Consensus guidelines for interventional cardiology services delivery during covid-19 pandemic in Australia and new Zealand.

The global coronavirus disease (COVID-19) pandemic poses an unprecedented stress on healthcare systems internationally. These Health system-wide demands call for efficient utilisation of resources at this time in a fair, consistent, ethical and efficient manner would improve our ability to treat patients. Excellent co-operation between hospital units (especially intensive care unit [ICU], emergency department [ED] and cardiology) is critical in ensuring optimal patient outcomes. The purpose of this document is to provide practical guidelines for the effective use of interventional cardiology services in Australia and New Zealand. The document will be updated regularly as new evidence and knowledge is gained with time. Goals Considerations.

Psychiatric disorders in children with Prader-Willi syndrome-Results of a 2-year longitudinal study.

Psychiatric disorders such as psychosis are highly prevalent in adults with Prader-Willi syndrome (PWS). However, knowledge about the presence and progression of psychiatric disorders in children with PWS is very limited. Sixty-one children with PWS aged 7-17 years were tested using the Diagnostic Interview Schedule for Children (DISC) and Compulsive Behaviour Checklist (CBC), and 38/61 were retested after 2 years. Prevalence of psychiatric disorders and the association with age, gender, genetic subtype, and total IQ were assessed. In addition, occurrence and characteristics of compulsions were determined. Prior to the study, two boys were known with psychotic symptoms and treated with antipsychotics. At baseline, none scored positive for psychotic disorder. During the follow-up, only one boy with known psychotic symptoms required a dose adjustment of his antipsychotic medication. After 2 years, none of the children had a psychotic disorder according to the DISC. Oppositional defiant disorder (ODD) was the most common diagnosis and present in 20% of children with PWS, and this was not associated with age (ß = -0.081, P = 0.546), gender (ß = 0.013, P = 0.923), genetic subtype (ß = -0.073, P = 0.584), or total IQ (ß = -0.150, P = 0.267). The most common compulsions were hoarding and fixed hygiene sequences. In our large group of 61 children with PWS, the majority had no psychotic disorder and no progression was found during 2-year follow-up. ODD was present in 20% of children. No changes in the prevalence of psychiatric disorders were found during the 2-year follow-up study and genetic subtype was not related to psychosis, depression, or ODD.

Visual-motor integration in children with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is characterised by hypotonia, hypogonadism, short stature, obesity, behavioural problems, intellectual disability, and delay in language, social and motor development. There is very limited knowledge about visual-motor integration in children with PWS. METHOD: Seventy-three children with PWS aged 7-17 years were included. Visual-motor integration was assessed using the Beery Visual-motor Integration test at the start of the study and after 2 years. The association between visual-motor integration and age, gender, genetic subtype and intelligence was assessed. RESULTS: Children with PWS scored 'very low' (-3 standard deviations) in visual-motor integration and 'below average' (-1 standard deviation) in visual perception and motor coordination compared with typically developing children. Visual-motor integration was higher in children with a deletion (ß = -0.170, P = 0.037), in older children (ß = 0.222, P = 0.009) and in those with a higher total IQ (ß = 0.784, P < 0.001). Visual perception was higher with a deletion (ß = -0.193, P = 0.044) and higher IQ (ß = -0.618, P < 0.001), but motor coordination was only higher with a higher total IQ (ß = 0.429, P = 0.001). Visual perception and motor coordination were not associated with age or gender. There was a trend for visual-motor integration decline over the 2 year follow-up period (P = 0.099). Visual perception and motor coordination did not change over the follow-up period. CONCLUSIONS: Visual-motor integration is very poor in children with PWS. Children scored higher on the time-limited subtests for visual perception and motor coordination than the combined test for visual-motor integration. Separation of visual-motor integration tasks into pure visual or motor tasks and allowing sufficient time to perform the tasks might improve daily activities, both at home and at school.

Transposed brachiobasilic fistula or PTFE arm graft - alternative or complementary?

