A multiple treatment comparison meta-analysis of monoamine oxidase type B inhibitors for Parkinson's disease.

AIMS: To the best of our knowledge, there are no systematic reviews or meta-analyses that compare rasagiline, selegiline and safinamide. Therefore, we aimed to perform a drug class review comparing all available monoamine oxidase type B (MAO-B) inhibitors in a multiple treatment comparison. METHODS: We performed a systematic literature search to identify randomized controlled trials assessing the efficacy of MAO-B inhibitors in patients with Parkinson's disease. MAO-B inhibitors were evaluated either as monotherapy or in combination with levodopa or dopamine agonists. Endpoints of interest were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score and serious adverse events. We estimated the relative effect of each MAO-B inhibitor versus the comparator drug by creating three networks of direct and indirect comparisons. For each of the networks, we considered a joint model. RESULTS: The systematic literature search and study selection process identified 27 publications eligible for our three network analyses. We found the relative effects of rasagiline, safinamide and selegiline treatment given alone and compared to placebo in a model without explanatory variables to be 1.560 (1.409, 1.734), 1.449 (0.873, 2.413) and 1.532 (1.337, 1.757) respectively. We also found all MAO-B inhibitors to be efficient when given together with levodopa. When ranking the MAO-B inhibitors given in combination with levodopa, selegiline was the most effective and rasagiline was the second best. CONCLUSIONS: All of the included MAO-B inhibitors were effective compared to placebo when given as monotherapy. Combination therapy with MAO-B inhibitors and levodopa showed that all three MAO-B inhibitors were effective compared to placebo, but selegiline was the most effective drug.

Sexually active groups in cattle-a novel estrus sign.

The current study presents a novel objective measure for characterizing sexually active groups (SAG 3-5) and relates this measure to other behaviors of lactating Holstein-Friesian cows. Cows in SAG 3-5 were required to participate in a minimum of 1 estrus behavior per 5min while staying within 3m (2 cow lengths) of its partner(s) for a minimum of 5min. Twenty Holstein-Friesian cows were video-monitored continuously through 1 complete estrous cycle (22d). Standing behavior, SAG 3-5, secondary estrus signs (SEC), and other social and agonistic behaviors were recorded continuously. The period of mounting estrus (MTE) was divided into the 3 parts: prestand, standing estrus (STE), and poststand. The mean durations of MTE, prestand, STE, and poststand period were 12.9±1.84, 4.0±1.93, 7.1±1.44, and 1.8±0.57h (n=13). The fractions of time spent in SAG 3-5 during MTE, prestand, STE, and poststand period were 13, 8, 19, and 1% (n=11). During MTE, cows participated, on average, in 5.8±1.24 SAG 3-5 and initiated 9.5±2.99 mounts, with mean durations of 0.25±0.03h and 4.00±0.36s, respectively. The novel measure SAG 3-5 was a sign of long duration not confined only to groups of STE cows. On one day when no cows were in estrus and during the periods 4 to 24h before and after MTE, no SAG 3-5 behaviors were observed. Luteal-phase cows participated in SAG 3-5 only when the partner was a single cow in estrus. The time spent in SAG 3-5 increased between 1 and 3h before MTE and the prestand period (3 vs. 8%) and reached a peak level during STE. From STE to poststand, time spent in SAG 3-5 decreased considerably (19 vs. 1%). The observed decrease in nonmutual agonistic behaviors 4 to 24h before MTE is suggested as an early sign of pre-estrus. Changes in SAG 3-5, agonistic behaviors, and SEC are suggested as indicators of the specific stages of MTE. Increased SEC initiated and SAG 3-5 were indicators of late pre-estrus and early estrus (prestand). Peak levels of SAG 3-5, SEC, and social agonistic behaviors were indicators of STE. A sudden decrease in behaviors, preceded by frequent interactions, was indicative of late estrus (poststand). On the basis of the findings reported here, we propose that SAG 3-5, as well as proceptive and receptive patterns of SEC and agonistic behaviors, be included in estrus detection protocols. Updated knowledge of these behavioral interactions may assist when determining the stage of estrus and the optimal time to breed dairy cows.

Parkinson's disease, treatment choice and survival over time.

