Decoding complex inherited phenotypes in rare disorders: the DECIPHERD initiative for rare undiagnosed diseases in Chile.

Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the "diagnostic odyssey" for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. We describe the implementation process and findings of the first 103 patients. They had heterogeneous phenotypes, including congenital anomalies, intellectual disabilities and/or immune system dysfunction. Patients underwent clinical exome or research exome sequencing, as solo cases or with parents using a trio design. We identified pathogenic, likely pathogenic or variants of unknown significance in genes related to the patients´ phenotypes in 47 (45.6%) of them. Half were de novo informative variants, and half of the identified variants have not been previously reported in public databases. DECIPHERD ended the diagnostic odyssey for many participants. This hybrid strategy may be useful for settings of similarly limited genomic resources and lead to discoveries in understudied populations.

Intellectual Property and the Politics of Public Good during COVID-19: Framing Law, Institutions, and Ideas during TRIPS Waiver Negotiations at the WTO.

CONTEXT: To facilitate the manufacturing of COVID-19 medical products, in October 2020 India and South Africa proposed a waiver of certain intellectual property (IP) provisions of a World Trade Organization (WTO) agreement. After nearly two years, a narrow waiver agreement that did little for vaccine access passed the ministerial despite the pandemic's impact on global trade, which the WTO is mandated to safeguard. METHODS: The authors conducted a content analysis of WTO legal texts, key-actor statements, media reporting, and the WTO's procedural framework to explore legal, institutional, and ideational explanations for the delay. FINDINGS: IP waivers are neither legally complex nor unprecedented within WTO law, yet these waiver negotiations exceeded their mandated 90-day negotiation period by approximately 18 months. Waiver opponents and supporters engaged in escalating strategic framing that justified and eventually secured political attention at head-of-state level, sidelining other pandemic solutions. The frames deployed discouraged consensus on a meaningful waiver, which ultimately favored the status quo that opponents preferred. WTO institutional design encouraged drawn-out negotiation while limiting legitimate players in the debate to trade ministers, empowering narrow interest group politics. CONCLUSIONS: Despite global political attention, the WTO process contributed little to emergency vaccine production, suggesting a pressing need for reforms aimed at more efficient and equitable multilateral processes.

Springs Produce Favorable Morphological Outcomes Relative to H-craniectomy According to a Two-center Comparison of Matched Cases.

BACKGROUND: Sagittal synostosis is the most common type of premature suture closure, and many surgical techniques are used to correct scaphocephalic skull shape. Given the rarity of direct comparisons of different surgical techniques for correcting craniosynostosis, this study compared outcomes of craniotomy combined with springs and H-craniectomy for non-syndromic sagittal synostosis. METHODS: Comparisons were performed using available pre- and postoperative imaging and follow-up data from the two craniofacial national referral centers in Sweden, which perform two different surgical techniques: craniotomy combined with springs (Gothenburg) and H-craniectomy (Renier's technique; Uppsala). The study included 23 pairs of patients matched for sex, preoperative cephalic index (CI), and age. CI, total intracranial volume (ICV), and partial ICV were measured before surgery and at 3 years of age, with volume measurements compared against those of pre- and postoperative controls. Perioperative data included operation time, blood loss, volume of transfused blood, and length of hospital stay. RESULTS: Craniotomy combined with springs resulted in less bleeding and lower transfusion rates than H-craniectomy. Although the spring technique requires two operations, the mean total operation time was similar for both methods. Of the three complications that occurred in the group treated with springs, two were spring-related. Importantly, the compiled analysis of changes in CI and partial volume distribution revealed that craniotomy combined with springs resulted in superior morphological correction. CONCLUSIONS: The findings showed that craniotomy combined with springs normalized cranial morphology to a greater extent than H-craniectomy based on changes in CI and total and partial ICVs over time.

Randomized Trial of Facilitated Adherence to Screening Colonoscopy vs Sequential Fecal-Based Blood Test.

