Does dissemination of guidelines alone increase the use of palliative single-fraction radiotherapy? Initial report of a longitudinal change management campaign at a provincial cancer program.

Background: Despite level 1 evidence demonstrating the equivalence of single-fraction radiotherapy (sfrt) and multiple-fraction radiotherapy (mfrt) for the palliation of painful bone metastases, sfrt remains underused. In 2015, to encourage the sustainable use of palliative radiation oncology resources, CancerCare Manitoba disseminated, to each radiation oncologist in Manitoba, guidelines from Choosing Wisely Canada (cwc) that recommend sfrt. We assessed whether dissemination of the guidelines influenced sfrt use in Manitoba in 2016, and we identified factors associated with mfrt. Methods: All patients treated with palliative radiotherapy for bone metastasis in Manitoba from 1 January 2016 to 31 December 2016 were identified from the provincial radiotherapy database. Patient, treatment, and disease characteristics were extracted from the electronic medical record and tabulated by fractionation schedule. Univariable and multivariable logistic regression analyses were performed to identify risk factors associated with mfrt. Results: In 2016, 807 patients (mean age: 70 years; range: 35-96 years) received palliative radiotherapy for bone metastasis, with 69% of the patients having uncomplicated bone metastasis. The most common primary malignancies were prostate (27.1%), lung (20.6%), and breast cancer (15.9%). In 62% of cases, mfrt was used-a proportion that was unchanged from 2015. On multivariable analysis, a gastrointestinal [odds ratio (or): 5.3] or lung primary (or: 3.3), complicated bone metastasis (or: 4.3), and treatment at a subsidiary site (or: 4.4) increased the odds of mfrt use. Conclusions: Dissemination of cwc recommendations alone did not increase sfrt use by radiation oncologists in 2016. A more comprehensive knowledge translation effort is therefore warranted and is now underway to encourage increased uptake of sfrt in Manitoba.

Practical consensus recommendatons for Paget's disease in breast cancer.

Paget's disease of the breast is a rare type of cancer of the nipple-areola complex and that is often associated with an underlying in situ or invasive carcinoma. Diagnosis and treatment of Paget's disease is controversial. Expert oncologists discuss on the update on the approaches of Paget's disease diagnosis and its treatment options. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Practical consensus recommendations regarding role of mastectomy in metastatic breast cancer.

Whether to recommend mastectomy in metastatic disease or not has been a matter of debate. Is local therapy, such as mastectomy, of any benefit in advanced breast cancer is the main question. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations for the benefit of community oncologists.

Practical consensus recommendations for tumor margins and breast conservative surgery.

My suggestion: There is no difference in survival of breast cancer patients treated with either mastectomy or with breast conservation therapy combined with external beam radiotherapy. A positive margin (s) is an important factor contributing to the increased risk of local recurrence. However, in published literature, there is a lack of consensus on the definition of acceptable margin (s). As a result decision process about need for re-excision after positive margins remains uncrear.

Practical consensus recommendations regarding role of postmastectomy radiation therapy.

The use of radiation therapy after mastectomy (PMRT) has been limited to those patients who are at significant risk of cancer recurring in the chest wall or in the nodal basins. The use of PMRT has been widely accepted for patients with four or more positive lymph nodes,[1],[2] but there is still controversy regarding the value of PMRT for those with one to three positive nodes. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at these practical consensus recommendations for the benefit of community oncologists.

Practical consensus recommendations on duration of adjuvant hormonal therapy in breast cancer.

Optimization of adjuvant systemic therapy in women with early-stage hormone receptor-positive breast cancer includes the consideration of chemotherapy and duration of hormone therapy. Adjuvant hormonal therapy significantly improves long-term survival of breast cancer patients with hormone receptor-positive disease. Despite the proven clinical efficacy of tamoxifen and aromatase inhibitors, many breast cancer survivors either fail to take the correct dosage at the prescribed frequency (adherence) or discontinue therapy (persistence). Expert oncologist discussed on the duration of adjuvant hormonal therapy for improvement of OS and quality of life of breast cancer patients by providing reduction in recurrence and mortality. This expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Synthesis, Characterization, and Thermal Kinetics of Mixed Gadolinium: Calcium Heptamolybdate System.

