Artificial insemination and in-vitro fertilization using donor spermatozoa: a report on 15 years of experience

Donor insemination (DI) using cryopreserved semen commenced at The Royal Women's Hospital in 1976. Over the next 15 years we performed 5953 treatment cycles to achieve 816 pregnancies (13.7% per cycle) and 706 live births. In-vitro fertilization (IVF) using donor spermatozoa commenced in 1986. Over the next 5 years we performed 303 treatment cycles for 185 couples. Including subsequent transfer of cryopreserved embryos, a total of 33% of couples achieved a successful pregnancy by IVF. Statistical analysis indicated that, for DI pregnancies, the most important semen variable was the percentage post-thaw motility, whilst for normal fertilization in IVF it was the pre-freeze motility. These results may be explained by the compensatory effects of post-thaw processing of spermatozoa for IVF, but not for DI in our clinic.      

Effect of shared care on blood pressure in patients with chronic kidney disease: a cluster randomised controlled trial

Background

Chronic kidney disease (CKD) is highly prevalent in patients with diabetes or hypertension in primary care. A shared care model could improve quality of care in these patients

Aim

To assess the effect of a shared care model in managing patients with CKD who also have diabetes or hypertension.

Design and setting

A cluster randomised controlled trial in nine general practices in The Netherlands.

Method

Five practices were allocated to the shared care model and four practices to usual care for 1 year. Primary outcome was the achievement of blood pressure targets (130/80 mmHg) and lowering of blood pressure in patients with diabetes mellitus or hypertension and an estimated glomerular filtration rate (eGFR)<60ml/min/1.73m².

Results

Data of 90 intervention and 74 control patients could be analysed. Blood pressure in the intervention group decreased with 8.1 (95% CI = 4.8 to 11.3)/1.1 (95% CI = −1.0 to 3.2) compared to −0.2 (95% CI = −3.8 to 3.3)/−0.5 (95% CI = −2.9 to 1.8) in the control group. Use of lipid-lowering drugs, angiotensin-system inhibitors and vitamin D was higher in the intervention group than in the control group (73% versus 51%, 81% versus 64%, and 15% versus 1%, respectively, [P = 0.004, P = 0.01, and P = 0.002]).

Conclusion

A shared care model between GP, nurse practitioner and nephrologist is beneficial in reducing systolic blood pressure in patients with CKD in primary care.     

Antibiogram and plasmid profiling of carbapenemase and extended spectrum Beta-lactamase (ESBL) producing Escherichia coli and Klebsiella pneumoniae in Abeokuta,South western,Nigeria

Background

The increased reports of ESBL dissemination from various centres in south western, Nigeria and the recent emergence of carbapenem resistant bacteria prompted the conception of this study.

Objectives

To demonstrate the relationship between high molecular weight plasmids and the expression of antibiotic multi-resistance including ESBL and carbapenemase.

Methods

We investigated 97 isolates of selected organisms consisting of 67 E. coli and 30 Klebseilla spp for the presence of plasmids expressing ESBL including carbapenem-hydrolysing enzymes. Beta-lactamase was determined using acidometric method, while ESBL and carbapenemase activity was determined using the double-disk diffusion test as well as the Modified Hodge test (MHT). Plasmid profiles of ESBL and carbapenemase positive isolates were determined according to standard protocols.

Results

An ESBL prevalence rate of 21.6% and carbapenem- resistance rate of 9.3% was recorded. Antibiotic susceptibility profile of ESBL isolates showed 100.0% resistance against Amoxicillin, Cotrimoxazole and Erythromycin. Moderate susceptibility was recorded against the Quinolone class of antibiotics; Meropenem remained the most active antibiotic against ESBL isolates with 62.5% against E. coli and 60% against K. pneumoniae. The plasmid profiles of our study isolates ranged from 11.8kbp to 35.5kbp.

Conclusion

Due to the relationship between high molecular weight plasmids and multi-drug resistance, we hereby recommend regular molecular surveillance of this form in our study setting.     

Detection of genomic deletions of PKP2 in arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease that predominantly affects the right ventricle and is associated with ventricular arrhythmias that may lead to sudden cardiac death. Mutations within at least seven separate genes have been identified to cause ARVC, however a genetic culprit remains elusive in approximately 50% of cases. Although negative genetic testing may be secondary to pathogenic mutations within undiscovered genes, an alternative explanation may be the presence of large deletions or duplications involving known genes. These large copy number variants may not be detected with standard clinical genetic testing which is presently limited to direct DNA sequencing. We describe two cases of ARVC possessing large deletions involving plakophilin‐2 (PKP2) identified with microarray analysis and/or multiplex ligation‐dependent probe amplification (MLPA) that would have been classified as genotype negative with standard clinical genetic testing. A deletion of the entire coding region of PKP2 excluding exon 1 was identified in patient 1 and his son. In patient 2, MLPA analysis of PKP2 revealed deletion of the entire gene with subsequent microarray analysis demonstrating a de novo 7.9 Mb deletion of chromosome 12p12.1p11.1. These findings support screening for large copy number variants in clinically suspected ARVC cases without clear disease causing mutations following initial sequencing analysis.     

Minimal important differences in the Migraine-Specific Quality of Life Questionnaire (MSQ) version 2.1

To propose minimal important differences (MID) for the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1). To our knowledge (to date), no published MID values exist for the MSQ v2.1 in any population. Analyses were performed on data from two pivotal clinical trials of topiramate for migraine prevention ( n  = 916), as well as from the QualityMetric National Headache Survey ( n  = 1016). Analyses included both distribution- and anchor-based MID techniques as well as group- and individual-level MID values. Group-level anchor-based MID values ranged from 3.2 [Role Restrictive domain (RR)] to 7.5 [Emotional Functioning domain (EF)], setting the minimum level of appropriate MID (which can also aid with power analysis). Individual-level distribution-based MID values resulted in highly similar estimates from two large databases: median MID of 8.5 for RR, 9.2 for Role Preventive (RP) and 12.0 for EF. Finally, individual-level anchor-based MID values ranged from 5.0 (RR and RP domains) to 10.6 (EF). For group-level purposes of calculating power for future studies, an MID of 3.2, 4.6 and 7.5 for RR, RP and EF is recommended. For within-group analyses for analysing clinical trial efficacy of each patient's change with responder analyses, 5 points is necessary for RR. For RP and EF, ranges are recommended: 5.0 to 7.9 for RP and 8.0 to 10.6 for EF. These latter two domains tend to have more error in the MID, and thus a sensitivity analysis with both ends of the range should be used to confirm significant differences in responder analyses.     

Is phenytoin contraindicated in patients receiving cranial irradiation ?

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation.