scholarly journals Pegvisomant in combination or pegvisomant alone after failure of somatostatin analogs in acromegaly patients: an observational French ACROSTUDY cohort study

Endocrine ◽  
2020 ◽  
Author(s):  
Emmanuelle Kuhn ◽  
Philippe Caron ◽  
Brigitte Delemer ◽  
Isabelle Raingeard ◽  
Hervé Lefebvre ◽  
...  

Abstract Objective After surgery, when somatostatin analogs (SAs) do not normalise IGF-I, pegvisomant (PEG) is indicated. Our aim was to define the medical reasons for the treatment of patients with PEG as monotherapy (M) or combined with SA, either as primary bitherapy, PB (PEG is secondarily introduced after SA) or as secondary bitherapy, SB (SAs secondarily introduced after PEG). Methods We retrospectively analysed French data from ACROSTUDY. Results 167, 88 and 57 patients were treated with M, PB or SB, respectively, during a median time of 80, 42 and 70 months. The median PEG dose was respectively 15, 10 and 20 mg. Before PEG, the mean IGF-I level did not differ between M and PB but the proportion of patients with suprasellar tumour extension was higher in PB group (67.5% vs. 44.4%, P = 0.022). SB regimen was used preferentially in patients with tumour increase and IGF-I level difficult to normalise under PEG. In both secondary regimens, the decrease of the frequency of PEG’s injections, compared to monotherapy was confirmed. However, the mean weekly dose of PEG between M and PB remained the same. Conclusions The medical rationale for continuing SAs rather than switching to PEG alone in patients who do not normalise IGF-I under SAs was a tumour concern with suprasellar extension and tumour shrinkage under SA. A potential explanation for introducing SA in association with PEG appears to be a tumour enlargement and difficulties to normalise IGF-I levels under PEG given alone. In both regimens, the prospect of lowering PEG injection frequency favoured the choice.

2020 ◽  
Vol 17 ◽  
Author(s):  
Abdullah Shehab ◽  
Asim Ahmed Elnour ◽  
Akshaya Srikanth Bhagavathula ◽  
Joseph Pulavelil Kurian ◽  
Gazi Hassan ◽  
...  

Aims: We aim to investigate the efficacy and safety of pitavastatin 4 mg in a population of people living in the United Arab Emirates (UAE). Background: Pitavastatin is a member of the HMG-CoA reductase inhibitors family which was approved for use in adult subjects with primary hyperlipidemia or mixed dyslipidemia. To date, no published studies have assessed the efficacy and safety of pitavastatin in the United Arab Emirates. Objective: The main objective of the current study was to investigate the efficacy and safety of pitavastatin in subjects with dyslipidemia for primary prevention of cardiovascular diseases based on total cardiovascular risk. Methods: This was a multicentre (four private hospitals) prospective cohort study to analyze data on the use of pitavastatin for dyslipidemia in adult outpatients in Abu Dhabi and Dubai emirates, United Arab Emirates. We have followed-up the clinical profiles of subjects in four hospitals for six-weeks during the period from June 2015 to June 2017. Efficacy was based on the evaluation of the mean (± standard deviation) change in low-density lipoprotein cholesterol between baseline and week six after the initiation of pitavastatin therapy. Safety was reported as the incidence of adverse events occurred with the use of pitavastatin and the development of new-onset diabetes. Results: A total of 400 subjects who were receiving pitavastatin 4 mg were included. The mean age of subjects was 50.7 ±10.8 years, of these 79.0% were males. At the baseline, the mean level of total cholesterol was 185.4 ±41.5 mg/dL, low density lipoprotein was 154.9 ±48.55 mg/dL, high-density lipoprotein cholesterol was 40.5 ±11.23 mg/dL and fasting blood glucose was 115.0 (±16.63) mg/dl. At the end of six weeks, low density lipoprotein levels significantly decreased to 112.09 ±41.90 mg/dl (standard mean difference [SMD] (-42.8%), 95% CI: -42.88 [-49.17 to -36.58] mg/dl, P <0.001), while high density lipoprotein levels improved (SMD, 95% CI: 1.77% [0.25 to 3.28] mg/dl, P <0.022). There were 55 subjects (13.7%) reported various adverse events such as myalgia (7.5%), sleep disorders (2.5%), and myopathy (2.2%). Furthermore, 4 (1.0%) have had developed new-onset diabetes post six-weeks of initiation of pitavastatin therapy. Conclusion: Pitavastatin 4 mg had howed robust efficacy in reducing LDL-C levels and improving HDL-C levels in subjects with dyslipidemias. The use of pitavastatin was associated with a low discontinuation rate, fewer adverse events, and very limited cases of new-onset diabetes.