PURPOSE: Our primary aims were (1) to examine the patency of transposed brachiobasilic (TBB) fistulae compared to arm arteriovenous graft (AVG) without prior transposition, and (2) to examine the patency of AVG with and without prior transposition. METHODS: Single institution; analysis of prospectively collected data between January 2001 and January 2007. Dedicated database and medical records were reviewed and results analyzed with SPSS. RESULTS: Ninety-one patients underwent 111 procedures (52 TBB: 39 AVG as index); 28 TBB failed with 17 (60%) being replaced with an ipsilateral AVG. TBB compared to AVG (without prior TBB) had significantly (log rank <0.05 ) better primary, primary assisted and secondary patency. Secondary patency at 2 yrs was 47% to 33%, respectively. Ipsilateral AVG after TBB to primary AVG had superior patency rates (secondary patency at 2 yrs 52 vs. 33%) but did not reach significance (log rank =0.073). Combined secondary patency of TBB and AVG after TBB was 81% at 2 yrs. CONCLUSIONS: The TBB offers an autogenous fistula in the upper arm which has superior patency rates to an arm AVG. Once a TBB has failed an ipsilateral AVG is technically feasible and may offer better patency than a primary AVG.

How compliant are we with guidelines for coronary angiography in clinical practice?

BACKGROUND: The American College of Cardiology and American Heart Association have published guidelines for coronary angiography. We evaluated the compliance rate with these guidelines in clinical practice, its correlation to results of angiography and aimed to identify problem areas of non-compliance. METHODS: We prospectively evaluated 802 consecutive referrals for coronary angiography over 5 months in 2002 in a tertiary referral hospital. These referrals were assessed by two independent reviewers blinded to the results of angiography. RESULTS: Patient age was 62 +/- 11 years (522 men, 433 inpatients, 369 day-only patients). Referrals were outside published guidelines in 34.3 and 36.2% as evaluated by the two reviewers (concordance rate 88.2%, kappa = 0.74, p < 0.001). Intraobserver agreement was 97.5%. The rate of angiography showing either normal arteries or only minor diseases (<50%) was higher for referrals outside guidelines (68.4 vs 22.6%, P < 0.001). Compliance rate was high with indications of non-ST-elevation myocardial infarction (99.2%) and ST-elevation myocardial infarction (95.8%), valvular disease (80%) and arrhythmia (80%). Compliance rate was lower with assessment of dyspnoea or heart failure (74.3%) and before non-cardiac surgery (72.7%) and was particularly low with assessment of chest pain (53.2%). Younger age (odds ratio (OR) 1.04, P < 0.001), female sex (OR 2.67, P < 0.001), day-only procedure (OR 2.27, P < 0.001) and non-invasive cardiologist referrer (OR 1.41, P = 0.046) were independent predictors of non-compliance. CONCLUSION: Referrals for coronary angiography were outside guidelines in a significant proportion of patients. Rate of negative angiography was higher when the referrals were outside guidelines. Problematic areas of non-compliance could be identified. Measures specifically targeting these areas may be more effective in improving the overall guideline compliance in clinical practice.

The influence of plaque orientation (pericardial or myocardial) on coronary arterial remodeling.

BACKGROUND: Many systemic, regional and lesion factors have been identified which may influence arterial remodeling, but little is known about the importance of extravascular resistance to vessel enlargement. As myocardial systolic splinting may significantly affect vessel expansion the effect of plaque orientation on arterial remodeling in eccentric coronary atherosclerotic lesions was examined. METHODS: Using intravascular ultrasound imaging to obtain cross-sectional vessel area (VA), plaque area (PA) and lumen area (LA), remodeling in eccentric left anterior descending coronary artery lesions was compared which predominantly involved the pericardial or free arc (P, n=25) and the myocardial side (M, n=40) of the vessel wall. Normalized vessel area (NVA, VA(lesion)/VA(reference)) was compared as a continuous and categorical variable (positive>1.05, intermediate 0.95-1.05, negative<0.95) as well as remodeling index (RI, VA(lesion)-VA(reference)/PA(lesion)-PA(reference)). RESULTS: The two groups were well matched for clinical and lesion characteristics known to affect remodeling. Reference segments areas were similar in the two groups; while lesion LA was also similar, in the pericardial group there was significantly greater lesion PA (P 12.78+/-0.72, M 10.26+/-0.50 mm(2), P<0.05) and VA (P 15.71+/-0.90, M 12.82+/-0.57 mm(2), P<0.05) demonstrating enhanced compensatory remodeling. Outward remodeling was significantly greater in P than in M by both NVA (P 1.03+/-0.03, M 0.86+/-0.03, P<0.01) and RI (P 0.02+/-0.07, M -1.10+/-0.32, P<0.01). Positive, intermediate and negative remodeling occurred in nine, nine and seven lesions in P and in four, ten and 26 lesions in M (P<0.01). CONCLUSIONS: Remodeling compensates more for plaque growth in eccentric coronary lesions which are surrounded by the pericardium than those surrounded by the myocardium. Extravascular resistance appears to influence arterial remodeling.