OBJECTIVES: We compared Monoamine oxidase B (MAO-B) - and dopamine agonist (DA) monotherapy patients with respect to survival, considering gender, age, first prescriber's specialty and relevant co-morbidity, and compared their specialist health care contacts and hospitalizations. METHODS: With data from health registries, we considered 21,047 patients without redemptions for MAO-B, DA or levodopa 6 months prior to their first MAO-B or DA redemption in 2006 and followed them throughout 2016. We considered Cox proportional hazard regression models for comparing the risk of death among MAO-B and DA monotherapy patients. RESULTS: MAO-B-users had a higher mortality than DA-users, [HR: 1.587, 95% CI: 1.056; 2.384] for patients under 74 years. There was an increased mortality risk with increasing age, women had lower risk than men and previous diabetes-, antihypertensive-, and cardiac drug users had higher risk compared to patients without such history. Previous use of hypothyroid drugs and having a specialist as first prescriber were not significant risk factors.Among patients without hospitalizations 13.7% died, while among patients who spent at least one night in hospital 36.73% died. The median duration of a hospitalization among those who died and not were 17.5 and 7 days. Among the small proportion with specialist health care contacts circulatory- and respiratory-system diseases were the most frequent cause of contact. CONCLUSIONS: DAs were most frequently given when initiating Parkinson's treatment. DA-users had a lower mortality risk compared to MAO-B-users and less specialist health care contact.

Behavior of lactating Holstein-Friesian cows during spontaneous cycles of estrus.

The objectives of the present study were to describe, in detail, behavior associated with standing estrus (STE) in lactating dairy cows and behavioral changes during complete estrous cycles. Estrus signs were monitored by continuous video recording of 20 Holstein-Friesian (HF) cows housed on an outdoor wood-chip pad during 1 estrous cycle (22 d). Other social behavior was recorded during STE and, for comparison, during 1 selected day when none of the cows were in estrus. Standing stationary when mounted was defined as the primary estrus sign. Anogenital sniff, chin rest, attempt to mount, and mount were defined as secondary estrus signs. Ovarian cyclicity was confirmed by progesterone measurements. This study reports short mean duration of STE (7.1±1.44h) and estrus (mount period; 12.9±1.84h) of the 13 cows expressing these signs. All mounting activities involved at least one cow in, or within 4h of, STE. The most frequent sign during STE was anogenital sniff initiated, followed by chin rest received, chin rest initiated, chase up initiated, anogenital sniff received, mount initiated, head butt, mount received, attempt to mount initiated, push away received, play rub, attempt to mount received, follow initiated, threat received, flehmen, avoid, bellow, and social lick received. Standing and mounting activity in HF cows was inconsistent during estrus, indicating that other signs could be of greater use. The frequency of secondary estrus signs initiated and received increased gradually during the last 12h before STE, revealing significant differences between periods from 4 to 6 and 1 to 3h before STE. A considerable increase in receptive behavior (secondary estrus signs received) was identified between 1 to 3h prior to STE and STE. Both frequent initiated and received behaviors were associated with STE. A significant decrease in the frequency of secondary estrus signs initiated and received occurred 3h after STE. Cows in STE simultaneously predominantly chose the other standing cow as mate and expressed secondary estrus signs more frequently. Based on the results of this study, we suggest that chase up could be regarded as a reliable indicator of estrus and that the changes in proceptive (initiated) and receptive (received) behavior could be used as predictors of different stages in estrus. Knowledge of these behavioral signs may improve heat detection rates and the ability to predict the optimum breeding time for dairy cows.

A radiographic study of the mandibular third molar root development in different ethnic groups.

BACKGROUND: The nature of differences in the timing of tooth formation between ethnic groups is important when estimating age. AIM: To calculate age of transition of the mandibular third (M3) molar tooth stages from archived dental radiographs from sub-Saharan Africa, Malaysia, Japan and two groups from London UK (Whites and Bangladeshi). MATERIALS AND METHODS: The number of radiographs was 4555 (2028 males, 2527 females) with an age range 10-25 years. The left M3 was staged into Moorrees stages. A probit model was fitted to calculate mean ages for transitions between stages for males and females and each ethnic group separately. The estimated age distributions given each M3 stage was calculated. To assess differences in timing of M3 between ethnic groups, three models were proposed: a separate model for each ethnic group, a joint model and a third model combining some aspects across groups. The best model fit was tested using Bayesian and Akaikes information criteria (BIC and AIC) and log likelihood ratio test. RESULTS: Differences in mean ages of M3 root stages were found between ethnic groups, however all groups showed large standard deviation values. The AIC and log likelihood ratio test indicated that a separate model for each ethnic group was best. Small differences were also noted between timing of M3 between males and females, with the exception of the Malaysian group. These findings suggests that features of a reference data set (wide age range and uniform age distribution) and a Bayesian statistical approach are more important than population specific convenience samples to estimate age of an individual using M3. CONCLUSION: Some group differences were evident in M3 timing, however, this has some impact on the confidence interval of estimated age in females and little impact in males because of the large variation in age.