Effect of Rivastigmine on Mobility of Patients with Higher-Level Gait Disorder: A Pilot Exploratory Study

Background

Higher-level gait disorder (HLGD) in older adults is characterized by postural instability, stepping dysrhythmicity, recurrent falls and progressive immobility. Cognitive impairments are frequently associated with HLGD.

Objectives

The aim of this study was to compare gait and cognitive performance before and after the use of rivastigmine in patients with HLGD, free from cognitive impairment or Parkinsonism.

Methods

Fifteen non-demented patients with HLGD (age 79.2 ± 5.9 years; 11 women; Mini-Mental State Examination [MMSE] 28.3 ± 1.4) received escalating doses of rivastigmine for 12 weeks in an open-label, pilot study. They were assessed before and after treatment (week 0 and week 12), and after a 4-week washout period (week 16). Assessments included the Mindstreams computerized neuropsychological battery, Activities-specific Balance Confidence Scale, State-Trait Anxiety Inventory, Geriatric Depression Scale, Timed Up and Go (TUG) test, gait speed and stride time variability. One-way multiple analysis of variance tests for repeated measures were used, and Pillai’s trace test was considered as robust to investigate significant differences.

Results

The mean dose of rivastigmine during the 8–12 week period was 5.1 ± 2.3 mg/day. A positive effect was observed on the Mindstreams memory subscale and anxiety scores [Pillai’s trace: F(6,724) = 0.508, p = 0.010; and F(7,792) = 0.545, p = 0.006, respectively, over the course of the study] as well as on mobility (TUG test) [Pillai’s trace: F(4,863) = 0.448; p = 0.028], whereas gait speed and stride time variability did not change.

Conclusions

The use of relatively low-dose rivastigmine did not affect gait speed and stride time variability; however, the general mobility and anxiety were improved. These preliminary results warrant a larger, randomized, placebo-controlled study.     

Endoscopic dacryocystorhinostomy among the old and oldest-old populations - A case control study

ObjectiveDespite increased risks of nasolacrimal duct obstruction (NLDO) with age, and the continuous growth of the old population proportion, data on endoscopic dacryocystorhinostomy (eDCR) among the old is lacking. This study aims to evaluate long-term eDCR efficacy and safety in the old and oldest-old population.MethodsA retrospective case-control study of patients aged 80 ≤ (oldest-old) and 65–79 (old) compared with younger controls who underwent eDCR, between 2002 and 2017. Pre-, intra- and postoperative factors were collected using an integrated hospital-community system. Success rates were analyzed and measured at the first visit following surgery (immediate success), and after five years. Demographics, comorbidities, complications rates, and outcomes were compared between the groups.ResultsThe study groups included 52 oldest-old patients (mean age 83.4 ± 3.6), 127 old patients (72.3 ± 4.14) and 142 control patients (57.8 ± 18.0). The immediate and success rates were 94.2%, 93.7% and 90.8% and five-year success rates were 80.0%, 76.6% and 80% among oldest-old, old and controls, respectively. No significant differences in success rates were found, even despite higher comorbidity rates among the study's group (96 and 92.8% vs. 63.2%, among oldest-old, old and controls respectively, p <0.001). Intra- and postoperative complications rates were low in all groups.ConclusionsAmong older population, including oldest-old and old, eDCR safety and long-term outcomes are comparable with younger patients, suggesting that eDCR should be offered to NLDO patients, regardless of age.     

Salivary levels of mutans streptococci and Lactobacilli among Palestinian school children in East Jerusalem

Objectives

The aim of the present study was to investigate the distribution of oral cariogenic bacteria among 12-year-old Palestinian children attending schools in East Jerusalem.

Materials and methods

Salivary levels of mutans streptococci (MS) and Lactobacilli (LB) were examined by semi-quantitative commercial kits and then correlated to social–demographic parameters.

