The genus Fomitopsis (Polyporales, Basidiomycota) reconsidered.

Based on seven- and three-gene datasets, we discuss four alternative approaches for a reclassification of Fomitopsidaceae (Polyporales, Basidiomycota). After taking into account morphological diversity in the family, we argue in favour of distinguishing three genera only, viz. Anthoporia, Antrodia and Fomitopsis. Fomitopsis becomes a large genus with 128 accepted species, containing almost all former Fomitopsis spp. and most species formerly placed in Antrodia, Daedalea and Laccocephalum. Genera Buglossoporus, Cartilosoma, Daedalea, Melanoporia, Neolentiporus, alongside twenty others, are treated as synonyms of Fomitopsis. This generic scheme allows for morphologically distinct genera in Fomitopsidaceae, unlike other schemes we considered. We provide arguments for retaining Fomitopsis and suppressing earlier (Daedalea, Caloporus) or simultaneously published generic names (Piptoporus) considered here as its synonyms. Taxonomy of nine species complexes in the genus is revised based on ITS, ITS + TEF1, ITS + TEF1 + RPB1 and ITS + TEF1 + RPB2 datasets. In total, 17 species are described as new to science, 26 older species are reinstated and 26 currently accepted species names are relegated to synonymy. A condensed identification key for all accepted species in the genus is provided. Taxonomic novelties: New species: Fomitopsis algumicola Grebenc & Spirin, F. caseosa Vlasák & Spirin, F. cupressicola Vlasák, J. Vlasák Jr. & Spirin, F. derelicta Vlasák & Spirin, F. dollingeri Vlasák & Spirin, F. fissa Vlasák & Spirin, F. lapidosa Miettinen & Spirin, F. lignicolor Vlasák & Spirin, F. maculosa Miettinen & Spirin, F. pannucea Runnel & Spirin, F. perhiemata Viner & Spirin, F. purpurea Spirin & Ryvarden, F. retorrida Spirin & Kotiranta, F. solaris Rivoire, A.M. Ainsworth & Vlasák, F. tristis Miettinen & Spirin, F. tunicata Miettinen & Spirin, F. visenda Miettinen & Spirin. New combinations: Fomitopsis aculeata (Cooke) Spirin & Miettinen, F. aethalodes (Mont.) Spirin, F. alaskana (D.V. Baxter) Spirin & Vlasák, F. albidoides (A. David & Dequatre) Bernicchia & Vlasák, F. amygdalina (Berk. & Ravenel) Spirin & Vlasák, F. angusta (Spirin & Vlasák) Spirin & Vlasák, F. atypa (Lév.) Spirin & Vlasák, F. caespitosa (Murrill) Spirin & Miettinen, F. calcitrosa (Spirin & Miettinen) Spirin & Miettinen, F. circularis (B.K. Cui & Hai J. Li) Spirin, F. concentrica (G. Cunn.) M.D. Barrett, F. cyclopis (Miettinen & Spirin) Miettinen & Spirin, F. dickinsii (Berk. ex Cooke) Spirin, F. elevata (Corner) Spirin & Miettinen, F. eucalypti (Kalchbr.) Spirin, F. ferrea (Cooke) Spirin & Viner, F. flavimontis (Vlasák & Spirin) Vlasák & Spirin, F. foedata (Berk.) Spirin & Miettinen, F. gilvidula (Bres.) Spirin & Miettinen, F. glabricystidia (Ipulet & Ryvarden) Miettinen & Ryvarden, F. globispora (Ryvarden & Aime) Spirin, F. hartmannii (Cooke) M.D. Barrett & Spirin, F. hyalina (Spirin, Miettinen & Kotir.) Spirin & Miettinen, F. hypoxantha (Bres.) Spirin & Miettinen, F. incana (Lév.) Spirin & V. Malysheva, F. infirma (Renvall & Niemelä) Miettinen & Niemelä, F. juniperina (Murrill) Spirin & Vlasák, F. kuzyana (Pilát ex Pilát) Spirin & Vlasák, F. leioderma (Mont.) Spirin & Vlasak, F. leucaena (Y.C. Dai & Niemelä) Spirin & Miettinen, F. luzonensis (Murrill) Spirin & Miettinen, F. maculatissima (Lloyd) Spirin, F. madronae (Vlasák & Ryvarden) Vlasák & Ryvarden, F. malicola (Berk. & M.A. Curtis) Spirin, F. marchionica (Mont.) Spirin & Miettinen, F. marianii (Bres.) Spirin, Vlasák & Cartabia, F. mellita (Niemelä & Penttilä) Niemelä & Miettinen, F. microcarpa (B.K. Cui & Shun Liu) Spirin, F. micropora (B.K. Cui & Shun Liu) Spirin, F. modesta (Kuntze ex Fr.) Vlasák & Spirin, F. monomitica (Yuan Y. Chen) Spirin & Viner, F. morganii (Lloyd) Spirin & Vlasák, F. moritziana (Lév.) Spirin & Miettinen, F. neotropica (D.L. Lindner, Ryvarden & T.J. Baroni) Vlasák, F. nigra (Berk.) Spirin & Miettinen, F. nivosella (Murrill) Spirin & Vlasák, F. oboensis (Decock, Amalfi & Ryvarden) Spirin, F. oleracea (R.W. Davidson & Lombard) Spirin & Vlasák, F. philippinensis (Murrill) Spirin & Vlasák, F. primaeva (Renvall & Niemelä) Miettinen & Niemelä, F. psilodermea (Berk. & Mont.) Spirin & Vlasák, F. pulverulenta (Rivoire) Rivoire, F. pulvina (Pers.) Spirin & Vlasák, F. pulvinascens (Pilát ex Pilát) Niemelä & Miettinen, F. quercina (L.) Spirin & Miettinen, F. ramentacea (Berk. & Broome) Spirin & Vlasák, F. renehenticii (Rivoire, Trichies & Vlasák) Rivoire & Vlasák, F. roseofusca (Romell) Spirin & Vlasák, F. sagraeana (Mont.) Vlasák & Spirin, F. sandaliae (Bernicchia & Ryvarden) Bernicchia & Vlasák, F. sclerotina (Rodway) M.D. Barrett & Spirin, F. serialiformis (Kout & Vlasák) Vlasák, F. serialis (Fr.) Spirin & Runnel, F. serrata (Vlasák & Spirin) Vlasák & Spirin, F. squamosella (Bernicchia & Ryvarden) Bernicchia & Ryvarden, F. stereoides (Fr.) Spirin, F. subectypa (Murrill) Spirin & Vlasák, F. substratosa (Malençon) Spirin & Miettinen, F. tropica (B.K. Cui) Spirin, F. tumulosa (Cooke) M.D. Barrett & Spirin, F. tuvensis (Spirin, Vlasák & Kotir.) Spirin & Vlasák, F. uralensis (Pilát) Spirin & Miettinen, F. ussuriensis (Bondartsev & Ljub.) Spirin & Miettinen, F. variiformis (Peck) Vlasák & Spirin, F. yunnanensis (M.L. Han & Q. An) Spirin, Daedaleopsis candicans (P. Karst.) Spirin, Megasporoporia eutelea (Har. & Pat.) Spirin & Viner, Neofomitella hemitephra (Berk.) M.D. Barrett, Pseudophaeolus soloniensis (Dubois) Spirin & Rivoire, P. trichrous (Berk. & M.A. Curtis) Vlasák & Spirin. New synonyms: Antrodia bondartsevae Spirin, A. huangshanensis Y.C. Dai & B.K. Cui, A. taxa T.T. Chang & W.N. Chou, A. wangii Y.C. Dai & H.S. Yuan, Antrodiella subnigra Oba, Mossebo & Ryvarden, Antrodiopsis Audet, Boletus quercinus Schrad., Brunneoporus Audet, Buglossoporus Kotl. & Pouzar, Buglossoporus eucalypticola M.L. Han, B.K. Cui & Y.C. Dai, Caloporus P. Karst., Cartilosoma Kotlaba & Pouzar, Coriolus clemensiae Murrill, C. cuneatiformis Murrill, C. hollickii Murrill, C. parthenius Hariot & Pat., C. rubritinctus Murrill, Daedalea Pers., Daedalea allantoidea M.L. Han, B.K. Cui & Y.C. Dai, D. americana M.L. Han, Vlasák & B.K. Cui, D. radiata B.K. Cui & Hai J. Li, D. rajchenbergiana Kossmann & Drechsler-Santos, D. sinensis Lloyd, Daedalella B.K. Cui & Shun Liu, Dentiporus Audet, Flavidoporia Audet, Fomes subferreus Murrill, Fomitopsis cana B.K. Cui, Hai J. Li & M.L. Han, F. caribensis B.K. Cui & Shun Liu, F. cystidiata B.K. Cui & M.L. Han, F. ginkgonis B.K. Cui & Shun Liu, F. iberica Melo & Ryvarden, F. incarnata K.M. Kim, J.S. Lee & H.S. Jung, F. subfeei B.K. Cui & M.L. Han, F. subtropica B.K. Cui & Hai J. Li, Fragifomes B.K. Cui, M.L. Han & Y.C. Dai, Leptoporus epileucinus Pilát, Melanoporia Murrill, Neoantrodia Audet, Neolentiporus Rajchenb., Nigroporus macroporus Ryvarden & Iturr., Niveoporofomes B.K. Cui, M.L. Han & Y.C. Dai, Pilatoporus Kotl. & Pouzar, Piptoporus P. Karst., Polyporus aurora Ces., P. durescens Overh. ex J. Lowe, P. griseodurus Lloyd, Poria incarnata Pers., Pseudoantrodia B.K. Cui, Y.Y. Chen & Shun Liu, Pseudofomitopsis B.K. Cui & Shun Liu, Ranadivia Zmitr., Rhizoporia Audet, Rhodofomes Kotl. & Pouzar, Rhodofomitopsis B.K. Cui, M.L. Han & Y.C. Dai, Rhodofomitopsis pseudofeei B.K. Cui & Shun Liu, R. roseomagna Nogueira-Melo, A.M.S. Soares & Gibertoni, Rubellofomes B.K. Cui, M.L. Han & Y.C. Dai, Subantrodia Audet, Trametes fulvirubida Corner, T. lignea Murrill, T. lusor Corner, T. pseudodochmia Corner, T. subalutacea Bourdot & Galzin, T. supermodesta Ryvarden & Iturr., T. tuberculata Bres., Tyromyces multipapillatus Corner, T. ochraceivinosus Corner, T. palmarum Murrill, T. singularis Corner, T. squamosellus Núñez & Ryvarden, Ungulidaedalea B.K. Cui, M.L. Han & Y.C. Dai. Lectotypes: Hexagonia sulcata Berk., Polyporus castaneae Bourdot & Galzin, Poria incarnata Pers., Trametes subalutacea Bourdot & Galzin, Ungulina substratosa Malençon. Neotypes: Agaricus soloniensis Dubois, Boletus pulvinus Pers. Citation: Spirin V, Runnel K, Vlasák J, Viner I, Barrett MD, Ryvarden L, Bernicchia A, Rivoire B, Ainsworth AM, Grebenc T, Cartabia M, Niemelä T, Larsson K-H, Miettinen O (2024). The genus Fomitopsis (Polyporales, Basidiomycota) reconsidered. Studies in Mycology 107: 149-249. doi: 10.3114/sim.2024.107.03.