Most nasal/nasopharyngeal lymphomas are peripheral T-cell neoplasms.

Eleven consecutive cases of nasal/nasopharyngeal lymphoma were studied histologically and with a panel of monoclonal antibodies. The disease showed a male predominance and occurred over a wide age range, with a median of 52 years. Five patients had midfacial destructive disease, and six had gross tumor masses involving the nose/nasopharynx. Three cases were classified as small cleaved cell, two cases as mixed cell, five cases as large cell, and one case as immunoblastic lymphoma. Those belonging to the first two categories also satisfied the diagnostic criteria of so-called polymorphic reticulosis. Epithelial invasion, angioinvasion, and coagulative necrosis were demonstrated in seven, eight, and nine cases respectively. Immunohistochemical studies confirmed that the atypical cells of all 11 cases exhibited T-cell markers. All but one case had lost one or more T-cell markers associated with peripheral T cells, particularly T1 and T3. Loss of T-cell markers in the five cases histologically consistent with polymorphic reticulosis provided further support to indicate that the lesion was neoplastic. A significant proportion of cases also expressed the activated T-cell markers 12 (HLA-DR) and interleukin-2 receptor (IL-2R1).

Angiocentric T-cell lymphoma of the skin. An aggressive lymphoma distinct from mycosis fungoides.

Among 37 consecutive cases of malignant lymphoma in which the skin was either the only site of disease or one of the prominent sites of initial involvement, 19 cases had a distinctive histological appearance. These cases corresponded to what has been termed "angiocentric lymphoma," and all were found to exhibit a T-cell phenotype either by frozen-section immunohistochemistry or by using monoclonal antibodies reactive in paraffin sections. There were nine men and 10 women; the mean age was 48.2 years. The lesions were nodular and were either ulcerated or had intact skin. One case presented with involvement of one anatomical region of skin, five had involvement of multiple regions of skin, and 13 had concurrent extracutaneous disease. The disease pursued an aggressive course and was not uncommonly resistant to treatment. Histologically, the lymphomatous infiltrate occurred predominantly in the mid to deep dermis with involvement of the subcutaneous layer. The pattern was mainly perivascular and peri-adnexal with or without confluence; the overlying epidermis and papillary dermis were often spared. A prominent feature was invasion of small or large blood vessels by lymphoma cells. Eight cases showed extensive coagulative necrosis of the neoplastic and normal tissues, and 12 cases showed intraneural invasion. The neoplastic lymphoid cells consisted of either a monomorphous population or a variable mixture of small, medium-sized, and large cells with stippled chromatin and distinct nucleoli. Although the nuclei were often irregularly folded, few exhibited a cerebriform configuration. The cytoplasm was pale to clear. These cases exhibit a remarkable histological similarity to the T-cell lymphomas of the nasal/nasopharyngeal region; in addition, there are features that overlap with so-called lymphomatoid granulomatosis of the skin.

Effect of audit on door-to-inflation times in primary angioplasty/stenting for acute myocardial infarction.

We found that after audit and physician-guided changes in our protocol, the door-to-inflation times for primary angioplasty/stenting were markedly reduced. Because our preaudit mean time was similar to the national average, this may have wide applicability.

Acute myocardial infarction and vascular remodeling.

We used intravascular ultrasound to show that outward remodeling predominates in lesions responsible for acute myocardial infarction, whereas negative remodeling is far more prevalent in lesions responsible for chronic stable angina. The total cholesterol:high-density lipoprotein ratio was also strongly correlated with outward remodeling.

Expression of natural killer cell markers in non-Hodgkin's lymphomas.

