The levonorgestrel-releasing intrauterine device containing 13.5 mg of levonorgestrel (LNG 13.5 mg IUD), Jaydess, was approved for contraception by the European Medicines Agency in 2013. We aimed to ...describe the characteristics of new users of LNG 13.5 mg IUD in Sweden within the first 3 years after approval (2014–2016).
We conducted an observational, population-based study using data from the Swedish national registers. Women with the first pharmacy dispensation of LNG 13.5 mg IUD between 2014 and 2016 were followed until December 31, 2020. Descriptive analyses included demographic characteristics, duration of the use of first-time LNG 13.5 mg IUD, and contraceptive switching patterns.
We included 38,327 women, with mean age at first-time LNG 13.5 mg IUD use of 26 (SD: 7) years. Over 80% were prescribed LNG 13.5 mg IUD by a midwife. The most common comorbidities in the year prior to LNG 13.5 mg IUD use (2%–3% prevalence) were depression, anxiety, premenstrual syndrome, and menorrhagia. The median duration of first-time LNG 13.5 mg IUD use was 2.6 years, and after use, more than 50% of women opted to continue using a hormonal intrauterine device.
In this postmarketing drug utilization study, there were over 38,000 first-time LNG 13.5 mg IUD users in Sweden between 2014 and 2016, with an estimated median duration of use of 2.6 years. First-time LNG 13.5 mg IUD users consisted mostly of young, healthy individuals with a history of hormonal contraceptive use. Over half of the women continued using a hormonal IUD after the first LNG 13.5 mg IUD.
The median duration of LNG 13.5 mg IUD use was 2.6 years, approaching the 3-year indicated use limit. The majority of users continued with another hormonal intrauterine device after LNG 13.5 mg IUD use.
Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n=80) to determine longitudinal changes in ...body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P<0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P=0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P=0.0005), disease risk (P<0.0001), age (P=0.0001), and BMI z-score (P<0.0001) at diagnosis and total dose of steroid during maintenance (P=0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.
Diatoms are a major, ubiquitous photosynthetic group representing most aquatic ecosystem’s microalgal communities. The species composition encompasses a wide range of cell sizes. Although cell size ...is vital in aquatic ecology and biogeochemistry, size-based diatom community studies are sparse, especially in tropical ecosystems. This study assesses the size-fractionated brackish diatom community based on the microscopic cell abundance and carbon-biomass metrics. Despite sufficient nutrient availability, the seasonal and spatial relative proportion of abundance and biomass of the three diatom size fractions declined under high turbidity. It increased under higher light and nutrient availability with lower turbidity. Turbulence was a favorable factor irrespective of the size groups. Light availability, increased nutrients, and lower temperature resulted in a higher contribution from the larger size group to the total diatom carbon biomass. The smaller size group dominance during highly turbid conditions could be attributed to the higher surface-to-volume ratios. The intermediate-size groups thrived under reduced turbidity. Seasonal intra-species size variations reflected changes induced either due to life-cycle stages or environmental stress. The size-based metrics permitted an in-depth understanding of the diatom responses at the community and species level, which could have implications on their ecological and biogeochemical roles in aquatic ecosystems.
•Diatom abundance and carbon biomass study with size-fractionated approach.•Method provides diatom responses at community and species level.•Implications on diatom’s ecological and biogeochemical roles in aquatic ecosystems.
Necessary and sufficient conditions are obtained so that every solution of (y(t)−p(t)y(t−τ))′+Q(t)G(y(t−σ))=f(t) is oscillatory or tends to zero or to ±∞ as t→∞. The problem is considered in various ...ranges for p(t).
