How to accelerate the supply of vaccines to all populations worldwide? Part I: Initial industry lessons learned and practical overarching proposals leveraging the COVID-19 situation.

The COVID-19 pandemic has shown itself to be an unprecedented challenge for vaccines which are widely recognized as the most important tool to exit this pandemic. We have witnessed vaccine scientists, developers, manufacturers, and stakeholders deliver several vaccines in just about a year. This is an unprecedented achievement in an environment that was not ready to manage such a global public health crisis. Indeed, the pandemic has highlighted some hurdles that need to be addressed in the system in order to streamline the regulatory processes and be in a situation where life-saving pharmaceutical solutions such as vaccines can be delivered quickly and equitably to people across the globe. More precisely, trade-offs had to be made between the need for regulatory flexibility in the requirements for manufacturing and controls to enable rapid availability of large volumes of vaccines vs the increased stringency and the lack of harmonization in the regulatory environment for vaccines globally. It is also characterized by a high heterogeneity in terms of review and approval processes, limiting equitable and timely access. We review and highlight the challenges relating to several topics, including process validation, comparability, stability, post-approval-changes, release testing, packaging, genetically modified organisms and variants. We see four areas for accelerating access to vaccines which provide solutions for the regulatory concerns, (1) science- and risk-based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. These solutions are not new and have been previously highlighted. In recent months, we have seen some progress at the health authority level, but still much needs to be done. It is now time to reflect on the first lessons learnt from a devastating pandemic to ultimately ensure quick and wide access to medicines and vaccines for the citizens and patients.

How to accelerate the supply of vaccines to all populations worldwide? Part II: Initial industry lessons learned and detailed technical reflections leveraging the COVID-19 situation.

Vaccine discovery and vaccination against preventable diseases are one of most important achievements of the human race. While medical, scientific & technological advancements have kept in pace and found their way into treatment options for a vast majority of diseases, vaccines as a prevention tool in the public health realm are found languishing in the gap between such innovations and their easy availability/accessibility to vulnerable populations. This paradox has been best highlighted during the unprecedented crisis of the COVID-19 pandemic. As part of a two series publication on the vaccine industry's view on how to accelerate the availability of vaccines worldwide, this paper offers a deep dive into detailed proposals to enable this objective. These first-of-its-kind technical proposals gleaned from challenges and learnings from the COVID-19 pandemic are applicable to vaccines that are already on the market for routine pathogens as well as for production of new(er) vaccines for emerging pathogens with a public health threat potential. The technical proposals offer feasible and sustainable solutions in pivotal areas such as process validation, comparability, stability, post-approval changes, release testing, packaging, genetically modified organisms and variants, which are linked to manufacturing and quality control of vaccines. Ultimately these proposals aim to ease high regulatory complexity and heterogeneity surrounding the manufacturing & distribution of vaccines, by advocating the use of (1) Science and Risk based approaches, (2) global regulatory harmonization, (3) use of reliance, work-sharing, and recognition processes and (4) digitalization. Capitalizing & collaborating on such new-world advancements into the science of vaccines will eventually benefit the world by turning vaccines into vaccination, ensuring the health of everyone.

Addressing vaccine supply challenges in Europe: Expert industry perspective and recommendations.

Shortages of medicines are an increasing concern worldwide. In the European Union (EU), several initiatives have been launched by authorities to address this important public health issue. To contribute in finding solutions, Vaccines Europe (VE), representing 14 vaccine companies operating in Europe, conducted an analysis of the main root causes of vaccine shortages in Europe. Vaccines Europe has identified six main causes of vaccine shortages. Finding solutions will require a concerted effort and dialogue with the involvement of all key stakeholders. In this publication, Vaccines Europe is making a series of recommendations aiming at improving vaccine availability for Europe and beyond.

Anesthetic Management of a Voluminous Left Atrial Myxoma Resection in a 19 Weeks Pregnant with Atypical Clinical Presentation.

We report the case of a semi-urgent cardiac surgery, in a 19 gestation age pregnant. Despite the fact that the patient was asymptomatic, except for some palpitations, a large left auricle (LA) myxoma was fortuitously diagnosed with transthoracic echocardiography (TEE). Considering the important embolic risk, the tumor was successfully removed during cardiac surgery under cardiopulmonary bypass (CPB). Fetal bradycardia following defibrillation under stable maternal and CPB conditions was successfully managed. The postoperative period and remainder of the pregnancy was smooth and the delivery uneventful.