Diversity of colacosome-interacting mycoparasites expands the understanding of the evolution and ecology of Microbotryomycetes.

Mycoparasites in Basidiomycota comprise a diverse group of fungi, both morphologically and phylogenetically. They interact with their hosts through either fusion-interaction or colacosome-interaction. Colacosomes are subcellular structures formed by the mycoparasite at the host-parasite interface, which penetrate the parasite and host cell walls. Previously, these structures were detected in 19 fungal species, usually by means of transmission electron microscopy. Most colacosome-forming species have been assigned to Microbotryomycetes (Pucciniomycotina, Basidiomycota), a highly diverse class, comprising saprobic yeasts, mycoparasites, and phytoparasites. In general, these myco- and phytoparasites are dimorphic organisms, with a parasitic filamentous morph and saprobic yeast morph. We investigated colacosome-forming mycoparasites based on fungarium material, freshly collected specimens, and cultures of yeast morphs. We characterised the micromorphology of filamentous morphs, the physiological characteristics of yeast morphs, and inferred phylogenetic relationships based on DNA sequence data from seven loci. We outline and employ an epifluorescence-based microscopic method to assess the presence and organisation of colacosomes. We describe five new species in the genus Colacogloea, the novel dimorphic mycoparasite Mycogloiocolax gerardii, and provide the first report of a sexual, mycoparasitic morph in Colacogloea philyla and in the genus Slooffia. We detected colacosomes in eight fungal species, which brings the total number of known colacosome-forming fungi to 27. Finally, we revealed three distinct types of colacosome organisation in Microbotryomycetes. Taxonomic novelties and typifications: New family: Mycogloiocolacaeae Schoutteten & Yurkov; New genus: Mycogloiocolax Schoutteten & Rödel; New species: Colacogloea bettinae Schoutteten & Begerow, C. biconidiata Schoutteten, C. fennica Schoutteten & Miettinen, C. microspora Schoutteten, C. universitatis-gandavensis Schoutteten & Verbeken, Mycogloiocolax gerardii Schoutteten & Rödel; New combinations: Slooffia micra (Bourdot & Galzin) Schoutteten, Fellozyma cerberi (A.M. Yurkov et al.) Schoutteten & Yurkov, Fellozyma telluris (A.M. Yurkov et al.) Schoutteten & Yurkov; Epitypifications (basionyms): Achroomyces insignis Hauerslev, Platygloea micra Bourdot & Galzin, Platygloea peniophorae Bourdot & Galzin; Lectotypification (basionym): Platygloea peniophorae Bourdot & Galzin Citation: Schoutteten N, Yurkov A, Leroux O, Haelewaters D, Van Der Straeten D, Miettinen O, Boekhout T, Begerow D, Verbeken A (2023). Diversity of colacosome-interacting mycoparasites expands the understanding of the evolution and ecology of Microbotryomycetes. Studies in Mycology 106: 41-94. doi: 10.3114/sim.2022.106.02.

Revision of Cerinomyces (Dacrymycetes, Basidiomycota) with notes on morphologically and historically related taxa.

Cerinomyces (Dacrymycetes, Basidiomycota) is a genus traditionally defined by corticioid basidiocarps, in contrast to the rest of the class, which is characterized by gelatinous ones. In the traditional circumscription the genus is polyphyletic, and the monotypic family Cerinomycetaceae is paraphyletic. Aiming for a more concise delimitation, we revise Cerinomyces s.l. with a novel phylogeny based on sequences of nrDNA (SSU, ITS, LSU) and protein-coding genes (RPB1, RPB2, TEF1-α). We establish that monophyletic Cerinomyces s.s. is best characterized not by the corticioid morphology, but by a combination of traits: hyphal clamps, predominantly aseptate thin-walled basidiospores, and low content of carotenoid pigments. In our updated definition, Cerinomyces s.s. encompasses five well-supported phylogenetic clades divided into two morphological groups: (i-iii) taxa with arid corticioid basidiocarps, including the generic type C. pallidus; and (iv-v) newly introduced members with gelatinous basidiocarps, like Dacrymyces enatus and D. tortus. The remaining corticioid species of Cerinomyces s.l. are morphologically distinct and belong to the Dacrymycetaceae: our analysis places the carotenoid-rich Cerinomyces canadensis close to Femsjonia, and we transfer the clamps-lacking C. grandinioides group to Dacrymyces. In addition, we address genera related to Cerinomyces s.l. historically and morphologically, such as Ceracea, Dacryonaema and Unilacryma. Overall, we describe twenty-four new species and propose nine new combinations in both Cerinomycetaceae and Dacrymycetaceae.

A revised genus-level classification for Cerrenaceae (Polyporales, Agaricomycetes).