Numerous studies have focused on the significance of modern marker proteins in the synovial fluid of the knee joint and in the serum both, for osteoarthritis (OA) and rheumatoid arthritis (RA). The ...relationship between the serum concentrations and the concentrations in the synovial fluid is still unclear. Synovial fluid and serum samples were obtained from 13 patients with advanced OA and from 8 patients with severe RA and concentrations of MMP-1, MMP-3, MMP-13, TIMP-1, COMP and MIA/CD-RAP were determined. All values were normalized against the total protein concentrations. Serum concentrations of MMP-13 in the RA-group were statistically higher than the synovial values (P<0.05). MMP-13 was the only marker protein that revealed distinct higher levels in the serum than in the synovial fluid. The study design allows only conclusions about advanced stages of RA and OA. Longitudinal investigations may provide further information about the value of MMP-13 as a potential marker to monitor the course of RA and OA.
Nowadays, complex arthroscopic procedures of the knee joint, such as ACL reconstruction, are routinely carried out on an outpatient basis. The reduced time spent with the patient places high demands ...on the surgeon with regard to the management of such cases. The aim of this study was to evaluate the current standards of perioperative management following outpatient arthroscopic surgery of the knee in Germany.
A questionnaire consisting of 18 questions was sent to 215 members of the German Association of Outpatient Arthroscopy (BVASK e. V.), dealing with the following topics: antibiotic prophylaxis, DVT prophylaxis, use of a tourniquet and suction drain, physical therapy, physiotherapy, analgesia, anaesthesia and emergency management. More than 51% of the forms were returned and considered suitable for statistical analysis.
A total of 62% of the surgeons reported the use of an antibiotic prophylaxis (i. v. single shot) in every arthroscopic case, while 19% administer antibiotics only occasionally, especially in ACL reconstruction. Postoperative antibiotic treatment was reserved for special situations, such as prior joint infection. Prophylaxis of DVT by means of low molecular weight heparin was carried out in 96% of the cases. 51% prescribed anticoagulant agents for 1 week, 39% for the duration of reduced weight bearing. Half of the surgeons used a tourniquet cuff, 22% exsanguinate the limb prior to cuff inflation. A suction drainage was applied by 36% of the surgeons regularly and by 45% occasionally. The drain is left for one day by 79% of the surgeons, while 11% reported a shortened use of only several hours. With regard to analgesia, 66% of all surgeons apply some kind of local anaesthetic into the knee joint post surgery. Systemic preoperative analgesics or anti-inflammatory agents are given regularly in 56 % of the cases. A total of 92% of the procedures are carried out under general anaesthesia. In 36% of the cases, some kind of additional regional peripheral anaesthesia is used. With regard to postoperative care, cryotherapy is considered standard (97%) and 64% of the surgeons recommend physiotherapy. Nearly all surgeons (97%) offer the patients the opportunity to reach them personally via mobile phone during the first night following arthroscopic surgery.
DVT prophylaxis with LMWH, general anaesthesia, postoperative cryotherapy and personal availability by phone can be considered part of the standard perioperative management following outpatient knee arthroscopy in Germany. However, a wide variety of treatment options can be found regarding topics such as analgesia, antibiotic prophylaxis, tourniquet, knee drainage and physiotherapy.
Sufficient conditions are obtained so that every solution of the neutral functional difference equation
oscillates or tends to zero or ±∞ as
n
→ ∞, where Δ is the forward difference operator given by ...Δ
x
n
=
x
n
+1
−
x
n
,
p
n
,
q
n
,
u
n
,
f
n
are infinite sequences of real numbers with
q
n
> 0,
u
n
≥ 0,
G,H
∈
C
(ℝ,ℝ) and
m
≥ 2 is any positive integer. Various ranges of {
p
n
} are considered. The results hold for
G
(
u
) ≡
u
, and
f
n
≡ 0. This paper corrects, improves and generalizes some recent results.
Context:
Intronic DNA frequently encodes potential exonic sequences called pseudoexons. In recent years, mutations resulting in aberrant pseudoexon inclusion have been increasingly recognized to ...cause disease.
Objectives:
To find the genetic cause of familial glucocorticoid deficiency (FGD) in two siblings.
