A high-volume study on the impact of diabetes mellitus on clinical outcomes after surgical and percutaneous cardiac interventions.

BACKGROUND: Type I and type II diabetes mellitus (DM) patients have a higher prevalence of cardiovascular diseases, as well as a higher mortality risk of cardiovascular diseases and interventions. This study provides an update on the impact of DM on clinical outcomes, including mortality, complications and reinterventions, using data on percutaneous and surgical cardiac interventions in the Netherlands. METHODS: This is a retrospective, nearby nationwide study using real-world observational data registered by the Netherlands Heart Registration (NHR) between 2015 and 2020. Patients treated for combined or isolated coronary artery disease (CAD) and aortic valve disease (AVD) were studied. Bivariate analyses and multivariate logistic regression models were used to evaluate the association between DM and clinical outcomes both unadjusted and adjusted for baseline characteristics. RESULTS: 241,360 patients underwent the following interventions; percutaneous coronary intervention(N = 177,556), coronary artery bypass grafting(N = 39,069), transcatheter aortic valve implantation(N = 11,819), aortic valve replacement(N = 8,028) and combined CABG and AVR(N = 4,888). The incidence of DM type I and II was 21.1%, 26.7%, 17.8%, 27.6% and 27% respectively. For all procedures, there are statistically significant differences between patients living with and without diabetes, adjusted for baseline characteristics, at the expense of patients with diabetes for 30-days mortality after PCI (OR = 1.68; p <.001); 120-days mortality after CABG (OR = 1.35; p <.001), AVR (OR = 1.5; p <.03) and CABG + AVR (OR = 1.42; p =.02); and 1-year mortality after CABG (OR = 1.43; p <.001), TAVI (OR = 1.21; p =.01) and PCI (OR = 1.68; p <.001). CONCLUSION: Patients with DM remain to have unfavourable outcomes compared to nondiabetic patients which calls for a critical reappraisal of existing care pathways aimed at diabetic patients within the cardiovascular field.

Improvement of angiographic and clinical outcomes of percutaneous coronary intervention for chronic total occlusion after implementation of a dedicated team: a single-centre experience.

INTRODUCTION: In a Dutch heart centre, a dedicated chronic total occlusion (CTO) team was implemented in June 2017. The aim of this study was to the evaluate treatment success and clinical outcomes before and after this implementation. METHODS: A total of 662 patients who underwent percutaneous coronary intervention (PCI) for a CTO between January 2013 and June 2020 were included and divided into pre- and post-CTO team groups. The primary endpoint was the angiographic success rate of CTO-PCI. Secondary endpoints included angiographic success stratified by complexity using the J­CTO score and the following clinical outcomes: in-hospital complications and myocardial infarction, target vessel revascularisation, all-cause mortality, quality of life (QoL) and major adverse cardiac events (MACE) at 30-day and 1­year follow-up. RESULTS: Compared with the pre-CTO team group, the success rate in the post-CTO team group was higher after the first attempt (81.4% vs 62.7%; p < 0.001) and final attempt (86.7% vs 73.8%; p = 0.001). This was mainly driven by higher success rates for difficult and very difficult CTO lesions according to the J­CTO score. The MACE rate at 1 year was lower in the post-CTO team group than in the pre-CTO team group (6.4% vs 16.0%; p < 0.01), while it was comparable at 30-day follow-up (0.1% vs 1.7%; p = 0.74). Angina symptoms were significantly reduced at 30-day and 1­year follow-up, and QoL scores were higher after 1 year. CONCLUSION: This study demonstrated higher success rates of CTO-PCI and improved clinical outcomes and QoL at 1­year follow-up after implementation of a dedicated CTO team using the hybrid algorithm.

Report on outcomes of valve-in-valve transcatheter aortic valve implantation and redo surgical aortic valve replacement in the Netherlands.