Cerrenaceae is a small family of polypores and hydnoid fungi in the order Polyporales (Basidiomycota). The family consists of white-rot fungi, some of which are serious tree pathogens. Combining morphological evidence with a phylogenetic dataset of six genetic markers, we revise generic concepts in the family and propose a seven-genus classification system for the family. Two genera are introduced as new: the monotypic Acanthodontia for Radulodon cirrhatinus, and Lividopora for the Rigidoporus vinctus complex. We re-introduce the name Somion for the Spongipellis delectans complex. Other recognized genera in the family are Cerrena, Irpiciporus, Pseudolagarobasidium, and Radulodon. New species introduced are Irpiciporus branchiformis from Tanzania, Lividopora armeniaca, and L. facilis from Southeast Asia, and Somion strenuum from East Asia. We provide nomenclatural comments on all the names combined to the above Cerrenaceae genera and typify Cerrena unicolor, C. zonata, Polyporus carneopallens (= L. vincta), Somion occarium, and S. unicolor. The genus Hyphoradulum belongs to Cystostereaceae (Agaricales), and we transfer the type species H. conspicuum to Crustomyces. Our study highlights the importance of integrating different basidiocarp types in analyses when revising genus classification in macrofungi. Citation: Miettinen O, Vlasák J, Larsson E, Vlasák J Jr., Seelan JSS, Hernawati, Levicky Q, Larsson K-H, Spirin V (2023). A revised genus-level classification for Cerrenaceae (Polyporales, Agaricomycetes). Fungal Systematics and Evolution 12: 271-322. doi: 10.3114/fuse.2023.12.14.

Additions to Dendrodacrys and outline of taxa with branched hyphidia in Dacrymycetes (Basidiomycota).

The genus Dendrodacrys is a monophyletic group that belongs to Dacrymycetes (Agaricomycotina, Basidiomycota) and accommodates species distinguished by strongly branched hyphidia in combination with 3-septate basidiospores. While the original circumscription mainly treated European taxa, here we shift the focus to tropical and sub-tropical material and uncover wider variation in morphology within Dendrodacrys. Still united by hyphidia shape and basidiospore septation, the genus is expanded with 10 taxa having pustulate, cerebriform, or stipitate basidiocarps of yellow to dark brown colours, cylindrical to ovoid basidiospores, and hyphal septa with or without clamps. Monophyly of the amended Dendrodacrys is confirmed with a phylogeny based on six markers (SSU, ITS, LSU, TEF1-α, RPB1, and RPB2). As a result, we describe two new species (De. laetum and De. rigoratum), transfer three existing species to Dendrodacrys (De. brasiliense, De. dendrocalami, and De. pezizoideum), and raise one variety to the species level (De. kennedyae ≡ Dacrymyces enatus var. macrosporus). In addition, we provide descriptions for the earlier combined De. paraphysatum and four new informal taxa. Lastly, we present illustrations, a character table, and an identification key that addresses all known dacrymycetes with branched hyphidia. Citation: Savchenko A, Zamora JC, Alvarenga R, Kõljalg U, Miettinen O (2022). Additions to Dendrodacrys and outline of taxa with branched hyphidia in Dacrymycetes (Basidiomycota). Fungal Systematics and Evolution 10: 103-126. doi: 10.3114/fuse.2022.10.04.

On six African species of Lyomyces and Xylodon.

We studied a number of sub-Saharan collections of corticioid Xylodon and Lyomyces species, including several types. Morphological descriptions and molecular analyses based on the ribosomal DNA loci nuc rDNA ITS1-5.8S-ITS2 and when possible nuc 28S rDNA, allow us to introduce four new species: L. densiusculus, X. angustisporus, X. dissiliens, and X. laxiusculus. DNA barcodes for X. submucronatus and X. pruniaceus are published for the first time and X. pruniaceus is re-described.

Screening for a cancer: thinking before rethinking.

A recent article (by Esserman et al.) called to serious question the diagnostic and prognostic premises of screening for breast and prostate cancers, and it proceeded to adduce, also, other radical rethinking of these screenings. That questioning was 'evidence-based' in the contemporary epidemiological meaning of this--use was made of cancer-registry data as well as of evidence from such randomized trials as epidemiologists now take to be essential in actual research on screening for a cancer--and, evidence-based as it was, that questioning has been left unquestioned. But that questioning, as to the interpretation of the evidence, was not adequately thinking-based. It was, instead, rife with the misunderstandings that permeate contemporary epidemiological thinking about screening for a cancer and about research for the scientific knowledge-base of this. In the truly called-for rethinking, the point of departure would be the recognition that the premises of screening for a cancer are clinical in nature, as obviously also are both the entire process potentially leading to a cancer's early, preclinical diagnosis and the individual counselling about submitting oneself to this. Epidemiologists should focus on epidemiology--practice of and research for community medicine, community-level preventive medicine, that is--and to have no presumptions of understanding, better than clinicians, the (clinical) issues surrounding the pursuit of early diagnosis of a cancer, whether matters of practice, research, or public policy. Clinicians and clinical researchers, in turn, should disregard epidemiologists'--and other public-health professionals'--ideas about screening for a cancer, the practice of and research on this. The need for this aprioristic rethinking is manifest, very eminently, in the fresh recommendations about screening for breast cancer, issued by the US Preventive Services Task Force, and in the public uproar provoked by these.

Etiologic study vis-à-vis intervention study.

Understanding of the logic-dictated essence of the etiologic study, and similarly that of the intervention-study, in the advancement of the knowledge-base of medicine, remains incomplete. Viewing experimental intervention-studies ('clinical trials') as paradigmatic for etiologic studies-necessarily non-experimental-has been wrongheaded. This misunderstanding continues to impede understanding of the essence of what logic dictates to be the etiologic study, adduced decades ago but still commonly confused with the essence of the (seriously malformed) 'case-control' study. Correct understanding of the essence of the etiologic study would pave the way to improved understanding of the intervention study, notably as to how prognostic probability functions could be derived from the data now routinely produced in clinical trials. This paradigm reversal, too, has been previously proposed, but its understanding has remained fogged by wanting understanding of the etiologic study.

Hydnoporia, an older name for Pseudochaete and Hymenochaetopsis, and typification of the genus Hymenochaete (Hymenochaetales, Basidiomycota).

The genus name Hydnoporia is reinstated to encompass the Hymenochaete tabacina group currently addressed to Pseudochaete (illegitimate genus) or Hymenochaetopsis. Identity of the type species of Hydnoporia, Sistotrema fuscescens (= Hydnoporia olivacea in current sense), is clarified, and a lectotype is selected. In total, 12 species are combined in Hydnoporia: H. corrugata, H. gigasetosa, H. lamellata, H. laricicola, H. latesetosa, H. lenta, H. rhododendri, H. rimosa, H. subrigidula, H. tabacina, H. tabacinoides, and H. yasudai. Hydnoporia diffissa is described as new. Analyses of all available ITS (94) and newly produced tef1 sequences (20) indicate that there are at least 20-27 species in the genus. Identity of the type species of Hymenochaete, H. rubiginosa, is clarified; the name is retained for the species so named in Europe while other species are present in North America and East Asia. Additionally, three new combinations in Hymenochaete are proposed: H. campylopora (= Cyclomyces fuscus), H. microcycla (= Cyclomyces tabacinus), and H. saepiaria.

Postia caesia complex (Polyporales, Basidiomycota) in temperate Northern Hemisphere.

Taxonomy of the Postia caesia complex is revised based on morphology and two genetic markers, ITS and tef1. In total, we recognize 24 species, multiplying the known species diversity in the complex. We provide descriptions for 20 temperate Northern Hemisphere taxa. Identity of the core species, P. caesia, is re-established, and a neotype from the type locality is selected. Four new combinations are proposed, and 10 new species are described: P. arbuti, P. auricoma, P. bifaria, P. comata, P. cyanescens, P. glauca, P. livens, P. magna, P. populi, and P. yanae.

A preliminary overview of the corticioid Atractiellomycetes (Pucciniomycotina, Basidiomycetes).

