dissatisfied. Most patients (78%) stated they would undergo the procedures again.

Surgical treatment of chronic lower extremity neuropathic pain.

The current authors retrospectively reviewed 147 lower extremity peripheral nerve procedures in 114 patients (average age, 42 years) with chronic lower extremity neuropathic pain to determine whether surgical treatment based on an empirically derived algorithm could reduce pain and improve function. This algorithm assigns crush, stretch, and chronic transection injuries to treatment with transection and containment. Peripheral nerve stimulation was used in conjunction with transection and containment for patients with more chronic presentations for whom previous transections had been unsuccessful. Patients with adhesive neuralgia underwent revision neurolysis with vein wrapping. Patients with repetitive nerve trauma (overuse) underwent primary or revision neurolysis. Duration of symptoms averaged 37 months, and mechanisms of nerve injury included chronic transection, crush, adhesive neuralgia, stretch, repetitive trauma, and idiopathic etiology. Time to followup averaged 38 months. Pain and dysfunction were ranked from 0 points (no pain or dysfunction) to 10 points (pain prompting request for amputation or functional deficit warranting wheelchair use); preoperative and followup work status were documented. Average pain and dysfunction scores improved: 8.8 to 5.6 points and 7.6 to 5.0 points, respectively. Of the 114 patients, 52 (46%) patients improved their work status, including 35 of 87 (40%) involved in workers' compensation. There were no statistically significant differences in outcome based on mechanism of nerve injury or type of procedure. The consistent average improvement suggests this algorithm assigns the appropriate procedure to a given mechanism of injury.

Early-onset colorectal cancer with stable microsatellite DNA and near-diploid chromosomes.

Colorectal cancer has been described in terms of genetic instability selectively affecting either microsatellite sequences (MIN) or chromosome number and structure (CIN). A subgroup with apparently stable, near-diploid chromosomes and stable microsatellites (MACS) also exists. These distinctions are important, partly because of their value in highlighting different pathways of carcinogenesis, and partly because of their direct relevance to prognosis. Study of early-onset cancer has often proved a fruitful resource for the identification of the nature and function of cancer susceptibility genes. In a study of colorectal cancer with stable microsatellite DNA, we describe 22 early-onset tumours (mean age=33), compared with 16 late-onset tumours (mean age=68). Both groups contained carcinomas with the MACS phenotype, characterized by near diploid DNA content, as defined by flow cytometry, and minimal chromosome arm deletion or amplification (six or less events per genome), determined by comparative genomic hybridization (CGH). Minimal chromosome imbalance correlated strongly with diploid DNA content (P<0.001). The proportion of MACS cancers was significantly greater in early-onset as compared to late-onset tumours (64 vs 13%, P=0.005). Of the chromosome arm imbalances commonly observed in late-onset tumours, only 18q- was observed more than twice amongst the 14 early-onset MACS tumours. Seventy-nine per cent of these MACS tumours were located in the distal colon, and 69% were at advanced clinico-pathological stages (with lymph node or distant metastasis). A positive family history of colorectal or other cancers was elicited in seven patients in the MACS early-onset group, and one additional patient in this group had a metachronous ovarian cancer. The results suggest that MACS cancer may have a genetic basis different from either MIN or CIN, and further studies of these cancers may lead to discovery of new mechanisms of colorectal carcinogenesis and cancer susceptibility.

Subtalar distraction bone block arthrodesis.

This retrospective study analyses the results of subtalar bone block distraction arthrodesis used in the treatment of late complications of calcaneal fractures, acute severely comminuted fractures, nonunion (and malunion) of attempted subtalar arthrodeses, avascular necrosis of the talus, and club-foot deformity. Of 39 patients (41 feet) who had this procedure, 35 (37 feet) returned for follow-up after a mean of 70 months (26 to 140). There were 24 men (25 feet) and 11 women (12 feet) with a mean age of 41 years (16 to 63). Each completed a standardised questionnaire, based on the hindfoot-scoring system of the American Orthopaedic Foot and Ankle Society and were reviewed both clinically and radiologically. Of the 37 operations, 32 (87%) achieved union. The mean hindfoot score (maximum of 94 points) increased from 21.1 points (8 to 46) preoperatively to 68.9 (14 to 82) at the final follow-up. The mean talocalcaneal and calcaneal pitch angles were 20.5 degrees and 4.9 degrees before operation, 25.9 degrees and 8.3 degrees immediately after, and 24.6 degrees and 7.7 degrees at the final follow-up, respectively. The mean talar declination angle improved from 6.5 degrees (-10 to 22) before operation to 24.8 degrees (14 to 32) at the final follow-up. The mean talocalcaneal height increased from 68.7 mm before operation to 74.5 mm immediately after and 73.5 mm at the final follow-up. Of the 37 arthrodeses available for review, 32 were successful; 29 patients (30 arthrodeses) were satisfied with the procedure. Minimal loss of hindfoot alignment occurred when comparing radiographs taken immediately after operation and at final follow-up.