Results

Overall, 52.1 % of the examined children presented the highest possible ranking score categories for MS bacteria, with only 5.4 % in the lowest category. Only 12.6 % of the school children presented the highest LB score, while 25 % had the lowest ranking score. Salivary MS levels in children attending private schools were lower than those of children in government schools and United Nations Relief and Works Agency (UNRWA) schools. Conversely, levels of LB were lowest in children attending UNRWA schools compared to government and private schools. Girls had significantly higher amounts of MS and LB than boys (p?=?0.001). Lower MS levels were significantly related to the following socioeconomic variables: higher father’s education level (p?=?0.037), higher mother’s education level (p?=?0.063), mother’s employment status (p?=?0.012), and lower home density (p?=?0.001). For LB, the only significant socioeconomic variable was higher father’s employment level, which was related to lower LB level (p?=?0.025).

Conclusions

Levels of MS and LB were found to be strongly related with socioeconomic status among Palestinian children in East Jerusalem. The relatively high prevalence of cariogenic bacteria suggests that oral care prevention and treatment demands special attention from the health care institutions and authorities.     

Targeted Next-generation Sequencing of Advanced Prostate Cancer Identifies Potential Therapeutic Targets and Disease Heterogeneity

Background

Most personalized cancer care strategies involving DNA sequencing are highly reliant on acquiring sufficient fresh or frozen tissue. It has been challenging to comprehensively evaluate the genome of advanced prostate cancer (PCa) because of limited access to metastatic tissue.

Objective

To demonstrate the feasibility of a novel next-generation sequencing (NGS)–based platform that can be used with archival formalin-fixed paraffin-embedded (FFPE) biopsy tissue to evaluate the spectrum of DNA alterations seen in advanced PCa.

Design, setting, and participants

FFPE samples (including archival prostatectomies and prostate needle biopsies) were obtained from 45 patients representing the spectrum of disease: localized PCa, metastatic hormone-naive PCa, and metastatic castration-resistant PCa (CRPC). We also assessed paired primaries and metastases to understand disease heterogeneity and disease progression.

Intervention

At least 50 ng of tumor DNA was extracted from FFPE samples and used for hybridization capture and NGS using the Illumina HiSeq 2000 platform.

Outcome measurements and statistical analysis

A total of 3320 exons of 182 cancer-associated genes and 37 introns of 14 commonly rearranged genes were evaluated for genomic alterations.

Results and limitations

We obtained an average sequencing depth of >900X. Overall, 44% of CRPCs harbored genomic alterations involving the androgen receptor gene (AR), including AR copy number gain (24% of CRPCs) or AR point mutation (20% of CRPCs). Other recurrent mutations included transmembrane protease, serine 2 gene (TMPRSS2):v-ets erythroblastosis virus E26 oncogene homolog (avian) gene (ERG) fusion (44%); phosphatase and tensin homolog gene (PTEN) loss (44%); tumor protein p53 gene (TP53) mutation (40%); retinoblastoma gene (RB) loss (28%); v-myc myelocytomatosis viral oncogene homolog (avian) gene (MYC) gain (12%); and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α gene (PIK3CA) mutation (4%). There was a high incidence of genomic alterations involving key genes important for DNA repair, including breast cancer 2, early onset gene (BRCA2) loss (12%) and ataxia telangiectasia mutated gene (ATM) mutations (8%); these alterations are potentially targetable with poly(adenosine diphosphate-ribose)polymerase inhibitors. A novel and actionable rearrangement involving the v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) was also detected.

Conclusions

This first-in-principle study demonstrates the feasibility of performing in-depth DNA analyses using FFPE tissue and brings new insight toward understanding the genomic landscape within advanced PCa.     