[Platelet collection in cardiac surgery: first experience with apheresis at the General Hospital in Douala]. / Prélèvement de plaquettes pour la chirurgie cardiaque: première expérience de d'aphérèse à l'Hôpital Général de Douala.

Cardiac surgery with extracorporeal circulation (ECC) is usually associated with the loss of a significant amount of blood. Adequate prophylaxis against blood loss and good perioperative hemostasis are known as processes limiting postoperative bleeding. Until now, the need for platelets in patients operated with extracorporeal circulation in our Department has been compensated for by total blood transfusion or platelet concentrates collected from several donors. We here report our first experience with platelet concentrate collection by apheresis at the General Hospital in Douala.

Outcome of permanent vascular access for haemodialysis in patients with end-stage renal disease in Cameroon: results from the pilot experience of the Douala general hospital.

Background Chronic Kidney disease is a major health problem in the world. Native arteriovenous Fistula (AVF) is well established as the best vascular access for haemodialysis. Little is known about the outcome of AVF in sub-Saharan Africa. We aim to analyze the outcome of patients undergoing AVF creation during the pilot program established at the Douala general hospital (DGH). Method This was hospital-based, longitudinal study with a retrospective phase (April 2010-January 2014) and a prospective phase (January 2014-April 2014). All consecutive patients operated for AVF creation were included in this study. Socio-demographics data, functionality, and complications were analyzed. Results Eighty-one patients including 52 men were enrolled in this study (49 prospectively and 32 retrospectively). The mean age was 52, 3 years (range 18-81 years). Hypertension (66, 7%), diabetes (17, 3%), and HIV (8, 6%) were the most observed co-morbidities. About 96.3% of AVF were native and 3.7% were prosthetic graft. Radiocephalic AVF was performed at a rate of 77.8%. The primary function rate was 97.7% and the mean follow-up period 43.4 weeks. The overall rate of complications was 44.4% of whom 30.5% were early, 30.5% secondary, and 39% lasted. The treatment of these complications was conservative in 48.7% of cases. Conclusions The results of the pilot program of AVF creation at the DGH are encouraging. However, the sustainability of this project requires human capacity building.

Total syntheses of pamamycin 607 and methyl nonactate: stereoselective cyclisation of homoallylic alcohols that had been prepared with remote stereocontrol using allylstannanes.

The tin(IV) chloride mediated cyclisation of (Z)-homoallylic alcohols using phenylselenenyl chloride or phthalimide in the presence of a Lewis acid followed by reductive removal of the phenylselenenyl group was found to give 2,5-cis-disubstituted tetrahydrofurans with excellent stereocontrol. Using this procedure, (2S,4S,8R,6Z)-9-benzyloxy-2-tert-butyldiphenylsilyloxy-8-methylnon-6-en-4-ol (11), prepared stereoselectively via the tin(iv) chloride promoted reaction between the (R)-5-benzyloxy-4-methylpent-2-enyl(tributyl)stannane (3) and (S)-3-tert-butyldiphenylsilyloxybutanal (10), gave (2S,3R,6S,8S)-1-benzyloxy-8-tert-butyldiphenylsilyloxy-3,6-epoxy-2-methylnonane (13) after deselenation. This tetrahydrofuran was selectively deprotected, oxidized and esterified to give methyl nonactate (2). Having established this synthesis of 2,5-cis-disubstituted tetrahydrofurans, it was applied to complete a synthesis of pamamycin 607 (1). (2S,3R,6S,8R)-1-Benzyloxy-8-[N-methyl-N-(toluene-4-sulfonyl)amino]-3,6-epoxy-2-methylundecane (35) was prepared stereoselectively from (R)-3-[N-(toluene-4-sulfonyl)-N-methylamino]hexanal (32) by reaction with the stannane 3 followed by cyclisation of the resulting alkenol 33 and deselenation. Following debenzylation and oxidation, an aldol reaction of the aldehyde 37 using the lithium enolate of 2,6-dimethylphenyl propanoate (61) gave mainly the 2,3-anti-3,4-syn-adduct 48. After protection of the secondary alcohol as its tert-butyldimethylsilyl ether 49, reduction using DIBAL-H and oxidation, the resulting aldehyde, (2S,3S,4R,5R,8S,10R)-3-tert-butyldimethylsilyloxy-2,4-dimethyl-5,8-epoxy-10-[N-methyl-N-(toluene-4-sulfonyl)amino]tridecanal (62), was taken through to the bis-tetrahydrofuran 65 by repeating the sequence of the reactions with the stannane 3, cyclisation and deselenation. The N-(toluene-4-sulfonyl) group was then replaced by an N-(tert-butoxycarbonyl) group and O-debenzylation and oxidation gave the carboxylic acid 70 that corresponds to the C(1)-C(18) fragment of pamamycin 607 (1). Similar chemistry was used to prepare the C(1')-C(11') fragment 89 of the pamamycin, except that in this case the configuration of the secondary alcohol introduced by the allylstannane reaction had to be inverted using a Mitsunobu reaction before the cyclisation. Esterification of the carboxylic acid of the C(1)-C(18)-fragment 70 using the alcohol 89 of the C(1')-C(11') fragment followed by selective deprotection, macrocyclisation, N-deprotection and N-methylation gave pamamycin 607 (1) that was identical to a sample of the natural product.