OBJECTIVE: We sought to investigate real-world outcomes of patients with degenerated biological aortic valve prostheses who had undergone valve-in-valve transcatheter aortic valve implantation (ViV-TAVI) or reoperative surgical aortic valve replacement (redo-SAVR) in the Netherlands. METHODS: Patients who had undergone ViV-TAVI or redo-SAVR for a degenerated biological aortic valve prosthesis in the Netherlands between January 2014 and December 2018 were eligible for this retrospective study. Patients with a prior homograft, active endocarditis or mechanical aortic valve prosthesis were excluded. Patients were matched using the propensity score. The primary endpoint was a composite of 30-day all-cause mortality and in-hospital postoperative stroke. Secondary endpoints were all-cause mortality at different time points, in-hospital postoperative stroke, pacemaker implantation and redo procedures within one year. Baseline characteristics and outcome data were collected from the Netherlands Heart Registration. RESULTS: From 16 cardiac centres, 653 patients were included in the study (374 ViV-TAVI and 279 redo-SAVR). European System for Cardiac Operative Risk Evaluation I (EuroSCORE I) was higher in ViV-TAVI patients (19.4, interquartile range (IQR) 13.3-27.9 vs 13.8, IQR 8.3-21.9, p < 0.01). After propensity score matching, 165 patients were matched with acceptable covariate balance. In the matched cohorts, the primary endpoint was not significantly different for ViV-TAVI and redo-SAVR patients (odds ratio 1.30, 95% confidence interval 0.57-3.02). Procedural, 30-day and 1­year all-cause mortality rates, incidence of in-hospital postoperative stroke, pacemaker implantation and redo procedures within one year were also similar between cohorts. CONCLUSION: Patients with degenerated aortic bioprostheses treated with ViV-TAVI or redo-SAVR have similar mortality and morbidity.

Better survival after transcatheter aortic valve replacement by process improvements.

OBJECTIVE: The aim of this study is to assess the effects on procedural, 30-day, and 1­year all-cause mortality by a newly introduced quality improvement strategy in patients after transcatheter aortic valve replacement (TAVR). METHODS: In October 2015, a coherent set of quality improving interventions with respect to patient geriatric screening, general diagnostic examination and safety of the procedure was implemented at a single centre in the Netherlands. Patients undergoing TAVR in 2013-2018 were included for retrospective analysis. Mortality was assessed in the pre-quality improvement strategy cohort (January 2013 to October 2015; cohort A) and in the post-quality improvement strategy cohort (November 2015 to December 2018; cohort B). Logistic regression analysis was used to estimate the influence of patient and procedural characteristics on the results of the quality improvement strategy in terms of procedural, 30-day, and 1­year all-cause mortality. RESULTS: In total, 806 patients were analysed with 274 patients in cohort A and 532 patients in cohort B. After introduction of the quality improvement strategy, procedural (4.4% to 1.3%, p < 0.01), 30-day (8.4% to 2.7%, p < 0.01) and 1­year (16.4% to 8.5%, p < 0.01) all-cause mortality significantly decreased. Multivariate regression analysis showed that the quality improvement strategy also significantly reduced 30-day (odds ratio [OR] 0.19, 95% confidence interval [CI] 0.09-0.42) and 1­year (OR 0.38, 95% CI 0.24-0.61) all-cause mortality if corrected for patient characteristics. CONCLUSION: Structural meetings on evaluation of outcomes highlight potential areas for improvement and subsequent outcome-based quality improvement initiatives can result in lower procedural, 30-day, and 1­year all-cause mortality.

IMPROV-ED trial: eHealth programme for faster recovery and reduced healthcare utilisation after CABG.

BACKGROUND: After coronary artery bypass grafting (CABG), healthcare utilisation is high and is partly unplanned. eHealth applications have been proposed to reduce healthcare consumption and to enable patients to get actively involved in their recovery. This way, healthcare expenses can be reduced and the quality of care can be improved. OBJECTIVES: We aim to evaluate whether the use of an eHealth programme can reduce unplanned healthcare utilisation and improve mental and physical health in the first 6 weeks after discharge in patients who underwent CABG. In addition, patient satisfaction and use of the eHealth programme will be evaluated. METHODS: For this single-centre randomised controlled trial, at least 280 patients referred for CABG will be included at the preoperative outpatient clinic and randomised to an intervention or control group. The intervention group will have access to an eHealth programme, which consists of online educational videos developed by the Dutch Heart Foundation and postoperative video consultations with a physician. The control group will receive standard care and will not have access to the eHealth programme. The primary endpoint is healthcare utilisation; other endpoints include anxiety, duration of recovery, quality of life and patient satisfaction. Participants will complete several questionnaires at 6 time points during the study. RESULTS: Patient enrolment started in February 2020 and completion of the follow-up period is expected in August 2021. CONCLUSION: This randomised trial was initiated to test the hypothesis that patients who are partaking in our eHealth programme use less unplanned care and experience a better quality of life, less anxiety and a faster recovery than controls.