BACKGROUND & AIMS: Colorectal cancer (CRC) screening guidelines include screening colonoscopy and sequential high-sensitivity fecal occult blood testing (HSgFOBT), with expectation of similar effectiveness based on the assumption of similar high adherence. However, adherence to screening colonoscopy compared with sequential HSgFOBT has not been reported. In this randomized clinical trial, we assessed adherence and pathology findings for a single screening colonoscopy vs sequential and nonsequential HSgFOBTs. METHODS: Participants aged 40-69 years were enrolled at 3 centers representing different clinical settings. Participants were randomized into a single screening colonoscopy arm vs sequential HSgFOBT arm composed of 4-7 rounds. Initial adherence to screening colonoscopy and sequential adherence to HSgFOBT, follow-up colonoscopy for positive HSgFOBT tests, crossover to colonoscopy, and detection of advanced neoplasia or large serrated lesions (ADN-SERs) were measured. RESULTS: There were 3523 participants included in the trial; 1761 and 1762 participants were randomized to the screening colonoscopy and HSgFOBT arms, respectively. Adherence was 1473 (83.6%) for the screening colonoscopy arm vs 1288 (73.1%) for the HSgFOBT arm after 1 round (relative risk [RR], 1.14; 95% CI, 1.10-1.19; P ≤ .001), but only 674 (38.3%) over 4 sequential HSgFOBT rounds (RR, 2.19; 95% CI, 2.05-2.33). Overall adherence to any screening increased to 1558 (88.5%) in the screening colonoscopy arm during the entire study period and 1493 (84.7%) in the HSgFOBT arm (RR, 1.04; 95% CI, 1.02-1.07). Four hundred thirty-six participants (24.7%) crossed over to screening colonoscopy during the first 4 rounds. ADN-SERs were detected in 121 of the 1473 participants (8.2%) in the colonoscopy arm who were adherent to protocol in the first 12 months of the study, whereas detection of ADN-SERs among those who were not sequentially adherent (n = 709) to HSgFOBT was subpar (0.6%) (RR, 14.72; 95% CI, 5.46-39.67) compared with those who were sequentially adherent (3.3%) (n = 647) (RR, 2.52; 95% CI, 1.61-3.98) to HSgFOBT in the first 4 rounds. When including colonoscopies from HSgFOBT patients who were never positive yet crossed over (n = 1483), 5.5% of ADN-SERs were detected (RR, 1.50; 95% CI, 1.15-1.96) in the first 4 rounds. CONCLUSIONS: Observed adherence to sequential rounds of HSgFOBT was suboptimal compared with a single screening colonoscopy. Detection of ADN-SERs was inferior when nonsequential HSgFOBT adherence was compared with sequential adherence. However, the greatest number of ADN-SERs was detected among those who crossed over to colonoscopy and opted to receive a colonoscopy. The effectiveness of an HSgFOBT screening program may be enhanced if crossover to screening colonoscopy is permitted. CLINICALTRIALS: gov, Number: NCT00102011.

Signs of a turning tide in social norms and attitudes toward abortion in Ethiopia: Findings from a qualitative study in four regions.

BACKGROUND: Despite the 2005 expansion in abortion legal indications in Ethiopia, which provided for abortions in cases of rape, incest, or fetal impairment and other circumstances, nearly half of abortions occurred outside health facilities in 2014. The purpose of this study is to explore and understand the social barriers women face in seeking and obtaining quality safe abortion care, as a means to generate evidence that could be used to improve access to and quality of abortion services. METHODS: Thirty-two focus group discussions with both men and women were held in four different regions of Ethiopia: Addis Ababa; Amhara; Oromia; and the Southern Nations, Nationalities, and Peoples' Region. The study team recruited participants (n = 193) aged 18-55 in each region using a purposive sample with snowball recruitment techniques. We conducted discussions in Amharic or Afaan Oromo using a semi-structured guide and transcribed and translated them into English for analysis. We used deductive coding and analysis to categorize findings into emergent themes around stigma, barriers, and the changing nature of attitudes around abortion. RESULTS: Despite changes in abortion law, findings show that women with unwanted pregnancies and those seeking abortions are still heavily stigmatized and sanctioned in a number of communities across Ethiopia. Abortion was deemed unacceptable in most cases, though respondents were more tolerant in cases of risk to the mother's life and of rape. We saw promising indications that changes are taking place in Ethiopian society's view of abortion, and several participants indicated progress toward a more supportive environment overall for women seeking abortion care. Still, this progress may be limited by variable knowledge of abortion laws and tightly held gender-based social norms, particularly in rural areas. Most participants noted the importance of education and outreach to improve abortion attitudes and norms. CONCLUSION: Policymakers should create further awareness in Ethiopia on the availability of quality abortion services in public health facilities and the indications for legal abortion. Such efforts should be based on principles of gender equality, as a means of ensuring enduring changes for women's reproductive choice throughout the country.