2020 ◽  
pp. bjophthalmol-2020-316401
Author(s):  
Qian Yang ◽  
Xiaohong Zhou ◽  
Yingqin Ni ◽  
Haidong Shan ◽  
Wenjing Shi ◽  
...  

PurposesTo develop an optimised retinopathy of prematurity (ROP) screening guideline by adjusting the screening schedule and thresholds of gestational age (GA) and birth weight (BW).MethodsA multicentre retrospective cohort study was conducted based on data from four tertiary neonatal intensive care units in Shanghai, China. The medical records of enrolled infants, born from 2012 to 2016 who underwent ROP examinations, were collected and analysed. The incidence and risk factors for ROP were analysed in all infants. Postnatal age (PNA) and postmenstrual age (PMA) of infants, detected to diagnose ROP for the first time, were compared with the present examination schedule. The predictive performance of screening models was evaluated by internally validating sensitivity and specificity.ResultsOf the 5606 eligible infants, ROP was diagnosed in 892 (15.9%) infants; 63 (1.1%) of them received treatment. The mean GA of ROP patients was 29.4±2.4 weeks, and the mean BW was 1260±330 g. Greater prematurity was associated with an older PNA at which ROP developed. The minimum PMA and PNA at which diagnosis of treatable ROP occurred were 32.43 and 3 weeks, respectively. The optimised criteria (GA <32 weeks or BW <1600 g) correctly predicted 98.4% type 1 ROP infants, reducing the infants requiring examinations by 43.2% when internally validated.ConclusionsThe incidence of type 1 ROP and the mean GA and BW of ROP infants have decreased in China. The suggested screening threshold and schedule may be reliably used to guide the modification of ROP screening guideline and decrease medical costs.


BMJ Open ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. e040819
Author(s):  
Pontus Rygh ◽  
Ina Asklund ◽  
Eva Samuelsson

ObjectivesThe efficacy of app-based treatment for stress urinary incontinence (SUI) has been demonstrated in a randomised controlled trial (RCT). In this study, we investigate the user characteristics and the effectiveness of the same app when freely available, and compare these results with the RCT.DesignProspective cohort study.ParticipantsDuring a 17-month period, 24 602 non-pregnant, non-postpartum women older than 18 years downloaded the app and responded anonymously to a questionnaire. Of these, 2672 (11%) responded to the 3-month follow-up.InterventionThree months’ use of the app Tät, containing information, a pelvic floor muscle training programme and lifestyle advice.Main outcome measuresChange in symptom severity (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF)) and subjective improvement (Patient Global Impression of Improvement (PGI-I)).ResultsOf the respondents, 88% lived in Sweden and 75% (18 384/24 602) were incontinent with a mean age of 45.5 (SD 14.1) years. The UI types, based on symptoms, were SUI (53%), urgency UI (12%), mixed UI (31%) and undefined (4%). The mean ICIQ-UI SF score was 8.2 (SD 4.0) at baseline. The mean ICIQ-UI SF score reduction at follow-up was 1.31 (95% CI: 1.19 to 1.44) with a larger reduction in those with more severe incontinence at baseline (severe/very severe 3.23 (95% CI: 2.85 to 3.61), moderate 1.41 (95% CI: 1.24 to 1.59) and slight 0.24 (95% CI 0.06 to 0.42). When the results were weighted to match the distribution of severity in the RCT, the ICIQ-UI SF score reduction was 2.2 compared with 3.9 in the RCT. Regarding PGI-I, 65% experienced improvement compared with 92% in the RCT.ConclusionsThe app Tät was effective for self-management of UI even in the real world. Although the reduction in incontinence symptoms was less than in the RCT, two-thirds of the users improved. App-based treatment reaches many women without requiring resources from ordinary healthcare services.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ioana Marcu ◽  
Adrian Balica ◽  
Jeffrey A. Gavard ◽  
Eugen C. Campian ◽  
Gustavo Leme Fernandes ◽  
...  