Synthesis of mixed gadolinium calcium heptamolybdate (GdCaHM) system in silica gel medium using single gel single tube technique has been successfully achieved. The grown crystal exhibits various morphologies, which includes spherulites, multifaceted, and square platelets. The nature of the grown material was established by X-ray diffraction (XRD) studies. Fourier transform infrared spectroscopy (FTIR) study signifies the presence of heptamolybdate (Mo7O24) and water symmetry structure, whereas energy dispersive X-ray analysis (EDAX) establishes the stoichiometric of the grown crystal as GdCaMo7O24·8H2O. The thermal behaviour was studied using the thermoanalytical techniques, which include thermogravimetry (TG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). Results obtained on the application of TG based models, namely, Horowitz-Metzger, Coats-Redfern, and Piloyan-Novikova, suggest the contracting cylindrical model as the relevant model for the thermal decomposition of the material. The kinetic parameters, namely, the order of reaction (n), activation energy (E a ), frequency factor (Z), and entropy (ΔS∗), were also calculated using these three models.

The transcriptome of the arbuscular mycorrhizal fungus Glomus intraradices (DAOM 197198) reveals functional tradeoffs in an obligate symbiont.

• The arbuscular mycorrhizal symbiosis is arguably the most ecologically important eukaryotic symbiosis, yet it is poorly understood at the molecular level. To provide novel insights into the molecular basis of symbiosis-associated traits, we report the first genome-wide analysis of the transcriptome from Glomus intraradices DAOM 197198. • We generated a set of 25,906 nonredundant virtual transcripts (NRVTs) transcribed in germinated spores, extraradical mycelium and symbiotic roots using Sanger and 454 sequencing. NRVTs were used to construct an oligoarray for investigating gene expression. • We identified transcripts coding for the meiotic recombination machinery, as well as meiosis-specific proteins, suggesting that the lack of a known sexual cycle in G. intraradices is not a result of major deletions of genes essential for sexual reproduction and meiosis. Induced expression of genes encoding membrane transporters and small secreted proteins in intraradical mycelium, together with the lack of expression of hydrolytic enzymes acting on plant cell wall polysaccharides, are all features of G. intraradices that are shared with ectomycorrhizal symbionts and obligate biotrophic pathogens. • Our results illuminate the genetic basis of symbiosis-related traits of the most ancient lineage of plant biotrophs, advancing future research on these agriculturally and ecologically important symbionts.

Tolosa-Hunt syndrome: MRI appearances.

A review of MRI findings in seven patients with Tolosa-Hunt syndrome was carried out. Seven patients presented with unilateral painful ophthalmoplegia. Magnetic resonance imaging studies were carried out to evaluate the cavernous sinuses and orbits. Coronal fast spin-echo T2-weighted images and fat-saturated T1-weighted coronal and transverse images with and without contrast enhancement were obtained for the cavernous sinuses and orbits. All patients showed focal-enhancing masses expanding the ipsilateral cavernous sinus. In one patient the mass was extending to the orbital apex and intraorbitally. All patients recovered on corticosteroid therapy and resolution of the masses was documented on follow-up MRI studies in five patients. One patient had a relapse of symptoms after discontinuing therapy. Magnetic resonance imaging studies of the cavernous sinus and orbital apex show high sensitivity for the detection and follow up of inflammatory mass lesions in Tolosa-Hunt syndrome. Magnetic resonance imaging should be the initial screening study in these patients.

A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23.