We conducted a study to explore and understand the social barriers women face in seeking and obtaining quality safe abortion care in Ethiopia. We implemented focus group discussions with both men and women in four different regions of Ethiopia. We analyzed our findings into themes around stigma, barriers, and the changing nature of attitudes around abortion. Our results show that women seeking abortions are still heavily stigmatized. We found that abortion was deemed unacceptable in most cases. However, we also saw promising indications that changes are taking place in Ethiopian society's view of abortion, and several participants indicated progress toward a more supportive environment overall for women seeking abortion care. Still, this progress may be limited by variable knowledge of abortion laws. Most participants noted the importance of education and outreach to improve abortion attitudes and norms. We concluded that further awareness is needed in Ethiopia on the availability of quality abortion services in public health facilities and the indications for legal abortion. These efforts should consider gender equality to ensure enduring changes for women's reproductive choice throughout the country.

Comparisons of Intracranial Volume and Cephalic Index After Correction of Sagittal Craniosynostosis With Either Two or Three Springs.

ABSTRACT: In this retrospective study, the authors determined changes in intracranial volume (ICV) and cephalic index (CI) in patients with sagittal craniosynostosis and operated with craniotomy combined with either 2 or 3 springs. The authors included patients (n = 112) with complete follow-up that had undergone surgical correction for isolated sagittal craniosynostosis with craniotomy combined with springs between 2008 and 2017. All patients underwent computed tomography examination preoperative, at the time of spring extraction, and at 3 years of age. Intracranial volume was measured using a semiautomatic MATLAB program, and CI was calculated as the width/length of the skull. The authors found that craniotomy combined with 2 springs increased the ICV from a preoperative value of 792 ±â€Š113 mL (mean ±â€Šstandard deviation) to 1298 ±â€Š181 mL at 3 years of age and increased the CI from 72.1 ±â€Š4.1 to 74.6 ±â€Š4.3, whereas craniotomy combined with 3 springs increased the ICV from 779 ±â€Š128 mL to 1283 ±â€Š136 mL and the CI from 70.7 ±â€Š4.3 to 74.8 ±â€Š3.7. The relative increase in ICV was 65 ±â€Š21% in the two-spring group and 68 ±â€Š34% in the three-spring group (P value = 0.559), and the relative increase in CI was 3.6 ±â€Š3.3% in the two-spring group as compared with 6.0 ±â€Š5.0% in the three-spring group (P = 0.004). These findings demonstrated that use of 3 springs resulted in additional absolute and relative CI-specific effects as compared with 2 springs during the time when the springs were in place, with this effect maintained at 3 years of age.

Cost-effectiveness of a multitarget stool DNA test for colorectal cancer screening of Medicare beneficiaries.

BACKGROUND: In 2014, the Centers for Medicare and Medicaid Services (CMS) began covering a multitarget stool DNA (mtSDNA) test for colorectal cancer (CRC) screening of Medicare beneficiaries. In this study, we evaluated whether mtSDNA testing is a cost-effective alternative to other CRC screening strategies reimbursed by CMS, and if not, under what conditions it could be. METHODS: We use three independently-developed microsimulation models to simulate a cohort of previously unscreened US 65-year-olds who are screened with triennial mtSDNA testing, or one of six other reimbursed screening strategies. Main outcome measures are discounted life-years gained (LYG) and lifetime costs (CMS perspective), threshold reimbursement rates, and threshold adherence rates. Outcomes are expressed as the median and range across models. RESULTS: Compared to no screening, triennial mtSDNA screening resulted in 82 (range: 79-88) LYG per 1,000 simulated individuals. This was more than for five-yearly sigmoidoscopy (80 (range: 71-89) LYG), but fewer than for every other simulated strategy. At its 2017 reimbursement rate of $512, mtSDNA was the most costly strategy, and even if adherence were 30% higher than with other strategies, it would not be a cost-effective alternative. At a substantially reduced reimbursement rate ($6-18), two models found that triennial mtSDNA testing was an efficient and potentially cost-effective screening option. CONCLUSIONS: Compared to no screening, triennial mtSDNA screening reduces CRC incidence and mortality at acceptable costs. However, compared to nearly all other CRC screening strategies reimbursed by CMS it is less effective and considerably more costly, making it an inefficient screening option.

