The effect of Covid-19 mRNA vaccine on serum anti-Müllerian hormone levels.

STUDY QUESTION: Does the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine have an association with ovarian reserve as expressed by circulating anti-Müllerian hormone (AMH) levels? SUMMARY ANSWER: Ovarian reserve as assessed by serum AMH levels is not altered at 3 months following mRNA SARS-CoV-2 vaccination. WHAT IS KNOWN ALREADY: A possible impact of SARS-CoV-2 infection or vaccination through an interaction between the oocyte and the somatic cells could not be ruled out, however, data are limited. STUDY DESIGN, SIZE, DURATION: This is a prospective study conducted at a university affiliated tertiary medical center between February and March 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Study population included reproductive aged women (18-42 years) that were vaccinated by two Pfizer-BioNTech Covid-19 vaccines (21 days apart). Women with ovarian failure, under fertility treatments, during pregnancy, previous Covid-19 infection or vaccinated were excluded from the study. Blood samples were collected for AMH levels before the first mRNA vaccine administration. Additional blood samples after 3 months were collected for AMH and anti-Covid-19 antibody levels. Primary outcome was defined as the absolute and percentage change in AMH levels. MAIN RESULTS AND THE ROLE OF CHANCE: The study group consisted of 129 women who received two mRNA vaccinations. Mean AMH levels were 5.3 (±SD 4.29) µg/l and 5.3 (±SD 4.50) µg/l at baseline and after 3 months, respectively (P = 0.11). To account for possible age-specific changes of AMH, sub-analyses were performed for three age groups: <30, 30-35 and >35 years. AMH levels were significantly lower for women older than 35 years at all times (P = 0.001 for pre and post vaccination AMH levels versus younger women). However, no significant differences for the changes in AMH levels before and after vaccinations (Delta AMH) were observed for the three age groups (P = 0.46). Additionally, after controlling for age, no association was found between the degree of immunity response and AMH levels. LIMITATIONS, REASONS FOR CAUTION: Although it was prospectively designed, for ethical reasons we could not assign a priori a randomized unvaccinated control group. This study examined plasma AMH levels at 3 months after the first vaccination. It could be argued that possible deleterious ovarian and AMH changes caused by the SARS-CoV-2 mRNA vaccinations might take effect only at a later time. Only longer-term studies will be able to examine this issue. WIDER IMPLICATIONS OF THE FINDINGS: The results of the study provide reassurance for women hesitant to complete vaccination against Covid 19 due to concerns regarding its effect on future fertility. This information could be of significant value to physicians and patients alike. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by Sheba Medical Center institutional sources. All authors have nothing to disclose. TRIAL REGISTRATION NUMBER: The study protocol was approved by the 'Sheba Medical Center' Ethical Committee Review Board (ID 8121-21-SMC) on 8 February 2021 and was registered at the National Institutes of Health (NCT04748172).

Germline mosaicism in Coffin-Lowry syndrome.

We have identified a Coffin-Lowry syndrome pedigree where the disorder is associated with a novel splice site mutation in the RSK2 gene, leading to in-phase skipping of exon 5. Western blot analysis, using an antibody directed against the C-terminus of RSK2, failed to reveal RSK2 in this patient, suggesting strongly that the resulting internally deleted protein is unstable. The mutation was present in the DNA of one affected son and one manifesting daughter but was absent in two asymptomatic daughters, who carry the at-risk haplotype, and in the mother's somatic cell (lymphocyte) DNA. The results are consistent with the mutation arising as a postzygotic event in the mother, who therefore is a germinal mosaic. The application of linked markers to identify the disease allele for conventional genetic counselling would have been misleading in this family. This observation again highlights the importance of precise identification of the disease-causing mutation.

Quality assurance in transition.

This paper outlines the early approaches to quality assurance, and its transition from business to health care. It then describes the development of the more recent trends in quality assurance of Total Quality Management and Continuous Quality Improvement and discusses the strengths and weaknesses of these approaches. The paper then goes on to show how these approaches have been modified for application to peripheral health services in developing countries through the work of the Primary Health Care Operations Research Project and the Quality Assurance Project.

