Management of chronic kidney disease: a Hong Kong consensus recommendation.

Chronic kidney disease (CKD) imposes a significant burden on healthcare systems worldwide, and diabetes is a major risk factor for CKD. There is currently no consensus in Hong Kong regarding the prioritisation of early identification and intervention for CKD. A comprehensive and Hong Kong-specific diabetes and CKD treatment guideline is also lacking. A multidisciplinary group of experts discussed issues surrounding the current management of CKD and reviewed evidence in the context of local experience to support recommendations. The experts used a modified Delphi approach to finalise recommendations. Consensus was regarded as ≥75% acceptability among all expert panel members. The panel members finalised 14 CKD-focused consensus statements addressing disease definition, screening, disease monitoring, lifestyle management, and treatment strategies. The recommendations provided are relevant to the Hong Kong healthcare setting and can be used as a guide by physicians across various specialties to facilitate the appropriate management of CKD.

Overcoming existential loneliness: a cross-cultural study.

BACKGROUND: Moving into a long-term care facility (LTCF) can reduce the ability for older adults to engage in meaningful roles and activities and the size of their social network. These changes and losses can lead them to experience existential loneliness (EL)-the intolerable emptiness and lack of meaningful existence resulted from the losses they have experienced. While EL has often been understood as a universal human experience, it has primarily been studied in people from Western cultures; little is known about how EL may be experienced by and manifested in people from Eastern cultures. Hence, this qualitative study aimed to describe the experience and coping of EL in Hong Kong Chinese and Swedish older adults living in LTCFs. METHODS: A qualitative study using Thorne's (2004) interpretive description was conducted. Thirteen Chinese and 9 Swedes living in LTCFs in Hong Kong, China and Malmo, Sweden, respectively were interviewed about their experience of EL in two series of semi-structured interviews. Data were analyzed using thematic analysis. RESULTS: The core theme of "overcoming EL" described the participants' experience of EL, which came about through the combined process of "Feeling EL" and "Self-Regulating". Both Chinese and Swedish participants had similar experience with EL. Realizing that they did not want to living with EL anymore, they coped by reframing their experience and identifying new meaning in their life. CONCLUSIONS: The study findings suggested that early and clear counselling support that help older adults to define new meaning in life may help them cope. In addition, more opportunities should be available at the LTCFs to promote quality relationships, enable older adults to reflect on their lives with pride, and support their ability to do the things they enjoy.

Secondary amputation after lower extremity free-flap reconstruction.

BACKGROUND: Microsurgical free-tissue transfer is often the definitive reconstructive option for lower extremity limb salvage. Despite an initial successful free-flap reconstruction, some patients ultimately undergo lower extremity amputation. The indications for secondary amputation include non- or malunion, infection, hardware failure, or chronic pain. This study aimed to identify the etiology and outcome of secondary amputation after lower extremity free-flap reconstruction. METHODS: A retrospective cohort study was performed including patients who underwent lower extremity free-flap reconstruction from January 2002 to December 2020. Patients who underwent secondary amputation were identified. A survey based on the PROMIS® Pain Interference Scale and activities of daily living (ADLs) was then conducted to assess patient-reported outcomes. Fifteen (52%) patients who underwent amputation responded to the survey, with a median follow-up time of 4.4 years. RESULTS: Of 410 patients who underwent lower extremity free-flap reconstruction, 40 (9.8%) patients underwent subsequent amputation. Of these, 10 patients had failed free-flap reconstruction and 30 patients had secondary amputation after an initially successful soft tissue coverage. The most common etiology for secondary amputation was infection (68%, n = 27). Eighty percent (n = 12) of survey respondents were able to use a prosthetic limb and ambulate. CONCLUSIONS: The most common etiology of secondary amputation was infection. Most patients who ultimately underwent amputation were able to ambulate with a prosthetic, but the majority of patients reported chronic pain. This study could be used to guide potential free-flap candidates regarding the risks and outcomes of lower extremity free-flap reconstruction.

INADEQUACY OF THORON DOSE CALCULATIONS FROM THORON PROGENY MEASUREMENT ALONE.