Robotically assisted laparoscopic microsurgical tubal reanastomosis: a retrospective study.

OBJECTIVE: To evaluate the pregnancy and delivery outcome of robot-assisted tubal reanastomosis. DESIGN: Retrospective cohort study. SETTING: University hospital. PATIENT(S): Ninety-seven patients with available follow-up who underwent the reversal of tubal ligation, with a median age of 37 years (range, 24-47 years). INTERVENTION(S): Tubal reanastomosis by robot-assisted laparoscopy. MAIN OUTCOME MEASURE(S): Analysis of the distribution of time to conception and to estimate the crude pregnancy and birth rates at 2 years. RESULT(S): The overall pregnancy and birth rates were 71%, (95% confidence interval [CI], 61%-80%) and 62% (95% CI, 52%-72%). Ninety-one percent (95% CI, 76%-98%) of patients <35 years old became pregnant, and 88% (95% CI, 72%-97%) delivered at least once. The corresponding pregnancy and delivery rates were 75% (95% CI, 57%-89%) and 66% (95% CI, 47%-81%) between 36 and 39 years old, 50% (95% CI, 25%-75%) and 43.8% (95% CI, 20%-70%) between 40 and 42 years old, 33% (95% CI, 10%-65%) and 8.3% (95% CI, <1%-38%) after the age of 43 years. CONCLUSION(S): This study reports satisfactory birth rates after tubal reanastomosis by robot-assisted laparoscopy in patients aged 40 years or less.

Role of laparoscopy in the management of visceral injuries following abdominal stab wounds.

BACKGROUND: Laparoscopy offers several advantages in the treatment of abdominal stab wounds. In this paper, we report our experience during 2004, where hemodynamically stable patients with stab wounds were managed laparoscopically. PATIENTS AND METHODS: Between January and December 2004, 8 hemodynamically stable patients (7 men, 1 woman) underwent laparoscopy for anterior abdominal stab wounds. Median age was 28.5 years (range, 17-55). All patients underwent an abdominal computed tomography (CT) prior to the laparoscopy. RESULTS: Exploration of the wound under aseptic conditions, carried out as a part of the physical examination, confirmed peritoneal penetration in 7 of the 8 cases. Abdominal CT revealed positive findings in 7 (87.5%) cases. Laparoscopy was performed after a median time of 60 minutes (range 30-90). Laparoscopic exploration evidenced peritoneal penetration in 100% of the cases and visceral lesions in 87.5% of the cases. All visceral injuries were managed laparoscopically. Median operative time was 135 minutes (range, 45-200). Operative mortality was 0% and early morbidity was 12.5%. Median hospital stay was 5 days (range, 1-11). After a median follow-up of 12 months (range, 1-28), 1 patient complained of persistent chest pain and a ventral hernia at the site of the abdominal stab wound was diagnosed in another patient. CONCLUSIONS: Laparoscopy should be included in management algorithms in patients with anterior abdominal stab wounds who are hemodynamically stable. In addition to its diagnostic ability, this study demonstrates that laparoscopy can be an effective management modality with minimal morbidity and no mortality.