BACKGROUND: The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous neurodegenerative disorders in which the cardinal pathologic feature is upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. To date, 14 autosomal recessive HSP loci have been mapped. METHODS: We have identified a large consanguineous Omani family in which an autosomal recessive form of HSP is segregating. The age at onset varied from 6 to 11 years and the course of the disease is progressive with intellectual disability and is associated with seizures in two individuals. To map the chromosomal location of the causative gene we undertook 250K gene chip SNP analyses of all affected individuals assuming that a founder mutation was responsible. RESULTS: All affected individuals shared a 20.4 Mb (3.25 cM) region of homozygosity located on chromosome 16q21-q23.1, defined by SNP markers rs149428 and rs9929635 (peak multipoint lod score of 4.86). Two candidate genes, dynein, cytoplasmic 1, light intermediate chain 2 (DYNC1LI2) and vacuolar protein sorting 4 homolog A (VPS4A), were sequenced but no disease causing mutations were identified. CONCLUSION: We have mapped the chromosomal location of a novel gene responsible for a form of hereditary spastic paraplegia (HSP) (SPG35) and defined its clinical presentation.

A novel locus for hereditary spastic paraplegia with thin corpus callosum and epilepsy.

BACKGROUND: Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loci have been linked to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC, but some HSP-TCC families have not been linked to this locus. METHODS: The authors characterized two families clinically and radiologically and performed a genome-wide scan and linkage analysis. RESULTS: The two families had complicated ARHSP. The affected individuals in Family A had thin corpus callosum and mental retardation, whereas in Family B two of three affected individuals had epilepsy. In both families linkage analysis identified a locus on chromosome 8 between markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form. CONCLUSION: Two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia were clinically characterized and genetically mapped to a new locus on 8p12-p11.21.

Congenital fiber-type disproportion myopathy with type I fiber predominance and type II fiber smallness and atrophy--a sterological analysis.

Congenital myopathy with fiber-type disproportion is an established disorder, where type I fibers predominate with smallness of the same type. We report a family with three siblings (12-year-old boy, 9-year-old girl, and 6-year-old boy) with clinical features of congenital myopathy, where muscle biopsy in the eldest sib showed fiber-type disproportion. Type I fibers predominated with small and atrophic type II fibers which is unusual, especially when the child did not have any other clinical or biochemical abnormality to account for this type of variation. Further, a stereological analysis highlighted the differences with regards to number, size and even volume of the fiber types. A 3-dimensional concept is proposed for this morphological abnormality.

Severe autosomal recessive rippling muscle disease.

Rippling muscle disease (RMD) has previously been reported as a skeletal myopathy that was attributed to a defect in the sarcomere. Here we report a new form of RMD that is more severe, characterized by fatal arrhythmic cardiomyopathy and delayed bone age. Mortality has previously not been associated with RMD. With this report we hope to raise awareness that a subset of patients with this clinical entity are predisposed to severe cardiac disease.

West syndrome: a university hospital based study from Oman.

Forty-four children (20 male: 24 female) with West syndrome (infantile spasms, mental retardation/regression and hypsarrhythmia) diagnosed at Sultan Qaboos University Hospital (Pediatric Neurology Division of the Department of Child Health) are reported, with thirty-four (77.3%) children constituting the symptomatic group. All children were followed up for an initial 1 year at this hospital. Thirty-seven cases (84%) still continue their follow-up with us. The age of onset ranged from 1 to 14 months (mean, 6.0 months). Developmental delay before the onset of infantile spasms was noted in 29 (65.9%) children. Brain computed tomography was abnormal in 29 (65.9%). Sodium valproate and vigabatrin were the most often used drugs, though other antiepileptic drugs were also used. Nine (24.5%) children achieved good seizure control, out of which five have normal development. Only one child could be weaned off antiepileptic drugs completely. There was one death in the whole series, related to aspiration pneumonia.

Vigabatrin associated retinal dysfunction in children with epilepsy.