To determine the dose received by thoron (220Rn) domestically, conventional methods measure the activity concentration of thoron progeny only (namely the 212Pb atoms) and calculate the dose by using a set of conversion factors. This may be due to the measurement of progeny being simpler since it is longer lived and will be evenly spread throughout the room, whereas the thoron gas, with its short half-life, will exist only near the source and hence will not be of major concern for the majority of the room. However, concrete walls are a source of thoron, and spending prolonged amounts of time near them may lead to greatly increased radiation exposure, the degree of which is not revealed through progeny activity alone. The present paper compares the energy received from the ionising radiation of both thoron gas and thoron progeny near its source. Converting the energy dose to radiation dose is not within the scope of this paper. The results suggest a difference of an order of magnitude higher when taking into account the dose received by thoron gas.

Birt-Hogg-Dubé syndrome: mapping of a novel hereditary neoplasia gene to chromosome 17p12-q11.2.

Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant neoplasia syndrome characterized mainly by benign skin tumors, and to a lesser extent, renal tumors and spontaneous pneumothorax. To map the BHD locus, we performed a genome-wide linkage analysis using polymorphic microsatellite markers on a large Swedish BHD family. Evidence of linkage was identified on chromosome 17p12-q11.2, with a maximum LOD score of 3.58 for marker D17S1852. Further haplotype analysis defined a approximately 35 cM candidate interval between the two flanking markers, D17S1791 and D17S798. This information will facilitate the identification of the BHD gene, leading to the understanding of its underlying molecular etiology.

Association of a novel constitutional translocation t(1q;3q) with familial renal cell carcinoma.

Four cases of late onset clear cell renal cell carcinoma (RCC), a case of gastric cancer, and a case of exocrine pancreatic cancer were identified in a Japanese family. In order to elucidate the underlying mechanism for tumorigenesis in this family, extensive genetic studies were performed including routine and spectral karyotyping (SKY), fluorescence in situ hybridisation (FISH), comparative genomic hybridisation (CGH), loss of heterozygosity studies (LOH), and VHL mutation analysis. A germline translocation t(1;3)(q32-q41;q13-q21) was identified by karyotyping in five members of the family including all three RCC cases tested. The translocation was refined to t(1;3)(q32;q13.3) by FISH analysis using locus specific genomic clones, and the two breakpoints were mapped to a 5 cM region in 3q13.3 and a 3.6 cM region in 1q32. Both CGH and allelotyping using microsatellite markers showed loss of the derivative chromosome 3 carrying a 1q segment in the three familial RCCs analysed. Additional chromosomal imbalances were identified by CGH, including amplifications of chromosomes 5 and 7 and loss of 8p and 9. No germline VHL mutation was found but two different somatic mutations, a splice (IVS1-2A>C) and a frameshift (726delG), were identified in two RCCs from the same patient confirming their distinct origin. Taken together, these results firmly support a three step model for tumorigenesis in this family. A constitutional translocation t(1q;3q) increased the susceptibility to loss of the derivative chromosome 3 which is then followed by somatic mutations of the RCC related tumour suppressor gene VHL located in the remaining copy of chromosome 3.

Familial isolated hyperparathyroidism as a variant of multiple endocrine neoplasia type 1 in a large Danish pedigree.

We report here our genetic findings of a family in which 14 members were affected with isolated primary hyperparathyroidism. Hyperparathyroidism is the main feature of multiple endocrine neoplasia type 1 (MEN1), making the recently cloned MEN1 gene a prime candidate gene in this family. Significantly positive lod scores were achieved with D11S4946 (3.36) and D11S4940 (3.53), and by combining the results from these two markers, a maximum positive lod score of 4.12 at recombination fraction 0.00 was obtained. Mutation analysis of MEN1 performed by full sequencing identified a missense mutation in exon 4, causing an amino acid change from glutamine to proline at codon 260. This mutation (Q260P) was present in all affected family members, and the inheritance of the mutation was in complete agreement with the disease-associated haplotype. In comparison with the recent functional studies of the menin protein interactions, this mutation is located in a region with little or no binding activity to JunD and activating protein-1 transcription factor. We conclude that some of the familial isolated primary hyperparathyroidism families constitute a milder variant of MEN 1, which is associated with a functionally milder missense mutation.

Familial isolated hyperparathyroidism maps to the hyperparathyroidism-jaw tumor locus in 1q21-q32 in a subset of families.