Abstract Background The objective of this study is to characterize participants in a laparoscopic cadaveric neuroanatomy course and assess knowledge of pelvic neuroanatomy before and after this course. Methods This is a survey-based cohort study with a setting in a university educational facility. The participants are surgeons in a multiday laparoscopic cadaveric pelvic neuroanatomy course. Participants completed a precourse survey, including demographics and comfort with laparoscopic surgery. They then completed an identical precourse and postcourse anatomic knowledge test. Main outcomes are scores on the anatomic knowledge test precourse and postcourse. Results 44 respondents were included: 25 completed fellowship, 15 completed residency, 2 were residents, and 2 were fellows. Participants were on average 11.09 years post training, with an average of 8.67 years from training if they completed fellowship and 18.62 years if they completed residency only. 22 of 42 respondents strongly agreed or agreed they are comfortable performing complex laparoscopic hysterectomies. The average precourse score was 32.18/50 points and the mean difference score (MDS, defined as mean of Postcourse scores minus Precourse scores) was 9.80, showing significant improvement (p <  0.001). Precourse and MDS scores were not significantly different when comparing country of practice, level of training, or time since training. Conclusion Baseline knowledge of pelvic neuroanatomy was similar among groups when comparing fellowship status, place of training, or time since training. There was significant improvement in knowledge after training in this dissection method. This course garnered interest from surgeons with broad training backgrounds.


Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 273
Author(s):  
Marc Schargus ◽  
Catharina Busch ◽  
Matus Rehak ◽  
Jie Meng ◽  
Manuela Schmidt ◽  
...  

The aim of this study was to compare the efficacy of trabeculectomy (TE), single XEN microstent implantation (solo XEN) or combined XEN implantation and cataract surgery (combined XEN) in primary open-angle glaucoma cases, naïve to prior surgical treatment, using a monocentric retrospective comparative cohort study. Intraocular pressure (IOP) and the number of IOP-lowering drugs (Meds) were monitored during the first 24 months after surgery. Further disease progression was monitored using peripapillary retinal nerve fiber layer (RNFL) thickness examinations using spectral domain optical coherence tomography (OCT) as well as visual acuity (VA) and visual field (VF) tests. In the TE group (52 eyes), the mean IOP decreased from 24.9 ± 5.9 to 13.9 ± 4.2 mmHg (p < 0.001) and Meds decreased from 3.2 ± 1.2 to 0.5 ± 1.1 (p < 0.001). In the solo XEN (38 eyes) and the combined XEN groups, the mean IOP decreased from 24.1 ± 4.7 to 15.7 ± 3.0 mmHg (p < 0.001) and 25.4 ± 5.6 to 14.7 ± 3.2 mmHg (p < 0.001), while Meds decreased from 3.3 ± 0.8 to 0.8 ± 1.2 (p < 0.001) and 2.7 ± 1.2 to 0.4 ± 1.0 (p < 0.001), respectively. The VF and VA indices showed no sign of further deterioration, the RNFL thickness further decreased in all treatment groups after surgery. TE and XEN led to comparable reductions in IOP and Meds. Although the VA and VF indices remained unaltered, the RNFL thickness continuously decreased in all treatment groups during the 24-month follow-up.


1991 ◽  
Vol 128 (2) ◽  
pp. 197-204 ◽  
Author(s):  
F. J. Ballard ◽  
S. E. Knowles ◽  
P. E. Walton ◽  
K. Edson ◽  
P. C. Owens ◽  
...  