Long-term course of L-dopa-responsive dystonia caused by tyrosine hydroxylase deficiency.

The authors report the long-term course of two siblings with L-dopa responsive dystonia (DRD) associated with a compound heterozygous mutation in the tyrosine hydroxylase (TH) gene. Both siblings manifested with lower-limb onset generalized DRD and had a sustained response to low-dose L-dopa therapy for over 35 years. Although the l-dopa therapy was delayed up to 20 years after disease onset, there were no cognitive or neurologic sequelae of the long-term catecholamine deficit.

Molecular analysis of myophosphorylase deficiency in Dutch patients with McArdle's disease.

We report on 8 Dutch patients with McArdle's disease from 6 unrelated families. Molecular analysis revealed the presence of four previously described mutations: the common R49X mutation, the IVS14+1G>A mutation and the recently reported R269X and Y84X nonsense mutations; and two new molecular defects: a missense mutation R138W in the homozygous state in two siblings, and a frameshift mutation c.1797delT. This first genetic study of patients from The Netherlands with McArdle's disease confirms that the R49X mutation is also the most common in Dutch patients, and that there is genetic heterogeneity within this population. Moreover, our data support the hypothesis that the Y84X mutation is a relatively frequent mutation in McArdle's patients with a Central European background, and expand the already crowded map of mutations within the PYGM gene responsible for McArdle's disease.

Clinical and molecular genetic characteristics of patients with cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease caused by a deficiency of the mitochondrial enzyme 27-sterol hydroxylase (CYP 27), due to mutations in its gene. In this study we report on mutations in 58 patients with CTX out of 32 unrelated families. Eight of these were novel mutations, two of which were found together with two already known pathogenic mutations. Twelve mutations found in this patient group have been described in the literature. In the patients from 31 families, mutations were found in both alleles. In the literature, 28 mutations in 67 patients with CTX out of 44 families have been described. Pooling our patient group and the patients from the literature together, 37 different mutations in 125 patients out of 74 families were obtained. Identical mutations have been found in families from different ethnic backgrounds. In 41% of all the patients, CYP 27 gene mutations are found in the region of exons 6-8. This region encodes for adrenodoxin and haem binding sites of the protein. Of these 125 patients, a genotype-phenotype analysis was done for 79 homozygous patients harbouring 23 different mutations, out of 45 families. The patients with compound heterozygous mutations were left out of the genotype-phenotype analysis. The genotype-phenotype analysis did not reveal any correlation.

Genetic characteristics of myoadenylate deaminase deficiency.

Two types of myoadenylate deaminase (MAD) deficiency have been described, primary or inherited, and secondary or acquired MAD deficiency. In this study, we investigated whether secondary MAD deficiency is indeed acquired or merely coincidental. We demonstrated the same underlying molecular defect, a C34T transition, in both types of deficiency. Furthermore, the same frequency of the mutant MAD allele was found in the general population as in patients with neuromuscular complaints. We therefore conclude that in the Dutch population, secondary MAD deficiency is merely a "coincidental" finding, and that MAD deficiency is a harmless genetic variant.

The impact of human immunodeficiency virus on response to treatment and recurrence rate in patients treated for tuberculosis: two-year follow-up of a cohort in Lusaka, Zambia.