In search of a single standardised system for reporting complications in craniofacial surgery: a comparison of three different classifications.

Comparing complication rates between centres is difficult due to the lack of unanimous criteria regarding what adverse events should be defined as complications and how these events should be compiled. This study analysed all adverse events in a cohort of craniofacial (CF) operations over a 10-year period and applied three different scales (Clavien-Dindo, Leeds and Oxford) for systematic comparison. A total of 1023 consecutive CF procedures in 641 patients was identified. The Clavien-Dindo scale captured 74 complications in 74 procedures (7.2%), whereas the Leeds and Oxford scales captured 163 complications in 134 procedures (13.1%) and 85 complications in 83 procedures (8.1%), respectively. The Clavien-Dindo scale appeared less suitable for CF surgery, because it is predominantly adapted to severe complications and also regards blood transfusion as a complication. The Leeds scale provided a detailed picture of all complications, as well as minor events, whereas the Oxford scale captured all major complications well but applied less accurate definitions for the minor events. Our findings contribute to the benchmarking of complications between CF centres and suggest that both the Leeds and the Oxford scale appear relevant, depending on the emphasis required for major and minor complications and inter-centre audits, respectively.

Health-Seeking Behavior and Barriers to Care in Patients With Rectal Bleeding in Nigeria.

Purpose Colorectal cancer (CRC) incidence rates are steadily increasing in Nigeria. Organized screening is still largely unused because of financial and logistical barriers; most CRCs are detected by symptoms. One symptom of CRC is rectal bleeding. This study sought to determine health-seeking behavior and barriers to care in patients with rectal bleeding in Nigeria. This study also surveyed physicians to determine major breakdowns in access to care. Methods The recruitment process for this study involved patients referred for colonoscopy because of rectal bleeding as well as response to a media advertisement for a free colonoscopy. Physicians were recruited at the African Research Group for Oncology meeting. Patient responses were scored on the basis of knowledge of rectal bleeding. The physician questionnaire was supporting information and mainly descriptive in nature. Results A total of 82 patients and 45 physicians participated in this study. Less than 40% of patients knew that rectal bleeding could be caused by cancer. Major barriers to care were resolution of the symptom (42%), no consideration of the bleeding as problematic (40%), and financial constraint (22%). Education was strongly correlated with knowledge of rectal bleeding and health-seeking behavior. Although physicians regularly saw patients with rectal bleeding, most of them provided a differential diagnosis of hemorrhoids and few referred patients for colonoscopy. Conclusion General awareness about the signs of colorectal cancer is lacking. This demonstrates the strong need for patient education programs about this issue. Physicians should also receive additional training on differentiation of a potential cancer diagnosis from something more benign, such as hemorrhoids.

Craniotomy of the Fused Sagittal Suture Over the Superior Sagittal Sinus Is a Safe Procedure.