Approximately 70 families with familial isolated hyperparathyroidism (FIHP) have been reported. Whether it is a separate entity or a variant of multiple endocrine neoplasia type 1 (MEN1 at 11q13) or hyperparathyroidism-jaw tumor (HPT-JT or HRPT2 at 1q21-32) syndrome is not known. We describe here 3 unreported families with familial primary hyperparathyroidism and evaluate their clinical, pathological, and genetic profiles. Biochemical and radiological screenings for MEN1 were negative for all families. In 2 families with a total of 10 affected cases and 3 female obligate carriers, there is no evidence of jaw or renal lesions despite careful radiological investigations. In both families the disease was linked to the 1q21-q32 region with the maximum logarithm of the odds (lod) scores of 3.10 and 3.43 for markers D1S222 and D1S249 respectively, at recombination fraction of 0. In 1 family 2 types of parathyroid pathology were found: 3 of chief cell type and 1 of oxyphil/oncocytic cell type. Two chief cell tumors and 1 oxyphil tumor were found to have loss of heterozygosity (LOH) involving loss of the wild-type alleles for chromosome 1q markers. In the third family, with 4 affected siblings, a parathyroid carcinoma and 2 cases of polycystic kidney disease were found. The parathyroid carcinoma also showed loss of heterozygosity in the 1q region. In conclusion, we found that the hyperparathyroidism traits in a subset of FIHP families are linked to the 1q21-32 markers in the HRPT2 region. We describe the spectrum of parathyroid disease in 1q-linked families involving 3 different types of pathology and demonstrate for the first time loss of wild-type alleles in these parathyroid tumors. Taken together, the results suggest that some of the FIHP are a variant of HPT-JT and that the gene involved is a tumor suppressor gene.

Alternative genetic pathways in parathyroid tumorigenesis.

In this study 44 parathyroid tumors from 26 sporadic cases, 10 cases previously given irradiation to the neck, and 8 familial cases were screened for sequence copy number alterations by comparative genomic hybridization. In the sporadic adenomas, commonly occurring minimal regions of loss could be defined to chromosome 11 (38%), 15q15-qter (27%), and 1p34-pter (19%), whereas gains preferentially involved 19p13.2-pter (15%) and 7pter-qter (12%). Multiple aberrations were found in sporadic tumors with a somatic mutation and/or loss of heterozygosity of the MEN1 gene. The irradiation-associated tumors also showed multiple comparative genomic hybridization alterations and frequent losses of 11q (50%), and subsequent analysis of the MEN1 gene demonstrated mutations in 4 of 8 cases (50%). The adenomas from familial cases showed few alterations, and in 3 of these tumors a gain of 19p13.2-pter was seen as the only aberration. In this study numerical copy number alterations were frequently detected in sporadic and irradiation-associated parathyroid adenomas, although these tumors are benign. The majority of these alterations were found in tumors with confirmed involvement of the MEN1 gene locus in agreement with a role of the MEN1 gene in genomic stability. Furthermore, the frequent occurrence of MEN1 mutations (50%) in irradiation-associated parathyroid tumors suggests that inactivation of the MEN1 gene is an important genetic alteration involved in the development of parathyroid tumors in postirradiation patients.

A genotypic and histopathological study of a large Dutch kindred with hyperparathyroidism-jaw tumor syndrome.

Familial primary hyperparathyroidism is the main feature of 2 familial endocrine neoplasia syndromes: multiple endocrine neoplasia type 1 (MEN 1) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The latter is a recently described syndrome that has been associated with ossifying fibroma of the jaw and various types of renal lesions, including benign cysts, Wilms' tumor, and hamartomas. To further illustrate the natural history of this syndrome, we describe a large, previously unreported Dutch kindred in which 13 affected members presented with either parathyroid adenoma or carcinoma; in 5 affected individuals, cystic kidney disease was found. Additionally, pancreatic adenocarcinoma, renal cortical adenoma, papillary renal cell carcinoma, testicular mixed germ cell tumor with major seminoma component, and Hürthle cell thyroid adenoma were also identified. Linkage analysis of the family using MEN1-linked microsatellite markers and mutation analysis excluded the involvement of the MEN1 gene. Using markers from the HPT-JT region in 1q2531, cosegregation with the disease was found, with a maximum logarithm of odds score of 2.41 obtained for 6 markers using the most conservative calculation. Meiotic telomeric recombination between D1S413 and D1S477 was identified in 3 affected individuals, and when combined with previous reports, delineated the HPT-JT region to 14 centimorgan. Combined comparative genomic hybridization and loss of heterozygosity data revealed complex genetic abnormalities in the tumors, suggesting different possible genetic mechanisms for the disease. In conclusion, we report a family with hyperparathyroidism linked to chromosome 1q, and exhibiting several types of renal and endocrine tumors that have not been previously described.

