An evaluation of concordance between head and neck advanced practice radiation therapist and radiation oncologists in toxicity assessment for nasopharyngeal carcinoma patients.

BACKGROUND: Weekly toxicity assessments for patients undergoing head and neck (HN) radiotherapy are essential to ensure that acute side effects are appropriately managed in order for patients to complete their treatment in a safe and timely manner. The incorporation of Advanced Practice Radiation Therapist (APRT) led treatment reviews has been reported for various subsites, but there is currently a lack of published literature regarding this role for patients with HN cancer. The purpose of this study is to assess the concordance of toxicity assessments performed during weekly radiotherapy treatment reviews for patients undergoing HN radiotherapy between the HN APRT and Radiation Oncologist (RO). METHODS: Twenty-three patients with nasopharyngeal cancer (NPC) under the care of 3 ROs were recruited from June to December 2018; weekly assessments were independently performed by HN APRT and ROs. The HN toxicity assessment was graded according to the Common Terminology Criteria for Advanced Events v4.0. Both assessors were blinded to each other's assessments. The percentage agreement of concordance and agreement level were interpreted by Cohen's Kappa statistic (κ), with the ROs' assessments deemed as the 'gold standard'. RESULTS: The overall concordance for all graded toxicity assessments between HN APRT and ROs was 78.4%. Xerostomia, dysgeusia, pharyngeal pain and dermatitis assessment were evaluated as 'Good' with agreement ranging from κ = 0.608-0.640 between the HN APRT and ROs while dysphagia scored an 'Almost Perfect' agreement of κ = 0.834. 'Moderate' agreement between the HN APRT and ROs was observed for oral pain and mucositis assessment. A scoring discrepancy of 1 and 2 grades was observed in 21.2% and 0.4% for these two toxicities. CONCLUSION:  There was high concordance in scoring of acute toxicity between the HN APRT and ROs. The results support the continuing involvement of HN APRT in weekly assessments for NPC patients.

The implementation of an advanced practice radiation therapy (APRT) program in Singapore.

BACKGROUND: The exploration of Advanced Practiced Radiation Therapists (APRTs) development in Singapore started in 2011. This study aims to provide an overview of the development of the APRT roles, and to discuss the approaches used to develop and implement these roles in Singapore. MATERIALS AND METHODS: A mixed methods approach was used in the development of the APRT program. A literature review was carried out to define the APRT scope of practice and core responsibilities. A competency and assessment framework were setup to assess the core competency areas. With this framework, a structured 1-year residency training program was developed. RESULTS: The scope of practice and core responsibilities of APRTs were defined with five proposed advanced practice profiles being successfully validated. A competency framework was set up to assess the core competency domains: clinical, technical and professional competencies, research, education and leadership. A 4-point scoring system was developed for the competency assessment based on two criteria; the frequency with which RTTs would demonstrate competency, and the ability of performing the task competently. A 1-year structured APRT residency program was developed and implemented. The programme consisted of structured lectures, and clinical practice-based modules where APRT residents receive structured mentoring under a mentorship program. CONCLUSION: The APRT program in Singapore employed an evidence-based implementation process that tested the feasibility of a new practice model. Multidisciplinary involvements, mentorship and clinical training were important factors for the success of the APRT program.

The effect of fetal gender on nuchal translucency at 10-14 weeks of gestation.

Recent data have suggested that fetal nuchal translucency (NT) is affected by fetal gender. We investigated the size of this effect in 12 189 unselected pregnancies with known normal outcomes that had undergone NT measurements between 10 and 14 weeks of gestation. NT increased with gestation and was converted to multiples of the median (MoM) for the gestational day. The median NT MoM (95% CI) for female fetuses was 0.98 (0.97-0.99). This was significantly lower than that of the male fetuses (1.03; range 1.02-1.04) (p<0.0005; Wilcoxon rank-sum test). The gender difference was not observed at 10 weeks but was observed from 11 weeks onwards. There is no obvious explanation for the above findings.

Prenatal diagnosis of glycogen storage disease type 1b using denaturing high performance liquid chromatography.