PIP: Continuous Quality Improvement (CQI) will, with time and patience, eventually become operational in most organizations, but developing countries must begin by establishing quality improvements at the primary level, and not at the periphery. Quality of care means, for instance, averting infection the first time around by maintaining sterile conditions, and not using unnecessary antibiotics. Quality of care becomes an important issue as services become more costly to the user, and as the world moves toward democratization and focusing on the rights of the client to effective, affordable care. Quality of care is the provision of services that maximize patient health status and personal satisfaction and minimize cost. Quality assurances can be traced back over 2000 years, to when Chinese physicians were tested on their knowledge. Most quality assurance has focused on outcomes of care and rarely on internal organization; outpatient care has been neglected. During the 1980s, there was an increased interest generated in Total Quality Management and CQI. The US established the National Demonstration Project on Quality Improvement in Health Care among 21 Health Maintenance Organizations and hospitals. The project concluded that flow charts, cause-effect diagrams, and control charts were useful devices for resolving health care service problems, and that CQI required the creation of process teams for solving cross-functional problems. CQI tools could be used with existing data and were particularly useful when time of day was included. Hospital staff enjoyed using analytic tools for problem analysis and problem solving. Physicians were uncooperative, but nurses participated enthusiastically in process improvement teams. CQI tools were found to be simple to use. Adaptation of CQI for developing countries resulted in the preparation of a Primary Health Care Thesaurus with job performance standards. Common problems found in evaluations were failure of health workers to communicate effectively with mothers of children, and weak supervision.

The Quality Assurance Project assists the vitamin A capsule program in Antique Province, Philippines.

PIP: Vitamin A deficiency remains an important problem in some parts of the Philippines. The Department of Health, with assistance from the Helen Keller Institute (HKI), established a vitamin A supplementation program in Antique Province providing for the administration of vitamin A capsules to malnourished children. Although the HKI cut off its assistance in 1992, continuation of the capsule supplementation program was an element of the National Nutrition Plan for 1992-96, and remains an element of the Antique Provincial health services program under the Philippines' devolved health services scheme. The Quality Assurance Program (QAP) in May 1993 began helping the Provincial Health Office improve the quality of the vitamin A program. A systems analysis was first undertaken to identify significant deviations from provider performance standards which had been adapted by the province from Nutrition Service guidelines. Many problems were observed, including lack of knowledge of the high-priority categories of children, incomplete counseling, and frequent mistakes in determining children's nutritional status. The provincial health office staff recommended that six of the province's seventeen municipalities participate in the quality improvement effort. The intent of the QAP staff was not only to help the provincial staff improve the quality of its vitamin A program by resolving some immediate operational problems, but to provide the health care workers with a quality improvement experience that they would intuitively transfer to other programs for which they were responsible. The coaching/facilitating approach of modern quality management allowed health workers to explore their own approaches to solving the problems chosen.^ieng

Interventional use of magnetic resonance imaging.

Among the currently available imaging techniques, magnetic resonance imaging (MRI) offers particular advantages for guiding, monitoring, and controlling diagnostic and therapeutic interventions, with particular appeal for most of the minimally invasive, minimal access approaches. The most obvious role of MRI is in monitoring and controlling a variety of interstitial ablative procedures, utilizing methods including thermal therapy (interstitial laser therapy, cryosurgery, focused ultrasound surgery). A fundamental requirement of MR monitoring is the implementation of pulse sequences with appropriate spatial and temporal resolution as well as overall image quality suitable for the dynamic imaging task. In addition, there is a need for a more accessible magnet configuration to enable execution of various interventional procedures. MR compatibility of instruments and devices, therefore, needs to be addressed, as must the integration of therapy delivery modalities with the MR system.

Comparative validity of three methods for assessment of the quality of primary health care.

OBJECTIVE: This study compared the sensitivity and specificity of three assessment methods to detect the performance of key clinical tasks by health workers in a primary care setting. DESIGN: Health worker performance during patient encounters for acute respiratory infections, acute diarrhea and family planning counseling was assessed through checklist-based observation of the consultation, interview with the mother following the consultation, and review of the patient's clinical record. The results of each method regarding the performance of key tasks by health workers were compared to a 'gold standard', defined as the application of the observation checklist by observers with extensive quality assessment experience. Patient encounters were studied in three Ministry of Health facilities in the Department of Totonicapán, Guatemala, involving care by physicians, nurses and auxiliary staff RESULTS: The three methods showed reasonably high levels of sensitivity (generally about 70%) for the detection of failures in the performance of most health worker tasks. The greatest problem experienced by each method related to specificity, i.e. capacity to recognize quality successes and only detect real failures. CONCLUSION: Direct observation demonstrated the best overall balance of sensitivity and specificity. Exit interview of the mother demonstrated good sensitivity and better specificity than record review.