ABSTRACT Incubation of 125I-labelled insulin-like growth factor-I (IGF-I) with rat plasma at 4 °C led to the transfer of approximately half the radioactivity to 150 kDa and smaller complexes with IGF-binding proteins. The extent of association was greater with labelled IGF-II and essentially absent with the truncated IGF-I analogue, des(1–3)IGF-I. A greater degree of binding of IGF peptides with binding proteins occurred after i.v. injection of the tracers into rats, but most of the des(1–3)IGF-I radioactivity remained free. Measurement of the total plasma clearances showed the rapid removal of des(1–3)IGF-I compared with IGF-I and IGF-II; the mean clearances were 4·59, 1·20 and 1·34 ml/min per kg respectively. The mean steadystate volume of distribution was larger for des(1–3)IGF-I than for IGF-I and IGF-II (461, 167 and 181 ml/kg respectively), probably because of the differences in plasma protein binding. With all tracers, radioactivity appeared in the kidneys to a greater extent than in other organs. The amount of radioactivity found in the adrenals, brain, skin, stomach, duodenum, ileum plus jejunum and colon was in rank order, des(1–3)IGF-I > IGF-I > IGF-II. Since this ranking is the opposite of the abilities of the three IGF peptides to form complexes with plasma binding proteins, we propose that the plasma binding proteins inhibit the transfer of the growth factors to their tissue sites of action. Moreover, we suggest that IGF analogues that are cleared rapidly from blood may have greater biological potencies in vivo. Journal of Endocrinology (1991) 128, 197–204


1984 ◽  
Vol 107 (2) ◽  
pp. 164-170 ◽  
Author(s):  
Gösta Enberg ◽  
Kerstin Hall

Abstract. A radioimmunoassay has been developed for IGF-II, using Sepharose-coupled antibodies. Porcine insulin, human insulin and human proinsulin showed no cross-reaction, whereas the cross-reaction for IGF-I was 10%. To minimize the influence of the binding protein(s), all serum samples were extracted with acid ethanol before assay. The mean serum level of immunoreactive IGF-II and 95% confidence limit in 46 healthy adults were 587 ng/ml and 354–974 ng/ml, respectively. In contrast to the declining levels of IGF-I with increasing age, no such age-dependent decrease was found for IGF-II levels between 20 to 70 years. No difference in IGF-II levels was found between patients with acromegaly and healthy adult controls. In cord serum and serum from adult patients with GH deficiency the levels were significantly lower (P < 0.001) compared to controls. In diabetic patients with uraemia the mean level and 95% confidence limit were 1222 ng/ml and 532–2808 ng/ml, respectively. Thus, significantly increased serum levels of immunoreactive IGF-II have only been found in serum from patients with uraemia. Whether this is due to an increased production of IGF-II, or secondary to other factors such as the binding protein(s), will require further investigation.


2021 ◽  
Author(s):  
Shang-Yih Chan ◽  
Yun-Ju Lai ◽  
Yu-Yen Hsin Chen ◽  
Shuo-Ju Chiang ◽  
Yi-Fan Tsai ◽  
...  

Abstract Purpose Studies to examine the impact of end-of-life (EOL) discussions on the utilization of life-sustaining treatments near death were limited and had inconsistent findings. This nationwide population-based cohort study determined the impact of EOL discussions on the utilization of life-sustaining treatments in the last three months of life in Taiwanese cancer patients. Methods This cohort study included adult cancer patients from 2012–2018, which were confirmed by pathohistological reports. Life-sustaining treatments during the last three months of life included cardiopulmonary resuscitation, intubation, and defibrillation. EOL discussions in cancer patients were confirmed by their medical records. Association of EOL discussions with utilization of life-sustaining treatments were assessed using multiple logistic regression. Results Of 381,207 patients, the mean age was 70.5 years and 19.4% of the subjects utilized life-sustaining treatments during the last three months of life. After adjusting for other covariates, those who underwent EOL discussions were less likely to receive life-sustaining treatments during the last three months of life compared to those who did not (Adjusted odds ratio [AOR]: 0.82; 95% confidence interval [CI]: 0.80–0.84). Considering the type of treatments, EOL discussions correlated with a lower likelihood of receiving cardiopulmonary resuscitation (AOR = 0.43, 95% CI: 0.41–0.45), endotracheal intubation (AOR = 0.87, 95%CI: 0.85–0.89), and defibrillation (AOR = 0.52, 95%CI: 0.48–0.57). Conclusion EOL discussions correlated with a lower utilization of life-sustaining treatments during the last three months of life among cancer patients. Our study supports the importance of providing these discussions to cancer patients to better align care with preferences during the EOL treatment.