Mutation analysis of the MEN1 gene in multiple endocrine neoplasia type 1, familial acromegaly and familial isolated hyperparathyroidism.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disease characterized by neoplasia of the parathyroid glands, the endocrine pancreas, and the anterior pituitary gland. In addition, families with isolated endocrine neoplasia, notably familial isolated hyperparathyroidism (FIHP) and familial acromegaly, have also been reported. However, whether these families constitute MEN 1 variants or separate entities remains speculative as the genetic bases for these diseases are unclear. The gene for MEN 1 has recently been cloned and characterized. Using single strand conformation analysis (SSCA) and sequencing, we performed mutation analysis in: a) a total of 55 MEN 1 families from 7 countries, b) 13 isolated MEN 1 cases without family history of the disease, c) 8 acromegaly families, and d) 4 FIHP families. Mutations were identified in 27 MEN 1 families and 9 isolated cases. The 22 different mutations spread across most of the 9 translated exons and included frameshift (11), nonsense (6), splice (2), missense mutations (2), and in-frame deletions (1). Among the 19 Finnish MEN 1 probands, a 1466del12 mutation was identified in 6 families with identical 11q13 haplotypes and in 2 isolated cases indicating a common founder. One frameshift mutation caused by 359del4 (GTCT) was found in 1 isolated case and 4 kindreds of different origin and haplotypes; this mutation therefore represents a common "warm" spot in the MEN1 gene. By analyzing the DNA of the parents of an isolated case one mutation was confirmed to be de novo. No mutation was found in any of the acromegaly and small FIHP families, suggesting that genetic defects other than the MEN1 gene might be involved and that additional such families need to be analyzed.

Mapping of the second locus for the Van der Woude syndrome to chromosome 1p34.

The Van der Woude syndrome (VWS) is a dominantly inherited developmental disorder characterized by pits and/or sinuses of the lower lip, cleft lip and/or cleft palate. It is the most common cleft syndrome. VWS has shown remarkable genetic homogeneity in all populations, and so far, all families reported have been linked to 1q32-q41. A large Finnish pedigree with VWS was recently found to be unlinked to 1q32-q41. In order to map the disease locus in this family, a genome wide linkage scan was performed. A maximum lod score of 3.18 was obtained with the marker D1S2797, thus assigning the disease locus to chromosomal region 1p34. By analyses of meiotic recombinants an approximately 30 cM region of shared haplotypes was identified. The results confirm the heterogeneity of the VWS syndrome, and they place the second disease locus in 1p34. This finding has a special interest because the phenotype in VWS closely resembles the phenotype in non-syndromic forms of cleft lip and palate.

Determination of the solute removal index for urea by using a partial spent dialysate collection method.

In 22 hemodialysis patients, during a dialysis session, the solute removal index (SRI) for urea obtained from the use of a partial spent dialysate collection method was compared with that derived from the use of a total spent dialysate collection technique. The partial spent dialysate collection method was used to harvest a small representative sample of the total spent dialysate. The volumes of spent dialysate collected by the partial and the total spent dialysate collection methods were 1.7 +/- 0.4 L and 129.6 +/- 15.3 L, respectively. The total amount of urea nitrogen removed by dialysis as estimated by the partial spent dialysate collection method was similar to that determined by the total spent dialysate collection approach. As a result, the SRI value for urea obtained by the partial spent dialysate collection method (namely, 63% +/- 8%) correlated very well (r = 0.95, P < 0.001) with that derived by the total spent dialysate collection technique (namely, 62% +/- 8%). Our data suggest that it is feasible to use a simple partial spent dialysate collection method to obtain SRI results in patients treated with hemodialysis.

Educating nurses to care for the dying in Hong Kong: a problem-based learning approach.

Caring for dying patients is an essential and major aspect of nursing care. However, previous studies have revealed that nurses felt uncomfortable and inadequate in dealing with the dying patients and their families. This study reports the effectiveness of a problem-based learning approach in death education among a group of registered nurses in Hong Kong. Three problems, with three segmented scenarios related to cancer nursing, were used. Students went through the problem-based learning process and documented their learning throughout the course in journals. A total of 72 sets of journals were collected and analyzed. The strategies of within case and cross-case analysis were employed. The within case analysis explored the learning development of students for each problem. The cross-case analysis compared and contrasted findings of the within case analysis. Three themes have been derived from the findings. They were: nurses acknowledging their emotions in facing death and dying, a need for the nurses to be better equipped in communication and counseling, and a holistic and family-centered approach to care. This study provides evidence showing that problem-based learning is an effective strategy to enhance nurses' self-awareness of death and dying issues, and to stimulate nurses to formulate a plan that addresses the physical, psychological, and social aspects of care. Findings also reveal that nurses need to take into account the particular reactions of death and dying in the Chinese culture when planning care.