A novel germline 1.8-kb deletion of hMLH1 mimicking alternative splicing: a founder mutation in the Chinese population.

We have previously reported that there is a high incidence of microsatellite instability (MSI) and germline mismatch repair gene mutation in colorectal cancer arising from young Hong Kong Chinese. Most of the germline mutations involve hMSH2, which is different from the mutation spectrum in the Western population. It is well known that alternative splicing is common in hMLH1, which complicates RNA based mutation detection methods. In contrast, large deletions in hMLH1, commonly observed in some ethnic groups, tend to escape detection by exon-by-exon direct DNA sequencing. Here we report the detection of a novel germline 1.8 kb deletion involving exon 11 of hMLH1 in a local hereditary non-polyposis colorectal cancer family. This mutation generates a mRNA transcript with deletion of exons 10-11, which is indistinguishable from one of the most common and predominant hMLH1 splice variants. A diagnostic test based on PCR of the breakpoint region led to the identification of an additional young colorectal cancer patient with this mutation. Haplotype analysis suggests that they may share a common ancestral mutation. Our results caution investigators in the interpretation of alternative splicing and have important implications for the design of hMLH1 mutation detection strategy in the Chinese population.

Distinct clinical features associated with microsatellite instability in colorectal cancers of young patients.

The Hong Kong Chinese population has an unusually high incidence of colorectal cancer in the young, suggestive of hereditary susceptibility. To search for a genetic basis for this predisposition, we studied the incidence of microsatellite instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50 years old) Chinese colorectal cancer patients referred to the Hong Kong Hereditary Gastrointestinal Cancer Registry from 1995 to 1998. By medical record review and personal interview, we searched for distinct clinical features associated with the manifestation of MSI in this group of patients. For patients with MSI tumours, blood was taken for detection of germline mutation in 2 mismatch repair (MMR) genes. MSI was present in 33 tumours from 23 males and 10 females (26.6%). Ongoing mutation analysis has so far identified MMR gene mutations in 8 patients with MSI tumours. The incidence of MSI increased significantly with decreasing age at cancer diagnosis. For patients aged 30 to 49, MSI tumours were located mainly at the proximal colon. However, for exceptionally young patients (<30 years), MSI tumours tended to be at the distal large bowel. This observation suggested a differential activity of the MMR pathway in colorectal carcinogenesis in different age groups. On multivariate analysis, young age at cancer diagnosis, proximal tumour location, a strong family history of colorectal cancer, and a personal history of metachronous cancer were independent predictors for MSI status. This knowledge may have an impact on the management of young colorectal cancer patients and their families.

Tibiocalcaneal arthrodesis for the management of severe ankle and hindfoot deformities.

PURPOSE: The purpose of this investigation was to evaluate the outcome of tibiocalcaneal arthrodesis using an adolescent condylar blade plate for severe ankle and hindfoot deformities. MATERIALS AND METHODS: We retrospectively reviewed the records of patients managed at our institutions between 1989 and 1996 whose tibiocalcaneal arthrodeses were performed with adolescent condylar blade plates and allograft bone. In these 30 patients (14 men, 16 women; average age, 53 years), the etiologies of the nonbraceable deformity included: diabetic neuroarthropathy with talar fragmentation and resorption (26), inflammatory arthritis (3), and posttraumatic avascular necrosis of the talus with collapse (1). Due to the severity of the deformity in 28 of these patients, the alternative treatment would have been amputation. Thirteen patients had undergone previous surgeries, eight had documented osteomyelitis, and 13 had ulcers ranging from 2 to 27 mm. At surgery, the remnants of the talus were removed. Morcellized bone graft mixed with tobramycin/vancomycin powder was inserted into the arthrodesis site and then fixed with a rigid plate. Intravenous antibiotics, followed by oral antibiotics, were given until wound healing and suture removal. Follow-up averaged 48 months (19 to 112 months). RESULTS: Tibiocalcaneal fusion was achieved in 28/30 patients at an average of 16 weeks (12 to 18 weeks). Complications occurred in seven patients: two developed stress fractures of the tibia at the proximal end of the blade plate, three had superficial cellulitis that resolved with antibiotic therapy, and two had nonunions. CONCLUSION: Tibiocalcaneal arthrodesis using an adolescent condylar blade plate and allograft bone can be a successful procedure in the patient with severe neuropathic ankle deformity and can achieve a stable plantigrade foot for limited community ambulation with relatively few complications.

The C282Y mutation of the HFE gene is not found in Chinese haemochromatotic patients: multicentre retrospective study.