One hundred forty-nine cases of non-Hodgkin's lymphoma were studied with a panel of monoclonal antibodies, including antibodies to natural killer (NK) cells--anti-NKH1, anti-Leu 7, and anti-Leu 11b. There were 95 B-cell, 51 T-cell, and three null cell lymphomas. Seventeen T-cell lymphomas (33 per cent) expressed NKH1, Leu 7, and/or Leu 11b. None of the B- or null cell lymphomas expressed the NK markers. In comparison with the NK-negative T-cell lymphomas, the NK-positive cases showed a predilection for the nasal and paranasal region. There was a more significant loss of the T-cell markers T3 (peripheral T cell) and T4 (T-helper cell) in NK-positive lymphomas. The difference was due to a high proportion of nasal/paranasal lymphomas, which were associated with a frequent loss of T-cell markers, among the NK-positive cases. However, a similar degree of loss of T-cell markers was observed among NK-positive and NK-negative nasal/paranasal lymphomas. We conclude that expression of NK markers occurs exclusively in a proportion of T-cell lymphomas, but not B-cell or null cell lymphomas. The reason this occurs predominantly in nasal and paranasal lymphomas is unknown.

Peripheral T and putative natural killer cell lymphomas commonly coexpress CD95 and CD95 ligand.

The CD95 (Fas)/CD95 ligand (CD95L) system is an important mechanism triggering apoptosis, and CD95L expression has recently been implicated for immune evasion and aggressive behavior in malignancies. This study aimed to investigate CD95 and CD95L expression in lymphomas and the possible relationship with tumor cell apoptosis, with emphasis on the natural killer (NK) cell lymphomas, which are highly aggressive neoplasms and frequently exhibit tumor cell apoptosis/necrosis. Frozen sections of 82 cases of lymphomas obtained from Queen Elizabeth Hospital and Caritas Medical Center, Hong Kong, were immunostained with polyclonal anti-CD95 and anti-CD95L antibodies. The NK-cell lymphomas were also studied for apoptosis by in situ end labeling (ISEL) method, and zonal tumor cell death was evaluated semiquantitatively. The cases studied included 27 NK-, 22 T-, and 33 B-cell lymphomas. CD95 was expressed in 25 (93%) NK-, 11 (50%) T-, and 14 (42%) B-cell lymphomas. CD95L was expressed in 19 (70%) NK-, 15 (68%) T-, and 3 (9%) B-cell lymphomas. There was significant difference in the frequency of CD95 expression between B- and NK- (P < .001), and between T- and NK-cell lymphomas (P < .05), and in CD95L expression between B- and T- (P < .01) or NK-cell (P < .01) lymphomas. Zonal tumor cell death was present in 21 (78%) NK-cell lymphomas and 1 (4.5%) T-cell lymphoma and showed no correlation with CD95 or CD95L expression. ISEL analysis showed apoptosis predominantly in the viable areas in only 5 (24%) NK-cell lymphomas. In conclusion, CD95L is frequently expressed in NK- and T-cell lymphomas, but rarely in B-cell lymphomas. Zonal tumor cell death is not correlated with CD95 or CD95L expression and thus the CD95/CD95L system probably does not contribute significantly to this phenomenon. We postulate that the frequent expression of CD95L by NK- and T-cell lymphomas may mediate local or systemic tissue damage and immune evasion, and may contribute to the clinical aggressiveness of these tumors.

IgA nephropathy and membranous nephropathy associated with hepatitis B surface antigenemia.

This is the first report of glomerular disease in a 13-year-old boy who was a carrier of hepatitis B virus both mesangial IgA and subepithelial IgG deposits in the glomeruli at the same time. The clinical findings resembled those of IgA nephropathy. On electron microscopy, electron-dense deposits were identified not only in the mesangium but also on the epithelial side of the glomerular basement membrane. Immunofluorescence and immunoperoxidase staining demonstrated hepatitis B surface antigen and hepatitis B core antigen in the glomeruli but hepatitis B e antigen was not detected. Our findings suggest hepatitis B virus antigens have a pathogenetic role in the simultaneous development of these two glomerulopathies.

Monoclonal antibodies reactive with normal and neoplastic T cells in paraffin sections.