The taxonomy of the corticioid fungi from the class Atractiellomycetes (Pucciniomycotina, Basidiomycetes) currently addressed to the genus Helicogloea, is revised based on morphological and nuclear ribosomal DNA (ITS and LSU) data. The genus is restricted to 25 species with semitranslucent, gelatinous basidiocarps lacking differentiated cystidia and clamps on hyphae, of which 11 are described as new to science. The asexual genus Leucogloea is placed as a synonym of Helicogloea s. str. Since the type species of Saccoblastia, S. ovispora, is combined to Helicogloea, a new genus, Saccosoma, is introduced to encompass Saccoblastia farinacea and six related species, one of which is described as new. In contrast to Helicogloea in the strict sense, the basidiocarps of Saccosoma are arid, not gelatinized, and hyphae are clamped. The third lineage of the corticioid Atractiellomycetes is represented by the Bourdotigloea vestita complex. Species of Bourdotigloea are devoid of clamps but often possess well-differentiated cystidia, as well as long, cylindrical-fusiform basidiospores. Bourdotigloea encompasses nine species, of which six are described here as new.

Hyperglycemia and plasma lipid levels: covariations in insulin-dependent diabetes.

Longitudinal relationships of plasma lipids with parameters of blood glucose control were studied in 124 young insulin-dependent diabetic patients who had multiple, simultaneous determinations of these parameters during a 1-yr period. Fluctuations in hemoglobin A1, a cumulative measure of blood glucose control, correlated with fluctuations in total cholesterol (r = 0.19, P less than 0.001) and low-density lipoprotein-cholesterol (r = 0.17, P less than 0.001). Similarly, fluctuations in fasting blood glucose correlated with those in total cholesterol (r = 0.20, P less than 0.001), very low-density lipoprotein-cholesterol (r = 0.13, P = 0.002), and total triglyceride (r = 0.23, P less than 0.001). These data indicate covariation between plasma lipid and blood glucose control parameters and suggest that poor blood glucose control contributes to the excess risk of coronary heart disease in insulin-dependent diabetes mellitus.

Obesity, sodium intake, and blood pressure in adolescents.

It has been postulated that increased dietary sodium associated with greater food intake by obese people is a mechanism for the relationship between obesity and blood pressure (BP). We have evaluated this hypothesis by exploring the interrelationships of measures of obesity, sodium intake, and BP in 248 "normal" adolescents, 16 to 17 years of age. As an index of sodium intake, the sodium excretion in three overnight urine collections was used. As a more specific index of saltiness of diet, we used a ratio of sodium excretion to calorie intake, with calories estimated from 3-day diet records and dietary interview. Body weight and other measures of obesity showed a positive relationship with systolic blood pressure (SBP), but not with diastolic (K5) blood pressure (DBP5). Measures of overnight sodium excretion were positively correlated with body weight and calculated body fat percentage, suggesting that heavier people indeed ingest more sodium. This may result not from increased intake of food per se, but from increased saltiness of diet, since calorie intake did not increase with body weight. No significant relationships were found between BP and concurrent measures of sodium excretion or diet saltiness.

Post-marketing studies of drug efficacy: why?

In order to quantify the need for post-marketing studies of drug efficacy, the 100 drug uses (i.e., drug-indication pairs) that were most common in 1978 were reviewed. Of the 100 most common drug uses, 31 were not Food and Drug Administration (FDA)-approved at the time of initial marketing and 18 had not become FDA-approved, even subsequently. In 13, the use was based on the drug's secondary effect rather than on the primary effects investigated before marketing. The efficacy of all was subject to modification by incompletely explored factors, including other drugs, patient age, other illnesses, pregnancy, etc. Specific examples are provided of important modifiers of the efficacy of these drugs that were not investigated prior to marketing. Thus, despite the existence of sufficient data for the regulatory process to permit the marketing of these commonly used drugs, considerable gaps remain in the information needed for their optimal clinical use. Post-marketing studies of drug efficacy will be needed to fill these gaps.

Post-marketing studies of drug efficacy: how?