Glycogen storage disease type 1b (GSD1b) is an autosomal recessive inborn error of metabolism caused by deficiency of glucose-6-phosphate translocase (G6PT1). Current laboratory diagnosis for GSD1b is established by a functional enzyme assay of glucose-6-phosphatase in both fresh and detergent-treated liver homogenates. This procedure requires liver biopsy and is impractical for routine prenatal diagnosis owing to the high morbidity of fetal liver biopsy. Recently, the gene for GSD1b has been cloned and the prevalent mutations in different ethnic groups have been determined. In this study, prenatal molecular diagnosis was performed for a Chinese family in which a previous child was born homozygous for the G149E mutation. We detected genomic sequence variants by heteroduplex formation, followed by denaturing high performance liquid chromatography (DHPLC). With this method, post-PCR analysis was shortened to 7 min. In the case we analysed, PCR products amplified from the fetal DNA yielded a single peak in the chromatogram, indicating a homozygous state in the fetus. When wild-type PCR products were mixed with fetal PCR products, two peaks were observed, indicating that the fetus was homozygous for the parental (G149E) mutation. Sequencing results confirmed this diagnosis. As a result, the pregnancy was terminated and the diagnosis was confirmed on DNA analysis of the aborted fetus. We show here that DNA mutation analysis can be used in the prenatal diagnosis of GSD1b and that DHPLC promises to be a robust technique for this and other prenatal molecular diagnoses.

Single foetal death in twin pregnancies: review of the maternal and neonatal outcomes and management.

OBJECTIVE: To review the maternal and neonatal outcomes, and management of single foetal death in twin pregnancies. DATA SOURCES: Medline literature search (1950 to 1999) and hospital audit of single antepartum foetal deaths in twin pregnancy from 1993 through 1997. DATA SELECTION: Key words for literature search: twin pregnancy/pregnancies; single fetal death/demise. DATA EXTRACTION: Data were extracted and reviewed independently by the authors. DATA SYNTHESIS: During the study period, 182 (0.76%) of 23,804 deliveries involved twin pregnancies. Seven (3.8%) of the twin pregnancies were complicated by the death of one foetus. Single foetal death in a twin pregnancy in the late second and third trimesters is associated with significant morbidity and mortality in the surviving co-twin, especially in a pregnancy involving monochorionic twins. Management should be individualised; conservative management is preferred by most obstetricians. CONCLUSION: Single foetal death in twin pregnancies should be managed in a tertiary referral centre, where intensive foetal surveillance and adequate neonatal support are available. A multidisciplinary approach should be adopted.

Ten years' experience of antenatal mean corpuscular volume screening and prenatal diagnosis for thalassaemias in Hong Kong.

OBJECTIVE: To determine the prevalence of thalassaemia carriers in Hong Kong. SUBJECTS AND METHODS: From 1988 to 1997, 25,834 (53.7%) of 48,089 mothers were screened for thalassaemias by mean corpuscular volume (MCV) at the first antenatal visit. RESULTS: In the screened population of 25,834, 2229 (8.6%) had MCV < or = 75 fl. Of these, 1121 (4.3%) were alpha-thal, 715 (2.8%) were beta-thal, 23 (0.1%) were alpha beta-thal, 57 (0.2%) were other haemoglobin variants, and 281 (1.1%) had either iron deficiency or uncertain causes. Out of 200 pregnancies at risk for homozygous alpha-thal-1 and 32 at risk for beta-thal major, 27 homozygous alpha-thal-1 and 7 beta-thal major were identified, compared favourably with the expected figures of 23 and 9. CONCLUSION: Antenatal screening for thalassaemias by MCV is simple, effective and reliable. Universal screening has a different impact as bone marrow or cord blood stem cell transplant provides cure for beta-thal major. At risk couples have, as an alternative to termination of pregnancy, the option of early detection and treatment for their affected newborns or fetuses.

Acceptability of serum screening as an alternative to cytogenetic diagnosis of down syndrome among women 35 years or older in Hong Kong.