OBJECTIVE: To detect two novel mutations (C282Y and H63D) of the HFE gene in Chinese patients with hepatic iron overload. DESIGN: Multicentre retrospective study. SETTING: Four public hospitals, Hong Kong. PARTICIPANTS: Fifty Chinese patients who presented from January 1987 through December 1999 with hepatic iron overload from various causes. MAIN OUTCOME MEASURES: The DNA from liver biopsy samples was tested for HFE mutations by restriction fragment length polymorphism analysis. RESULTS: The sample DNA quality was unsatisfactory for analysis of the C282Y mutation in one case and the H63D mutation in nine cases. The C282Y mutation was not detected in any of the 49 satisfactory samples. Three of the 41 samples were heterozygous for the H63D mutation and only one was homozygous, giving an allele frequency of 6.1%. Of the three H63D-heterozygotes, one had beta-thalassaemia major, one had beta-thalassaemia minor, and one had hereditary spherocytosis. None of the 12 patients who were presumed to have primary haemochromatosis were positive for either mutation. CONCLUSIONS: The classical form of human leukocyte antigen-linked hereditary haemochromatosis appears to be absent form this locality. The H63D mutation is found in a minority (9.8%) of the patients, in whom it may act synergistically with an erythropoietic factor.

Fine-needle aspiration cytologic diagnosis of intrahepatic biliary papillomatosis (intraductal papillary tumor): report of three cases and comparative study with cholangiocarcinoma.

Biliary papillomatosis is a rare tumor of the intrahepatic and extrahepatic biliary tree, and its FNA findings have not been reported. The cytologic features of 3 cases of intrahepatic biliary papillomatosis were studied and compared with 5 cases of cholangiocarcinoma. The distinctive features include: 1) hypercellular smear, 2) very broad and often double-cell layered sheets of ductal columnar epithelium, 3) papillary configuration, 4) preserved honeycomb pattern with even nuclear spacing, and 5) dysplastic but not frankly malignant nuclear features. The constellation of these features is highly characteristic of biliary papillomatosis and helpful in distinguishing it from cholangiocarcinoma and other differential diagnoses. A firm preoperative diagnosis can thus be achieved, allowing better planning in management of this borderline malignant tumor.

Nasal pleomorphic adenoma with skeletal muscle differentiation: potential misdiagnosis as rhabdomyosarcoma.

Pleomorphic adenoma can show diverse lines of differentiation in the epithelial and myoepithelial elements, such as cartilage, bone, and fat. Myoid differentiation, however, has not been documented. We report an unusual case of nasal pleomorphic adenoma which shows focal skeletal muscle differentiation. The tumor was discovered only after successful radiation therapy for an undifferentiated carcinoma of the nasopharynx. Apart from being of morphological interest, the presence of cells with skeletal muscle differentiation also raises the practical issue of possible confusion with rhabdomyosarcoma in a biopsy. The distinguishing features are lack of cytological atypia and presence of a neoplastic glandular element.

Clinics in diagnostic imaging (15). Carotid body tumour.

A 30-year-old Chinese woman presented with an enlarging pulsatile swelling in the left neck. A similar right neck mass was excised 2 years previously. Digital subtraction angiography showed a well-defined, hypervascular tumour situated at the left common carotid arterial bifurcation, typical of a carotid body tumour. Complete resection of the second carotid body tumour was achieved. The clinical and imaging features of this tumour are described.

Fibrosing cholestatic hepatitis in renal transplant recipients.

Fibrosing cholestatic hepatitis in a specific histologic manifestation of hepatitis B virus infection consisting of periportal fibrosis, hepatocyte ballooning, cholestasis, a relatively scant inflammatory infiltrate, and marked overexpression of hepatitis B viral antigens in hepatocytes. Until recently, fibrosing cholestatic hepatitis had been reported only in recipients of liver allografts. In this report, we present two patient in whom this lesion developed following renal transplantation. Both patients had previous liver biopsies showing relatively mild histologic changes. In one patient, the lesion developed early after retransplantation, during the period of maximal immunosuppression. However, in the second patient this lesion developed after withdrawal of immunosuppression. In both cases, death occurred within a few months because of progressive liver disease. Since this lesion can develop in "relatively healthy" hepatitis B carriers following transplantation of organs other than liver, these patients should have careful monitoring of their liver disease. Moreover, since the disease may progress despite withdrawal of immunosuppression, these patients would clearly benefit from the development of more effective therapies for posttransplant hepatitis B.

Clinics in diagnostic imaging (2). Juvenile gouty arthropathy with associated nephropathy.

A 36-year-old Chinese man presented with clinical and biochemical features of renal failure. He has had recurrent attacks of acute gouty arthritis since the age of 15 years. Present radiographic features of extensive chronic tophaceous gout included soft tissue masses, calcification, and typical erosions in the hand and feet. The condition of familial juvenile gouty nephropathy is discussed. Awareness of juvenile-onset gouty arthropathy should lead to early investigation, diagnosis and appropriate management. The complication of associated nephropathy may potentially be prevented.