Serum blood urea nitrogen and long-term mortality in acute ST-elevation myocardial infarction

Older age is an independent predictor of mortality after percutaneous coronary intervention (PCI) in patients with Non-ST elevation Acute Coronary Syndrome (ACS). GPIIb/IIIa inhibitors are proved to improve outcome in high risk patients, but conflicting data are available about the effects of these inhibitors in elderly. Accordingly, we studied a consecutive population of elderly patients undergoing PCI for Non-ST elevation ACS. A total of 500 patients were divided in: GPI group (247 pts; mean age 77 ± 1.9 years) treated by stenting plus abciximab and, no GPI group (253 pts; mean age 77 ± 2.4 years) treated by stenting alone. Propensity analysis was used to account for the nonrandomized use of GPIIb/IIIa inhibitors. During hospitalization, incidence of death was similar among groups (3.2% vs 4.6%) without difference regarding incidence of major (1.6% vs 1.1%) and minor bleedings (4% vs 3%). At long-term follow-up the rate of death was significantly lower in GPI group (4.5% vs 12.3%; p = 0.002) as well as the rate of acute myocardial infarction (2.8% vs 11.1%; p = 0.0001), and pre-PCI (5.7% vs 13.4%; p = 0.003). Cox regression analysis identified abciximab use as an independent predictor of lower long-term major adverse cardiac event (MACE) after adjustment for propensity score (Exp (B) 0.620, 95%CI 0.394–0.976, p = 0.039). Our results suggest that addition of abciximab to stenting improves outcome in elderly patients with Non-ST elevation ACS, leading to an absolute benefit for reduction of death and MACE, with an acceptable rate of major and minor bleedings.     

The effect of age on morphology and eruption of the lower incisors in mature rats

OBJECTIVE: This study investigated the effect of age on tooth and periodontium morphology and on tooth eruption in the lower incisors of 28 female rats, initial age 10 weeks. DESIGN: Morphometric data of the incisors in three young mature rats (weight 199+/-2.4 g) were compared to that of three 18-week-old (weight 260+/-5 g) animals. The rate of eruption was monitored during 12 months in 11 rats with all teeth in occlusion and in 11 rats with one lower incisor kept constantly out of occlusion. RESULTS:: The incisors continued to enlarge after the animals reached maturity with the size of the teeth increasing both longitudinally and circumferentially. Tooth volume increased by 21%, while that of the periodontal ligament was enlarged by only 12%. The rate of impeded eruption declined steadily from a mean value of 542+/-49 microm/day during the first experimental month to a mean value of 443+/-25 microm/day during the concluding month (p<0.05). The eruption rate of the teeth exceeded that of attrition rate by 2.4%. The unimpeded eruption proceeded steadily throughout the experimental year, at a mean rate of 811+/-12. CONCLUSIONS: Apparently in mature rats age has no effect on the genetic potential as expressed by the unimpeded eruption. In the impeded teeth age does affect the phenotypic expression of the eruptive function governed by occlusal forces as well as by the form and size ratio of the tooth and its PDL.     

Pamidronate treatment in rheumatology practice: a comprehensive review

Pamidronate, along with other bisphosphonates, has been used for treatment of bone pain secondary to malignant involvement or metastatic disease for years. Some data, however, have also accumulated on the utility of pamidronate in a variety of benign conditions frequently handled by rheumatologists. This study aims to review the available published data regarding the potential use of pamidronate in rheumatology practice. Methods include the review of relevant articles retrieved by a PUBMED search utilizing the index term “pamidronate”. All available randomized control trials, open trials, and case series, as well as properly reported case studies evaluating usage of pamidronate in rheumatic disorders, have been included in the literature review. The efficacy of pamidronate in patients with spondyloarthropathies; synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome; hypertrophic osteoarthropathy; osteoporotic vertebral fractures; chronic back pain due to disk disease or spinal stenosis; Charcot arthropathy; transient osteoporosis; and complex regional pain syndrome-I, has been demonstrated in more than 40 reports, the majority of which, however, were not controlled studies. In some of reviewed conditions, aside from providing analgesic relief, pamidronate may also have disease-modifying properties. While used in different doses in a variety of rheumatic disorders, pamidronate was generally reported to be well tolerated with an overall good safety profile. Pamidronate may represent an effective and safe choice for a spectrum of rheumatic patients, suffering from intractable musculoskeletal pain, unresponsive to traditionally recommended therapies. Large randomized, controlled studies examining the efficacy of pamidronate in the rheumatic conditions are urgently needed.