To examine the effect of HIV on response to treatment and recurrence rate in patients with tuberculosis (TB), we have followed 239 previously untreated, adult, TB patients in a prospective cohort study in Lusaka, Zambia. One hundred and seventy-four (73%) were HIV-1 antibody positive. Patients with sputum smear positive, miliary, or meningeal TB were prescribed 2 months daily streptomycin, thiacetazone, isoniazid, rifampicin, pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. Thirty-five per cent of HIV-positive (HIV+ve) and 9% of HIV-negative (HIV-ve) patients were known to have died before the scheduled end of treatment. Surviving HIV+ve patients showed weight gain and improvement in symptoms and laboratory and radiological findings similar to HIV-ve patients. The risk of cutaneous drug reaction was 17% (95% CI: 12-25%) in HIV+ve, and 4% (1-13%) in HIV-ve patients. Severe rashes were attributed to thiacetazone. Recurrence of active TB was examined among 64 HIV+ve and 37 HIV-ve patients who successfully completed treatment, with mean follow-up after the end of treatment of 13.5 and 16.8 months, respectively. The rate of recurrence was 22/100 person years (pyr) for HIV+ve patients and 6/100 pyr for HIV-ve patients, giving a recurrence rate ratio of 4.0 (95% CI 1.2-13.8, P = 0.03).

PIP: In 1989, researchers followed 239 newly diagnosed adult patients with tuberculosis (TB), never previously treated for TB, for two years to examine the response to TB treatment among patients with and without HIV infection and the TB recurrence rate. They were patients in the medical wards and the chest clinic outpatients' department of the University Teaching Hospital in Lusaka, Zambia. 174 (73%) tested positive for HIV. HIV-positive patients were more likely than HIV-negative patients to have extrapulmonary and both pulmonary and extrapulmonary TB (35% and 26% for both, respectively vs. 17% and 12%, respectively; p 0.001). They were less likely to have positive sputum tests than HIV-negative patients (36% vs. 57% for smear; p = 0.005 and 39% vs. 55% for culture; p = 0.03). HIV-positive patients were more likely to receive standard TB therapy (62% vs. 37%), while HIV-negative patients were more likely to receive short course therapy (62% vs. 37%; p = 0.001). HIV-positive patients were more likely than HIV-negative patients to die before completion of treatment (35% vs. 9%). Surviving HIV-positive patients gained weight and experienced improvement in symptoms at the same rate as did surviving HIV-negative patients. They also had similar laboratory and radiological findings. HIV-positive patients had a higher risk of cutaneous drug reaction than HIV-negative patients (17% vs. 4%; hazard ratio = 5.1; p = 0.03). One HIV-positive patient with a rash died. Thiacetazone was responsible for the rashes. Among the HIV-positive and HIV-negative patients who successfully completed treatment, the active TB recurrence rate was greatest for HIV-positive patients (22 vs. 6/100 person years; rate ratio = 4; p = 0.03). Yet, all but one of the HIV-positive cases with recurrent TB responded well to TB treatment. High recurrence rates pose renewed potential sources of infection and a high cost of renewed treatment.

The impact of human immunodeficiency virus on mortality of patients treated for tuberculosis in a cohort study in Zambia.

We have examined the impact of human immunodeficiency virus (HIV) on mortality of patients treated for tuberculosis in a prospective study in Lusaka, Zambia. Patients with sputum smear-positive, miliary, or meningeal tuberculosis were prescribed 2 months' daily streptomycin, thiacetazone, isoniazid, rifampicin, and pyrazinamide followed by 6 months thiacetazone and isoniazid; others, 2 months streptomycin, thiacetazone and isoniazid followed by 10 months thiacetazone and isoniazid. 239 patients (65 HIV-negative and 174 HIV-positive) were followed to 2 years from start of treatment. The crude mortality rate ratio for HIV-positive compared with HIV-negative patients over 2 years was 5.00 (95% confidence interval 2.30-10.86). Median survival for HIV-positive patients from the start of treatment was 22 months. At least 34% of HIV-positive patients for whom cause of death was known died from tuberculosis, three-quarters of these during the first month of treatment. Risk factors for death in HIV-positive patients included multi-site tuberculosis, history of prolonged diarrhoea or fever, oral thrush, splenomegaly, anergy to tuberculin, low weight, anaemia or lymphopenia, and poor compliance with regimens containing rifampicin and pyrazinamide. Tuberculosis, even treated, was a major cause of death in patients with HIV infection.