The addition of second trimester serum markers to maternal age increases the efficacy of screening for Down syndrome by maternal age alone. Among women aged 35 years or older, serum screening makes a large proportion of amniocentesis unnecessary. However, there are ethical and medicolegal concerns about serum screening in 'old' women, largely because some of the pregnancies affected by Down syndrome and other chromosomal abnormalities may not be detected. We investigated the acceptability of serum screening in women aged 35 years or older when it was offered as an alternative to prenatal cytogenetic diagnosis after detailed counselling. Women referred for prenatal diagnosis of Down syndrome because of advanced maternal age were given the options of cytogenetic diagnosis by chorionic villus sampling (CVS) or amniocentesis. As an alternative, they could choose to undergo second trimester serum human chorionic gonadotrophin (hCG) and alpha-fetoprotein (AFP) screening first before deciding on whether to undergo amniocentesis. Between January 1997 and October 1999, 3419 subjects were recruited. 1807 women (52. 9%) chose to undergo serum screening, 1516 women (44.3%) chose to have amniocentesis and 96 women chose to have CVS (2.8%). The proportion of women who chose serum screening rose steadily from 38. 8% in the year of 1997 to 63.4% in 1999. Significantly fewer Chinese women chose serum screening than non-Chinese. The decision as to whether to undergo an invasive diagnostic procedure or to be content with the relatively safer but less accurate screening test varies, being affected by the women's background and culture.

Second-trimester maternal serum alpha-fetoprotein and human chorionic gonadotrophin screening for Down's syndrome in Hong Kong.

Second-trimester maternal serum screening for fetal Down's syndrome is well established in many Western countries. Its usefulness and acceptability is unknown in the Asian countries. Between June 1994 and December 1996, we offered second-trimester serum AFP and hCG screening to pregnant women in Hong Kong who were less than 35 years old and without other risk factors for chromosome abnormalities. Each woman was assigned a risk of having a Down's syndrome term pregnancy by using a computer software program that took into account her age. weight, AFP and hCG MOMs. All those with a risk of one in 250 or greater were designated screen-positive, subject to the revision of gestation by ultrasound examination. 9,177 women with singleton pregnancies (93 per cent were Chinese) were screened. The uptake of screening was 75 per cent. 281 women (three per cent) were initially classified to be screen-positive. After revision of the gestation by ultrasound examination, 183 women (two per cent) were 'true' screen-positive and 164 (90 per cent) accepted the offer of amniocentesis. Eight of these pregnancies were affected by Down's syndrome and all the women elected pregnancy termination. The odds of being affected, given a positive screening result, were one in 23. Six Down's syndrome pregnancies were missed by screening programme. The detection rate was 57 per cent. The study showed that second-trimester serum screening for fetal Down's syndrome was feasible and accepted in the Hong Kong population.

Prenatal sonographic diagnosis of conjoined twins in the first trimester: two case reports.

Conjoined twins are a rare occurrence. We present two cases of conjoined twins diagnosed by ultrasound examination at 8 and 13 weeks' gestation, respectively. These cases demonstrated the possibility of making an accurate diagnosis of conjoined twins and delineating the extent of organ sharing in the first trimester.

Clinical significance of amniotic-fluid-cell culture failure.

Recent reports suggest an increased incidence of chromosomal abnormalities in pregnancies with amniotic fluid-cell culture failure. We retrospectively reviewed the cytogenetic results of 14,165 amniotic fluid samples processed in our laboratory from 1987 to 1996. Ninety-eight per cent of the samples were obtained before 24 weeks' gestation, mainly because of advanced maternal age; 2 per cent were obtained after or at 24 weeks because of the ultrasonographic finding of fetal structural defects. Amniotic-fluid-cell culture failure occurred in 62 cases (0.44 per cent). Culture failure was more common in samples obtained after or at 24 weeks' gestation (10 per cent) than in those obtained before 24 weeks (0.27 per cent) (P < 0.001, chi-square test). This difference was also observed when the results were analysed according to the cases with known normal or abnormal karyotypes. The frequency of culture failure did not differ significantly between the groups with normal and abnormal karyotypes. We conclude that amniotic-fluid-cell culture failure is more common in advanced pregnancy with an ultrasonographic finding of fetal structural defects and is not associated with a higher incidence of chromosomal abnormalities.

Conservative management of patients with histological incomplete excision of cervical intraepithelial neoplasia after large loop excision of transformation zone.