This report reviews the 100 most recently approved drugs in order to quantify the frequency with which post-marketing studies of drug efficacy can be performed experimentally and non-experimentally. These drugs represent 131 potential drug uses. Of them, the absolute efficacy of 89 (68 percent) could be evaluated from clinical observations. Of the remaining 42, six (14 percent) could be studied experimentally or non-experimentally, six (14 percent) only experimentally, one (2 percent) only non-experimentally, and 29 (69 percent) by neither technique. Answers to all questions of relative efficacy required formal research. Of these, 94 (72 percent) could be studied using either experimental or non-experimental techniques. The remaining 37 (28 percent) could be studied experimentally only. Thus, clinical observations and non-experimental research can contribute a large proportion of the information about drug efficacy still needed after marketing.

Risk factors for retrolental fibroplasia: experience with 3,025 premature infants. National Collaborative Study on Patent Ductus Arteriosus in Premature Infants.

The rate of retrolental fibroplasia in relation to prenatal and neonatal characteristics was explored on the basis of a cohort of 3,025 neonates with birth weight less than 1,750 g. The overall rate of retrolental fibroplasia of any degree at hospital discharge was 11%, varying from 43% for those with birth weight between 500 and 749 g to 3% for those in the 1,500- to 1,750-g category. Among the potential determinants, the main interest was in nonhyperoxic characteristics, conditional on measures of prematurity and oxygen supplementation. Maternal diabetes and antihistamine use during the last 2 weeks of pregnancy were associated with significantly higher rates of retrolental fibroplasia, whereas toxemia was associated with lower rates. Frequent apneic spells, bronchopulmonary dysplasia, and sepsis in the neonate were also associated with significantly higher rates. On the other hand, the data indicate no independent role of low Apgar score, intraventricular hemorrhage, exchange transfusion, patent ductus arteriosus, or certain other characteristics previously postulated as risk factors.

Electrocardiogram of the premature infant at 1 year of age.

ECGs were examined from 461 premature infants at 1 year of age. Data from those without a history of bronchopulmonary dysplasia were generally similar to published norms for healthy 1-year old infants. History and persistence of residual lung disease were reflected in the ECG by a high prevalence of findings suggestive of right ventricular hypertrophy. Clinically significant patent ductus arteriosus during the neonatal period did not influence the 1-year ECG findings. The data expand the published experience with follow-up ECGs from premature infants and suggest that the ECG may be a useful tool in follow-up of chronic residual lung disease in this population.

Congenital valvular aortic stenosis: clinical detection of small pressure gradient. Prepared for the joint study on the joint study on the natural history of congenital heart defects.

Clinical variables (from the history, physical examination, electrocardiogram and chest radiograph) were related to the pressure gradient measured between the left ventricle and the aorta in 434 young patients with congenital valvular aortic stenosis admitted to a national collaborative study. The aim was to devise a composite clinical criterion for the recognition of patients with a small pressure gradient, so as to expand the opportunity for avoiding cardiac catheterization in such patients. Flattened or inverted T waves in lead V6 were found to be inconsistent with mild disease. Therefore, a composite criterion, providing an estimate of pressure gradient, was developed for patients without T wave changes. The final criterion, based on multivariate analysis, involved only the intensity of the systolic murmor, the presence or absence of an early diastolic murmur, and voltages of the Q and R waves in lead V6. Patients with a low estimate by this procedure rarely had a large measured gradient. Only 3.7 percent (6 of 161) with an estimated gradient of less than 45 mm Hg had a gradient at cardiac catheterization of 80 or more mm Hg; none (0 of 32) with an estimated gradient of less than 30 mm Hg had a gradient of 50 or more mm Hg. This criterion should be helpful in avoiding unnecessary catheterization by identifying some patients with valvular aortic stenosis who have a small pressure gradient.

Side effects of non-narcotic analgesics as a determinant of prescribing.

In the prescription of non-narcotic analgesics the physician's main responsibility is to make sure that the quality-of-life improvement expected from the drug's use justifies the associated risk, low though it is, of fatal side effects. The range of acceptable risk depends, naturally, on the dosage and duration of the treatment and on those characteristics of the patient which bear on the drug's efficacy and safety. In the treatment of acute pain an additional, very important, factor is the patient's remaining life expectancy. Quantification of maximal acceptable risks is aided by formal decision-analytic considerations. Such analyses indicate that maximal acceptable risks vary by several orders of magnitude among various clinical situations and that they are more liberal than intuition might generally suggest.