PIP: The impact of HIV on mortality is described in a prospective study of tuberculosis patients in Lusaka, Zambia, where more than 70% of newly diagnosed tuberculosis patients have concurrent HIV infection. Patients attending the University Teaching Hospital in Lusaka, Zambia, were recruited to a prospective cohort study from April to December 1989. Of the 239 patients included in the follow-up study, 174 (73%) were HIV-1 positive by ELISA. A higher proportion of HIV-positive patients were 25-34 years old, and they more often had a negative tuberculin response, anemia, or lymphopenia at recruitment. The probability of survival for HIV-negative and HIV-positive patients was, respectively: at 2 months 95% and 89%; at 6 months 95% and 76%; at 12 months 91% and 66%; at 18 months 87% and 55%; and at 24 months 87% and 48%. The median survival of HIV-positive patients was 22 months. The crude, 2-year mortality rate ratio for HIV-positive compared with HIV-negative patients was 5 (p 0.001). Mortality was higher for patients with both pulmonary and extrapulmonary disease than for those with either pulmonary or extrapulmonary disease alone; for individual sites, only lymph node disease was associated with a significantly higher mortality than other sites (p = 0.01). At presentation prolonged fever, prolonged diarrhea, oral Candida or splenomegaly, negative tuberculin response, anemia or lymphopenia and low weight were associated with higher mortality. Among the 39 patients seen at 2 months who had been prescribed short-course chemotherapy, subsequent mortality was lower in the group who reported receiving all 60 doses of either rifampicin or pyrazinamide or both (20 patients) than among those who had not (19 patients¿ (rate ratio 0.24, p = 0.02). 47 of the 81 patients died within 24 months of the start of treatment, 5 HIV-negative and 42 HIV-positive. 3 of 5 HIV-negative patients for whom information was available died of active tuberculosis. Among HIV-positive patients, 14 of 42 died of active tuberculosis and 2 more of complications of tuberculosis.

Cross-sectional assessment of ELISA reactivity in leprosy patients, contacts, and normal population using the semisynthetic antigen natural disaccharide octyl bovine serum albumin (ND-O-BSA) in Cebu, The Philippines.

An indirect enzyme-linked immunosorbent assay (ELISA) using natural disaccharide octyl bovine serum albumin (ND-O-BSA) as antigen was used in testing leprosy patients, contacts and a normal population in Cebu, The Philippines, from 1985 to 1989. A total of 1413 persons were studied. The results suggested that ELISA reactivity and the bacterial index (BI) correlate in a general way. In multibacillary (MB) leprosy, positivity ranges from 54.2% to 92.3% among patients with a BI of < 2+ to > 4+ on the Ridley scale, with an overall average of 84.5%. Paucibacillary (PB) leprosy patients have a low degree of reactivity, with only 15.0% ELISA positive. The test is more efficient in detecting MB than PB leprosy. The contacts of MB leprosy showed 6.5% positivity; contacts of PB leprosy, 7.0% positivity. The normal population showed 1.7% positive ELISA or 17 per thousand population, which is very much less than that of the household contacts. However, because the normal population is a much larger population than the household contact population in a community, more new leprosy cases would emanate from it. Leprosy workers are concerned about the transmission of the disease to household contacts. However, for the reason stated above, we should be more concerned with the silent spread of the disease to the normal population in the community.(ABSTRACT TRUNCATED AT 250 WORDS)

The impact of human immunodeficiency virus on presentation and diagnosis of tuberculosis in a cohort study in Zambia.