2021 ◽  
Vol 9 ◽  
Author(s):  
Francesco Nunziata ◽  
Marco Poeta ◽  
Edoardo Vassallo ◽  
Grazia Isabella Continisio ◽  
Andrea Lo Vecchio ◽  
...  

Introduction: The transmission rates severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from children to adults are unclear due to a lack of controlled conditions.Materials and Methods: We investigated the occurrence of SARS-CoV-2 transmission among 12 discordant child-parent pairs in our ward. In each hospital isolation room, caregivers and children lived in close contact during the entire hospitalization period.Results: A total of 136 swab-positive children (mean age, 3.6 ± 4.9 median age, 1; IQR 0–6.2, range 0.1–17) attended by their caregivers were hospitalized. Of those, 12/136 (8.8%, mean age, 6.1 ± 5.3 median age, 4.5) were attended by caregivers who were swab and serology negative at admission despite previous close contact with positive children at home. Three children were completely dependent on their mothers, one of whom was being breastfed. The mean duration of overall exposure to the index case was 20.5 ± 8.2 days.Conclusion: None of the infected children transmitted SARS-CoV-2 infection to their caregivers, raising the hypothesis of a cluster of resistant mothers or of limited transmission from children to adults despite prolonged exposure and close contact. These data might provide reassurance regarding school openings and offer the chance of investigating SARS-CoV-2 variants in the future under the same quasi-experimental conditions.


F1000Research ◽  
2021 ◽  
Vol 10 ◽  
pp. 224
Author(s):  
Cristian Díaz-Vélez ◽  
Diego Urrunaga-Pastor ◽  
Anthony Romero-Cerdán ◽  
Eric Ricardo Peña-Sánchez ◽  
Jorge Luis Fernández Mogollon ◽  
...  

Background: Peru was one of the countries with the highest COVID-19 mortality worldwide during the first stage of the pandemic. It is then relevant to evaluate the risk factors for mortality in patients hospitalized for COVID-19 in three hospitals in Peru in 2020, from March to May, 2020.  Methods: We carried out a retrospective cohort study. The population consisted of patients from three Peruvian hospitals hospitalized for a diagnosis of COVID-19 during the March-May 2020 period. Independent sociodemographic variables, medical history, symptoms, vital functions, laboratory parameters and medical treatment were evaluated. In-hospital mortality was assessed as the outcome. We performed Cox regression models (crude and adjusted) to evaluate risk factors for in-hospital mortality. Hazard ratios (HR) with their respective 95% confidence intervals (95% CI) were calculated.  Results: We analyzed 493 hospitalized adults; 72.8% (n=359) were male and the mean age was 63.3 ± 14.4 years. COVID-19 symptoms appeared on average 7.9 ± 4.0 days before admission to the hospital, and the mean oxygen saturation on admission was 82.6 ± 13.8. While 67.6% (n=333) required intensive care unit admission, only 3.3% (n=16) were admitted to this unit, and 60.2% (n=297) of the sample died. In the adjusted regression analysis, it was found that being 60 years old or older (HR=1.57; 95% CI: 1.14-2.15), having two or more comorbidities (HR=1.53; 95% CI: 1.10-2.14), oxygen saturation between 85-80% (HR=2.52; 95% CI: 1.58-4.02), less than 80% (HR=4.59; 95% CI: 3.01-7.00), and being in the middle (HR=1.65; 95% CI: 1.15-2.39) and higher tertile (HR=2.18; 95% CI: 1.51-3.15) of the neutrophil-to-lymphocyte ratio, increased the risk of mortality.  Conclusions: The risk factors found agree with what has been described in the literature and allow the identification of vulnerable groups in whom monitoring and early identification of symptoms should be prioritized in order to reduce mortality.


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