Without fresh or frozen tissue, it previously has been impossible to confirm the T-cell nature of reactive or neoplastic lymphoid cells. The availability of antibodies reactive with T cells in paraffin sections now allows retrospective analysis of a large number of cases. Two commercially available monoclonal antibodies, MT1 and MT2, were tested for their reactivities with T cells in a wide range of formalin-fixed, paraffin-embedded tissues, including 130 cases of immunologically characterized lymphoma. In reactive lymph nodes, MT1 stained the T-cell areas, whereas MT2 stained both the T-cell areas and mantle-zone B lymphocytes. MT1 stained 38 of 55 T-cell lymphomas (69.1%; 94.7% of cases from one hospital that used a shorter fixation time, and 55.6% of cases from another hospital that used a longer fixation time). MT2 stained only 6 (10.9%) of the T-cell lymphomas. Among the 74 cases of B-cell lymphoma, 3 (4.0%) were stained by MT1 and 30 (40.5%) by MT2.MT1 was also reactive with 3 of 4 cases of granulocytic sarcoma, as expected from its reactivity with normal granulocytes. Neither MT1 nor MT2 stained Reed-Sternberg cells or their variants in HodgKin's disease. We conclude that MT1 is a valuable marker for T cells, particularly when used with a panel of antibodies reactive with B cells in paraffin sections. MT2 is of limited value because of its cross-reactivity with many B-cell lymphomas.

CD56+ putative natural killer cell lymphomas: production of cytolytic effectors and related proteins mediating tumor cell apoptosis?

Apoptosis is a regulated form of cell death that may be triggered by natural killer (NK) or cytotoxic T cells, which effect target cell lysis by cytolytic effector and related proteins through complex intracellular signals. This study was aimed to investigate whether there is selective expression of these cytolytic markers in the putative NK-cell lymphomas and whether there is correlation with zonal tumor cell death in these tumors. Expression of the cytolytic effectors perforin, granzyme B9, and the granule membrane protein TIA1 were examined in 24 putative NK-cell lymphomas, 18 postthymic T-cell lymphomas (one case CD8+ CD56+ and three anaplastic large cell lymphomas (ALCL), three T-lymphoblastic lymphomas, and 20 B-cell lymphomas. Nineteen (79%) putative NK-cell lymphomas expressed perforin, and all 24 cases expressed granzyme B9 and TIA1. The only CD8+ CD56+ postthymic T-cell lymphoma also expressed all three cytolytic markers, two CD8- ALCL expressed TIA1; other postthymic T-cell, T-lymphoblastic, and B-cell lymphomas were consistently negative. There was strong correlation between percentage perforin-positive cells and zonal tumor cell death. Angioinvasion, in contrast, was present only in a proportion (37%) of these lymphomas despite the frequent presence of zonal tumor cell death (71%). We propose that cytolytic effector and related proteins produced by putative NK and some CD8+ CD56+ postthymic T-cell lymphomas, probably in conjunction with other mechanisms, may effect massive tumor cell apoptosis. The frequent expression of cytolytic effector markers in the CD2+ surface CD3- CD56+ putative NK-cell lymphomas lends further support to their probable NK cell origin.

Hepatitis with isolated serum antibody to hepatitis B core antigen. A variant of non-A, non-B hepatitis?

Antibody to hepatitis B core antigen (anti-HBc) has previously been recognized to be a sensitive marker of hepatitis B virus (HBV) infection. In addition, anti-HBc has recently been suggested to be a surrogate marker for non-A, non-B hepatitis agents in donated blood. The authors studied prospectively the HBV antigen and antibody status in four patients with chronic hepatitis and persistent presence of isolated anti-HBc in their sera. The serologic and histopathologic findings of these four patients were compared with those of three groups of patients having chronic hepatitis with or without HBV markers. A low concentration of serum HBV DNA was detected in only one of the four patients with hepatitis with isolated anti-HBc and in another patient with previous HBV infection. HBV antigens and HBV DNA were not detected in the sera and liver biopsies from the remaining patients with hepatitis with isolated anti-HBc and other patients with hepatitis with or without serologic markers of previous hepatitis A or HBV infection. In contrast, all patients with chronic HBV-associated hepatitis had detectable HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B e antigen (HBeAg) in their sera and/or liver biopsies. These findings suggest that chronic hepatitis associated with isolated anti-HBc is a heterogenous pathologic entity. The condition of some of these patients may represent a variant of non-A, non-B hepatitis, whereas the remaining patients are chronic hepatitis B carriers with low serum concentrations of HBV.