Patients:
The proband and his affected sibling, from nonconsanguineous parents of East Asian and South African origin, were diagnosed with FGD at the ages of 21 and 8 months, respectively.
Design:
Whole exome sequencing was performed on genomic DNA (gDNA) of the siblings. Variants in genes known to cause FGD were assessed for causality. Further analysis of gDNA and cDNA was performed by PCR/RT-PCR followed by automated Sanger sequencing.
Results:
Whole exome sequencing identified a single, novel heterozygous variant (p.Arg71*) in nicotinamide nucleotide transhydrogenase (NNT) in both affected individuals. Follow-up cDNA analysis in the proband identified a 69-bp pseudoexon inclusion event, and Sanger sequencing of his gDNA identified a 4-bp duplication responsible for its activation. The variants segregated with the disease: p.Arg71* was inherited from the mother, the pseudoexon change was inherited from the father, and an unaffected sibling had inherited only the p.Arg71* variant.
Conclusions:
FGD in these siblings is caused by compound heterozygous mutations in NNT; one causing pseudoexon inclusion in combination with another leading to Arg71*. Discovery of this pseudoexon activation mutation highlights the importance of identifying sequence changes in introns by cDNA analysis. The clinical implications of these findings include: facilitation of antenatal genetic diagnosis, early institution of potentially lifesaving therapy, and the possibility of preventative or curative intervention.
The non-operative treatment of medial degenerative joint disease of the knee has proven to be difficult due to the underlying deformity and the pathological mechanical loading. Valgus knee bracing ...offers the possibility to directly address the mechanical deficit. The aim of this study was to analyse whether or not part-time valgus knee bracing in patients with medial osteoarthrits can effectively reduce knee pain and lead to reproducible changes in the gait analysis in comparison to an elastic knee bandage and an untreated control group.
In a prospective trial, 33 patients with symptomatic medial osteoarthritis of the knee joint with a minimum of grade 2 according to the radiographic classification of Kellegren & Lawrence were randomised into a treatment group with a valgus brace (n = 13; M4 OA®, Medi) and an elastic knee bandage (n = 10; Genumedi®, Medi). Both supportive devices were to be applied for 2-4 hours per day, especially during activity. The control group (n = 10) consisted of untreated individuals. The deviation of the leg axis and the degree of degenerative joint disease were evaluated radiographically at the onset of the study by a standing whole leg X-ray. The evaluation at the beginning of the study and after 16 weeks consisted of a clinical examination including various knee scores (Insall score, Lequesne score, HSS score, Tegner score, WOMAC, and VAS for pain). Additionally, at both times a 3-dimensional, instrumented gait analysis was carried out to document the joint angles of the affected knee in all planes. The obtained knee joint angles from all groups at both time points were compared to a control group of healthy persons without a history of knee pain by qualitative measurement.
Radiographically, the medial deviation of the load axis from the knee joint centre (MAD) was 29 mm. In 27 patients we found a combination of femoral, intra-articular and tibial changes contributing to the varus alignment. The joint line conversion angle (JLCA) was pathological in all subjects. Clinically, in 4 of 5 subjective and objective scores (Insall score, Lequesne score, Tegner score, WOMAC, and VAS for pain) a statistically significant improvement of the symptoms, joint function and activity level thanks to the application of the corrective valgus knee brace was documented after 16 weeks. The knee bandage also led to an improvement, but only in 2 scores (Insall score, Tegner score). No changes were documented for the control group. The gait analysis of the orthosis group revealed an improvement in the extension and flexion angles (sagittal plane) and the knee rotation angles (horizontal plane) when compared to a control group.
The correction obtained by this knee orthosis, which places a valgus stress on the medially osteoarthritic knee, is an effective addition to the conservative treatment protocols and is superior to the isolated use of an elastic knee bandage. Further research is warranted to evaluate the longevity of such treatment and to further improve the technique of gait analysis by the development of quantitative parameters.
PDF