The Danfa family planning program in rural Ghana.

PIP: The objectives of the Danfa Family Planning Program in rural Ghana are to provide family planning services to the people in the region and to conduct research into ways of making these services as effective and accessible as possible within given resource limitations. The effort is made to describe the planning and operating experience of the program during its 1st 2 1/2 years. In order to test the hypotheses and satisfy service, research, and teaching objectives, the region in which the project operates was divided into 4 areas with each area receiving different service inputs. This division was related to the following arguments with the 4th area used as a control area to learn how much family planning occurs in the absence of special health, education, and family planning programs: 1) couples will want to limit the number of their children only if they perceive that they need no longer fear that several of them will die before reaching adulthood; 2) the most cost-effective approach is to provide family planning services in conjunction with an intensive educational program promoting good health practices and family planning but without comprehensive health services; and 3) by amking family planning services available without concern for comprehensive health services or a special education program, adequate acceptance of family planning and a favorable fertility change at minimum cost will be achieved. The 4 research areas covering about 200 square miles are located in a rural region 8-50 miles north of Accra, the capital of Ghana, and have a population of 60,000. It was learned that it is easier to operate a family planning program in this region of rural Ghana than had originally been anticipated and that education about the benefits of family planning and the methods available along with accessibility to services are 2 elements that are crucial to the success of a family planning program in this setting.^ieng

Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation.

BACKGROUND: The fragile X syndrome, the most common form of inherited mental retardation, is caused by mutations that increase the size of a specific DNA fragment of the X chromosome (in Xq27.3). Affected persons have both a full mutation and abnormal DNA methylation. Persons with a smaller increase in the size of this DNA fragment (a premutation) have little or no risk of retardation but are at high risk of having affected children or grandchildren. The passage from premutation to full-mutation status occurs only with transmission from the mother. We have devised a method of identifying carriers of these mutations by direct DNA analysis. METHOD: We studied 511 persons from 63 families with the fragile X syndrome. Mutations and abnormal methylation were detected by Southern blotting with a probe adjacent to the mutation target. Analysis of EcoRI and EagI digests of DNA distinguished clearly in a single test between the normal genotype, the premutation, and the full mutation. RESULTS: DNA analysis unambiguously established the genetic status at the fragile X locus for all samples tested. This method was much more powerful and reliable than cytogenetic testing or segregation studies with closely linked polymorphic markers. The frequency of mental retardation in persons with premutations was similar to that in the general population, whereas all 103 males and 31 of 59 females with full mutations had mental retardation. About 15 percent of those with full mutations had some cells carrying only the premutation. All the mothers of affected children were carriers of either a premutation or a full mutation. CONCLUSIONS: Direct diagnosis by DNA analysis is now an efficient and reliable primary test for the diagnosis of the fragile X syndrome after birth, as well as for prenatal diagnosis and genetic counseling.

Quality assurance planning and structure.

PIP: Planning for the introduction, implementation, and conduct of quality assurance activities has been the key issue from the outset of the project. Despite the various approaches to planning, no single Quality Assurance (QA) planning can be universally accepted by developing countries due to variations in the socioeconomic, cultural and political makeup of individual countries. This paper summarizes the lessons learned from the Quality Assurance Project in planning a QA program: 1) the need to understand organizational strengths and weaknesses to develop appropriate strategies for QA skills training and organizational change; 2) the need to build on existing systems or activities that support the objectives of the organization and provide an adequate foundation for the QA program; 3) the need to assign responsibility for quality assurance through the creation of QA councils and committees and the assignment of coordinators and other individuals; 4) the need to secure top-level management support to legitimize any changes; 5) the need to determine the method of introducing innovations into organizations, either by a top-down or bottom-up approach; 6) the plan should have well-defined priorities and objectives despite its flexibility as projects evolve and grow over time.^ieng