OBJECTIVE: To evaluate conservative management of patients with histological incomplete excision of CIN after large loop excision of transformation zone (LLETZ). METHODS: Two hundred and seventeen patients with high grade CIN were treated with LLETZ from October 1, 1992 to December 31, 1994. Fifty-three patients (24.4%) had incomplete excision on histology. All patients were followed up cytologically every 3 to 6 months during the first 18 months and then yearly till December 1996. Those patients with positive endocervical margins were followed up with both cervical smear and endocervical smear. RESULTS: The mean follow-up duration was 30.4 months. Ten patients were found to have persistent or recurrent disease. Five patients had second LLETZ and complete excision was achieved in 4 of them, one patient had cone biopsy and two had hysterectomy. One patient was found to have stage I a cervical cancer. CONCLUSION: A report of incomplete excision of CIN after LLETZ calls for follow-up with cytology and colposcopy and not aggressive retreatment.

Early ultrasound prediction of pregnancies affected by homozygous alpha-thalassaemia-1.

Homozygous alpha-thalassaemia-1 is conventionally diagnosed by invasive testing on all at-risk pregnancies. We evaluated the diagnostic efficacy of non-invasive abdominal ultrasonographic cardiothoracic ratio measurement in 62 pregnancies at 13-14 weeks and 75 pregnancies at 17-18 weeks. This performed better than placental thickness measurement. Using a cardiothoracic ratio cut-off level of > or = 0.5, 75 per cent of affected pregnancies were detected at 13-14 weeks and all cases were detected at 17-18 weeks. False-positive rates were 7 and 8 per cent, respectively. There was no false-positive diagnosis if the cardiothoracic ratio was > or = 0.53. With this approach, invasive procedures can be selectively performed and fewer pregnancies will be lost unnecessarily. The reduction in medical expenses is likely to be substantial.

Second-trimester hydrops fetalis in pregnancies affected by homozygous alpha-thalassaemia-1.

Homozygous alpha-thalassaemia-1 is the commonest cause of hydrops fetalis in South-East Asia. Ultrasonographic features of hydrops fetalis were said to be evident only after 20 weeks of gestation. We studied 111 pregnancies at risk of homozygous alpha-thalassaemia-1 at 12-14 gestational weeks and 101 pregnancies at 17-18 weeks by abdominal ultrasound examination. Ultrasonographic features of hydrops fetalis were seen in 3 out of 44 pregnancies affected by homozygous alpha-thalassaemia-1 at 12-14 weeks [7 per cent; 95 per cent confidence interval (CI) 1-19 per cent] and in 7 out of 21 affected pregnancies at 17-18 weeks (33 per cent; 95 per cent CI 15-57 per cent). In conclusion, homozygous alpha-thalassaemia-1 can cause hydrops fetalis in the early second trimester. It should constitute one of the differential diagnoses in the work-up of second-trimester hydrops fetalis.

A three-year review of treatment of cervical intraepithelial neoplasia with large loop excision of the transformation zone.

One hundred and eighty-five patients were treated with large loop excision of the transformation zone for cervical intraepithelial neoplasia from October 1992 through September 1994. All patients were followed up regularly until September 1995 to review the outcome and morbidity. Cure rates of 97.2% in the first six months and 95.4% at the end of the first 12 months were obtained. Thirteen patients (7.0%) were admitted as emergency cases for post-operative haemorrhage, which required suturing, cauterisation with silver nitrate or electrocoagulation, vaginal douching, or antibiotic treatment. One patient developed cervical stenosis and incomplete excisions were noted in 46 (24.9%) patients. Eleven (6.0%) patients had cervical carcinomas detected. Our findings further confirm that this method is a reliable and safe way to treat cervical intraepithelial neoplasia with an acceptable rate of morbidity.

Limb reduction defects in fetuses with homozygous alpha-thalassaemia-1.

Limb reduction defect is a rare event. Its exact pathogenesis is unknown. We retrospectively reviewed the outcome of 130 fetuses affected by homozygous alpha-thalassaemia-1 and found that 11 of them (8 per cent; 95 per cent confidence interval: 4-13 per cent) had terminal transverse limb reduction defects. Chromosome study was available in ten fetuses with limb defects and the results were normal. We postulate that the strong association between homozygous alpha-thalassaemia-1 and limb reduction is related to the hypoxic insult in early gestation. This may be the final common pathway in the pathogenesis of other forms of limb reduction defects.