Acid-base values of single pass, batch system, bicarbonate based hemodialysate.

The bicarbonate, calcium, and magnesium values of a single pass, batch system, bicarbonate based hemodialysate were found to be stable during a period of 5 hours, whether the solution was extensively covered by a floating polystyrene lid or not. The pH and PCO2 of the dialysate that had been covered with a floating lid remained stable during the 5 hours, whereas the corresponding values of the dialysate that had not been so covered did show changes that were secondary to the loss of carbon dioxide. The changes were not marked enough to preclude the clinical use of the latter uncovered dialysate.

A partial dialysate collection method.

This study validates Ing's partial dialysate collection method, which employs proportionate collection using a side tube capped with a small-gauge plastic needle. The urea nitrogen and creatinine levels of the small representative fraction of spent dialysate collected in the above fashion are undistinguishable from those obtained from the total spent dialysate. The estimated urea nitrogen removed during hemodialysis using this approach is similar to that using the total dialysate collection method; Ing's method is simple and useful in quantifying the dialysis dosage and in its assessment of the nutritional status of patients on hemodialysis.

Neutrophil intracellular pH after exposure of neutrophils to a euhydric, lactate-based peritoneal dialysis solution and its euhydric, bicarbonate-based counterpart.

The effects of euhydric, lactate-based peritoneal dialysis solutions and those of their euhydric, bicarbonate-based counterparts, on neutrophil intracellular pH are comparable. This similarity in effects on intracellular acidity may have bearings on the influences of these solutions on cellular functions in general.

Computerization of clinical practice in Hong Kong.

The objective of this study was to assess the current level of computerization in clinical practice in Hong Kong through a population-based, physician survey conducted in 2000.A self-completed, 20-question, postal questionnaire was sent to 4850 randomly selected doctors in Hong Kong. We received 897 completed responses. Over one-third of doctors in the overall sample were already recording patient summaries, processing laboratory results and specialist reports, and preparing referral notes electronically. Patient registration (52.2%), billing systems (40.2%), appointment scheduling (39.9%), and payroll (36.9%), were the commonest administrative functions to have been computerized. Seventy per cent of doctors in solo or small-group ('individual') practices did not yet have any clinical function computerized compared with only 30.7% for those working in large, corporate organizations. Similarly, approximately two-thirds of administrative tasks in 'individual' clinics were not computerized, while corporate physicians reported a corresponding percentage of 39.3%. Younger age, male gender, specialist qualifications, more computers in the practice, higher numbers of administrative tasks already computerized, higher levels of knowledge about and positive attitudes towards computer applications in clinical practice were all positively associated with more clinical tasks already computerized in the practice. The present study has systematically documented the extent of clinical computer use in Hong Kong and identified areas for improvement as well as specific groups of physicians who might benefit from targeted efforts promoting computerization in practice.

Peritoneal equilibration test in Chinese patients.

Since the introduction of the peritoneal equilibration test (PET) by Twardowski in 1987, it became a widely accepted test that provided useful prognostic information on continuous ambulatory peritoneal dialysis (CAPD). It had been shown to be a readily reproducible test if the standard procedure was followed. Although there was wide interpersonal difference in the test results, the mean and range (and standard deviation, SD) were remarkably similar as suggested by Davies et al. in 1993 (3). We had performed PET on our CAPD patients for a few years, and all along we used the reference range established by Twardowski to classify our patients into High, High average, Low average, and Low transporters because no reference range had ever been established in Chinese. The aim of this study was to define the normal mean and range of the PET results in Chinese CAPD patients. We analyzed 100 PET results from 100 Chinese CAPD patients. The mean +/- (SD) of the ratio of dialysate/plasma of creatinine and glucose at four-hour dwell times were 0.71 (0.15) and 0.37 (0.12), respectively. There was a significant difference in the dialysate/plasma ratio of creatinine (p < 0.01) while that of glucose was similar when compared with those found by Twardowski. There was no difference in the solute transfer in diabetic and nondiabetic patients. We concluded that the creatinine clearance of the peritoneal membrane in Chinese CAPD patients was higher than the previously reported result in North American patients.