INTRODUCTION: Spring-assisted cranioplasty to correct sagittal synostosis is based on midline craniotomy through the closed sagittal suture, over the superior sagittal sinus (SSS). The aim of the present study was to evaluate the perioperative safety of this technique. MATERIALS AND METHODS: This is a retrospective study of all patients operated with median craniotomy and springs from 1998 to the end of 2015. For comparison, all Pi-plasties performed during the same time interval were also evaluated. The safety measures were evaluated based on incidence of damage to SSS, incidence of dural tears, perioperative blood loss, operative time, and hospital stay. RESULTS: In the group that had undergone midline craniotomy combined with springs (n = 225), 4 perioperative damages to SSS and 1 dural tear were seen. The perioperative blood loss was 62.8 ±â€Š65.3 mL (mean ±â€Šstandard deviation). The operative time was 67.9 ±â€Š21.5 minutes and the hospital stay was 4.8 ±â€Š1.1 days. In the group that had undergone pi-plasty (n = 105), no damages to SSS but 3 dural tears were seen. The perioperative blood loss was 352.8 ±â€Š174.4 mL. The operative time was 126.0 ±â€Š31.7 minutes and the hospital stay was 7.1 ±â€Š1.4 days. CONCLUSION: Craniotomy SSS in sagittal synostosis is a safe procedure with low morbidity in terms of damage to the SSS. Midline craniotomy combined with springs has significantly lower preoperative blood loss, operative time, and hospital stay (P < 0.001 for all) compared to pi-plasty.

Establishing a Cancer Research Consortium in Low- and Middle-Income Countries: Challenges Faced and Lessons Learned.

PURPOSE: There is an increasing effort in the global public health community to strengthen research capacity in low- and middle-income countries, but there is no consensus on how best to approach such endeavors. Successful consortia that perform research on HIV/AIDS and other infectious diseases exist, but few papers have been published detailing the challenges faced and lessons learned in setting up and running a successful research consortium. METHODS: Members of the African Research Group for Oncology (ARGO) participated in generating lessons learned regarding the foundation and maintenance of a cancer research consortium in Nigeria. RESULTS: Drawing on our experience of founding ARGO, we describe steps and key factors needed to establish a successful collaborative consortium between researchers from both high- and low-income countries. In addition, we present challenges we encountered in building our consortium, and how we managed those challenges. Although our research group is focused primarily on cancer, many of our lessons learned can be applied more widely in biomedical or public health research in low-income countries. CONCLUSIONS: As the need for cancer care in LMICs continues to grow, the ability to create sustainable, innovative, collaborative research groups will become vital. Assessing the successes and failures that occur in creating and sustaining research consortia in LMICs is important for expansion of research and training capacity in LMICs.

Comparison Between Two Different Isolated Craniosynostosis Techniques: Does It Affect Cranial Bone Growth?

INTRODUCTION: Craniosynostosis is a premature closure of a cranial suture. Cranioplasty is indicated to correct skull deformity, relieve increased intracranial pressure, and promote homogenous cranial growth. Different techniques have been adopted to achieve optimal outcomes. Although surgical benefits are widely accepted, this intervention might also affect cranial skeletal growth. METHODS: The authors conducted a retrospective case-control study including patients operated for isolated metopic or sagittal synostosis. These patients had undergone a computed tomography (CT) scan before surgery and/or at 3 years of age postoperatively. These were operated between 2002 and 2012. Intracranial volume was measured using a MATLAB application. The control group was age and sex-matched individuals who had CT scans for trauma or neurological indications. All results with P value <0.05 were considered statistically significant. RESULTS: A total of 185 patients were included in the study with a preoperative CT scan (143 sagittal synostosis and 42 metopic synostosis). Postoperatively 160 patients were identified including 103 sagittal synostosis and 57 metopic synostosis. These patients were compared to 414 controls. There was a statistically significant reduction in intracranial volume (ICV) in patients operated for metopic synostosis with both techniques. It also demonstrated a statistically significant difference in ICV in patients with sagittal synostosis operated with Pi-plasty and a nonsignificant difference in ICV in patients operated with strip craniotomy and springs. CONCLUSION: In conclusion, these measurements of ICV have revealed that extensive cranioplasties for premature craniosynostosis can lead to minor but significant growth restriction and reduced ICV at long-term follow-up.

Power and Agenda-Setting in Tanzanian Health Policy: An Analysis of Stakeholder Perspectives.