Two hundred and forty-nine patients with tuberculosis were recruited to a cohort study to investigate the interaction between tuberculosis and HIV in Lusaka, Zambia; findings at presentation are presented here. One hundred and eighty-two (73%; 95% confidence interval 67-79%) of the cases were HIV-1 antibody positive. The diagnosis of tuberculosis was confirmed by microscopy for acid-alcohol fast bacilli, culture of Mycobacterium tuberculosis, or histology in 74% of all cases. HIV negative and positive cases differed in site of disease: among HIV negative patients 72% had pulmonary disease alone, 16% extrapulmonary disease alone and 12% had both, whereas among HIV positive patients 40% had pulmonary disease alone, 34% extrapulmonary disease alone and 26% both (P < 0.001). HIV negative and positive cases were compared with regard to outcome of diagnostic procedures: 55% of HIV negative cases could be diagnosed at enrollment by sputum smear, but only 35% of HIV positive cases (P < 0.01). Among pulmonary cases confirmed by sputum culture, 76% of HIV negative patients had a positive sputum smear, compared with 57% of HIV positive patients (P = 0.09). Pleural and pericardial disease were difficult to confirm, but culture of pleural fluid was positive in 12/46 HIV positive patients, compared with 0/11 HIV negative patients. Lymph node disease was readily confirmed by biopsy. The tuberculin test was positive in only 30/110 (27%) of HIV positive cases, but in 21/38 (55%) of HIV negative cases (P < 0.01). Mycobacterium tuberculosis was cultured in 57% of HIV negative cases and 54% of HIV positive cases; no atypical mycobacteria were isolated. Initial resistance to isoniazid was present in isolates from 5% of cases with a positive culture.

Leprosy control in Zambia.

Leprosy was a serious public health problem in Zambia until recently, with over 16,000 cases in 1982. Since then leprosy patients in the country have been put under multidrug therapy (MDT), as recommended by WHO, with support from the Sasakawa Memorial Health Foundation. Leprosy control in Zambia is combined with tuberculosis control and integrated within general health services. By 1990 52 districts (93%) had MDT, with an overall coverage of about 70% of all patients. As a result the number of registered cases has come down steadily from 16,642 in 1982 to 3,663 in 1989. Similarly, the number of new cases detected has been reduced from 1,010 cases in 1982 to 577 in 1989. On the whole the programme has gained significant momentum, although it is too early to expect a complete eradication of the disease in the near future, given the continued low level of observed new cases. Further, the implementation of MDT still lags behind the projected targets so that the potential of MDT is not being fully utilized. In addition, the problem of rehabilitation of disabled patients needs special attention. A subprogramme aimed at reducing disability through community participation is being developed within the framework of primary health care.

Impact of HIV on tuberculosis in Zambia: a cross sectional study.

OBJECTIVE: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis in central Africa. DESIGN: Cross sectional study. SETTING: Outpatient clinic in teaching hospital, Lusaka, Zambia. PATIENTS: 346 Adult patients with tuberculosis. RESULTS: Overall, 206 patients (60%; 95% confidence interval 54% to 65%) were positive for HIV: in one or both assays used. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 73/149 (49%; 41% to 57%) were positive for HIV; 67/83 (81%; 70% to 89%) patients with pleural disease and 16/19 (84%; 60% to 97%) patients with pericardial disease were positive. HIV positive patients with positive sputum culture were less likely to have had a positive sputum smear, and their chest x ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. CONCLUSIONS: The high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.

PIP: To examine the contribution of HIV infection to the apparently increasing incidence of tuberculosis patients of an outpatient clinic in a teaching hospital in Lusaka, Zambia. Overall, 206 patients (60%) tested positive for HIV. The peaks for both tuberculosis and HIV infection were among men aged 25-34 years and women aged 14-24 years. Of patients with confirmed pulmonary tuberculosis, 49% were positive for HIV. 81% of patients with pleural disease and 84% of patients with pericardial disease were positive. HIV positive patients with a positive sputum culture were less likely to have had a positive sputum smear, and their chest x-ray films less often showed classic upper zone disease or cavitation. Of 72 patients who fulfilled clinical criteria for AIDS, 17 were negative for HIV. In conclusion, the high prevalence of HIV in patients with tuberculosis suggests that an epidemic of reactivating tuberculosis is arising in those who are infected with HIV. The redirection of public health priorities towards tuberculosis would focus on a major treatable and preventable complication of the AIDS epidemic.