Molecular detection of Mycobacterium tuberculosis in tissues showing granulomatous inflammation without demonstrable acid-fast bacilli.

Early diagnosis of tuberculosis (TB) is important for early medical intervention and prevention of spread of the bacteria. It is not uncommon to observe granulomatous inflammation but without demonstrable acid-fast bacilli (AFB) on Ziehl-Neelsen (ZN) staining in tissues sent for histologic examination, and the definitive diagnosis of TB cannot be made because no concurrent tissue is sent for TB culture. In this study, the authors explored the feasibility of using polymerase chain reaction (PCR) for early detection of Mycobacterium tuberculosis (Mtb) in formalin-fixed, paraffin-embedded tissues where a definite diagnosis of TB cannot be made. One hundred fifteen patients (131 paraffin blocks of biopsy specimens) with granulomatous inflammation but ZN-negative for AFB were studied. DNA was extracted from paraffin sections and amplified by PCR with the IS6110 primers (specific for the Mtb complex) and the specific 122-base pairs (bp) PCR product was detected by agarose gel electrophoresis. Sixty-eight of the 115 (59%) patients were TB-PCR positive, thus enabling definite diagnosis of TB in significant numbers of these patients in 3 days. The authors conclude that molecular diagnosis by PCR is useful for early detection of TB in histologic material where morphologic features are suggestive but not confirmatory because of negative staining for AFB.

Meningiomas and arachnoid cells: an immunohistochemical study of epithelial markers.

Twenty-nine cases of meningioma were studied by immunoperoxidase staining using broad-spectrum antibodies to cytokeratin (AE1/AE3), carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA). Twenty-six cases (90%) showed positive staining for EMA. All cases were negative for cytokeratin and CEA except for the two cases of secretory meningioma. Normal arachnoidal cells of the leptomeninges from 15 autopsies were studied similarly, and 10 cases (67%) demonstrated positive staining for EMA, but not for CEA and cytokeratin. Literature from previous investigations on epithelial markers of meningiomas is reviewed. It is concluded that meningiomas and normal arachnoidal cells share similar immunohistochemical properties, and that EMA is a useful epithelial marker for meningiomas.

Immunophenotypic analysis of non-Hodgkin's lymphomas in Chinese. A study of 75 cases in Hong Kong.

The cell surface markers of 75 cases of non-Hodgkin's lymphoma were studied on cryostat sections using a panel of monoclonal antibodies. Forty-nine cases (65.3%) were found to express a B-cell phenotype, 23 cases (30.7%) a T-cell phenotype, 1 case (1.3%) a histiocytic phenotype and 2 cases (2.7%) no demonstrable surface markers. Follicular lymphoma accounted for only 10.7% of the cases. Most B-cell lymphomas expressed IgM-lambda or IgM-IgD-lambda, but a few failed to express surface immunoglobulin. Among the 23 cases of T-cell lymphoma, 22 were of peripheral T-cell type; most were of helper-cell (T4) phenotype and a significant number expressed J5 (CALLA) and I2 (HLA-DR). The present study shows that the percentage of T-cell lymphoma in Chinese is higher than in Caucasians, but lower than in Japanese. However, when the age-adjusted incidence of non-Hodgkin's lymphoma is considered, the incidence rates of T-cell lymphoma in Hong Kong Chinese and Japanese in areas non-endemic for adult T-cell lymphoma/leukemia are similar; the incidence in Americans is similar or slightly lower. The major difference between the races is that B-cell lymphoma, particularly the follicular type, is much rarer in Asians than Americans.

Rapid detection of common southeast Asian beta-thalassemia mutations by nonisotopic multiplex PCR-SSCP analysis.

This report describes the detection of seven beta-thalassemia mutations common in Southeast Asia by amplifying three short PCR fragments in two separate tubes, followed by single-strand conformation polymorphism (SSCP) analysis in single lanes. These mutations are -28 A --> G, codon 17 A --> T, IVS1 + 5 G --> C, codon 41/42 -CTTT, codon 43 G --> T, codon 71/72 + A, and IVS2 + 654 C --> T, and account for 70% to over 95% of the cases in this region. This rapid nonisotopic method was also found capable of detecting other mutations within the amplified fragments. It is simple, rapid, and cheap, and thus suitable for carrier screening and prenatal diagnosis in Southeast Asia.