BACKGROUND: Global health policy is created largely through a collaborative process between development agencies and aid-recipient governments, yet it remains unclear whether governments retain ownership over the creation of policy in their own countries. An assessment of the power structure in this relationship and its influence over agenda-setting is thus the first step towards understanding where progress is still needed in policy-making for development. METHODS: This study employed qualitative policy analysis methodology to examine how health-related policy agendas are adopted in low-income countries, using Tanzania as a case study. Semi-structured, in-depth, key informant interviews with 11 policy-makers were conducted on perspectives of the agenda-setting process and its actors. Kingdon's stream theory was chosen as the lens through which to interpret the data analysis. RESULTS: This study demonstrates that while stakeholders each have ways of influencing the process, the power to do so can be assessed based on three major factors: financial incentives, technical expertise, and influential position. Since donors often have two or all of these elements simultaneously a natural power imbalance ensues, whereby donor interests tend to prevail over recipient government limitations in prioritization of agendas. One way to mediate these imbalances seems to be the initiation of meaningful policy dialogue. CONCLUSION: In Tanzania, the agenda-setting process operates within a complex network of factors that interact until a "policy window" opens and a decision is made. Power in this process often lies not with the Tanzanian government but with the donors, and the contrast between latent presence and deliberate use of this power seems to be based on the donor ideology behind giving aid (defined here by funding modality). Donors who used pooled funding (PF) modalities were less likely to exploit their inherent power, whereas those who preferred to maintain maximum control over the aid they provided (ie, non-pooled funders) more readily wielded their intrinsic power to push their own priorities.

Estimation of Benefits, Burden, and Harms of Colorectal Cancer Screening Strategies: Modeling Study for the US Preventive Services Task Force.

IMPORTANCE: The US Preventive Services Task Force (USPSTF) is updating its 2008 colorectal cancer (CRC) screening recommendations. OBJECTIVE: To inform the USPSTF by modeling the benefits, burden, and harms of CRC screening strategies; estimating the optimal ages to begin and end screening; and identifying a set of model-recommendable strategies that provide similar life-years gained (LYG) and a comparable balance between LYG and screening burden. DESIGN, SETTING, AND PARTICIPANTS: Comparative modeling with 3 microsimulation models of a hypothetical cohort of previously unscreened US 40-year-olds with no prior CRC diagnosis. EXPOSURES: Screening with sensitive guaiac-based fecal occult blood testing, fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy with or without stool testing, computed tomographic colonography (CTC), or colonoscopy starting at age 45, 50, or 55 years and ending at age 75, 80, or 85 years. Screening intervals varied by modality. Full adherence for all strategies was assumed. MAIN OUTCOMES AND MEASURES: Life-years gained compared with no screening (benefit), lifetime number of colonoscopies required (burden), lifetime number of colonoscopy complications (harms), and ratios of incremental burden and benefit (efficiency ratios) per 1000 40-year-olds. RESULTS: The screening strategies provided LYG in the range of 152 to 313 per 1000 40-year-olds. Lifetime colonoscopy burden per 1000 persons ranged from fewer than 900 (FIT every 3 years from ages 55-75 years) to more than 7500 (colonoscopy screening every 5 years from ages 45-85 years). Harm from screening was at most 23 complications per 1000 persons screened. Strategies with screening beginning at age 50 years generally provided more LYG as well as more additional LYG per additional colonoscopy than strategies with screening beginning at age 55 years. There were limited empirical data to support a start age of 45 years. For persons adequately screened up to age 75 years, additional screening yielded small increases in LYG relative to the increase in colonoscopy burden. With screening from ages 50 to 75 years, 4 strategies yielded a comparable balance of screening burden and similar LYG (median LYG per 1000 across the models): colonoscopy every 10 years (270 LYG); sigmoidoscopy every 10 years with annual FIT (256 LYG); CTC every 5 years (248 LYG); and annual FIT (244 LYG). CONCLUSIONS AND RELEVANCE: In this microsimulation modeling study of a previously unscreened population undergoing CRC screening that assumed 100% adherence, the strategies of colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, and CTC every 5 years performed from ages 50 through 75 years provided similar LYG and a comparable balance of benefit and screening burden.

Comparison of Intracranial Volume and Cephalic Index After Correction of Sagittal Synostosis With Spring-assisted Surgery or Pi-plasty.