BACKGROUND: Recent reports have established that eye changes occur in patients treated with vigabatrin. AIM: To identify the eye changes associated with vigabatrin, based on a prospective study of children treated for seizures. METHODS: Twenty nine children on vigabatrin (mainly as add on therapy) were followed up for 6.5 years. Ophthalmic examination was performed before starting treatment and then six monthly in the outpatient clinic. RESULTS: Twenty one children fulfilled the inclusion criteria. Most had epileptic syndromes with infantile spasms-namely West syndrome, Lennox-Gastaut syndrome, and partial seizures. Vigabatrin dose was 25-114 mg/kg/day (mean 55.8); duration of therapy was 6-85 months (mean 35.7). Four children (19%) developed eye changes (retinal pigmentation, hypopigmented retinal spots, vascular sheathing, and optic atrophy). Visual evoked potentials were abnormal in 16 children. Electroretinography and electro-oculography, which could have picked up eye changes in early stages, were not performed, as this facility was not available. CONCLUSIONS: Vigabatrin causes eye damage. Most children with epileptic syndromes on vigabatrin cannot complain of their eye problems, hence 3-6 monthly ophthalmic follow up is strongly advised, along with regular electroretinography, electro-oculography, and visual evoked potentials if possible.

Aicardi-Goutieres syndrome in siblings.

Two siblings with familial encephalopathy, calcification of the basal ganglia, and cerebrospinal fluid lymphocytosis, constituting the triad of Aicardi-Goutieres syndrome, are reported. This syndrome resembles congenital intrauterine infections, which must be meticulously excluded. Aicardi-Goutieres syndrome is extremely rare and is being reported from the Arab world for the first time to our knowledge.

Poliomyelitis in Oman. I. The last outbreak?

Since 1988, the Sultanate of Oman has experienced three outbreaks of paralytic poliomyelitis. The last outbreak occurred in December 1993 and involved two children aged 10 months and 4 1/2 years. The children had received five and four doses, respectively, of trivalent oral polio vaccine (OPV) and lived in the same village. Serum neutralizing antibody tests suggested that paralytic polio in these children was due to poor antibody response to OPV. Wild poliovirus type 1 was isolated from both patients, as well as from seven of ten close contacts of the older child, and one of eight contacts of the younger child. All contacts had received three to six doses of OPV. Genomic sequence studies indicated that the virus isolates belonged to a genotypic group prevalent in southern and western Asia, but differed markedly from virus isolated during the 1988/89 outbreak, suggesting another importation of poliovirus. In response to the outbreak, supplementary immunization with OPV was given to children <6 years of age, initially in the affected district, and subsequently to children in the whole country. This study demonstrates that immunization with three to six doses of OPV did not prevent infection with wild poliovirus. In those children with sub-optimal response to OPV, infection resulted in paralytic poliomyelitis. The outbreak remained localized in one village, indicating that the outbreak control measures were effective.

Poliomyelitis in Oman. II. Toward eradication.

In the past decade, the Sultanate of Oman has experienced three outbreaks of paralytic poliomyelitis--a widespread polio type 1 epidemic in 1988/1989, four cases of polio type 3 in three different regions in 1991, and a localized type 1 outbreak in 1993. The lessons learnt from each of these epidemics have guided us to modify and improve our polio eradication activities. Currently, these activities include administration of five primary and three booster doses of trivalent oral polio vaccine, yearly national immunization campaigns (NIDs) since 1995 with coverage of >90%, localized immunization campaigns, acute flaccid paralysis (AFP) surveillance which involves reporting of all cases by facsimile to the Department of Surveillance within 24 h of detecting a case and weekly zero reporting from 22 sentinel sites, and virological testing of stool specimens of all AFP cases and their close contacts at the national, World Health Organization accredited laboratory. The cumulative success of these activities has resulted in Oman being free from polio for the past 6 years. However, the possibility of importation of wild poliovirus, particularly from southern and western Asia still exists.