BACKGROUND: The aim of the current study was to determine the intracranial volume (ICV) and cephalic index (CI) in patients operated for sagittal synostosis, and to compare the outcome of 2 different surgical techniques: craniotomy combined with springs and modified pi-plasty. METHODS: The authors studied all patients who had been operated for isolated sagittal synostosis and registered in the Gothenburg Craniofacial Registry until the end of 2012 and who had undergone a preoperative and/or postoperative (at 3 years of age) computed tomography examination. Sex- and age-matched controls were identified from children who had undergone computed tomography for other reasons. RESULTS: Craniotomy combined with springs increased the ICV and CI from 802 ±â€Š127 mL (mean ±â€ŠSD) and 70.1 ±â€Š4.0 to 1300 ±â€Š158 mL and 73.1 ±â€Š3.3, respectively. The corresponding values for controls were 796 ±â€Š136 mL and 83.6 ±â€Š7.3 preoperatively and 1334 ±â€Š136 mL and 80.0 ±â€Š4.5 at 3 years of age. Pi-plasty increased the ICV and CI from 1014 ±â€Š115 mL and 69.7 ±â€Š3.3 to 1286 ±â€Š122 mL and 74.1 ±â€Š2.6, respectively. Corresponding values for controls were 1043 ±â€Š153 mL and 83.4 ±â€Š7.0 preoperatively and 1362 ±â€Š122 mL and 79.6 ±â€Š3.9 at 3 years of age. CONCLUSIONS: There was no significant difference between craniotomy combined with springs in children younger than 6 months and pi-plasty in older children regarding the efficacy of improving ICV and CI. Neither of the techniques fully normalized the head shape.

Spring-assisted surgery in the treatment of sagittal synostosis: A systematic review.

BACKGROUND: Premature sagittal synostosis (SS) can be surgically corrected using extensive cranioplasties or using less invasive methods, e.g. spring-assisted surgery (SAS). AIM: The aim of the present study was to perform a proper systematic review of springs in the treatment of SS. METHODS: A literature search was performed with the assistance of a professional librarian in the databases PubMed, EMBASE, and The Cochrane Library between 1997 and September 2013. Studies that fulfilled the PICO (patients, interventions, controls, outcome) criteria were included. All studies were graded for methodological quality according to MINORS, and all retrospective studies were assessed according to a scale developed for retrospective studies in paediatric surgery. The quality of evidence was rated according to GRADE. RESULTS: A total of 241 abstracts were extracted in the literature search. Five studies met the PICO criteria. Two of these five were considered as preliminary reports and excluded. Assessment according to MINORS showed a mean score of 21, i.e. fair quality. The clinical outcome regarding cephalic index did not differ between the surgical techniques, but the quality of evidence, according to GRADE, that SAS was equally efficient, was very low. Clinical outcome regarding operation time, blood loss, ICU stay and hospital stay was in favour for SAS, but the quality of evidence was low. CONCLUSIONS: This systematic review has revealed that the level of evidence for SAS being an equally efficient surgical method as more extensive cranioplasties for SS is low or very low. The results point out the need for well-designed prospective studies within craniofacial surgery.

Intracranial volume is normal in infants with sagittal synostosis.

Premature sagittal synostosis results in an elongated, narrow skull shape, scaphocephaly. It has been unclear whether the intracranial volume (ICV) of these children is different from that of normal children. The aim of the present study was to precisely determine the ICV in a large cohort of children with premature sagittal synostosis and to compare it to the ICV of a sex- and age-matched control group. All patients (n = 143) with isolated sagittal synostosis registered in the Göteborg Craniofacial Registry until the end of 2012 with a preoperative CT examination were identified. For each case, a sex- and age- (±30 days) matched control was identified from children who had undergone CT for post-traumatic or neurological reasons. The ICV was measured in a semi-automatic MATLAB program with functions such as region growing, watershed, and thresholding in axial CT slices. The ICV was calculated using the Cavalieri principle. The mean (± SEM) values of ICV for children with sagittal synostosis and for corresponding controls were 866 ± 13 ml and 870 ± 15 ml, respectively. The mean ages of these groups were 173 ± 8 days and 172 ± 8 days, respectively. Subgroup analysis of sex and age at CT (≤180 days and >180 days) did not reveal any differences in ICV between cases and controls. Precise determination of ICV in addition to the use of adequate controls has made it possible to conclude that children with premature isolated sagittal synostosis have a normal ICV.